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31/07/2020 Manuscript
The Multidimensional Challenge of Treating COVID-19: Remdesivir is a F...

The Multidimensional Challenge of Treating COVID-19: Remdesivir is a Foot in the Door

OXFORD ACADEMY

Authors
Rajesh T Gandhi



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31/07/2020 Articles
Recombinant SARS-CoV-2 spike S1-Fc fusion protein induced high levels ...

Recombinant SARS-CoV-2 spike S1-Fc fusion protein induced high levels of neutralizing responses in nonhuman primates

ELSEVIER

Authors
Wenlin Ren, Hunter Sun, George F. Gao, Jianxin Chen, Sean Sun, Rongqing Zhao, Guang Gao, Yalin Hu, Gan Zhao, Yuxin Chen, Xia Jin, Feng Fang, Jinggong Chen, Qi Wang, Sitao Gong, Wen Gao, Yufei Sun, Junchi Su, Ailiang He, Xin Cheng, Min Li, Chenxi Xia, Maohua Li, Le Sun



ABSTRACT
The COVID-19 outbreak has become a global pandemic responsible for over 2,000,000 confirmed cases and over 126,000 deaths worldwide. In this study, we examined the immunogenicity of CHO-expressed recombinant SARS-CoV-2 S1-Fc fusion protein in mice, rabbits, and monkeys as a potential candidate for a COVID-19 vaccine. We demonstrate that the S1-Fc fusion protein is extremely immunogenic, as evidenced by strong antibody titers observed by day 7. Strong virus neutralizing activity was observed on day 14 in rabbits immunized with the S1-Fc fusion protein using a pseudovirus neutralization assay. Most importantly, in <20 days and three injections of the S1-Fc fusion protein, two monkeys developed higher virus neutralizing titers than a recovered COVID-19 patient in a live SARS-CoV-2 infection assay. Our data strongly suggests that the CHO-expressed SARS-CoV-2 S1-Fc recombinant protein could be a strong candidate for vaccine development against COVID-19.

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30/07/2020 PERSPECTIVE
Emerging evidence of a COVID-19 thrombotic syndrome has treatment impl...

Emerging evidence of a COVID-19 thrombotic syndrome has treatment implications

NATURE

Authors
Joan T. Merrill, Doruk Erkan, Jerald Winakur, Judith A. James



ABSTRACT
Reports of widespread thromboses and disseminated intravascular coagulation (DIC) in patients with coronavirus disease 19 (COVID-19) have been rapidly increasing in number. Key features of this disorder include a lack of bleeding risk, only mildly low platelet counts, elevated plasma fibrinogen levels, and detection of both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and complement components in regions of thrombotic microangiopathy (TMA). This disorder is not typical DIC. Rather, it might be more similar to complement-mediated TMA syndromes, which are well known to rheumatologists who care for patients with severe systemic lupus erythematosus or catastrophic antiphospholipid syndrome. This perspective has critical implications for treatment. Anticoagulation and antiviral agents are standard treatments for DIC but are gravely insufficient for any of the TMA disorders that involve disorders of complement. Mediators of TMA syndromes overlap with those released in cytokine storm, suggesting close connections between ineffective immune responses to SARS-CoV-2, severe pneumonia and life-threatening microangiopathy.

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29/07/2020 Manuscript
The risk of COVID-19 transmission in train passengers: an epidemiologi...

The risk of COVID-19 transmission in train passengers: an epidemiological and modelling study

OXFORD ACADEMY

Authors
Maogui Hu, Hui Lin, Jinfeng Wang, Chengdong Xu, Andrew J Tatem, Bin Meng, Xin Zhang, Yifeng Liu, Pengda Wang, Guizhen Wu, Haiyong Xie, Shengjie Lai



ABSTRACT
Background Train is a common mode of public transport across the globe; however, the risk of COVID-19 transmission among individual train passengers remains unclear.
Methods We quantified the transmission risk of COVID-19 on high-speed train passengers using data from 2,334 index patients and 72,093 close contacts who had co-travel times of 0–8 hours from 19 December 2019 through 6 March 2020 in China. We analysed the spatial and temporal distribution of COVID-19 transmission among train passengers to elucidate the associations between infection, spatial distance, and co-travel time.
Results The attack rate in train passengers on seats within a distance of 3 rows and 5 columns of the index patient varied from 0 to 10.3% (95% confidence interval [CI] 5.3% – 19.0%), with a mean of 0.32% (95%CI 0.29% – 0.37%). Passengers in seats on the same row as the index patient had an average attack rate of 1.5% (95%CI 1.3% – 1.8%), higher than that in other rows (0.14%, 95%CI 0.11% – 0.17%), with a relative risk (RR) of 11.2 (95%CI 8.6 –14.6). Travellers adjacent to the index patient had the highest attack rate (3.5%, 95%CI 2.9% – 4.3%) of COVID-19 infections (RR 18.0, 95%CI 13.9 – 23.4) among all seats. The attack rate decreased with increasing distance, but it increased with increasing co-travel time. The attack rate increased on average by 0.15% (p = 0.005) per hour of co-travel; for passengers at adjacent seats, this increase was 1.3% (p = 0.008), the highest among all seats considered.
Conclusions COVID-19 has a high transmission risk among train passengers, but this risk shows significant differences with co-travel time and seat location. During disease outbreaks, when travelling on public transportation in confined spaces such as trains, measures should be taken to reduce the risk of transmission, including increasing seat distance, reducing passenger density, and use of personal hygiene protection.

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28/07/2020 Articles
Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Pri...

Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
K.S. Corbett, B. Flynn, K.E. Foulds, J.R. Francica, S. Boyoglu‐Barnum, A.P. Werner, B. Flach, S. O’Connell, K.W. Bock, M. Minai, B.M. Nagata, H. Andersen, D.R. Martinez, A.T. Noe, N. Douek, M.M. Donaldson, N.N. Nji, G.S. Alvarado, D.K. Edwards, D.R. Flebbe, E. Lamb, N.A. Doria‐Rose, B.C. Lin, M.K. Louder, S. O’Dell, S.D. Schmidt, E. Phung, L.A. Chang, C. Yap, J.-P.M. Todd, L. Pessaint, A. Van Ry, S. Browne, J. Greenhouse, T. Putman‐Taylor, A. Strasbaugh, T.-A. Campbell, A. Cook, A. Dodson, K. Steingrebe, W. Shi, Y. Zhang, O.M. Abiona, L. Wang, A. Pegu, E.S. Yang, K. Leung, T. Zhou, I-T. Teng, A. Widge, I. Gordon, L. Novik, R.A. Gillespie, R.J. Loomis, J.I. Moliva, G. Stewart‐Jones, S. Himansu, W.-P. Kong, M.C. Nason, K.M. Morabito, T.J. Ruckwardt, J.E. Ledgerwood, M.R. Gaudinski, P.D. Kwong, J.R. Mascola, A. Carfi, M.G. Lewis, R.S. Baric, A. McDermott, I.N. Moore, N.J. Sullivan, M. Roederer, R.A. Seder, and B.S. Graham



ABSTRACT
BACKGROUND Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on viral replication in both upper and lower airways is important to evaluate in nonhuman primates.
METHODS Nonhuman primates received 10 or 100 μg of mRNA-1273, a vaccine encoding the prefusion-stabilized spike protein of SARS-CoV-2, or no vaccine. Antibody and T-cell responses were assessed before upper- and lower-airway challenge with SARS-CoV-2. Active viral replication and viral genomes in bronchoalveolar-lavage (BAL) fluid and nasal swab specimens were assessed by polymerase chain reaction, and histopathological analysis and viral quantification were performed on lung-tissue specimens.
RESULTS The mRNA-1273 vaccine candidate induced antibody levels exceeding those in human convalescent-phase serum, with live-virus reciprocal 50% inhibitory dilution (ID50) geometric mean titers of 501 in the 10-μg dose group and 3481 in the 100-μg dose group. Vaccination induced type 1 helper T-cell (Th1)–biased CD4 T-cell responses and low or undetectable Th2 or CD8 T-cell responses. Viral replication was not detectable in BAL fluid by day 2 after challenge in seven of eight animals in both vaccinated groups. No viral replication was detectable in the nose of any of the eight animals in the 100-μg dose group by day 2 after challenge, and limited inflammation or detectable viral genome or antigen was noted in lungs of animals in either vaccine group.
CONCLUSIONS Vaccination of nonhuman primates with mRNA-1273 induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung. (Funded by the National Institutes of Health and others.)

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28/07/2020 Articles
Pharmacokinetics/Pharmacodynamics of Antiviral Agents Used to Treat SA...

Pharmacokinetics/Pharmacodynamics of Antiviral Agents Used to Treat SARS‐CoV‐2 and Their Potential Interaction with Drugs and Other Supportive Measures: A Comprehensive Review by the PK/PD of Anti‐Infectives Study Group of the European Society of Antimicrobial Agents

CLINICAL PHARMACOKINETICS

Authors
Markus Zeitlinger, Birgit C P Koch, Roger Bruggemann, Pieter De Cock, Timothy Felton, Maya Hites, Jennifer Le, Sonia Luque, Alasdair P MacGowan, Deborah J E Marriott, Anouk E Muller, Kristina Nadrah, David L Paterson, Joseph F Standing, João P Telles, Michael Wölfl-Duchek, Michael Thy, Jason A Roberts



ABSTRACT
There is an urgent need to identify optimal antiviral therapies for COVID-19 caused by SARS-CoV-2. We have conducted a rapid and comprehensive review of relevant pharmacological evidence, focusing on (1) the pharmacokinetics (PK) of potential antiviral therapies; (2) coronavirus-specific pharmacodynamics (PD); (3) PK and PD interactions between proposed combination therapies; (4) pharmacology of major supportive therapies; and (5) anticipated drug-drug interactions (DDIs). We found promising in vitro evidence for remdesivir, (hydroxy)chloroquine and favipiravir against SARS-CoV-2; potential clinical benefit in SARS-CoV-2 with remdesivir, the combination of lopinavir/ritonavir (LPV/r) plus ribavirin; and strong evidence for LPV/r plus ribavirin against Middle East Respiratory Syndrome (MERS) for post-exposure prophylaxis in healthcare workers. Despite these emerging data, robust controlled clinical trials assessing patient-centred outcomes remain imperative and clinical data have already reduced expectations with regard to some drugs. Any therapy should be used with caution in the light of potential drug interactions and the uncertainty of optimal doses for treating mild versus serious infections.

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27/07/2020 PERSPECTIVE
Self-disseminating vaccines to suppress zoonoses

NATURE

Authors
Scott L. Nuismer, James J. Bull



ABSTRACT
The SARS-CoV-2 epidemic is merely the most recent demonstration that our current approach to emerging zoonotic infectious disease is ineffective. SARS, MERS, Ebola, Nipah and an array of arenavirus infections sporadically spillover into human populations and are often contained only as a result of their poor transmission in human hosts, coupled with intense public health control efforts in the early stages of an emerging epidemic. It is now more apparent than ever that we need a better and more proactive approach. One possibility is to eliminate the threat of spillover before it occurs using vaccines capable of autonomously spreading through wild animal reservoirs. We are now poised to begin developing self-disseminating vaccines targeting a wide range of human pathogens, but important decisions remain about how they can be most effectively designed and used to target pathogens with a high risk of spillover and/or emergence. In this Perspective, we first review the basic epidemiological theory establishing the feasibility and utility of self-disseminating vaccines. We then outline a road map for overcoming remaining technical challenges: identifying high-risk pathogens before they emerge, optimizing vaccine design with an eye to evolution, behaviour and epidemiology, and minimizing the risk of unintended consequences.

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25/07/2020 Comment
Offline: Preparing for a vaccine against COVID-19

THE LANCET

Authors
Richard Horton



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24/07/2020 Articles
Discovery of SARS-CoV-2 antiviral drugs through large-scale compound r...

Discovery of SARS-CoV-2 antiviral drugs through large-scale compound repurposing

NATURE

Authors
Laura Riva, Shuofeng Yuan, Xin Yin, Laura Martin-Sancho, Naoko Matsunaga, Lars Pache, Sebastian Burgstaller-Muehlbacher, Paul D. De Jesus, Peter Teriete, Mitchell V. Hull, Max W. Chang, Jasper Fuk-Woo Chan, Jianli Cao, Vincent Kwok-Man Poon, Kristina M. Herbert, Kuoyuan Cheng, Tu-Trinh H. Nguyen, Andrey Rubanov, Yuan Pu, Courtney Nguyen, Angela Choi, Raveen Rathnasinghe, Michael Schotsaert, Lisa Miorin, Marion Dejosez, Thomas P. Zwaka, Ko-Yung Sit, Luis Martinez-Sobrido, Wen-Chun Liu, Kris M. White, Mackenzie E. Chapman, Emma K. Lendy, Richard J. Glynne, Randy Albrecht, Eytan Ruppin, Andrew D. Mesecar, Jeffrey R. Johnson, Christopher Benner, Ren Sun, Peter G. Schultz, Andrew I. Su, Adolfo García-Sastre, Arnab K. Chatterjee, Kwok-Yung Yuen & Sumit K. Chanda



ABSTRACT
The emergence of the novel SARS coronavirus 2 (SARS-CoV-2) in 2019 has triggered an ongoing global pandemic of severe pneumonia-like disease designated as coronavirus disease 2019 (COVID-19)1. The development of a vaccine is likely to require at least 12-18 months, and the typical timeline for approval of a novel antiviral therapeutic can exceed 10 years. Thus, repurposing of known drugs could significantly accelerate the deployment of novel therapies for COVID-19. Towards this end, we profiled a library of known drugs encompassing approximately 12,000 clinical-stage or FDA-approved small molecules. We report the identification of 100 molecules that inhibit viral replication, including 21 known drugs that exhibit dose response relationships. Of these, thirteen were found to harbor effective concentrations likely commensurate with achievable therapeutic doses in patients, including the PIKfyve kinase inhibitor apilimod2–4, and the cysteine protease inhibitors MDL-28170, Z LVG CHN2, VBY-825, and ONO 5334. Notably, MDL-28170, ONO 5334, and apilimod were found to antagonize viral replication in human iPSC-derived pneumocyte-like cells, and the PIKfyve inhibitor also demonstrated antiviral efficacy in a primary human lung explant model. Since most of the molecules identified in this study have already advanced into the clinic, the known pharmacological and human safety profiles of these compounds will enable accelerated preclinical and clinical evaluation of these drugs for the treatment of COVID-19.

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23/07/2020 Letter
High doses of hydroxychloroquine do not affect viral clearance in pati...

High doses of hydroxychloroquine do not affect viral clearance in patients with SARS-CoV-2 infection.

WILEY ONLINE LIBRARY

Authors
Lucia Taramasso, Antonio Di Biagio, Malgorzata Mikulska, Daniele Roberto, Giacobbe Antonio Vena, Chiara Dentone, Andrea De Maria, Emanuele Delfino, Marco Berruti, Chiara Russo, Andrea Orsi, Bianca Bruzzone, Matteo Bassetti



ABSTRACT
The use of hydroxychloroquine (HCQ) has been considered a therapeutic option by international guidelines and expert opinions during the first phase of COVID‐19 pandemics, 1‐10 although scientific evidence remained too scarce to make a definitive recommendation 11. While HCQ use has now been questioned by recent data 7, some previous works draw attention to contrasting results on enhanced viral clearance after HCQ treatment

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23/07/2020 Articles
Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Co...

Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
A.B. Cavalcanti, F.G. Zampieri, R.G. Rosa, L.C.P. Azevedo, V.C. Veiga, A. Avezum, L.P. Damiani, A. Marcadenti, L. Kawano-Dourado, T. Lisboa, D.L.M. Junqueira, P.G.M. de Barros e Silva, L. Tramujas, E.O. Abreu-Silva, L.N. Laranjeira, A.T. Soares, L.S. Echenique, A.J. Pereira, F.G.R. Freitas, O.C.E. Gebara, V.C.S. Dantas, R.H.M. Furtado, E.P. Milan, N.A. Golin, F.F. Cardoso, I.S. Maia, C.R. Hoffmann Filho, A.P.M. Kormann, R.B. Amazonas, M.F. Bocchi de Oliveira, A. Serpa-Neto, M. Falavigna, R.D. Lopes, F.R. Machado, O. Berwanger



ABSTRACT
BACKGROUND Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited.
METHODS We conducted a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed.
RESULTS A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. As compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% confidence interval [CI], 0.69 to 2.11; P=1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P=1.00). Prolongation of the corrected QT interval and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin, than in those who were not receiving either agent.
CONCLUSIONS Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care. (Funded by the Coalition Covid-19 Brazil and EMS Pharma; ClinicalTrials.gov number, NCT04322123. opens in new tab.)

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23/07/2020 Comment
Next-generation vaccine platforms for COVID-19

NATURE

Authors
Debby van Riel, Emmie de Wit


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22/07/2020 Articles
Chloroquine does not inhibit infection of human lung cells with SARS-C...

Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2

NATURE

Authors
Markus Hoffmann, Kirstin Mösbauer, Heike Hofmann-Winkler, Artur Kaul, Hannah Kleine-Weber, Nadine Krüger, Nils C. Gassen, Marcel A. Müller, Christian Drosten, Stefan Pöhlmann



ABSTRACT
The COVID-19 pandemic, which is caused by the novel coronavirus SARS-CoV-2, has been associated with more than 470,000 fatal cases worldwide. In order to develop antiviral interventions quickly, drugs used for treatment of unrelated diseases are currently being repurposed to combat COVID-19. Chloroquine is a anti-malaria drug that is frequently employed for COVID-19 treatment since it inhibits SARS-CoV-2 spread in the kidney-derived cell line Vero1–3. Here, we show that engineered expression of TMPRSS2, a cellular protease that activates SARS-CoV-2 for entry into lung cells4, renders SARS-CoV-2 infection of Vero cells insensitive to chloroquine. Moreover, we report that chloroquine does not block SARS-CoV-2 infection of the TMPRSS2-positive lung cell line Calu-3. These results indicate that chloroquine targets a pathway for viral activation that is not operative in lung cells and is unlikely to protect against SARS-CoV-2 spread in and between patients.

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20/07/2020 Comment
Encouraging results from phase 1/2 COVID-19 vaccine trials

THE LANCET

Authors
Naor Bar-Zeev, William J Moss


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20/07/2020 Articles
Immunogenicity and safety of a recombinant adenovirus type-5-vectored ...

Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo- controlled, phase 2 trial

THE LANCET

Authors
Feng-Cai Zhu, Xu-Hua Guan, Yu-Hua Li, Jian-Ying Huang, Tao Jiang, Li-Hua Hou, Jing-Xin Li, Bei-Fang Yang, Ling Wang, Wen-Juan Wang, Shi-Po Wu, Zhao Wang, Xiao-Hong Wu, Jun-Jie Xu, Zhe Zhang, Si-Yue Jia, Bu-Sen Wang, Yi Hu, Jing-Jing Liu, Jun Zhang, Xiao-Ai Qian, Qiong Li, Hong-Xing Pan, Hu-Dachuan Jiang, Peng Deng, Jin-Bo Gou, Xue-Wen Wang, Xing-Huan Wang, Wei Chen


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20/07/2020 Articles
Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-...

Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial

THE LANCET

Authors
Pedro M Folegatti, Katie J Ewer, Parvinder K Aley, Brian Angus, Stephan Becker, Sandra Belij-Rammerstorfer, Duncan Bellamy, Sagida Bibi, Mustapha Bittaye, Elizabeth A Clutterbuck, Christina Dold, Saul N Faust, Adam Finn, Amy L Flaxman, Bassam Hallis, Paul Heath, Daniel Jenkin, Rajeka Lazarus, Rebecca Makinson, Angela M Minassian, Katrina M Pollock, Maheshi Ramasamy, Hannah Robinson, Matthew Snape, Richard Tarrant, Merryn Voysey, Catherine Green, Alexander D Douglas, Adrian V S Hill, Teresa Lambe, Sarah C Gilbert, Andrew J Pollard


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18/07/2020 Reviews
Vaccines for COVID-19: The current state of play

ELSEVIER

Authors
Archana Koirala, Ye Jin Joo, Ameneh Khatami, Clayton Chiu, Philip N. Britton



ABSTRACT
There is a strong consensus globally that a COVID-19 vaccine is likely the most effective approach to sustainably controlling the COVID-19 pandemic. An unprecedented research effort and global coordination has resulted in a rapid development of vaccine candidates and initiation of trials. Here, we review vaccine types, and progress with 10 vaccine candidates against SARS-CoV-2 – the virus that causes COVID-19 – currently undergoing early phase human trials. We also consider the many challenges of developing and deploying a new vaccine on a global scale, and recommend caution with respect to our expectations of the timeline that may be ahead.

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16/07/2020 Communication
Convalescent plasma treatment for SARS-CoV-2 infection: analysis of th...

Convalescent plasma treatment for SARS-CoV-2 infection: analysis of the first 436 donors in England, 22 April to 12 May 2020

EUROSUIRVELLANCE

Authors
Heli Harvala, Jennifer Mehew, Matthew L Robb, Samreen Ijaz, Steven Dicks, Monika Patel, Nicholas Watkins, Peter Simmonds, Tim Brooks, Rachel Johnson, Robin Gopal, David J Roberts, Maria Zambon



ABSTRACT
Serological reactivity was analysed in plasma from 436 individuals with a history of disease compatible with COVID-19, including 256 who had been laboratory-confirmed with SARS-CoV-2 infection. Over 99% of laboratory-confirmed cases developed a measurable antibody response (254/256) and 88% harboured neutralising antibodies (226/256). Antibody levels declined over 3 months following diagnosis, emphasising the importance of the timing of convalescent plasma collections. Binding antibody measurements can inform selection of convalescent plasma donors with high neutralising antibody levels.

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16/07/2020 Articles
Pharmacological and non-pharmacological efforts at prevention, mitigat...

Pharmacological and non-pharmacological efforts at prevention, mitigation, and treatment for COVID-19

FRANCIS & TAYLOR ONLINE

Authors
Mohammed M. Alvi ,Sowmya Sivasankaran, Mahima Singh



ABSTRACT
A global outbreak of the SARS-CoV-2 virus has infected millions of people over a short period of time. The communicability and increased mortality from the SARS-CoV-2 infection mandated the WHO to declare COVID-19 a worldwide pandemic. The virus outbreak has spread when there are no approved vaccines, treatments, or prophylactic therapies available. Researchers from all over the world have prioritised development of vaccines and antivirals. Several vaccine projects have seen successes in preclinical, phase I, and phase II clinical trials using recombinant DNA, mRNA, live attenuated virus, S-protein subunits, virus like particles, and viral vectors. Initial findings from antivirals such as remdesivir, favipiravir, danoprevir or lopinavir with ritonavir are presented. Immunomodulatory molecules such as sarilumab, tocilizumab, janus kinase inhibitors, and hyperimmune convalescent plasma have mixed outcomes from initial clinical findings; however, pending randomised controlled trials will assist national health institutions to make treatment recommendations for COVID-19. Where compassionate use of remdesivir has shown some benefits, therapies such as hydroxychloroquine have proven harmful due to their toxicities. This review discusses pharmacological interventions at play and evidence-based successes and limitations of non-pharmacological therapies such as social distancing, personal protective equipment, and ventilator support associated with the prevention and treatment of COVID-19.

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15/07/2020 Articles
COVID-19 vaccine development and a potential nanomaterial path forward

NATURE

Authors
Matthew D. Shin, Sourabh Shukla, Young Hun Chung, Veronique Beiss, Soo Khim Chan, Oscar A. Ortega-Rivera, David M. Wirth, Angela Chen, Markus Sack, Jonathan K. Pokorski, Nicole F. Steinmetz



ABSTRACT
The COVID-19 pandemic has infected millions of people with no clear signs of abatement owing to the high prevalence, long incubation period and lack of established treatments or vaccines. Vaccines are the most promising solution to mitigate new viral strains. The genome sequence and protein structure of the 2019-novel coronavirus (nCoV or SARS-CoV-2) were made available in record time, allowing the development of inactivated or attenuated viral vaccines along with subunit vaccines for prophylaxis and treatment. Nanotechnology benefits modern vaccine design since nanomaterials are ideal for antigen delivery, as adjuvants, and as mimics of viral structures. In fact, the first vaccine candidate launched into clinical trials is an mRNA vaccine delivered via lipid nanoparticles. To eradicate pandemics, present and future, a successful vaccine platform must enable rapid discovery, scalable manufacturing and global distribution. Here, we review current approaches to COVID-19 vaccine development and highlight the role of nanotechnology and advanced manufacturing.

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14/07/2020 Articles
An mRNA Vaccine against SARS-CoV-2 — Preliminary Report

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
L.A. Jackson, E.J. Anderson, N.G. Rouphael, P.C. Roberts, M. Makhene, R.N. Coler, M.P. McCullough, J.D. Chappell, M.R. Denison, L.J. Stevens, A.J. Pruijssers, A. McDermott, B. Flach, N.A. Doria-Rose, K.S. Corbett, K.M. Morabito, S. O’Dell, S.D. Schmidt, P.A. Swanson II, M. Padilla, J.R. Mascola, K.M. Neuzil, H. Bennett, W. Sun, E. Peters, M. Makowski, J. Albert, K. Cross, W. Buchanan, R. Pikaart-Tautges, J.E. Ledgerwood, B.S. Graham, J.H. Beigel



ABSTRACT
BACKGROUND The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. The candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein.
METHODS We conducted a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 to 55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 μg, 100 μg, or 250 μg. There were 15 participants in each dose group.
RESULTS After the first vaccination, antibody responses were higher with higher dose (day 29 enzyme-linked immunosorbent assay anti–S-2P antibody geometric mean titer [GMT], 40,227 in the 25-μg group, 109,209 in the 100-μg group, and 213,526 in the 250-μg group). After the second vaccination, the titers increased (day 57 GMT, 299,751, 782,719, and 1,192,154, respectively). After the second vaccination, serum-neutralizing activity was detected by two methods in all participants evaluated, with values generally similar to those in the upper half of the distribution of a panel of control convalescent serum specimens. Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250-μg dose group reported one or more severe adverse events.
CONCLUSIONS The mRNA-1273 vaccine induced anti–SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 ClinicalTrials.gov number, NCT04283461. opens in new tab).

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13/07/2020 Highlights
Successful treatment with plasma exchange followed by intravenous immu...

Successful treatment with plasma exchange followed by intravenous immunoglobulin in a critically ill patient with COVID-19

ELSEVIER

Authors
Hua Shi, Chaomin Zhoua, Pinghong Hea, Sheng Huang, Youjun Duanb, Xuesheng Wang , Kexiong Linb, Chao Zhoub, Xiangyan Zhangc, Yan Zhaa



ABSTRACT
Here we report a case of a laboratory-confirmed 2019 novel coronavirus (2019-nCoV)-infected patient with COVID-19 (coronavirus disease 2019) who developed respiratory failure and shock accompanied by persistent diarrhoea despite conventional therapeutic interventions. The patient avoided mechanical ventilation and showed an immediate clinical and radiological improvement following treatment with intensive plasma exchange (PE) followed by intravenous immunoglobulin (IVIG). Successful therapeutic strategies in this case suggest that timely initiation of PE treatment followed by IVIG in critically ill patients with COVID-19 may prevent the disease from worsening and help to reduce the requirement for mechanical ventilation and intensive supportive care. Moreover, it may improve poor clinical outcomes of these patients.

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13/07/2020 Articles
Immune-mediated approaches against COVID-19

NATURE

Authors
Helena F. Florindo, Ron Kleiner, Daniella Vaskovich-Koubi, Rita C. Acúrcio, Barbara Carreira, Eilam Yeini, Galia Tiram, Yulia Liubomirski, Ronit Satchi-Fainaro



ABSTRACT
The coronavirus disease-19 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The long incubation period of this new virus, which is mostly asymptomatic yet contagious, is a key reason for its rapid spread across the world. Currently, there is no worldwide-approved treatment for COVID-19. Therefore, the clinical and scientific communities have joint efforts to reduce the severe impact of the outbreak. Research on previous emerging infectious diseases have created valuable knowledge that is being exploited for drug repurposing and accelerated vaccine development. Nevertheless, it is important to generate knowledge on SARS-CoV-2 mechanisms of infection and its impact on host immunity, to guide the design of COVID-19 specific therapeutics and vaccines suitable for mass immunization. Nanoscale delivery systems are expected to play a paramount role in the success of these prophylactic and therapeutic approaches. This Review provides an overview of SARS-CoV-2 pathogenesis and examines immune-mediated approaches currently explored for COVID-19 treatments, with an emphasis on nanotechnological tools.

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12/07/2020 Letter
Insights from compassionate use of tocilizumab for COVID‐19 to inform ...

Insights from compassionate use of tocilizumab for COVID‐19 to inform appropriate design of randomised controlled trials

BRITISH PHARMACOLOGICAL SOCIETY

Authors
Emma H. Baker Kamal Patel Jonathan Ball Sarah Edwards Thomas S. Harrison Arvind Kaul Mickey Koh Sanjeev Krishna Susannah Leaver Vinodh Kumar Daniel M. Forton


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10/07/2020 Reviews
That Escalated Quickly: Remdesivir's Place in Therapy

SPRINGER LINK

Authors
Matthew R. Davis, Erin K. McCreary, Jason M. Pogue



ABSTRACT
Remdesivir is a nucleoside antiviral recently studied in several randomized trials for treatment of COVID-19. The available observational and prospective data are conflicting, requiring clinicians to critically evaluate and reconcile results to determine patient populations that may optimally benefit from remdesivir therapy, especially while drug supply is scarce. In this review, we analyze pertinent clinical remdesivir data for patients with COVID-19 from January 1, 2020, through May 31, 2020.

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10/07/2020 Comment
Planning for COVID-19 vaccines safety surveillance

ELSEVIER

Authors
SonaliKochharab, Daniel A.Salmonc


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09/07/2020 Comment
Retraction and republication: cardiac toxicity of hydroxychloroquine i...

Retraction and republication: cardiac toxicity of hydroxychloroquine in COVID-19

THE LANCET

Authors
Christian Funck-Brentano, Lee S Nguyen, Joe-Elie Salem


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09/07/2020 Reviews
Current pharmacological modalities for management of novel coronavirus...

Current pharmacological modalities for management of novel coronavirus disease 2019 (COVID‐19) and the rationale for their utilization: A review

WILEY ONLINE LIBRARY

Authors
Richard A. Giovane, Shadi Rezai, Ellen Cleland, Cassandra E. Henderson



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03/07/2020 Articles
COVID-19 Outpatients – Early Risk-Stratified Treatment with Zinc Plus ...

COVID-19 Outpatients – Early Risk-Stratified Treatment with Zinc Plus Low Dose Hydroxychloroquine and Azithromycin: A Retrospective Case Series Study

PRE PRINTS

Authors
Martin Scholz , Roland Derwand , Vladimir Zelenko



ABSTRACT
Objective: To describe outcomes of patients with coronavirus disease 2019 (COVID-19) in the outpatient setting after early treatment with zinc, low dose hydroxychloroquine, and azithromycin (the triple therapy) dependent on risk stratification. Design: Retrospective case series study. Setting: General practice. Participants: 141 COVID-19 patients with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the year 2020. Main Outcome Measures: Risk-stratified treatment decision, rate of hospitalization and all-cause death. Results: Of 335 positively PCR-tested COVID-19 patients, 127 were treated with the triple therapy. 104 of 127 met the defined risk stratification criteria and were included in the analysis. In addition, 37 treated and eligible patients who were confirmed by IgG tests were included in the treatment group (total N=141). 208 of the 335 patients did not meet the risk stratification criteria and were not treated. After 4 days (median, IQR 3-6, available for N=66/141) of onset of symptoms, 141 patients (median age 58 years, IQR 40-60; 73% male) got a prescription for the triple therapy for 5 days. Independent public reference data from 377 confirmed COVID-19 patients of the same community were used as untreated control. 4 of 141 treated patients (2.8%) were hospitalized, which was significantly less (p<0.001) compared with 58 of 377 untreated patients (15.4%) (odds ratio 0.16, 95% CI 0.06-0.5). Therefore, the odds of hospitalization of treated patients were 84% less than in the untreated group. One patient (0.7%) died in the treatment group versus 13 patients (3.5%) in the untreated group (odds ratio 0.2, 95% CI 0.03-1.5; p=0.16). There were no cardiac side effects. Conclusions: Risk stratification-based treatment of COVID-19 outpatients as early as possible after symptom onset with the used triple therapy, including the combination of zinc with low dose hydroxychloroquine, was associated with significantly less hospitalizations and 5 times less all-cause deaths.

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02/07/2020 Articles
A candidate multi‐epitope vaccine against SARS‐CoV‐2

NATURE

Authors
Tamalika Kar, Utkarsh Narsaria, Srijita Basak, Debashrito Deb, Filippo Castiglione, David M. Mueller, Anurag P. Srivastava



ABSTRACT
In the past two decades, 7 coronaviruses have infected the human population, with two major outbreaks caused by SARS-CoV and MERS-CoV in the year 2002 and 2012, respectively. Currently, the entire world is facing a pandemic of another coronavirus, SARS-CoV-2, with a high fatality rate. The spike glycoprotein of SARS-CoV-2 mediates entry of virus into the host cell and is one of the most important antigenic determinants, making it a potential candidate for a vaccine. In this study, we have computationally designed a multi-epitope vaccine using spike glycoprotein of SARS-CoV-2. The overall quality of the candidate vaccine was validated in silico and Molecular Dynamics Simulation confirmed the stability of the designed vaccine. Docking studies revealed stable interactions of the vaccine with Toll-Like Receptors and MHC Receptors. The in silico cloning and codon optimization supported the proficient expression of the designed vaccine in E. coli expression system. The efficiency of the candidate vaccine to trigger an effective immune response was assessed by an in silico immune simulation. The computational analyses suggest that the designed multi-epitope vaccine is structurally stable which can induce specific immune responses and thus, can be a potential vaccine candidate against SARS-CoV-2.

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02/07/2020 Articles
Treatment with Hydroxychloroquine, Azithromycin, and Combination in Pa...

Treatment with Hydroxychloroquine, Azithromycin, and Combination in Patients Hospitalized with COVID-19

ELSEVIER

Authors
Samia Arshad, Paul Kilgore, Zohra S. Chaudhry, Gordon Jacobsen, Dee Dee Wang, Kylie Huitsing, Indira Brar, George J. Alangaden, Mayur S. Ramesh, John E. McKinnon, William O’Neill, Marcus Zervos, Henry Ford, Varidhi Nauriyal, Asif Abdul Hamed, Owais Nadeem, Jennifer Swiderek, Amanda Godfrey, Jeffrey Jennings, Jayna Gardner-Gray, Adam M Ackerman, Jonathan Lezotte, Joseph Ruhala, Raef Fadel, Amit Vahia, Smitha Gudipati, Tommy Parraga, Anita Shallal, Gina Maki, Zain Tariq, Geehan Suleyman, Nicholas Yared, Erica Herc, Johnathan Williams, Odaliz Abreu Lanfranco, Pallavi Bhargava, Katherine Reyes, Anne Chen



ABSTRACT
Significance The United States is in an acceleration phase of the COVID-19 pandemic. Currently there is no known effective therapy or vaccine for treatment of SARS-CoV-2, highlighting urgency around identifying effective therapies. Objective The purpose of this study was to evaluate the role of hydroxychloroquine therapy alone and in combination with azithromycin in hospitalized patients positive for COVID-19. Design Multi-center retrospective observational study Setting The Henry Ford Health System (HFHS) in Southeast Michigan: large six hospital integrated health system; the largest of hospitals is an 802-bed quaternary academic teaching hospital in urban Detroit, Michigan. Participants Consecutive patients hospitalized with a COVID-related admission in the health system from March 10,2020 to May 2,2020 were included. Only the first admission was included for patients with multiple admissions. All patients evaluated were 18 years of age and older and were treated as inpatients for at least 48 hours unless expired within 24 hours. Exposure Receipt of hydroxychloroquine alone, hydroxychloroquine in combination with azithromycin, azithromycin alone, or neither. Main Outcome The primary outcome was in-hospital mortality. Results Of 2,541 patients, with a median total hospitalization time of 6 days (IQR: 4-10 days), median age was 64 years (IQR:53-76 years), 51% male, 56% African American, with median time to follow-up of 28.5 days (IQR:3-53). Overall in-hospital mortality was 18.1% (95% CI:16.6%-19.7%); by treatment: hydroxychloroquine + azithromycin, 157/783 (20.1% [95% CI: 17.3%-23.0%]), hydroxychloroquine alone, 162/1202 (13.5% [95% CI: 11.6%-15.5%]), azithromycin alone, 33/147 (22.4% [95% CI: 16.0%-30.1%]), and neither drug, 108/409 (26.4% [95% CI: 22.2%-31.0%])​. Primary cause of mortality was respiratory failure (88%); no patient had documented torsades de pointes. From Cox regression modeling, predictors of mortality were age>65 years (HR:2.6 [95% CI:1.9-3.3]), white race (HR:1.7 [95% CI:1.4-2.1]), CKD (HR:1.7 [95%CI:1.4-2.1]), reduced O2 saturation level on admission (HR:1.5 [95%CI:1.1-2.1]), and ventilator use during admission (HR: 2.2 [95%CI:1.4-3.3]). Hydroxychloroquine provided a 66% hazard ratio reduction, and hydroxychloroquine + azithromycin 71% compared to neither treatment (p < 0.001). Conclusions and Relevance In this multi-hospital assessment, when controlling for COVID-19 risk factors, treatment with hydroxychloroquine alone and in combination with azithromycin was associated with reduction in COVID-19 associated mortality. Prospective trials are needed to examine this impact.

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02/07/2020 Articles
COVID-19 vaccine tracker

REGULATORY FOCUS

Authors
JEFF CRAVEN


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02/07/2020 Editorial
Potential drug‐drug interactions associated with drugs currently propo...

Potential drug‐drug interactions associated with drugs currently proposed for COVID‐19 treatment in patients receiving other treatments

WILEY ONLINE LIBRARY

Authors
Nicolas Venisse



ABSTRACT
Pharmacologists, pharmacists and other drug experts have been at the forefront during the COVID‐19 outbreak. Pharmacological expertise was required in various areas such as the daily healthcare of patients admitted to our hospitals [1], the implementation of pharmacokinetic and pharmacokinetic‐pharmacodynamic studies in clinical trials of repurposed drugs [2] and even in providing up‐to‐date information to the general population [3].

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01/07/2020 Advanced Research
COVID-19 Resources

AMERICAN SOCIETY OF HEMATOLOGY

Authors
AMERICAN SOCIETY OF HEMATOLOGY


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01/07/2020 Research
Treatment with ACE inhibitors or ARBs and risk of severe/lethal COVID-...

Treatment with ACE inhibitors or ARBs and risk of severe/lethal COVID-19: a meta-analysis

BMJ JOURNALS

Authors
Maria Elena Flacco, Cecilia Acuti Martellucci, Francesca Bravi, Giustino Parruti, Rosaria Cappadona, Alfonso Mascitelli, Roberto Manfredini, Lorenzo G Mantovani, Lamberto Manzoli



ABSTRACT
Objective It has been hypothesised that the use of ACE inhibitors and angiotensin receptor blockers (ARBs) might either increase or reduce the risk of severe or lethal COVID-19. The findings from the available observational studies varied, and summary estimates are urgently needed to elucidate whether these drugs should be suspended during the pandemic, or patients and physicians should be definitely reassured. This meta-analysis of adjusted observational data aimed to summarise the existing evidence on the association between these medications and severe/lethal COVID-19. Methods We searched MedLine, Scopus and preprint repositories up to 8 June 2020 to retrieve cohort or case–control studies comparing the risk of severe/fatal COVID-19 (either mechanical ventilation, intensive care unit admission or death), among hypertensive subjects treated with: (1) ACE inhibitors, (2) ARBs and (3) both, versus untreated subjects. Data were combined using a random-effect generic inverse variance approach. Results Ten studies, enrolling 9890 hypertensive subjects were included in the analyses. Compared with untreated subjects, those using either ACE inhibitors or ARBs showed a similar risk of severe or lethal COVID-19 (summary OR: 0.90; 95% CI 0.65 to 1.26 for ACE inhibitors; 0.92; 95% CI 0.75 to 1.12 for ARBs). The results did not change when both drugs were considered together, when death was the outcome and excluding the studies with significant, divergent results. Conclusion The present meta-analysis strongly supports the recommendation of several scientific societies to continue ARBs or ACE inhibitors for all patients, unless otherwise advised by their physicians who should thus be reassured.

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01/07/2020 Articles
Identification of a druggable binding pocket in the spike protein reve...

Identification of a druggable binding pocket in the spike protein reveals a key site for existing drugs potentially capable of combating Covid-19 infectivity

BMC

Authors
Elliot D. Drew, Robert W. Janes



ABSTRACT
Background Following the recent outbreak of the new coronavirus pandemic (Covid-19), the rapid determination of the structure of the homo-trimeric spike glycoprotein has prompted the study reported here. The aims were to identify potential “druggable” binding pockets in the protein and, if located, to virtual screen pharmaceutical agents currently in use for predicted affinity to these pockets which might be useful to restrict, reduce, or inhibit the infectivity of the virion.
Results Our analyses of this structure have revealed a key potentially druggable pocket where it might be viable to bind pharmaceutical agents to inhibit its ability to infect human cells. This pocket is found at the inter-chain interface that exists between two domains prior to the virion binding to human Angiotensin Converting Enzyme 2 (ACE2) protein. One of these domains is the highly mobile receptor binding domain, which must move into position to interact with ACE2, which is an essential feature for viral entry to the host cell. Virtual screening with a library of purchasable drug molecules has identified pharmaceuticals currently in use as prescription and over the counter medications that, in silico, readily bind into this pocket.
Conclusions This study highlights possible drugs already in use as pharmaceuticals that may act as agents to interfere with the movements of the domains within this protein essential for the infectivity processes and hence might slow, or even halt, the infection of host cells by this new coronavirus. As these are existing pharmaceuticals already approved for use in humans, this knowledge could accelerate their roll-out, through repurposing, for affected individuals and help guide the efforts of other researchers in finding effective treatments for the disease.

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29/06/2020 Articles
Numerical evaluation of spray position for improved nasal drug deliver...

Numerical evaluation of spray position for improved nasal drug delivery

NATURE

Authors
Saikat Basu, Landon T. Holbrook, Kathryn Kudlaty, Olulade Fasanmade, Jihong Wu, Alyssa Burke, Benjamin W. Langworthy, Zainab Farzal, Mohammed Mamdani, William D. Bennett, Jason P. Fine, Brent A. Senior, Adam M. Zanation, Charles S. Ebert Jr., Adam J. Kimple, Brian D. Thorp, Dennis O. Frank-Ito, Guilherme J. M. Garcia, Julia S. Kimbell


ABSTRACT
Topical intra-nasal sprays are amongst the most commonly prescribed therapeutic options for sinonasal diseases in humans. However, inconsistency and ambiguity in instructions show a lack of definitive knowledge on best spray use techniques. In this study, we have identified a new usage strategy for nasal sprays available over-the-counter, that registers an average 8-fold improvement in topical delivery of drugs at diseased sites, when compared to prevalent spray techniques. The protocol involves re-orienting the spray axis to harness inertial motion of particulates and has been developed using computational fluid dynamics simulations of respiratory airflow and droplet transport in medical imaging-based digital models. Simulated dose in representative models is validated through in vitro spray measurements in 3D-printed anatomic replicas using the gamma scintigraphy technique. This work breaks new ground in proposing an alternative user-friendly strategy that can significantly enhance topical delivery inside human nose. While these findings can eventually translate into personalized spray usage instructions and hence merit a change in nasal standard-of-care, this study also demonstrates how relatively simple engineering analysis tools can revolutionize everyday healthcare. Finally, with respiratory mucosa as the initial coronavirus infection site, our findings are relevant to intra-nasal vaccines that are in-development, to mitigate the COVID-19 pandemic.

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29/06/2020 Reviews
Drug targets for COVID-19 therapeutics: Ongoing global efforts

SPRINGER LINK

Authors
Ambrish Saxena



ABSTRACT
The current global pandemic COVID-19 caused by the SARS-CoV-2 virus has already inflicted insurmountable damage both to the human lives and global economy. There is an immediate need for identification of effective drugs to contain the disastrous virus outbreak. Global efforts are already underway at a war footing to identify the best drug combination to address the disease. In this review, an attempt has been made to understand the SARS-CoV-2 life cycle, and based on this information potential druggable targets against SARS-CoV-2 are summarized. Also, the strategies for ongoing and future drug discovery against the SARS-CoV-2 virus are outlined. Given the urgency to find a definitive cure, ongoing drug repurposing efforts being carried out by various organizations are also described. The unprecedented crisis requires extraordinary efforts from the scientific community to effectively address the issue and prevent further loss of human lives and health.

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28/06/2020 Articles
Effects of Hydroxychloroquine Treatment on QT Interval

ELSEVIER

Authors
MatthewHooks, Bradley Barty, OrlyVardeny, Anders Westanmo, Selçuk Adabag



ABSTRACT
Background Hydroxychloroquine (HCQ) has been promoted as a potential treatment for COVID-19 but there are safety concerns.
Objectives To determine the effect of HCQ treatment on QT interval
Methods We retrospectively studied the electrocardiograms of 819 patients treated with HCQ for rheumatologic diseases from 2000 to 2020. The primary outcome was corrected QT (QTc) interval, by Bazett formula, during HCQ therapy.
Results The patients were 64.0 (±10.9) years in age and 734 (90%) were men. The median dosage and duration of HCQ were 400mg daily and 1006 (471-2075) days, respectively. The mean on-treatment QTc was 430.9 (±31.8) msec. In total, 55 (7%) patients had QTc 470-500 msec and 12 (1.5%) had QTc >500msec. Chronic kidney disease (CKD), history of atrial fibrillation (AF) and heart failure were independent risk factors for prolonged QTc. In a subset of 591 patients who also had a pre-treatment ECG, the mean QTc increased from 424.4 (±29.7) msec. to 432.0 (±32.3) msec (p<0.0001) during HCQ treatment. Of these, 23 (3.9%) patients had either prolongation of QTc >15% or an on-treatment QTc >500 msec. Over 5.97 (3.33-10.11) years of follow-up, 269 (33%) patients died. QTc >470 msec during HCQ treatment was associated with a greater mortality risk of (hazard ratio 1.78, 95% confidence interval 1.16-2.71; p=0.008) in univariable but not in multivariable analysis.
Conclusion Hydroxychloroquine is associated with QT prolongation in a significant fraction of patients. The risk of QT prolongation is higher among patients with CKD, AF and heart failure, who may benefit from greater scrutiny.

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27/06/2020 Reviews
Corticosteroid administration for viral pneumonia: COVID-19 and beyond

ELSEVIER

Authors
W.Yang, L.Yang, R.-G.Luo, J.-F.Xu



ABSTRACT
Background Corticosteroids are commonly used as adjuvant therapy for acute respiratory distress syndrome by many clinicians because of their perceived anti-inflammatory effects. However, for patients with severe viral pneumonia, the corticosteroid treatment is highly controversial.
Objectives The purpose of this review is to systematically evaluate the effect and potential mechanism of corticosteroid administration in pandemic viral pneumonia.
Sources We comprehensively searched all manuscripts on corticosteroid therapy for influenza, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and SARS coronavirus 2 (SARS-CoV-2) viral pneumonia from the PubMed, EMBASE, Web of Science and Cochrane Library databases.
Content We systematically summarized the effects of corticosteroid therapy for pandemic viral pneumonia and the potential mechanism of action for corticosteroids in coronavirus disease 2019 (COVID-19).
Implications Observational studies showed that corticosteroid treatment was associated with increased mortality and nosocomial infections for influenza and delayed virus clearance for SARS-CoV and MERS-CoV. Limited data on corticosteroid therapy for COVID-19 were reported. Corticosteroids were used in about a fifth of patients (670/2995, 22.4%). Although clinical observational studies reported the improvement in symptoms and oxygenation for individuals with severe COVID-19 who received corticosteroid therapy, case fatality rate in the corticosteroid group was significantly higher than that in the non-corticosteroid group (69/443, 15.6% versus 56/1310, 4.3%). Compared individuals with non-severe disease, those with severe disease were more likely to receive corticosteroid therapy (201/382, 52.6% versus 201/1310, 15.3%). Although there is no evidence that corticosteroid therapy reduces mortality in people with COVID-19, some improvements in clinical symptoms and oxygenation were reported in some clinical observational studies. Excessive inflammatory response and lymphopenia might be critical factors associated with severity of and mortality from COVID-19. Sufficiently powered randomized controlled trials with rigorous inclusion/exclusion criteria and standardized dose and duration of corticosteroids are needed to verify the effectiveness and safety of corticosteroid therapy.

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27/06/2020 Articles
Ventricular Arrhythmia Risk Based on Ethnicity in COVID-19 Patients on...

Ventricular Arrhythmia Risk Based on Ethnicity in COVID-19 Patients on Hydroxychloroquine and Azithromycin Combination: Viewpoint

SPRINGER LINK

Authors
Sayak Roy, MainakMukhopadhyay



ABSTRACT
There are many reports available now, which are mostly observational or registry trial outcomes having varied results on coronavirus 2019 (COVID-19) patients put on hydroxychloroquine and azithromycin combination. Some are showing increased in-hospital mortality and ventricular arrhythmia increase, while some are showing overall benefit with significant viral RNA load reduction. Everyday things are getting more complicated with the publication of these different outcomes. This needs to be addressed.

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27/06/2020 Case Report
Successful recovery from COVID-19 pneumonia after receiving baricitini...

Successful recovery from COVID-19 pneumonia after receiving baricitinib, tocilizumab, and remdesivir. A case report: Review of treatments and clinical role of computed tomography analysis

ELSEVIER

Authors
Pietro Sodani, Luciano Mucci, Rita Girolimetti, Silvia Tedesco, Francesca Monaco, Daniele Campanozzi, Marino Brunori, Stefania Maltoni, Samuele Bedetta, Anna M. Di Carlo, Piero Candoli, Mauro Mancini, Alberto Rebonato, Francesca D'Adamo, Maria Capalbo, Gabriele Frausini



ABSTRACT
The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic, threatening global public health. In the current paper, we describe our successful treatment of one COVID-19 pneumonia patient case with high mortality risk factors. Our experience underlines the importance of the use of a multidisciplinary therapeutic approach in order to achieve a favorable clinical outcome. Further, enhancing the capability of the COVID-19 diagnosis with the use of the chest imaging modalities is discussed.

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27/06/2020 News
New potential interaction with emergency COVID-19 medicine remdesivir

SPRINGER LINK

Authors
SPRINGER LINK


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26/06/2020 PERSPECTIVE
Ensuring Uptake of Vaccines against SARS-CoV-2

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Michelle M. Mello, Ross D. Silverman, Saad B. Omer


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26/06/2020 Comment
Can tocilizumab calm the cytokine storm of COVID-19?

THE LANCET

Authors
Grant S Schulert


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25/06/2020 Press Release
First COVID-19 treatment recommended for EU authorisation

EUROPEAN MEDICINES AGENCY

Authors
EMA press office


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24/06/2020 Articles
Tocilizumab in patients with severe COVID-19: a retrospective cohort s...

Tocilizumab in patients with severe COVID-19: a retrospective cohort study

THE LANCET

Authors
Giovanni Guaraldi, Marianna Meschiari, Alessandro Cozzi-Lepri, Jovana Milic, Roberto Tonelli, Marianna Menozzi, Erica Franceschini, Gianluca Cuomo, Gabriella Orlando, Vanni Borghi, Antonella Santoro, Margherita Di Gaetano, Cinzia Puzzolante, Federica Carli, Andrea Bedini, Luca Corradi, Riccardo Fantini, Ivana Castaniere, Luca Tabbì, Massimo Girardis, Sara Tedeschi, Maddalena Giannella, Michele Bartoletti, Renato Pascale, Giovanni Dolci, Lucio Brugioni, Antonello Pietrangelo, Andrea Cossarizza, Federico Pea, Enrico Clini, Carlo Salvarani, Marco Massari, Pier Luigi Viale, Cristina Mussini


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24/06/2020 Original Investigation
Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biom...

Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019

JAMA

Authors
Spyridon G. Deftereos, Georgios Giannopoulos Dimitrios A. Vrachatis, Gerasimos D. Siasos, Sotiria G. Giotaki, Panagiotis Gargalianos, Simeon Metallidis, George Sianos, Stefanos Baltagiannis, Periklis Panagopoulos, Konstantinos Dolianitis, Efthalia Randou, Konstantinos Syrigos, Anastasia Kotanidou, Nikolaos G. Koulouris, Haralampos Milionis, Nikolaos Sipsas, Charalampos Gogos, George Tsoukalas, Christoforos D. Olympios, Eleftheria Tsagalou, Ilias Migdalis, Styliani Gerakari, Christos Angelidis, Dimitrios Alexopoulos, Pericles Davlouros, George Hahalis, Ioannis Kanonidis, Demosthenes Katritsis, Theofilos Kolettis, Antonios S. Manolis, Lampros Michalis, Katerina K. Naka, Vlasios N. Pyrgakis, Konstantinos P. Toutouzas, Filippos Triposkiadis, Konstantinos Tsioufis, Emmanouil Vavouranakis, Luis Martinèz-Dolz, Bernhard Reimers, Giulio G. Stefanini, Michael Cleman, John Goudevenos, Sotirios Tsiodras, Dimitrios Tousoulis, Efstathios Iliodromitis, Roxana Mehran, George Dangas, Christodoulos Stefanadis


ABSTRACT
Importance Severe acute respiratory syndrome coronavirus 2 infection has evolved into a global pandemic. Low-dose colchicine combines anti-inflammatory action with a favorable safety profile.
Objective To evaluate the effect of treatment with colchicine on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019 (COVID-19).
Design, Setting, and Participants In this prospective, open-label, randomized clinical trial (the Greek Study in the Effects of Colchicine in COVID-19 Complications Prevention), 105 patients hospitalized with COVID-19 were randomized in a 1:1 allocation from April 3 to April 27, 2020, to either standard medical treatment or colchicine with standard medical treatment. The study took place in 16 tertiary hospitals in Greece.
Intervention Colchicine administration (1.5-mg loading dose followed by 0.5 mg after 60 min and maintenance doses of 0.5 mg twice daily) with standard medical treatment for as long as 3 weeks.
Main Outcomes and Measures Primary end points were (1) maximum high-sensitivity cardiac troponin level; (2) time for C-reactive protein to reach more than 3 times the upper reference limit; and (3) time to deterioration by 2 points on a 7-grade clinical status scale, ranging from able to resume normal activities to death. Secondary end points were (1) the percentage of participants requiring mechanical ventilation, (2) all-cause mortality, and (3) number, type, severity, and seriousness of adverse events. The primary efficacy analysis was performed on an intention-to-treat basis.
Results A total of 105 patients were evaluated (61 [58.1%] men; median [interquartile range] age, 64 [54-76] years) with 50 (47.6%) randomized to the control group and 55 (52.4%) to the colchicine group. Median (interquartile range) peak high-sensitivity cardiac troponin values were 0.0112 (0.0043-0.0093) ng/mL in the control group and 0.008 (0.004-0.0135) ng/mL in the colchicine group (P = .34). Median (interquartile range) maximum C-reactive protein levels were 4.5 (1.4-8.9) mg/dL vs 3.1 (0.8-9.8) mg/dL (P = .73), respectively. The clinical primary end point rate was 14.0% in the control group (7 of 50 patients) and 1.8% in the colchicine group (1 of 55 patients) (odds ratio, 0.11; 95% CI, 0.01-0.96; P = .02). Mean (SD) event-free survival time was 18.6 (0.83) days the in the control group vs 20.7 (0.31) in the colchicine group (log rank P = .03). Adverse events were similar in the 2 groups, except for diarrhea, which was more frequent with colchicine group than the control group (25 patients [45.5%] vs 9 patients [18.0%]; P = .003).
Conclusions and Relevance In this randomized clinical trial, participants who received colchicine had statistically significantly improved time to clinical deterioration. There were no significant differences in high-sensitivity cardiac troponin or C-reactive protein levels. These findings should be interpreted with caution.

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22/06/2020 Articles
COVID-19 treatment: Combining anti-inflammatory and antiviral therapeu...

COVID-19 treatment: Combining anti-inflammatory and antiviral therapeutics using a network-based approach

CLEVELAND CLINICLE JOURNAL OF MEDICINE

Authors
Feixiong Cheng, Sujata Rao, Reena Mehra



ABSTRACT
To date, there are no effective antiviral medications for COVID-19. Drug repurposing, a strategy that uses existing drugs, offers potential prevention and treatment options for COVID-19. We discuss one treatment strategy that combines anti-inflammatory (melatonin) and antiviral (toremifene) agents for patients infected with SARS-CoV-2 from network medicine-based findings. We also describe the pathobiology and immunologic characteristics of COVID-19 and highlight the rationale of combination drug treatment to rescue the pulmonary and cardiovascular conditions resulting from COVID-19. A preliminary analysis reveals a high potential for the synergistic effects of melatonin and toremifene to reduce viral infection and replication, and the aberrant host inflammatory responses, offering strong biologic plausibility as an effective therapy for COVID-19.

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22/06/2020 Reviews
Nanotechnology for COVID-19: Therapeutics and Vaccine Research

ACS NANO

Authors
Gaurav Chauhan, Marc J. Madou, Sourav Kalra, Vianni Chopra, Deepa Ghosh, Sergio O Martinez-Chapa



ABSTRACT
The current global health threat by the Novel coronavirus disease (COVID-19) requires an urgent deployment of available advanced therapeutic options available. The role of nanotechnology is highly relevant to counter this “virus” nano enemy. Nano intervention is discussed in terms of designing effective nanocarriers to counter the conventional limitations of antiviral and biological therapeutics. This strategy directs the safe and effective delivery of available therapeutic options using engineered nanocarriers, blocking the initial interactions of viral spike glycoprotein with host cell surface receptors, and disruption of virion construction. Controlling and eliminating the spread and reoccurrence of this pandemic demands a safe and effective vaccine strategy. Nanocarriers have potential to design risk-free and effective immunization strategies for SARS-CoV-2 vaccine candidates such as protein constructs and nucleic acids. We discuss recent as well as ongoing nanotechnology-based therapeutic and prophylactic strategies to fight against this pandemic, outlining the key areas for Nanoscientists to step-in.

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22/06/2020 Comment
Use of aerosolised medications at home for COVID-19

THE LANCET

Authors
Arzu Ari


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21/06/2020 Letter
Clinical feedback from experience with COVID-19: specific consideratio...

Clinical feedback from experience with COVID-19: specific considerations for ExtraCorporeal Membrane Oxygenation

ELSEVIER

Authors
Antonio Fiore, Quentinde Roux, Nejla Daami, Simon Clariot, Thierry Folliguet, Fabio SilvioT accone, Nicolas Mongardon



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19/06/2020 Articles
Structure-based design of antiviral drug candidates targeting the SARS...

Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease

SCIENCE

Authors
Wenhao Dai, Bing Zhang, Xia-Ming Jiang, Haixia Su, Jian Li, Yao Zhao, Xiong Xie, Zhenming Jin, Jingjing Peng, Fengjiang Liu, Chunpu Li, You Li , Fang Bai, Haofeng Wang, Xi Cheng, Xiaobo Cen , Shulei Hu, Xiuna Yang, Jiang Wang, Xiang Liu, Gengfu Xiao, Hualiang Jiang, Zihe Rao, Lei-Ke Zhang, Yechun Xu, Haitao Yang, Hong Liu



ABSTRACT
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the etiological agent responsible for the global COVID-19 (coronavirus disease 2019) outbreak. The main protease of SARS-CoV-2, Mpro, is a key enzyme that plays a pivotal role in mediating viral replication and transcription. We designed and synthesized two lead compounds (11a and 11b) targeting Mpro. Both exhibited excellent inhibitory activity and potent anti–SARS-CoV-2 infection activity. The x-ray crystal structures of SARS-CoV-2 Mpro in complex with 11a or 11b, both determined at a resolution of 1.5 angstroms, showed that the aldehyde groups of 11a and 11b are covalently bound to cysteine 145 of Mpro. Both compounds showed good pharmacokinetic properties in vivo, and 11a also exhibited low toxicity, which suggests that these compounds are promising drug candidates.

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18/06/2020 Editorial
The Urgency of Care during the Covid-19 Pandemic — Learning as We Go

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Eric J. Rubin, David P. Harrington, Joseph W. Hogans, Constantine Gatsonis, Lindsey R. Baden, Mary Beth Hamel


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18/06/2020 CLINICAL IMPLICATIONS OF BASIC RESEARCH
Amplifying RNA Vaccine Development

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Deborah H. Fuller, Peter Berglund


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17/06/2020 Research Letter
Prone Positioning in Awake, Nonintubated Patients With COVID-19 Hypoxe...

Prone Positioning in Awake, Nonintubated Patients With COVID-19 Hypoxemic Respiratory Failure

JAMA

Authors
Alison E. Thompson, Benjamin L. Ranard, Ying Wei, Sanja Jelic


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16/06/2020 Articles
GM-CSF blockade with mavrilimumab in severe COVID-19 pneumonia and sys...

GM-CSF blockade with mavrilimumab in severe COVID-19 pneumonia and systemic hyperinflammation: a single-centre, prospective cohort study

THE LANCET

Authors
Giacomo De Luca, Giulio Cavalli, Corrado Campochiaro, Emanuel Della-Torre, Piera Angelillo, Alessandro Tomelleri, Nicola Boffini, Stefano Tentori, Francesca Mette, Nicola Farina, Patrizia Rovere-Querini, Annalisa Ruggeri, Teresa D’Aliberti, Paolo Scarpellini, Giovanni Landoni, Francesco De Cobelli, John F Paolini, Alberto Zangrillo, Moreno Tresoldi, Bruce C Trapnell, Fabio Ciceri, Lorenzo Dagna

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16/06/2020 Editorial
Routine vaccination during covid-19 pandemic response

THE BMJ

Authors
Sonia Saxena, Helen Skirrow, Helen Bedford


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08/06/2020 Articles
Association between angiotensin blockade and COVID-19 severity in Hong...

Association between angiotensin blockade and COVID-19 severity in Hong Kong

CMAJ

Authors
Ka Shing Cheung, Ivan F.N. Hung, Wai K. Leung


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08/06/2020 Articles
Re-envisioning Discharge Planning and Expanding Post-Acute Care Capaci...

Re-envisioning Discharge Planning and Expanding Post-Acute Care Capacity During a Pandemic

NEJM CATALYST

Authors
Amelia Shapiro, Nancy O’Toole, Donna Tinling-Solages, Timothy McGarvey, Michael Tretola, Paul Dunphey


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04/06/2020 ORIGINAL INVESTIGATION
Association of Noninvasive Oxygenation Strategies With All-Cause Morta...

Association of Noninvasive Oxygenation Strategies With All-Cause Mortality in Adults With Acute Hypoxemic Respiratory Failure A Systematic Review and Meta-analysis

JAMA

Authors
Bruno L. Ferreyro, Federico Angriman, Laveena Munshi, Lorenzo Del Sorbo, Niall D. Ferguson, Bram Rochwerg, Michelle J. Ryu, Refik Saskin, Hannah Wunsch, Bruno R. da Costa, Damon C. Scales

ABSTRACT

Importance Treatment with noninvasive oxygenation strategies such as noninvasive ventilation and high-flow nasal oxygen may be more effective than standard oxygen therapy alone in patients with acute hypoxemic respiratory failure.
Objective To compare the association of noninvasive oxygenation strategies with mortality and endotracheal intubation in adults with acute hypoxemic respiratory failure.
Data Sources The following bibliographic databases were searched from inception until April 2020: MEDLINE, Embase, PubMed, Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, and LILACS. No limits were applied to language, publication year, sex, or race.
Study Selection Randomized clinical trials enrolling adult participants with acute hypoxemic respiratory failure comparing high-flow nasal oxygen, face mask noninvasive ventilation, helmet noninvasive ventilation, or standard oxygen therapy.
Data Extraction and Synthesis Two reviewers independently extracted individual study data and evaluated studies for risk of bias using the Cochrane Risk of Bias tool. Network meta-analyses using a bayesian framework to derive risk ratios (RRs) and risk differences along with 95% credible intervals (CrIs) were conducted. GRADE methodology was used to rate the certainty in findings.
Main Outcomes and Measures The primary outcome was all-cause mortality up to 90 days. A secondary outcome was endotracheal intubation up to 30 days.
Results Twenty-five randomized clinical trials (3804 participants) were included. Compared with standard oxygen, treatment with helmet noninvasive ventilation (RR, 0.40 [95% CrI, 0.24-0.63]; absolute risk difference, −0.19 [95% CrI, −0.37 to −0.09]; low certainty) and face mask noninvasive ventilation (RR, 0.83 [95% CrI, 0.68-0.99]; absolute risk difference, −0.06 [95% CrI, −0.15 to −0.01]; moderate certainty) were associated with a lower risk of mortality (21 studies [3370 patients]). Helmet noninvasive ventilation (RR, 0.26 [95% CrI, 0.14-0.46]; absolute risk difference, −0.32 [95% CrI, −0.60 to −0.16]; low certainty), face mask noninvasive ventilation (RR, 0.76 [95% CrI, 0.62-0.90]; absolute risk difference, −0.12 [95% CrI, −0.25 to −0.05]; moderate certainty) and high-flow nasal oxygen (RR, 0.76 [95% CrI, 0.55-0.99]; absolute risk difference, −0.11 [95% CrI, −0.27 to −0.01]; moderate certainty) were associated with lower risk of endotracheal intubation (25 studies [3804 patients]). The risk of bias due to lack of blinding for intubation was deemed high.
Conclusions and Relevance In this network meta-analysis of trials of adult patients with acute hypoxemic respiratory failure, treatment with noninvasive oxygenation strategies compared with standard oxygen therapy was associated with lower risk of death. Further research is needed to better understand the relative benefits of each strategy.

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04/06/2020 Editorial
Alternatives to Invasive Ventilation in the COVID-19 Pandemic

JAMA

Authors
Bhakti K. Patel, John P. Kress, Jesse B. Hall

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03/06/2020 Editorial
Hydroxychloroquine for the Prevention of Covid-19 — Searching for Evid...

Hydroxychloroquine for the Prevention of Covid-19 — Searching for Evidence

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Myron S. Cohen

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03/06/2020 Articles
Tocilizumab for treatment of mechanically ventilated patients with COV...

Tocilizumab for treatment of mechanically ventilated patients with COVID-19

MEDRXIV

Authors
Emily C Somers, Gregory A Eschenauer, Jonathan P Troost, Jonathan L Golob, Tejal N Gandhi, Lu Wang, Nina Zhou, Lindsay A Petty, Ji Hoon Baang, Nicholas O Dillman, David Frame, Kevin S Gregg, Dan R Kaul, Jerod Nagel, Twisha S Patel, Shiwei Zhou, Adam S Lauring, David A Hanauer, Emily Toth Martin, Pratima Sharma, Christopher M Fung, Jason M Pogue



ABSTRACT
Background Severe COVID-19 can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers. This presentation is consistent with cytokine release syndrome in chimeric antigen receptor T cell therapy, for which IL-6 blockade is approved treatment. Methods We assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability post-intubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared to tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability weighting (IPTW). Findings 154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean 55 vs. 60 years), less likely to have chronic pulmonary disease (10% vs. 28%), and had lower D-dimer values at time of intubation (median 2.4 vs. 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death [hazard ratio 0.55 (95% CI 0.33, 0.90)] and improved status on the ordinal outcome scale [odds ratio per 1-level increase: 0.59 (0.36, 0.95)]. Though tocilizumab was associated with an increased proportion of patients with superinfections (54% vs. 26%; p<0.001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection [22% vs. 15%; p=0.42]. Interpretation In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with a decreased likelihood of death despite higher superinfection occurrence. Randomized controlled trials are urgently needed to confirm these findings.

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01/06/2020 New Result
Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a po...

Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody

BIORXIV

Authors
Zhe Lv, Yong-Qiang Deng, Qing Ye, Lei Cao, Chun-Yun Sun, Changfa Fan, Weijin Huang, Shihui Sun, Yao Sun, Ling Zhu, Qi Chen, Nan Wang, Jianhui Nie, Zhen Cui, Dandan Zhu, Neil Shaw, Xiao-Feng Li, Qianqian Li, Liangzhi Xie, Youchun Wang, Zihe Rao, Cheng-Feng Qin, Xiangxi Wang



ABSTRACT
The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we reported a humanized monoclonal antibody, H014, efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nM level by engaging the S receptor binding domain (RBD). Importantly, H014 administration reduced SARS-CoV-2 replication and prevented pulmonary pathology in hACE2 mouse model. Cryo-EM characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a novel conformational epitope, which is only accessible when the RBD is in open conformation. Biochemical, cellular, virological and structural studies demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. Epitope analysis of available neutralizing antibodies against SARS-CoV and SARS-CoV-2 uncover broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19.
One sentence summary A potent neutralizing antibody conferred protection against SARS-CoV-2 in an hACE2 humanized mouse model by sterically blocking the interaction of the virus with its receptor.

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28/05/2020 Comment
The starting line for COVID-19 vaccine development

The Lancet

Authors
Nelson Lee, Allison McGeer

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27/05/2020 Articles
Remdesivir for 5 or 10 Days in Patients with Severe Covid-19

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Jason D. Goldman, M.D., M.P.H., David C.B. Lye, M.B., B.S., David S. Hui, M.D., Kristen M. Marks, M.D., Raffaele Bruno, M.D., Rocio Montejano, M.D., Christoph D. Spinner, M.D., Massimo Galli, M.D., Mi-Young Ahn, M.D., Ronald G. Nahass, M.D., Yao-Shen Chen, M.D., Devi SenGupta, M.D., Robert H. Hyland, D.Phil., Anu O. Osinusi, M.D., Huyen Cao, M.D., Christiana Blair, M.S., Xuelian Wei, Ph.D., Anuj Gaggar, M.D., Ph.D., Diana M. Brainard, M.D., William J. Towner, M.D., Jose Muñoz, M.D., Kathleen M. Mullane, D.O., Pharm.D., Francisco M. Marty, M.D., Karen T. Tashima, M.D., George Diaz

ABSTRACT
BACKGROUND Remdesivir is an RNA polymerase inhibitor with potent antiviral activity in vitro and efficacy in animal models of coronavirus disease 2019 (Covid-19).
METHODS We conducted a randomized, open-label, phase 3 trial involving hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation of 94% or less while they were breathing ambient air, and radiologic evidence of pneumonia. Patients were randomly assigned in a 1:1 ratio to receive intravenous remdesivir for either 5 days or 10 days. All patients received 200 mg of remdesivir on day 1 and 100 mg once daily on subsequent days. The primary end point was clinical status on day 14, assessed on a 7-point ordinal scale.
RESULTS In total, 397 patients underwent randomization and began treatment (200 patients for 5 days and 197 for 10 days). The median duration of treatment was 5 days (interquartile range, 5 to 5) in the 5-day group and 9 days (interquartile range, 5 to 10) in the 10-day group. At baseline, patients randomly assigned to the 10-day group had significantly worse clinical status than those assigned to the 5-day group (P=0.02). By day 14, a clinical improvement of 2 points or more on the ordinal scale occurred in 64% of patients in the 5-day group and in 54% in the 10-day group. After adjustment for baseline clinical status, patients in the 10-day group had a distribution in clinical status at day 14 that was similar to that among patients in the 5-day group (P=0.14). The most common adverse events were nausea (9% of patients), worsening respiratory failure (8%), elevated alanine aminotransferase level (7%), and constipation (7%).
CONCLUSIONS In patients with severe Covid-19 not requiring mechanical ventilation, our trial did not show a significant difference between a 5-day course and a 10-day course of remdesivir. With no placebo control, however, the magnitude of benefit cannot be determined. (Funded by Gilead Sciences; GS-US-540-5773 ClinicalTrials.gov number, NCT04292899. opens in new tab.)

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27/05/2020 Article
STEMI Care and COVID-19: The Value Proposition of Fibrinolytic Therapy...

STEMI Care and COVID-19: The Value Proposition of Fibrinolytic Therapy and the Pharmacoinvasive Strategy

AHA JOURNALS

Authors
Kevin R. Bainey, Eric R. Bates, Paul W. Armstrong

ABSTRACT

The Coronavirus 2019 (COVID-19) pandemic has dramatically altered the delivery of reperfusion therapy for patients with ST-elevation myocardial infarction (STEMI). At this crucial time, it seems prudent to re-evaluate STEMI reperfusion pathways.

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26/05/2020 Communication
AIFA sospende l’autorizzazione all’utilizzo di idrossiclorochina per i...

AIFA sospende l’autorizzazione all’utilizzo di idrossiclorochina per il trattamento del COVID-19 al di fuori degli studi clinici

AIFA

Authors
AIFA

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26/05/2020 Articles
Can Stem Cells Beat COVID-19: Advancing Stem Cells and Extracellular V...

Can Stem Cells Beat COVID-19: Advancing Stem Cells and Extracellular Vesicles Toward Mainstream Medicine for Lung Injuries Associated With SARS-CoV-2 Infections

FRONTIERS IN BIOENGENEERING AND BIOTECHNOLOGY

Authors
Wojciech Chrzanowski, Sally Yunsun Kim, Lana McClements


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22/05/2020 Articles
Hydroxychloroquine or chloroquine with or without a macrolide for trea...

Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19...

The Lancet

Authors
Mandeep R Mehra, Sapan S Desai, Frank Ruschitzka, Amit N Patel

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22/05/2020 Original Article
Remdesivir for the Treatment of Covid-19 — Preliminary Report

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
J.H. Beigel, K.M. Tomashek, L.E. Dodd, A.K. Mehta, B.S. Zingman, A.C. Kalil, E. Hohmann, H.Y. Chu, A. Luetkemeyer, S. Kline, D. Lopez de Castilla, R.W. Finberg, K. Dierberg, V. Tapson, L. Hsieh, T.F. Patterson, R. Paredes, D.A. Sweeney, W.R. Short, G. Touloumi, D.C. Lye, N. Ohmagari, M. Oh, G.M. Ruiz-Palacios, T. Benfield, G. F&auml;tkenheuer, M.G. Kortepeter, R.L. Atmar, C.B. Creech, J. Lundgren, A.G. Babiker, S. Pett, J.D. Neaton, T.H. Burgess, T. Bonnett, M. Green, M. Makowski, A. Osinusi, S. Nayak, and H.C. Lane,

ABSTRACT

BACKGROUND Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious.

METHODS We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only.

RESULTS A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%).

CONCLUSIONS Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACCT-1 ClinicalTrials.gov number, NCT04280705. opens in new tab.)

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22/05/2020 Articles
Efficacy and safety of tocilizumab in severe COVID-19 patients: a sing...

Efficacy and safety of tocilizumab in severe COVID-19 patients: a single- centre retrospective cohort study

EUROPEAN JOURNAL OF INTERNAL MEDICINE

Authors
Corrado Campochiaro, Emanuel Della-Torre, Giulio Cavalli, Giacomo De Luca, Marco Ripa, Nicola Boffini, Alessandro Tomelleri, Elena Baldissera, Patrizia Rovere-Querini, Annalisa Ruggeri, Giacomo Monti, Francesco De Cobelli, Alberto Zangrillo, Moreno Tresoldi, Antonella Castagna, Lorenzo Dagna



ABSTRACT
Background Tocilizumab (TCZ), a humanized monoclonal antibody targeting the interleukin-6 (IL-6) receptor, has been proposed for the treatment of COVID-19 patients; however, limited data are available on the safety and efficacy. Methods We performed a retrospective study on severe COVID-19 patients with hyper-inflammatory features admitted outside intensive care units (ICUs). Patients treated with intravenous TCZ in addition to standard of care were compared to patients treated with standard of care alone. Safety and efficacy were assessed over a 28-day follow-up. Results 65 patients were included. Among them, 32 were treated with TCZ. At baseline, all patients were on high-flow supplemental oxygen and most (78% of TCZ patients and 61% of standard treatment patients) were on non-invasive ventilation. During the 28-day follow-up, 69% of TCZ patients experienced a clinical improvement compared to 61% of standard treatment patients (p = 0.61). Mortality was 15% in the tocilizumab group and 33% in standard treatment group (p = 0.15). In TCZ group, at multivariate analysis, older age was a predictor of death, whereas higher baseline PaO2:FiO2 was a predictor of clinical improvement at day 28. The rate of infection and pulmonary thrombosis was similar between the two groups. Conclusions At day 28, clinical improvement and mortality were not statistically different between tocilizumab and standard treatment patients in our cohort. Bacterial or fungal infections were recorded in 13% of tocilizumab patients and in 12% of standard treatment patients. Confirmation of efficacy and safety will require ongoing controlled trials.


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22/05/2020 Articles
Remdesivir for the Treatment of Covid-19 — Preliminary Report

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
John H. Beigel, Kay M. Tomashek, Lori E. Dodd, Aneesh K. Mehta, Barry S. Zingman, Andre C. Kalil, Elizabeth Hohmann, Helen Y. Chu, Annie Luetkemeyer, Susan Kline, Diego Lopez de Castilla, Robert W. Finberg, Kerry Dierberg, Victor Tapson, Lanny Hsieh, Thomas F. Patterson, Roger Paredes, Daniel A. Sweeney, William R. Short, Giota Touloumi, David Chien Lye, Norio Ohmagari, Myoung-don Oh, Guillermo M. Ruiz-Palacios, Thomas Benfield, Gerd Fätkenheuer, Mark G. Kortepeter, Robert L. Atmar, C. Buddy Creech, Jens Lundgren, Abdel G. Babiker, Sarah Pett, James D. Neaton, Timothy H. Burgess,, Tyler Bonnett, Michelle Green, Mat Makowski, Anu Osinusi, Seema Nayak, H. Clifford Lane



ABSTRACT
BACKGROUND Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious.
METHODS We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only.
RESULTS A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%).
CONCLUSIONS Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705. opens in new tab.)

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21/05/2020 Editorial
High dose intravenous immunoglobulins as a therapeutic option for COVI...

High dose intravenous immunoglobulins as a therapeutic option for COVID-19 patients

European Review for Medical and Pharmacological Sciences

Authors
C. SCOPPETTA, G. DI GENNARO, F. POLVERINO

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20/05/2020 Case Report
Successful Q1 recovery of severe COVID-19 with cytokine storm 3 treati...

Successful Q1 recovery of severe COVID-19 with cytokine storm 3 treating with extracorporeal blood purification

ELSEVIER

Authors
Qiang Wang, Zhao Hu

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20/05/2020 Articles
SARS-CoV-2 infection protects against rechallenge in rhesus macaques

SCIENCE

Authors
Abishek Chandrashekar, Jinyan Liu, Amanda J. Martinot, Katherine McMahan, Noe B. Mercado

ABSTRACT

An understanding of protective immunity to SARS-CoV-2 is critical for vaccine and public health strategies aimed at ending the global COVID-19 pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against re-exposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. Following initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with primary infection. Anamnestic immune responses following rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against re-exposure in nonhuman primates.

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20/05/2020 In Focus
Vitamin-D and COVID-19: do deficient risk a poorer outcome?

The Lancet

Authors
FIONA MITCHELL

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20/05/2020 Articles
DNA vaccine protection against SARS-CoV-2 in rhesus macaques

SCIENCE

Authors
Jingyou Yu, Lisa H. Tostanoski, Lauren Peter, Noe B. Mercado, Katherine McMahan, Shant H. Mahrokhian, Joseph P. Nkolola, Jinyan Liu, Zhenfeng Li, Abishek Chandrashekar, David R. Martinez, Carolin Loos, Caroline Atyeo, Stephanie Fischinger, John S. Burke, Matthew D. Slein, Yuezhou Chen, Adam Zuiani, Felipe J. N. Lelis, Meghan Travers, Shaghayegh Habibi, Laurent Pessaint, ET ALL.

ABSTRACT

The global COVID-19 pandemic caused by the SARS-CoV-2 virus has made the development of a vaccine a top biomedical priority. In this study, we developed a series of DNA vaccine candidates expressing different forms of the SARS-CoV-2 Spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers comparable to those found in convalescent humans and macaques infected with SARS-CoV-2. Following vaccination, all animals were challenged with SARS-CoV-2, and the vaccine encoding the full-length S protein resulted in >3.1 and >3.7 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, as compared with sham controls. Vaccine-elicited neutralizing antibody titers correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate vaccine protection against SARS-CoV-2 in nonhuman primates.

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18/05/2020 Opinion
COVID-19 Pandemic: Hopes from Proteomics and Multiomics Research

OMICS

Authors
Sandipan Ray, Sanjeeva Srivastava

ABSTRACT

The successful sequencing of the novel coronavirus SARS-CoV-2 nucleic acid paved the way for exploration of omics systems science and integrative biology research approaches for combating this unprecedented planetary health challenge. Omics-scale studies on this viral infection are emerging rapidly and offer a tremendous potential to unravel the puzzles of the SARS-CoV-2 pathobiology, and ways forward for diagnostic and therapeutic innovation.

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18/05/2020 Viewpoint
Planning for a COVID-19 Vaccination Program

JAMA

Authors
Sarah Schaffer DeRoo, Natalie J. Pudalov, Linda Y. Fu

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17/05/2020 Research Letter
Favipiravir, an antiviral for COVID-19?

Oxford University Press

Authors
Eric A Coomes, Hourmazd Haghbayan

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15/05/2020 Articles
Low dose of hydroxychloroquine reduces fatality of critically ill pati...

Low dose of hydroxychloroquine reduces fatality of critically ill patients with COVID-19

PUBLMED

Authors
Bo Yu, Chenze Li, Peng Chen, Ning Zhou, Luyun Wang , Jia Li , Hualiang Jiang, Dao-Wen Wang

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a pandemic with no specific drugs and high fatality. The most urgent need is to find effective treatments. We sought to determine whether hydroxychloroquine (HCQ) application may reduce the death risk of critically ill COVID-19 patients. In this retrospective study, we included 550 critically ill COVID-19 patients who need mechanical ventilation in Tongji Hospital, Wuhan, from February 1, 2020 to April 4, 2020. All 550 patients received comparable basic treatments including antiviral drugs and antibiotics, and 48 of them were treated with oral HCQ treatment (200 mg twice a day for 7-10 days) in addition to the basic treatments. Primary endpoint is fatality of patients, and inflammatory cytokine levels were compared between HCQ and non-hydroxychloroquine (NHCQ) treatments. We found that fatalities are 18.8% (9/48) in HCQ group, which is significantly lower than 47.4% (238/502) in the NHCQ group (P<0.001). The time of hospital stay before patient death is 15 (10-21) days and 8 (4-14) days for the HCQ and NHCQ groups, respectively (P<0.05). The levels of inflammatory cytokine IL-6 were significantly reduced from 22.2 (8.3-118.9) pg mL-1 at the beginning of the treatment to 5.2 (3.0-23.4) pg mL-1 (P<0.05) at the end of the treatment in the HCQ group but there is no change in the NHCQ group. These data demonstrate that addition of HCQ on top of the basic treatments is highly effective in reducing the fatality of critically ill patients of COVID-19 through attenuation of inflammatory cytokine storm. Therefore, HCQ should be prescribed as a part of treatment for critically ill COVID-19 patients, with possible outcome of saving lives. hydroxychloroquine, IL-6, mortalities, COVID-19.

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15/05/2020 Critical Care
Angiotensin II infusion in COVID-19-associated vasodilatory shock: a c...

Angiotensin II infusion in COVID-19-associated vasodilatory shock: a case series

BMC

Authors
Alberto Zangrillo, Giovanni Landoni, Luigi Beretta, Federica Morselli, Ary Serpa Neto, Rinaldo Bellomo


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13/05/2020 Summary
TOCIVID-19 è il primo e più ampio studio sul tocilizumab aut...

TOCIVID-19 è il primo e più ampio studio sul tocilizumab autorizzato...

ISTITUTO NAZIONALE TUMORI DI NAPOLI

Authors
ISTITUTO NAZIONALE TUMORI DI NAPOLI

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11/05/2020 Original Investigation
Association of Treatment With Hydroxychloroquine or Azithromycin...

JAMA

Authors
Eli S. Rosenberg, Elizabeth M. Dufort, Tomoko Udo, Larissa A. Wilberschied, Jessica Kumar, James Tesoriero, Patti Weinberg, James Kirkwood, Alison Muse, Jack DeHovitz, Debra S. Blog, Brad Hutton, David R. Holtgrave, Howard A. Zucker

ABSTRACT Importance Hydroxychloroquine, with or without azithromycin, has been considered as a possible therapeutic agent for patients with coronavirus disease 2019 (COVID-19). However, there are limited data on efficacy and associated adverse events.

Objective To describe the association between use of hydroxychloroquine, with or without azithromycin, and clinical outcomes among hospital inpatients diagnosed with COVID-19.

Design, Setting, and Participants Retrospective multicenter cohort study of patients from a random sample of all admitted patients with laboratory-confirmed COVID-19 in 25 hospitals, representing 88.2% of patients with COVID-19 in the New York metropolitan region. Eligible patients were admitted for at least 24 hours between March 15 and 28, 2020. Medications, preexisting conditions, clinical measures on admission, outcomes, and adverse events were abstracted from medical records. The date of final follow-up was April 24, 2020.

Exposures Receipt of both hydroxychloroquine and azithromycin, hydroxychloroquine alone, azithromycin alone, or neither.

Main Outcomes and Measures Primary outcome was in-hospital mortality. Secondary outcomes were cardiac arrest and abnormal electrocardiogram findings (arrhythmia or QT prolongation).

Results Among 1438 hospitalized patients with a diagnosis of COVID-19 (858 [59.7%] male, median age, 63 years), those receiving hydroxychloroquine, azithromycin, or both were more likely than those not receiving either drug to have diabetes, respiratory rate >22/min, abnormal chest imaging findings, O2 saturation lower than 90%, and aspartate aminotransferase greater than 40 U/L. Overall in-hospital mortality was 20.3% (95% CI, 18.2%-22.4%). The probability of death for patients receiving hydroxychloroquine + azithromycin was 189/735 (25.7% [95% CI, 22.3%-28.9%]), hydroxychloroquine alone, 54/271 (19.9% [95% CI, 15.2%-24.7%]), azithromycin alone, 21/211 (10.0% [95% CI, 5.9%-14.0%]), and neither drug, 28/221 (12.7% [95% CI, 8.3%-17.1%]). In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in mortality for patients receiving hydroxychloroquine + azithromycin (HR, 1.35 [95% CI, 0.76-2.40]), hydroxychloroquine alone (HR, 1.08 [95% CI, 0.63-1.85]), or azithromycin alone (HR, 0.56 [95% CI, 0.26-1.21]). In logistic models, compared with patients receiving neither drug cardiac arrest was significantly more likely in patients receiving hydroxychloroquine + azithromycin (adjusted OR, 2.13 [95% CI, 1.12-4.05]), but not hydroxychloroquine alone (adjusted OR, 1.91 [95% CI, 0.96-3.81]) or azithromycin alone (adjusted OR, 0.64 [95% CI, 0.27-1.56]), . In adjusted logistic regression models, there were no significant differences in the relative likelihood of abnormal electrocardiogram findings.

Conclusions and Relevance Among patients hospitalized in metropolitan New York with COVID-19, treatment with hydroxychloroquine, azithromycin, or both, compared with neither treatment, was not significantly associated with differences in in-hospital mortality. However, the interpretation of these findings may be limited by the observational design.

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11/05/2020 Pharmacological Research
Compassionate remdesivir treatment of severe Covid-19 pneumonia in int...

Compassionate remdesivir treatment of severe Covid-19 pneumonia in intensive care unit (ICU)...

ELSEVIER

Authors
Spinello Antinori, Maria Vittoria Cossu, Anna Lisa Ridolfo, Roberto Rech, Cecilia Bonazzetti, Gabriele Pagani, Guido Gubertini, Massimo Coen, Carlo Magni, Antonio Castelli, Beatrice Borghi, Riccardo Colombo, Riccardo Giorgi, Elena Angeli, Davide Mileto, Laura Milazzo, Stefania Vimercati, Martina Pellicciotta, Massimo Galli

ABSTRACT

SARS-CoV-2 is causing an increasing number of deaths worldwide because no effective treatment is currently available. Remdesivir has shown in vitro activity against coronaviruses and is a possible antiviral treatment for SARS-CoV-2 infection. This prospective (compassionate), open-label study of remdesivir, which was conducted at Luigi Sacco Hospital, Milan, Italy, between February 23 and March 20, 2020, involved patients with SARS-CoV-2 pneumonia aged ≥18 years undergoing mechanical ventilation or with an oxygen saturation level of ≤94% in air or a National Early Warning Score 2 of ≥4. The primary outcome was the change in clinical status based on a 7-category ordinal scale (1 = not hospitalised, resuming normal daily activities; 7 = deceased). The 35 patients enrolled from February 23 to March 20, 2020, included 18 in intensive care unit (ICU), and 17 in our infectious diseases ward (IDW). The 10-day course of remdesivir was completed by 22 patients (63%) and discontinued by 13, of whom eight (22.8%) discontinued because of adverse events. The median follow-up was 39 days (IQR 25-44). At day 28, 14 (82.3%) patients from IDW were discharged, two were still hospitalized and one died (5.9%), whereas in ICU 6 (33.3%) were discharged, 8 (44.4%) patients died, three (16.7%) were still mechanically ventilated and one (5.6%) was improved but still hospitalized. Hypertransaminasemia and acute kidney injury were the most frequent severe adverse events observed (42.8% and 22.8% of the cases, respectively). Our data suggest that remdesivir can benefit patients with SARS-CoV-2 pneumonia hospitalised outside ICU where clinical outcome was better and adverse events are less frequently observed. Ongoing randomised controlled trials will clarify its real efficacy and safety, who to treat, and when.

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11/05/2020 News
EMA recommends expanding remdesivir compassionate use to patients not ...

EMA recommends expanding remdesivir compassionate use to patients not on mechanical ventilation

EMA

Authors
EUROPEAN MEDICINES AGENCY

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09/05/2020 Articles
Tocilizumab for Treatment of Severe COVID-19 Patients: Preliminary Res...

Tocilizumab for Treatment of Severe COVID-19 Patients: Preliminary Results...

MDPI

Authors
Marta Colaneri, Laura Bogliolo, Pietro Valsecchi, Paolo Sacchi, Valentina Zuccaro, Fabio Brandolino, Carlomaurizio Montecucco, Francesco Mojoli, Emanuele Maria Giusti, Raffaele Bruno and the COVID IRCCS San Matteo Pavia Task Force

ABSTRACT

Objective: This study aimed to assess the role of Tocilizumab therapy (TCZ) in terms of ICU admission and mortality rate of critically ill patients with severe COVID-19 pneumonia. Design: Patients with COVID-19 pneumonia were prospectively enrolled in SMAtteo COvid19 REgistry (SMACORE). A retrospective analysis of patients treated with TCZ matched using propensity score to patients treated with Standard Of Care (SOC) was conducted. Setting: The study was conducted at IRCCS Policlinico San Matteo Hospital, Pavia, Italy, from March 14, 2020 to March 27, 2020. Participants: Patients with a confirmed diagnosis of COVID-19 hospitalized in our institution at the time of TCZ availability. Interventions: TCZ was administered to 21 patients. The first administration was 8 mg/kg (up to a maximum 800 mg per dose) of Tocilizumab intravenously, repeated after 12 h if no side effects were reported after the first dose. Main Outcomes and Measures: ICU admission and 7-day mortality rate. Secondary outcomes included clinical and laboratory data. Results: There were 112 patients evaluated (82 were male and 30 were female, with a median age of 63.55 years). Using propensity scores, the 21 patients who received TCZ were matched to 21 patients who received SOC (a combination of hydroxychloroquine, azithromycin and prophylactic dose of low weight heparin). No adverse event was detected following TCZ administration. This study found that treatment with TCZ did not significantly affect ICU admission (OR 0.11; 95% CI between 0.00 and 3.38; p = 0.22) or 7-day mortality rate (OR 0.78; 95% CI between 0.06 and 9.34; p = 0.84) when compared with SOC. Analysis of laboratory measures showed significant interactions between time and treatment regarding C-Reactive Protein (CRP), alanine aminotransferase (ALT), platelets and international normalized ratio (INR) levels. Variation in lymphocytes count was observed over time, irrespective of treatment. Conclusions: TCZ administration did not reduce ICU admission or mortality rate in a cohort of 21 patients. Additional data are needed to understand the effect(s) of TCZ in treating patients diagnosed with COVID-19.

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09/05/2020 Editorial
New Zealand eliminates COVID-19

The Lancet

Authors
Sophie Cousins

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08/05/2020 Editorial
Our recommendations for acute management of COVID-19

BMC

Authors
Francesco Mojoli, Silvia Mongodi, Anita Orlando, Eric Arisi, Marco Pozzi, Luca Civardi, Guido Tavazzi, Fausto Baldanti, Raffaele Bruno, Giorgio Antonio Iotti & COVID-19 Pavia Crisis Unit

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08/05/2020 Perspectives
Rapid COVID-19 vaccine development

SCIENCE

Authors
Barney S. Graham

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08/05/2020 Review
COVID-19 and ECMO: the interplay between coagulation and inflammation—...

COVID-19 and ECMO: the interplay between coagulation and inflammation—a narrative review

CRITICAL CARE

Authors
Mariusz Kowalewski, Dario Fina, Artur Słomka, Giuseppe Maria Raffa, Gennaro Martucci, Valeria Lo Coco, Maria Elena De Piero, Marco Ranucci, Piotr Suwalski, Roberto Lorusso

ABSTRACT

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has presently become a rapidly spreading and devastating global pandemic. Veno-venous extracorporeal membrane oxygenation (V-V ECMO) may serve as life-saving rescue therapy for refractory respiratory failure in the setting of acute respiratory compromise such as that induced by SARS-CoV-2. While still little is known on the true efficacy of ECMO in this setting, the natural resemblance of seasonal influenza’s characteristics with respect to acute onset, initial symptoms, and some complications prompt to ECMO implantation in most severe, pulmonary decompensated patients. The present review summarizes the evidence on ECMO management of severe ARDS in light of recent COVID-19 pandemic, at the same time focusing on differences and similarities between SARS-CoV-2 and ECMO in terms of hematological and inflammatory interplay when these two settings merge.

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07/05/2020 Release
Coronavirus (COVID-19) related deaths by ethnic group, England and Wal...

Coronavirus (COVID-19) related deaths by ethnic group, England and Wales...

Office for National Statistics

Authors
Office for National Statistics

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07/05/2020 Articles
Observational Study of Hydroxychloroquine in Hospitalized Patients wit...

Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Joshua Geleris, Yifei Sun, Jonathan Platt, Jason Zucker, Matthew Baldwin, George Hripcsak, Angelena Labella, Daniel Manson, Christine Kubin, R. Graham Barr, Magdalena E. Sobieszczyk, Neil W. Schluger

ABSTRACT

BACKGROUND

Hydroxychloroquine has been widely administered to patients with Covid-19 with- out robust evidence supporting its use.

METHODS We examined the association between hydroxychloroquine use and intubation or death at a large medical center in New York City. Data were obtained regarding consecutive patients hospitalized with Covid-19, excluding those who were intu- bated, died, or discharged within 24 hours after presentation to the emergency department (study baseline). The primary end point was a composite of intubation or death in a time-to-event analysis. We compared outcomes in patients who re- ceived hydroxychloroquine with those in patients who did not, using a multivariable Cox model with inverse probability weighting according to the propensity score.

RESULTS Of 1446 consecutive patients, 70 patients were intubated, died, or discharged within 24 hours after presentation and were excluded from the analysis. Of the remaining 1376 patients, during a median follow-up of 22.5 days, 811 (58.9%) received hydroxy- chloroquine (600 mg twice on day 1, then 400 mg daily for a median of 5 days); 45.8% of the patients were treated within 24 hours after presentation to the emer- gency department, and 85.9% within 48 hours. Hydroxychloroquine-treated patients were more severely ill at baseline than those who did not receive hydroxychloro- quine (median ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen, 223 vs. 360). Overall, 346 patients (25.1%) had a primary end-point event (180 patients were intubated, of whom 66 subsequently died, and 166 died without intubation). In the main analysis, there was no significant association between hydroxychloroquine use and intubation or death (hazard ratio, 1.04, 95% confidence interval, 0.82 to 1.32). Results were similar in multiple sensitivity analyses.

CONCLUSIONS In this observational study involving patients with Covid-19 who had been admitted to the hospital, hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death. Randomized, controlled trials of hydroxychloroquine in patients with Covid-19 are needed. (Funded by the National Institutes of Health.)

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07/05/2020 Articles
Interleukin-1 blockade with high-dose anakinra in patients with COVID-...

Interleukin-1 blockade with high-dose anakinra in patients with COVID-19...

THE LANCET

Authors
Giulio Cavalli, Giacomo De Luca, Corrado Campochiaro, Emanuel Della-Torre, Marco Ripa, Diana Canetti, Chiara Oltolini, Barbara Castiglioni, Chiara Tassan Din, Nicola Boffini, Alessandro Tomelleri, Nicola Farina, Annalisa Ruggeri, Patrizia Rovere-Querini, Giuseppe Di Lucca, Sabina Martinenghi, Raffaella Scotti, Moreno Tresoldi, Fabio Ciceri, Giovanni Landoni, Alberto Zangrillo, Paolo Scarpellini, Lorenzo Dagna

ABSTRACT

Background Mortality of patients with coronavirus disease 2019 (COVID-19), acute respiratory distress syndrome (ARDS), and systemic inflammation is high. In areas of pandemic outbreak, the number of patients can exceed maximum capacity of intensive care units (ICUs), and, thus, these individuals often receive non-invasive ventilation outside of the ICU. Effective treatments for this population are needed urgently. Anakinra is a recombinant interleukin-1 receptor antagonist that might be beneficial in this patient population.

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07/05/2020 Letter
Baseline use of hydroxychloroquine in systemic lupus erythematosus doe...

Baseline use of hydroxychloroquine in systemic lupus erythematosus does not...

BMJ

Authors
Maximilian F Konig , Alfred HJ Kim, Marc H Scheetz, Elizabeth R Graef, Jean W Liew, Julia Simard, Pedro M Machado , Milena Gianfrancesco, Jinoos Yazdany, Daman Langguth, Philip C Robinson

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06/05/2020 Report
Development of an inactivated vaccine candidate for SARS-CoV-2

SCIENCE

Authors
Qiang Gao, Linlin Bao, Haiyan Mao, Lin Wang, Kangwei Xu, Minnan Yang, Yajing Li, Ling Zhu, Nan Wang

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are currently no SARS-CoV-2-specific treatments or vaccines available due to the novelty of the virus. Hence, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here we developed a pilot-scale production of a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats and non-human primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against SARS-CoV-2 strains. Three immunizations using two different doses (3 μg or 6 μg per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support clinical development of SARS-CoV-2 vaccines for humans.

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05/05/2020 Articles
Early treatment of COVID-19 patients with hydroxychloroquine and azith...

Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin...

ELSEVIER

Authors
Matthieu Million, Jean-Christophe Lagier, Philippe Gautret, Philippe Colson, Pierre- Edouard Fournier, Sophie Amrane, Marie Hocquart, Morgane Mailhe, Vera Esteves- Vieira, Barbara Doudier, Camille Aubry, Florian Correard, Audrey Giraud-Gatineau, Yanis Roussel, Cyril Berenger, Nadim Cassir, Piseth Seng, Christine Zandotti, Catherine Dhiver, Isabelle Ravaux, Christelle Tomei, Carole Eldin, Hervé Tissot- Dupont, Stéphane Honoré, Andreas Stein, Alexis Jacquier, Jean-Claude Deharo, Eric Chabrière, Anthony Levasseur, Florence Fenollar, Jean-Marc Rolain, Yolande Obadia, Philippe Brouqui, Michel Drancourt, Bernard La Scola, Philippe Parola, Didier Raoult

ABSTRACT

Background In France, the combination hydroxychloroquine (HCQ) and azithromycin (AZ) is used in the treatment of COVID-19.

Methods We retrospectively report on 1061 SARS-CoV-2 positive tested patients treated for at least three days with the following regimen: HCQ (200 mg three times daily for ten days) + AZ (500 mg on day 1 followed by 250 mg daily for the next four days). Outcomes were death, clinical worsening (transfer to ICU, and >10 day hospitalization) and viral shedding persistence (>10 days).

Results A total of 1061 patients were included in this analysis (46.4% male, mean age 43.6 years – range 14–95 years). Good clinical outcome and virological cure were obtained in 973 patients within 10 days (91.7%). Prolonged viral carriage was observed in 47 patients (4.4%) and was associated to a higher viral load at diagnosis (p < .001) but viral culture was negative at day 10. All but one, were PCR-cleared at day 15. A poor clinical outcome (PClinO) was observed for 46 patients (4.3%) and 8 died (0.75%) (74–95 years old). All deaths resulted from respiratory failure and not from cardiac toxicity. Five patients are still hospitalized (98.7% of patients cured so far). PClinO was associated with older age (OR 1.11), severity of illness at admission (OR 10.05) and low HCQ serum concentration. PClinO was independently associated with the use of selective beta-blocking agents and angiotensin II receptor blockers (p < .05). A total of 2.3% of patients reported mild adverse events (gastrointestinal or skin symptoms, headache, insomnia and transient blurred vision).

Conclusion Administration of the HCQ+AZ combination before COVID-19 complications occur is safe and associated with a very low fatality rate in patients.

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05/05/2020 Review
Convalescent plasma in Covid-19: Possible mechanisms of action

ELSEVIER

Authors
Manuel Rojas, Yhojan Rodriguez, Diana M. Monsalve, Yeny Acosta-Ampudia, Bernardo Camacho, Juan Esteban Gallo, Adriana Rojas-Villarraga, Carolina Ram&iacute;rez-Santana, Juan C. D&iacute;az-Coronado, Rub&eacute;n Manrique, Ruben D. Mantilla, Yehuda Shoenfeld, Juan-Manuel Anaya

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible of the coronavirus disease 2019 (COVID-19) pandemic. Therapeutic options including antimalarials, antivirals, and vaccines are under study. Meanwhile the current pandemic has called attention over old therapeutic tools to treat infectious diseases. Convalescent plasma (CP) constitutes the first option in the current situation, since it has been successfully used in other coronaviruses outbreaks. Herein, we discuss the possible mechanisms of action of CP and their repercussion in COVID-19 pathogenesis, including direct neutralization of the virus, control of an overactive immune system (i.e., cytokine storm, Th1/Th17 ratio, complement activation) and immunomodulation of a hypercoagulable state. All these benefits of CP are expected to be better achieved if used in non-critically hospitalized patients, in the hope of reducing morbidity and mortality.

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05/05/2020 Letter
Tocilizumab for cytokine storm syndrome in COVID-19 pneumonia: an incr...

Tocilizumab for cytokine storm syndrome in COVID-19 pneumonia: an increased risk for candidemia?

ELSEVIER

Authors
Spinello Antinori, Cecilia Bonazzetti, Guido Gubertini, Amedeo Capetti, Cristina Pagani, Valentina Morena, Sara Rimoldi, Laura Galimberti, Piercarlo Sarzi-Puttini, Anna Lisa Ridolfo

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05/05/2020 Review
Continuous hydroxychloroquine or colchicine therapy does not prevent i...

Continuous hydroxychloroquine or colchicine therapy does not prevent infection with...

ELSEVIER

Authors
Omer Gendelman, Howard Amital, Nicola Luigi Bragazzi, Abdulla Watad, Gabriel Chodick

Background Some disease-modifying agents commonly used to treat patients with rheumatic diseases/autoimmune disorders, such as hydroxychloroquine and colchicine, are under investigation as potential therapies for the “coronavirus disease 2019” (COVID-19). However, the role of such agents as prophylactic tools is still not clear.

Methods This is a retrospective study based on a large healthcare computerized database including all patients that were screened for the “Severe Acute Respiratory Syndrome Coronavirus type 2” (SARS-CoV-2) in the study period from February 23rd 2020 to March 31st 2020. A comparison was conducted between subjects tested positive for SARS-CoV-2 and those found negative in terms of rate of administration of hydroxychloroquine/colchicine therapy.

Results An overall sample of 14,520 subjects were screened for SARS-CoV-2 infection and 1317 resulted positive. No significant difference was found in terms of rates of usage of hydroxychloroquine or colchicine between those who were found positive for SARS-CoV-2 and those who were found negative (0.23% versus 0.25% for hydroxychloroquine, and 0.53% versus 0.48% for colchicine, respectively).

Conclusion These findings raise doubts regarding the protective role of these medications in the battle against SARS-CoV-2 infection.

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05/05/2020 Editorial
The Urgency of Care during the Covid-19 Pandemic — Learning as We Go

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Eric J. Rubin, David P. Harrington, Joseph W. Hogan, Constantine Gatsonis, Lindsey R. Baden and Mary Beth Hamel

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04/05/2020 Editorial
Developing a vaccine for covid-19

BMJ

Authors
Sarah Caddy

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01/05/2020 Articles
Treatments Administered to the First 9152 Reported Cases of COVID-19: ...

Treatments Administered to the First 9152 Reported Cases of COVID-19: A Systematic Review

MEDRXIV

Authors
David C. Fajgenbaum . Johnson S. Khor . Alexander Gorzewski . Mark-Avery Tamakloe . Victoria Powers . Joseph J. Kakkis . Mileva Repasky . Anne Taylor . Alexander Beschloss . Laura Hernandez-Miyares . Beatrice Go . Vivek Nimgaonkar . Madison S. McCarthy . Casey J. Kim . Ruth-Anne Langan Pai . Sarah Frankl . Philip Angelides . Joanna Jiang . Rozena Rasheed . Erin Napier . Duncan Mackay . Sheila K. Pierson

ABSTRACT
Background The emergence of SARS-CoV-2/2019 novel coronavirus (COVID19) has created a global pandemic with no approved treatments or vaccines. Repurposing existing drugs and rapidly launching clinical trials present the greatest near-term opportunities for mitigating COVID19s impact. Many treatments have already been administered to COVID19 patients but have not been systematically evaluated. We performed a systematic literature review to identify and assess all treatments reported to be administered to COVID19 patients. Methods We searched PubMed, BioRxiv, MedRxiv, and ChinaXiv for articles reporting treatments for COVID19 patients published between Dec 1, 2019 and Mar 27, 2020. All studies reporting treatments were included. Data for each paper were manually extracted by two independent extractors. Outcomes included the duration from drug administration to clinically-meaningful response (complete symptom resolution or hospital discharge). Data were analysed descriptively. Results We identified 2,706 articles from single patient case reports to single-centre interventional studies. Of these, 155 studies met inclusion criteria, comprising 9,152 patients from 14 different countries. The cohort was 45.4% female and 98.3% hospitalised, and mean (SD) age was 44.4 years (SD 21.0). The most frequently administered drug classes were antivirals, antibiotics, and corticosteroids, and of the 115 reported drugs, the most frequently administered was combination lopinavir/ritonavir, which was associated with a response time of 11.7 (1.09) days. Discussion A large number of treatments have been administered to the first 9,152 reported cases of COVID19. Further work is needed to prioritise drugs for investigation in well-controlled clinical trials and treatment protocols. Funding None.

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01/05/2020 Accepted Manuscript
COVID-19, superinfections and antimicrobial development: What can we e...

COVID-19, superinfections and antimicrobial development: What can we expect?

Oxford Academy

Authors
Cornelius J Clancy, M Hong Nguyen

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01/05/2020 Articles
Five “P”s to Watch

AVAC

Authors
AVAC

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01/05/2020 News
Covid-19: Remdesivir is helpful but not a wonder drug, say researchers

BMJ

Authors
Elisabeth Mahase

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01/05/2020 Letter
Remdesivir-EUA-Letter-Of-Authorization

U.S. Food and Drug Administration

Authors
U.S. Food and Drug Administration

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01/05/2020 Editorial
Hydroxychloroquine, Coronavirus Disease 2019, and QT Prolongation

JAMA

Authors
Robert O. Bonow, Adrian F. Hernandez, Mintu Turakhia

Read More »

01/05/2020 Letter
Assessment of QT Intervals in a Case Series of Patients With Coronavir...

Assessment of QT Intervals in a Case Series of Patients With Coronavirus Disease...

JAMA

Authors
Bessière F, Roccia H, Delinière A, Charrière R, Chevalier P, Argaud L, Cour M

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01/05/2020 Report
Structural basis for inhibition of the RNA-dependent RNA polymerase fr...

Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir

SCIENCE

Authors
Wanchao Yin, Chunyou Mao, Xiaodong Luan, Dan-Dan Shen, Qingya Shen, Haixia Su, Xiaoxi Wang, Fulai Zhou, Wenfeng Zhao, Minqi Gao, Shenghai Chang, Yuan-Chao Xie , Guanghui Tian, He-Wei Jiang, Sheng-Ce Tao, Jingshan Shen, Yi Jiang, Hualiang Jiang, Yechun Xu, Shuyang Zhang, Yan Zhang, H. Eric Xu

ABSTRACT

The pandemic of Corona Virus Disease 2019 (COVID-19) caused by SARS-CoV-2 has become a global crisis. The replication of SARS-CoV-2 requires the viral RNA-dependent RNA polymerase (RdRp), a target of the antiviral drug, Remdesivir. Here we report the cryo-EM structure of the SARS-CoV-2 RdRp either in the apo form at 2.8 Å resolution or in complex with a 50-base template-primer RNA and Remdesivir at 2.5 Å resolution. The complex structure reveals that the partial double-stranded RNA template is inserted into the central channel of the RdRp where Remdesivir is covalently incorporated into the primer strand at the first replicated base pair and terminates chain elongation. Our structures provide critical insights into the mechanism of viral RNA replication and a rational template for drug design to combat the viral infection.

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01/05/2020 News Release
Coronavirus (COVID-19) Update: FDA Issues Emergency Use Authorization ...

Coronavirus (COVID-19) Update: FDA Issues Emergency Use Authorization for...

U.S. Food and Drug Administration

Authors
U.S. Food and Drug Administration

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01/05/2020 Brief Report
Risk of QT Interval Prolongation Associated With Use of Hydroxychloroq...

Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine...

JAMA

Authors
Nicholas J. Mercuro; Christina F. Yen, David J. Shim; Timothy R. Maher, Christopher M. McCoy; Peter J. Zimetbaum; Howard S. Gold

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01/05/2020 Review
Convalescent plasma transfusion for the treatment of COVID-19: Systema...

Convalescent plasma transfusion for the treatment of COVID-19: Systematic review

WILEY ONLINE LIBRARY

Authors
Karthick Rajendran, Krishnasamy Narayanasamy, Jayanthi Rangarajan, Jeyalalitha Rathinam, Murugan Natarajan, Arunkumar Ramachandran

ABSTRACT

The recent emergence of COVID-19 pandemic has reassessed the usefulness of historic convalescent plasma transfusion (CPT). This review was conducted to evaluate the effectiveness of CPT therapy in COVID-19 patients based on the publications reported till date. To our knowledge, this is the first systematic review on convalescent plasma on clinically relevant outcomes in individuals with COVID-19.

Methods PubMed, EMBASE and Medline databases were searched upto 19 April 2020. All records were screened as per the protocol eligibility criteria.

Results We included 5 studies reporting CPT to COVID-19 patients. The main findings from available data are as follows: (1) Convalescent plasma may reduce mortality in critically ill patients (2) Increase in neutralizing antibody titers and disappearance of SARS-CoV-2 RNA was observed in almost all the patients after CPT therapy (3) Beneficial effect on clinical symptoms after administration of convalescent plasma.

Conclusions Based on the limited scientific data, CPT therapy in COVID-19 patient appears safe, clinically effective and reduces mortality. Well-designed large multi center clinical trial

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30/04/2020 Press Release
EMA starts rolling review of remdesivir for COVID-19

EMA

Authors
EUROPEAN MEDICINES AGENCY

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30/04/2020 Medical News & Perspectives
Testing an Old Therapy Against a New Disease: Convalescent Plasma for ...

Testing an Old Therapy Against a New Disease: Convalescent Plasma for COVID-19

JAMA

Authors
Rita Rubin

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30/04/2020 Features
The race for coronavirus vaccines a graphical guide

Nature

Authors
Ewen Callaway

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29/04/2020 Articles
The first case of COVID-19 treated with the complement C3 inhibitor AM...

The first case of COVID-19 treated with the complement C3 inhibitor AMY-101

ELSEVIER

Authors
Sara Mastaglioa, Annalisa Ruggeria, Antonio M. Risitanob, Piera Angelilloa, Despina Yancopoulouc, Dimitrios C. Mastellosd, Markus Huber-Lange, Simona Piemontesea, Andrea Assanellia, Cecilia Garlandaf, John D. Lambrish, Fabio Ciceria

ABSTRACT

Acute respiratory distress syndrome (ARDS) is a devastating clinical manifestation of COVID-19 pneumonia and is mainly based on an immune-driven pathology. Mounting evidence suggests that COVID-19 is fueled by a maladaptive host inflammatory response that involves excessive activation of innate immune pathways. While a “cytokine storm” involving IL-6 and other cytokines has been documented, complement C3 activation has been implicated as an initial effector mechanism that exacerbates lung injury in preclinical models of SARS-CoV infection. C3-targeted intervention may provide broader therapeutic control of complement-mediated inflammatory damage in COVID-19 patients. Herein, we report the clinical course of a patient with severe ARDS due to COVID-19 pneumonia who was safely and successfully treated with the compstatin-based complement C3 inhibitor AMY-101.

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29/04/2020 Comment
Remdesivir for COVID-19: challenges of underpowered studies

The Lancet

Authors
JOHN DAVID NORRIE

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29/04/2020 Articles
Remdesivir in adults with severe COVID-19: a randomised, double-blind....

Remdesivir in adults with severe COVID-19: a randomised, double-blind...

The Lancet

Authors
Yeming Wang, Dingyu Zhang, Guanhua Du, Ronghui Du, Jianping Zhao, Yang Jin, Shouzhi Fu, Ling Gao, Zhenshun Cheng, Qiaofa Lu, Yi Hu, Guangwei Luo, Ke Wang, Yang Lu, Huadong Li, Shuzhen Wang, Shunan Ruan, Chengqing Yang, Chunlin Mei, Yi Wang, Dan Ding, Feng Wu, Xin Tang, Xianzhi Ye, Yingchun Ye, Bing Liu, Jie Yang, Wen Yin, Aili Wang, Guohui Fan, Fei Zhou, Zhibo Liu, Xiaoying Gu, Jiuyang Xu, Lianhan Shang, Yi Zhang, Lianjun Cao, Tingting Guo, Yan Wan, Hong Qin, Yushen Jiang, Thomas Jaki, Frederick G Hayden, Peter W Horby, Bin Cao, Chen Wang

Read More »

28/04/2020 Mini-Review
Rapid review for the anti-coronavirus effect of remdesivir

Drug Discoveries & Therapeutics

Authors
Ziyi Li, Xiaojie Wang, Donglin Cao, Ruilin Sun, Cheng Li, Guowei Li

ABSTRACT

The outbreak of SARS-CoV-2 rapidly spread across China and worldwide. Remdesivir had been proposed as a promising option for treating coronavirus disease 2019 (COVID-19). We provided a rapid review to critically assess the potential anti-coronavirus effect of remdesivir on COVID-19 and other coronaviruses based on the most up-to-date evidence. Even though remdesivir was proposed as a promising option for treating COVID-19 based on laboratory experiments and reports from compassionate use, its safety and effect in humans requires high-quality evidence from well- designed and adequately-powered clinical trials for further clarification.

Read More »

27/04/2020 Articles
Covid-19: What do we know so far about a vaccine?

BMJ

Authors
Elisabeth Mahase

Read More »

26/04/2020 Review
Repurposing Antiviral Protease Inhibitors Using Extracellular Vesicles...

Repurposing Antiviral Protease Inhibitors Using Extracellular Vesicles for...

MDPI

Authors
Santosh Kumar, Kaining Zhi, Ahona Mukherji and Kelli Gerth

Abstract

In January 2020, Chinese health agencies reported an outbreak of a novel coronavirus-2 (CoV-2) which can lead to severe acute respiratory syndrome (SARS). The virus, which belongs to the coronavirus family (SARS-CoV-2), was named coronavirus disease 2019 (COVID-19) and declared a pandemic by the World Health Organization (WHO). Full-length genome sequences of SARS-CoV-2 showed 79.6% sequence identity to SARS-CoV, with 96% identity to a bat coronavirus at the whole-genome level. COVID-19 has caused over 133,000 deaths and there are over 2 million total confirmed cases as of April 15th, 2020. Current treatment plans are still under investigation due to a lack of understanding of COVID-19. One potential mechanism to slow disease progression is the use of antiviral drugs to either block the entry of the virus or interfere with viral replication and maturation. Currently, antiviral drugs, including chloroquine/hydroxychloroquine, remdesivir, and lopinavir/ritonavir, have shown effective inhibition of SARS-CoV-2 in vitro. Due to the high dose needed and narrow therapeutic window, many patients are experiencing severe side effects with the above drugs. Hence, repurposing these drugs with a proper formulation is needed to improve the safety and efficacy for COVID-19 treatment. Extracellular vesicles (EVs) are a family of natural carriers in the human body. They play a critical role in cell-to-cell communications. EVs can be used as unique drug carriers to deliver protease inhibitors to treat COVID-19. EVs may provide targeted delivery of protease inhibitors, with fewer systemic side effects. More importantly, EVs are eligible for major aseptic processing and can be upscaled for mass production. Currently, the FDA is facilitating applications to treat COVID-19, which provides a very good chance to use EVs to contribute in this combat.

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26/04/2020 Technical report
Disinfection of environments in healthcare and non-healthcare settings...

Disinfection of environments in healthcare and non-healthcare settings potentially contaminated with SARS-CoV-2

European Centre for Disease Prevention and Control

Authors
European Centre for Disease Prevention and Control

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24/04/2020 Review Article
The Current and Future State of Vaccines, Antivirals and Gene Therapie...

The Current and Future State of Vaccines, Antivirals and Gene Therapies...

FRONTIERS IN MICROBIOLOGY

Authors
Longping V. Tse, Rita M. Meganck, Rachel L. Graham, Ralph S. Baric

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24/04/2020 Letter
COVID-19 and Diabetes Mellitus: May Old Anti-diabetic Agents Become th...

COVID-19 and Diabetes Mellitus: May Old Anti-diabetic Agents Become the New Philosopher’s Stone?

SPRINGER LINK

Authors
Theano Penlioglou, Stella Papachristou, Nikolaos Papanas

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible of the coronavirus disease 2019 (COVID-19) pandemic. Therapeutic options including antimalarials, antivirals, and vaccines are under study. Meanwhile the current pandemic has called attention over old therapeutic tools to treat infectious diseases. Convalescent plasma (CP) constitutes the first option in the current situation, since it has been successfully used in other coronaviruses outbreaks. Herein, we discuss the possible mechanisms of action of CP and their repercussion in COVID-19 pathogenesis, including direct neutralization of the virus, control of an overactive immune system (i.e., cytokine storm, Th1/Th17 ratio, complement activation) and immunomodulation of a hypercoagulable state. All these benefits of CP are expected to be better achieved if used in non-critically hospitalized patients, in the hope of reducing morbidity and mortality.

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24/04/2020 Editorial
Caution Needed on the Use of Chloroquine and Hydroxychloroquine for Co...

Caution Needed on the Use of Chloroquine and Hydroxychloroquine for Coronavirus Disease 2019

JAMA

Authors
Stephan D. Fihn; Eli Perencevich; Steven M. Bradley

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22/04/2020 Head to head
Is it wrong to prioritise younger patients with covid-19?

BMJ

Authors
Dave Archard , Arthur Caplan William F, Virginia Connolly Mitty

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20/04/2020 Review
Transfusion and Apheresis Science

ELSEVIER

Authors
Bethany L. Browna, Jeffrey McCulloughb

Abstract Use of convalescent plasma transfusions could be of great value in the current pandemic of coronavirus disease (COVID-19), given the lack of specific preventative and therapeutic options. This convalescent plasma therapy is of particular interest when a vaccine or specific therapy is not yet available for emerging viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. This report summarizes ex- isting literature around convalescent plasma as a therapeutic option for COVID-19. It also includes re- commendations for establishing a convalescent plasma program, enhancement considerations for convalescent plasma, and considerations around pathogen reduction treatment of convalescent plasma. Time is of the essence to set up protocols for collection, preparation, and administration of apheresis-collected convalescent plasma in response to the current pandemic. The immediate use of convalescent plasma provides prompt availability of a promising treatment while specific vaccines and treatments are evaluated and brought to scale. Further devel- opment of improved convalescent plasma, vaccines and other therapeutics depends on quick generation of additional data on pathogenesis and immune response. Additionally, given the lack of information around the natural history of this disease, PRT should be considered to add a layer of safety to protect recipients of con- valescent plasma.

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20/04/2020 Articles
Nafamostat mesylate blocks activation of SARS-CoV New treatment option...

Nafamostat mesylate blocks activation of SARS-CoV New treatment option 2 for COVID-19

American Society for Microbiology.

Authors
Markus Hoffmann, Simon Schroeder, Hannah Kleine-Weber, Marcel A. M&uuml;ller, Christian Drosten, Stefan P&ouml;hlmann

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18/04/2020 Perspectives
Sarah Gilbert: carving a path towards a COVID-19 vaccine

The Lancet

Authors
Richard Lane

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17/04/2020 Articles
COVID-19 and Renin Angiotensin Blockers: Current Evidence and Recommen...

COVID-19 and Renin Angiotensin Blockers: Current Evidence and Recommendations

AMERICAN COLLEGE OF CARDIOLOGY

Authors
Messerli FH, Siontis GC, Rexhaj E.

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17/04/2020 Articles
What’s happening in covid-19 ICUs? An intensive care doctor answers so...

What’s happening in covid-19 ICUs? An intensive care doctor answers some common questions

THE BMJ

Authors
Abi Rimmer , Emma Wilkinson

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17/04/2020 Articles
Weak Induction of Interferon Expression by SARS-CoV-2...

OXFORD ACADEMY

Authors
Thomas R O&rsquo;Brien, David L Thomas, Sarah S Jackson, Ludmila Prokunina-Olsson, Raymond P Donnelly, Rune Hartmann

Read More »

16/04/2020 Letter
Off-label Use of Tocilizumab in Patients with SARS-CoV-2 Infection

WILEY ONLINE LIBRARY

Authors
Simona Di Giambenedetto, Arturo Ciccullo, Alberto Borghetti, Giovanni Gambassi, Francesco Landi, Elena Visconti, Lorenzo Zileri Dal Verme, Roberto Bernabei, Enrica Tamburrini, Roberto Cauda, Antonio Gasbarrini, GEMELLI AGAINST COVID‐19 group

ABSTRACT
The spread of the novel-Coronavirus infection worldwide represents a challenge for physicians. Particularly, no approved therapy has demonstrated to have an impact in treating patients who develop severe respiratory insufficiency so far. The use of humanized anti-human inteleukine-6 receptor antibody tocilizumab seems a promising strategy for these patients.

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16/04/2020 Editorial
Ivermectin and Novel Coronavirus Disease (COVID-19): Keeping Rigor in ...

Ivermectin and Novel Coronavirus Disease (COVID-19): Keeping Rigor in Times of Urgency

The American Journal of Tropical Medicine and Hygiene

Authors
Carlos Chaccour, Felix Hammann, Santiago Ram&oacute;n-Garc&iacute;a, N. Regina Rabinovich

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13/04/2020 Review
Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19) A Rev...

Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19) A Review

JAMA

Authors
James M. Sanders, Pharm; Marguerite L. Monogue, Pharm; Tomasz Z. Jodlowski, Pharm; James B. Cutrell

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11/04/2020 World Report
Regulators split on antimalarials for COVID-19

The Lancet

Authors
Susan Jaffe

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10/04/2020 Perspectives
Compassionate Use of Remdesivir for Patients with Severe Covid-19

The New England Journal of Medicine

Authors
J. Grein, N. Ohmagari, D. Shin, G. Diaz, E. Asperges, A. Castagna, T. Feldt, G. Green, M.L. Green, F.-X. Lescure, E. Nicastri, R. Oda, K. Yo, E. Quiros-Roldan, A. Studemeister, J. Redinski, S. Ahmed, J. Bernett, D. Chelliah, D. Chen, S. Chihara, S.H. Cohen, J. Cunningham, A. D&rsquo;Arminio Monforte, S. Ismail, Kato, G. Lapadula, E. L&rsquo;Her, T. Maeno, S. Majumder, M. Massari, AA.VV.

Read More »

09/04/2020 PERSPECTIVE
Mesenchymal Stromal Cell Secretome for Severe COVID-19 Infections: Pre...

Mesenchymal Stromal Cell Secretome for Severe COVID-19 Infections: Premises for the Therapeutic Use

MPDI

Authors
Elia Bari, Ilaria Ferrarotti, Laura Saracino, Sara Perteghella, Maria Luisa Torre, Angelo Guido Corsico

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09/04/2020 Comment
Attention should be paid to venous thromboembolism prophylaxis in the ...

Attention should be paid to venous thromboembolism prophylaxis in the management of COVID-19

The Lancet

Authors
Tao Wang, Ruchong Chen, Chunli Liu, Wenhua Liang, Weijie Guan, Ruidi Tang, Chunli Tang, Nuofu Zhang, Nanshan Zhong, Shiyue Li

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07/04/2020 Research
Should chloroquine and hydroxychloroquine be used to treat COVID-19? A...

Should chloroquine and hydroxychloroquine be used to treat COVID-19? A rapid review

BJGP OPEN

Authors
Kome Gbinigie, Kerstin Frie

ABSTRACT

Background
On the 11 March 2020, the World Health Organization (WHO) declared that COVID-19 was a pandemic. To date, there are no medical treatments for COVID-19 with proven effectiveness. Novel treatments and/or vaccines will take time to be developed and distributed to patients. In light of this, there has been growing interest in the use of existing medications, such as chloroquine (CQ) and hydroxychloroquine (HCQ), as potential treatments of this disease. Aim To establish the current evidence for the effectiveness of CQ and HCQ in treating COVID-19. Design & setting A rapid review of the literature was conducted. Method Electronic searches in PubMed and Google Scholar were conducted on 21 March 2020. A further search was conducted in Google for relevant literature on 28 March 2020. 

Results
There is limited evidence of in vitro activity of CQ/HCQ against SARS-CoV-2. A number of in vivo clinical trials are underway. The empirical data available from two of these trials reveal conflicting results. Both trials are characterised by small numbers of participants (n = 30 and n = 36) and suffer methodological limitations. No medium or long-term follow-up data is available. 

Conclusion
At present, there is insufficient evidence to determine whether CQ/HCQ are safe and effective treatments for COVID-19. High quality, adequately powered randomised clinical trials in primary and secondary care settings are urgently required to guide policymakers and clinicians. These studies should report medium- and long-term follow-up results, and safety data.

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07/04/2020 Communication
Farmaci utilizzabili per il trattamento della malattia COVID19

AIFA

Authors
AIFA

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06/04/2020 Review
Prediction models for diagnosis and prognosis of covid-19 infection...

The bmj

Authors
Laure Wynants, Ben Van Calster, Marc M J Bonten, Gary S Collins, Thomas P A Debray, Maarten De Vos, Maria C Haller, Georg Heinze

Read More »

06/04/2020 Articles
In Silico Discovery of Candidate Drugs against Covid-19

Research Gate

Authors
Peter J Richardson, Mario Corbellino, Justin Stebbing

ABSTRACT 

Previous studies reported that Angiotensin converting enzyme 2 (ACE2) is the main cell receptor of SARS-CoV and SARS-CoV-2. It plays a key role in the access of the virus into the cell to produce the final infection. In the present study we investigated in silico the basic mechanism of ACE2 in the lung and provided evidences for new potentially effective drugs for Covid-19. Specifically, we used the gene expression profiles from public datasets including The Cancer Genome Atlas, Gene Expression Omnibus and Genotype-Tissue Expression, Gene Ontology and pathway enrichment analysis to investigate the main functions of ACE2-correlated genes. We constructed a protein-protein interaction network containing the genes co-expressed with ACE2. Finally, we focused on the genes in the network that are already associated with known drugs and evaluated their role for a potential treatment of Covid-19. Our results demonstrate that the genes correlated with ACE2 are mainly enriched in the sterol biosynthetic process, Aryldialkylphosphatase activity, adenosylhomocysteinase activity, trialkylsulfonium hydrolase activity, acetate-CoA and CoA ligase activity. We identified a network of 193 genes, 222 interactions and 36 potential drugs that could have a crucial role. Among possible interesting drugs for Covid-19 treatment, we found Nimesulide, Fluticasone Propionate, Thiabendazole, Photofrin, Didanosine and Flutamide.

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06/04/2020 Articles
An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in...

An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in...

SCIENCE

Authors
Timothy P. Sheahan, Amy C. Sims, Shuntai Zhou, Rachel L. Graham

ABSTRACT

Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2, the causative agent of COVID-19. Herein, we show that the ribonucleoside analog β-D-N4-hydroxycytidine (NHC, EIDD-1931) has broad spectrum antiviral activity against SARS-CoV-2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c Bat-CoVs, as well as increased potency against a coronavirus bearing resistance mutations to the nucleoside analog inhibitor remdesivir. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC-prodrug (β-D-N4-hydroxycytidine-5′-isopropyl ester), improved pulmonary function, and reduced virus titer and body weight loss. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral but not host cell RNA, supporting a mechanism of lethal mutagenesis in CoV. The potency of NHC/EIDD-2801 against multiple coronaviruses and oral bioavailability highlight its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses.

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06/04/2020 Correspondence
Preventing COVID-19-induced pneumonia with anticytokine therapy

The Lancet

Authors
Giovanni Monteleone, Pier Carlo Sarzi-Puttini, Sandro Ardizzone

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05/04/2020 Letter
Macrolide treatment for COVID-19: Will this be the way forward?

BioScience Trends

Authors
Masashi Ohe, Haruki Shida, Satoshi Jodo, Yoshihiro Kusunoki, Masahide Seki, Ken Furuya, Houman Goudarzi

Abstract:
ABSTRACT The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic that has developed in late 2019 and 2020 is a serious threat to human health. With no vaccines or drugs approved for prevention and treatment until now, all efforts at drug design and/or clinical trials of already approved drugs are worthy and creditable. Using structure-based drug selection for identification of SARS-CoV-2 protease inhibitors, old drugs such as macrolides (MAC) were predicted to be effective for COVID-19. Lately, the anti-viral effects of macrolides have attracted considerable attention. Very recently, hydroxychloroquine in combination with azithromycin treatment was reported to be effective for COVID-19. We believe that treatments with macrolides alone or in combination with other drugs are promising and open the possibility of an international strategy to fight this emerging viral infection. 

KEYWORDS
COVID-19, SARS-CoV-2, macrolide

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03/04/2020 Correspondence
Baricitinib for COVID-19: a suitable treatment?

The Lancet

Authors
Ennio G Favalli, Martina Biggioggero,Gabriella Maioli, Roberto Caporali

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03/04/2020 News
Rheumatologists rapidly adjust patient care during COVID-19 pandemic

The Lancet

Authors
Tony Kirby

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02/04/2020 Articles
The possible of immunotherapy for COVID-19: A systematic review

NCBI

Authors
Akram AminJafaria, Sorayya Ghasemib

ABSTRACT

The novel coronavirus (2019-nCoV) is an emerging pathogen that was first described in late December 2019 and causes a severe respiratory infection in humans. Since the outbreak of COVID-19, international attention has raised to develop treatment and control options such as types of immunotherapies. The immunotherapy is an effective method for fighting against similar viral infections such as SARS-CoV, and MERS-CoV. These methods include several types of vaccines, monoclonal antibody candidates, and etc. This systematic review article was designed to evaluate the existing evidence and experience related to immunotherapy for 2019-nCoV. Web of Science (ISI), PubMed, and Scopus databases were used to search for suitable keywords such as 2019-nCoV, novel coronavirus, Immunotherapy, interleukin, vaccine and the related words for relevant publications up to 24.3.2020. The present systematic review was performed based on PRISMA protocol. Data extraction and quality valuation of articles were performed by two reviewers. 51 articles were the results of the search and based on the inclusions and exclusions criteria, 7 articles were included in the final review. As a conclusion of these studies demonstratedthat although no serious research has been done on this subject at the time of writing this article, similar studies on the related viruses showed notable results. So immunotherapy for this virus can also be a suitable option

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02/04/2020 Comment
Caution and clarity required in the use of chloroquine for COVID-19

The Lancet

Authors
Yin Kwan Wong, Jing Yang, Yingke He

Read More »

02/04/2020 Articles
Microneedle array delivered recombinant coronavirus vaccines...

Elsevier

Authors
Eun Kim, Geza Erdos, Shaohua Huang, Thomas W. Kenniston, Stephen C. Balmert, Cara Donahue Carey, V. Stalin Raj, Michael W. Epperly, William B. Klimstra, Bart L. Haagmans, Emrullah Korkmaz, Louis D. Falo Jr., Andrea Gambotto

Abstract:
Background

Coronaviruses pose a serious threat to global health as evidenced by Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and COVID-19. SARS Coronavirus (SARS-CoV), MERS Coronavirus (MERS-CoV), and the novel coronavirus, previously dubbed 2019-nCoV, and now officially named SARS-CoV-2, are the causative agents of the SARS, MERS, and COVID-19 disease outbreaks, respectively. Safe vaccines that rapidly induce potent and long-lasting virus-specific immune responses against these infectious agents are urgently needed. The coronavirus spike (S) protein, a characteristic structural component of the viral envelope, is considered a key target for vaccines for the prevention of coronavirus infection.

Methods
We first generated codon optimized MERS-S1 subunit vaccines fused with a foldon trimerization domain to mimic the native viral structure. In variant constructs, we engineered immune stimulants (RS09 or flagellin, as TLR4 or TLR5 agonists, respectively) into this trimeric design. We comprehensively tested the pre-clinical immunogenicity of MERS-CoV vaccines in mice when delivered subcutaneously by traditional needle injection, or intracutaneously by dissolving microneedle arrays (MNAs) by evaluating virus specific IgG antibodies in the serum of vaccinated mice by ELISA and using virus neutralization assays. Driven by the urgent need for COVID-19 vaccines, we utilized this strategy to rapidly develop MNA SARS-CoV-2 subunit vaccines and tested their pre-clinical immunogenicity in vivo by exploiting our substantial experience with MNA MERS-CoV vaccines.

Findings
Here we describe the development of MNA delivered MERS-CoV vaccines and their pre-clinical immunogenicity. Specifically, MNA delivered MERS-S1 subunit vaccines elicited strong and long-lasting antigen-specific antibody responses. Building on our ongoing efforts to develop MERS-CoV vaccines, promising immunogenicity of MNA-delivered MERS-CoV vaccines, and our experience with MNA fabrication and delivery, including clinical trials, we rapidly designed and produced clinically-translatable MNA SARS-CoV-2 subunit vaccines within 4 weeks of the identification of the SARS-CoV-2 S1 sequence. Most importantly, these MNA delivered SARS-CoV-2 S1 subunit vaccines elicited potent antigen-specific antibody responses that were evident beginning 2 weeks after immunization.

Interpretation
MNA delivery of coronaviruses-S1 subunit vaccines is a promising immunization strategy against coronavirus infection. Progressive scientific and technological efforts enable quicker responses to emerging pandemics. Our ongoing efforts to develop MNA-MERS-S1 subunit vaccines enabled us to rapidly design and produce MNA SARS-CoV-2 subunit vaccines capable of inducing potent virus-specific antibody responses. Collectively, our results support the clinical development of MNA delivered recombinant protein subunit vaccines against SARS, MERS, COVID-19, and other emerging infectious diseases. 

Keywords
Subunit vaccines / Trimerization / Microneedle array/ MERS-CoV S1 / SARS-CoV-2 /COVID-19

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01/04/2020 News
NIH Clinical Trial Shows Remdesivir Accelerates Recovery from Advanced...

NIH Clinical Trial Shows Remdesivir Accelerates Recovery from Advanced COVID-19

NIH: National Institute of Allergy and Infectious Diseases

Authors
NIH: National Institute of Allergy and Infectious Diseases

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01/04/2020 Communication
Raccomandazioni sull’uso dei farmaci nella popolazione esposta al viru...

Raccomandazioni sull’uso dei farmaci nella popolazione esposta al virus

AIFA

Authors
AIFA

Read More »

01/04/2020 Articles
Use of Corticosteroids in Coronavirus Disease 2019 Pneumonia...

NULL

Use of Corticosteroids in Coronavirus Disease 2019 Pneumonia: A Systematic Review of the Literature

FRONTIERS IN MEDICINE

Authors:
Nicola Veronese, Jacopo Demurtas, Lin Yang, Roberto Tonelli, Mario Barbagallo, Pierluigi Lopalco, Erik Lagolio, Stefano Celotto, Damiano Pizzol, Liye Zou, Mark A. Tully, Petre Cristian Ilie, Mike Trott, Guillermo F. López-Sánchez, Lee Smith

Read More »

30/03/2020 Perspective
Developing Covid-19 Vaccines at Pandemic Speed

The New England Journal of Medicine

Authors
Nicole Lurie, Melanie Saville, Richard Hatchett, Jane Halton

Read More »

27/03/2020 Preliminary Communication
Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent...

Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma

JAMA

Authors
Chenguang Shen, Zhaoqin Wang, Fang Zhao, Yang Yang, Jinxiu Li, Jing Yuan, Fuxiang Wang, Delin Li, Minghui Yang, Li Xing, Jinli Wei, Haixia Xiao, Yan Yang, Jiuxin Qu, Ling Qing, Li Chen, Zhixiang Xu, Ling Peng, Yanjie Li; Haixia Zheng, Feng Chen; Kun Huang; Yujing Jiang; Dongjing Liu; Zheng Zhang; Yingxia Liu; Lei Liu

Abstract

Importance Coronavirus disease 2019 (COVID-19) is a pandemic with no specific therapeutic agents and substantial mortality. It is critical to find new treatments.

Objective To determine whether convalescent plasma transfusion may be beneficial in the treatment of critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Design, Setting, and Participants Case series of 5 critically ill patients with laboratory-confirmed COVID-19 and acute respiratory distress syndrome (ARDS) who met the following criteria: severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment; Pao2/Fio2 <300; and mechanical ventilation. All 5 were treated with convalescent plasma transfusion. The study was conducted at the infectious disease department, Shenzhen Third People's Hospital in Shenzhen, China, from January 20, 2020, to March 25, 2020; final date of follow-up was March 25, 2020. Clinical outcomes were compared before and after convalescent plasma transfusion.

Exposures Patients received transfusion with convalescent plasma with a SARS-CoV-2–specific antibody (IgG) binding titer greater than 1:1000 (end point dilution titer, by enzyme-linked immunosorbent assay [ELISA]) and a neutralization titer greater than 40 (end point dilution titer) that had been obtained from 5 patients who recovered from COVID-19. Convalescent plasma was administered between 10 and 22 days after admission.

Main Outcomes and Measures Changes of body temperature, Sequential Organ Failure Assessment (SOFA) score (range 0-24, with higher scores indicating more severe illness), Pao2/Fio2, viral load, serum antibody titer, routine blood biochemical index, ARDS, and ventilatory and extracorporeal membrane oxygenation (ECMO) supports before and after convalescent plasma transfusion.

Results All 5 patients (age range, 36-65 years; 2 women) were receiving mechanical ventilation at the time of treatment and all had received antiviral agents and methylprednisolone. Following plasma transfusion, body temperature normalized within 3 days in 4 of 5 patients, the SOFA score decreased, and Pao2/Fio2 increased within 12 days (range, 172-276 before and 284-366 after). Viral loads also decreased and became negative within 12 days after the transfusion, and SARS-CoV-2–specific ELISA and neutralizing antibody titers increased following the transfusion (range, 40-60 before and 80-320 on day 7). ARDS resolved in 4 patients at 12 days after transfusion, and 3 patients were weaned from mechanical ventilation within 2 weeks of treatment. Of the 5 patients, 3 have been discharged from the hospital (length of stay: 53, 51, and 55 days), and 2 are in stable condition at 37 days after transfusion.

Conclusions and Relevance In this preliminary uncontrolled case series of 5 critically ill patients with COVID-19 and ARDS, administration of convalescent plasma containing neutralizing antibody was followed by improvement in their clinical status. The limited sample size and study design preclude a definitive statement about the potential effectiveness of this treatment, and these observations require evaluation in clinical trials.

Read More »

27/03/2020 Editorials
Non-steroidal anti-inflammatory drugs and covid-19

The bmj

Authors
Paul Little

Read More »

26/03/2020 Correspondence
Antihypertensive drugs and risk of COVID-19?

The Lancet

Authors
Christopher J Tignanelli, Nicholas E Ingraham, Matthew A Sparks, Ronald Reilkoff, Tamara Bezdicek, Bradley Benson, Timothy Schacker, Jeffrey G Chipman, Michael A Puskarich

Abstract:
Coronaviruses (CoVs) act as cross-species viruses and have the potential to spread rapidly into new host species and cause epidemic diseases. Despite the severe public health threat of severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome CoV (MERS-CoV), there are currently no drugs available for their treatment; therefore, broad-spectrum inhibitors of emerging and endemic CoVs are urgently needed. To search for effective inhibitory agents, we per- formed high-throughput screening (HTS) of a 2,000-compound library of approved drugs and pharmacologically active compounds using the established genetically en- gineered human CoV OC43 (HCoV-OC43) strain expressing Renilla luciferase (rOC43- ns2Del-Rluc) and validated the inhibitors using multiple genetically distinct CoVs in vitro. We screened 56 hits from the HTS data and validated 36 compounds in vitro using wild-type HCoV-OC43. Furthermore, we identified seven compounds (lycorine, emetine, monensin sodium, mycophenolate mofetil, mycophenolic acid, phenazo- pyridine, and pyrvinium pamoate) as broad-spectrum inhibitors according to their strong inhibition of replication by four CoVs in vitro at low-micromolar concentra- tions. Additionally, we found that emetine blocked MERS-CoV entry according to pseudovirus entry assays and that lycorine protected BALB/c mice against HCoV- OC43-induced lethality by decreasing viral load in the central nervous system. This represents the first demonstration of in vivo real-time bioluminescence imaging to monitor the effect of lycorine on the spread and distribution of HCoV-OC43 in a mouse model. These results offer critical information supporting the development of an effective therapeutic strategy against CoV infection.


IMPORTANCE
Currently, there is no approved therapy to treat coronavirus infection; therefore, broad-spectrum inhibitors of emerging and endemic CoVs are needed. Based on our high-throughput screening assay using a compound library, we identi- fied seven compounds with broad-spectrum efficacy against the replication of four CoVs in vitro. Additionally, one compound (lycorine) was found to protect BALB/c mice against HCoV-OC43-induced lethality by decreasing viral load in the central nervous system. This inhibitor might offer promising therapeutic possibilities for combatting novel CoV infections in the future.

Coronaviruses, bioluminescence imaging, broad-spectrum, high-throughput screening, inhibitor, mice

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26/03/2020 Review
Management of Critically Ill Adults With COVID-19

JAMA

Authors
Jason T. Poston, Bhakti K. Patel, Andrew M. Davis

Abstract:

Summary of the Clinical Problem Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of COVID-19, a pandemic that has affected more than 400 000 individuals and caused nearly 20 000 deaths as of late March 2020. Approximately 5% to 10% of patients require intensive care unit (ICU) admission and mechanical ventilation.1

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25/03/2020 Articles
Urgent Guidance for Navigating and Circumventing the QTc Prolonging...

Authors
John R. Giudicessi, Peter A. Noseworthy,, Paul A. Friedman, Michael J. Ackerman

Abstract:
As the COVID-19 global pandemic rages across the globe, the race to prevent and treat this deadly disease has led to the “off label” re-purposing of drugs such as hydroxychloroquine and lopinavir/ritonavir with the potential for unwanted QT interval prolongation, and a risk of druginduced sudden cardiac death. With the possibility that a significant proportion of the world’s population could receive soon COVID-19 pharmacotherapies with torsadogenic potential for therapy or post-exposure prophylaxis, this document serves to help healthcare providers mitigate the risk of drug-induced ventricular arrhythmias while minimizing risk to personnel of COVID19 exposure and conserving the limited supply of personal protective equipment

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24/03/2020 Viewpoint
Potential inhibitors against 2019-nCoV coronavirus M protease from cli...

Potential inhibitors against 2019-nCoV coronavirus M protease from clinically approved medicines

JAMA

Authors
Andre C. Kalil

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20/03/2020 Comment
Treatment for severe acute respiratory distress syndrome

The Lancet

Authors
Michael A Matthay, J Matthew Aldrich, Jeffrey E Gotts

Read More »

20/03/2020 Articles
A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covi...

A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19

The New England Journal of Medicine

Authors
B. Cao, Y. Wang, D. Wen, W. Liu, Jingli Wang, G. Fan, L. Ruan, B. Song, Y. Cai, M. Wei, X. Li, J. Xia, N. Chen, J. Xiang, T. Yu, T. Bai, X. Xie, L. Zhang, C. Li, Y. Yuan, H. Chen, Huadong Li, H. Huang, S. Tu, F. Gong, Y. Liu, Y. Wei, C. Dong, F. Zhou, X. Gu, J. Xu, Z. Liu, Y. Zhang, Hui Li, L. Shang, K. Wang, K. Li, X. Zhou, X. Dong, Z. Qu, S. Lu, X. Hu, S. Ruan, S. Luo, J. Wu, L. Peng, F. Cheng, L. Pan, J. Zou, C. Jia, Juan Wang, X. Liu, S. Wang, X. Wu, Q. Ge, J. He, H. Zhan, F. Qiu, L. Guo, C. Huang, T. Jaki, F.G. Hayden, P.W. Horby, D. Zhang, and C. Wang

BACKGROUND
No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2.

METHODS
We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2 ) to the fraction of inspired oxygen (Fio2) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir–ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first.

RESULTS
A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir–ritonavir group, and 100 to the standard-care group. Treatment with lopinavir–ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.24; 95% confidence interval [CI], 0.90 to 1.72). Mortality at 28 days was similar in the lopinavir–ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, −5.8 percentage points; 95% CI, −17.3 to 5.7). The per- centages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir–ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir–ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir–ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events.

CONCLUSIONS
In hospitalized adult patients with severe Covid-19, no benefit was observed with lopi- navir–ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit. (Funded by Major Projects of National Science and Technology on New Drug Creation and Development and others; Chinese Clinical Trial Register number, ChiCTR2000029308.)

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20/03/2020 Articles
Hydroxychloroquine and azithromycin as a treatment of COVID-19...

Elsevier

Authors
Philippe Gautret , Jean-Christophe Lagier , Philippe Parola , Thuan Hoang , Line Meddeb , Morgane Mailhe , Barbara Doudier , Johan Courjon , Valerie Giordanengo, Vera Esteves Vieira , Herve Tissot Dupont , Stephane Honor, Philippe Colson , Eric Chabriere , Bernard La Scola, Jean-Marc Rolain , Philippe Brouqui , Didier Raoult

Abstract:


Conclusions:
Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the role of hydroxychloroquine on respiratory viral loads. 

Patients and methods
French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point. 

Results
Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported of untreated patients in the literature. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination. 

Conclusion
Despite its small sample size our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin. 

 

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20/03/2020 Articles
COVID-19: a recommendation to examine the effect of hydroxychloroquine...

COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression

Oxford Academy

Authors
Dan Zhou, Sheng-Ming Dai, Qiang Tong

Abstract:
A novel coronavirus disease (COVID-19), caused by infection with SARS-CoV-2, has swept across 31 provinces in China and over 40 countries worldwide. The transition from first symptoms to acute respiratory distress syndrome (ARDS) is highly likely to be due to uncontrolled cytokine release. There is an urgent need to identify safe and effective drugs for treatment. Chloroquine (CQ) exhibits a promising inhibitory effect. However, the clinical use of CQ can cause severe side effects. We propose that hydroxychloroquine (HCQ), which exhibits an antiviral effect highly similar to that of CQ, could serve as a better therapeutic approach. HCQ is likely to attenuate the severe progression of COVID-19, inhibiting the cytokine storm by suppressing T cell activation. It has a safer clinical profile and is suitable for those who are pregnant. It is cheaper and more readily available in China. We herein strongly urge that clinical trials are performed to assess the preventive effects of HCQ in both disease infection and progression.

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19/03/2020 World view
Don’t rush to deploy COVID-19 vaccines and drugs

Springer Nature

Authors
Shibo Jiang

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19/03/2020 Correspondence
Use of antiviral drugs to reduce COVID-19 transmission

The Lancet

Authors
Oriol Mitj&agrave;, Bonaventura Clotet

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18/03/2020 Research Articles
Effectiveness of convalescent plasma therapy in severe COVID-19 patien...

Effectiveness of convalescent plasma therapy in severe COVID-19 patients

PNAS

Authors
Kai Duan, Bende Liu, Cesheng Li, Huajun Zhang, Ting Yu, Jieming Qu, Min Zhou, Li Chen, Shengli Meng, Yong Hu, Cheng Peng, Mingchao Yuan, Jinyan Huang, Zejun Wang, Jianhong Yu, Xiaoxiao Gao, Dan Wang, Xiaoqi Yu, Li Li, Jiayou Zhang, Xiao Wu, Bei Li, Yanping Xu, Wei Chen, Yan Peng, Yeqin Hu, Lianzhen Lin, Xuefei Liu, Shihe Huang, Zhijun Zhou, Lianghao Zhang, Yue Wang, Zhi Zhang, Kun Deng, Zhiwu Xia, Qin Gong, Wei Zhang, Xiaobei Zheng, Ying Liu, Huichuan Yang, Dongbo Zhou, Ding Yu, Jifeng Hou, Zhengli Shi, Saijuan Chen, Zhu Chen, Xinxin Zhang, and Xiaoming Yang

ABSTRACT Currently, there are no approved specific antiviral agents for novel coronavirus disease 2019 (COVID-19). In this study, 10 severe pa- tients confirmed by real-time viral RNA test were enrolled prospec- tively. One dose of 200 mL of convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. The primary end- point was the safety of CP transfusion. The second endpoints were the improvement of clinical symptoms and laboratory parameters within 3 d after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 d. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). The clinical symptoms were significantly improved along with increase of oxyhemoglobin saturation within 3 d. Several parameters tended to improve as compared to pretransfusion, in- cluding increased lymphocyte counts (0.65 × 109/L vs. 0.76 × 109 /L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Ra- diological examinations showed varying degrees of absorption of lung lesions within 7 d. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed. This study showed CP therapy was well tolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases. The opti- mal dose and time point, as well as the clinical benefit of CP ther- apy, needs further investigation in larger well-controlled trials.

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18/03/2020 Editorial
Covid-19 — The Search for Effective Therapy

The New England Journal of Medicine

Authors
Lindsey R. Baden, M.D., and Eric J. Rubin, M.D., Ph.D.

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16/03/2020 Editorial
Treatment of COVID-19: old tricks for new challenges

Springer Nature

Authors
Anne Catherine Cunningham, Hui Poh Goh, David Koh

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15/03/2020 Review
Targeting the Endocytic Pathway and Autophagy Process as a Novel Thera...

Targeting the Endocytic Pathway and Autophagy Process as a Novel Therapeutic Strategy in COVID-19

International Journal of Biological Sciences

Authors
Naidi Yang, Han-Ming Shen

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13/03/2020 Correspondence
COVID-19, ECMO, and lymphopenia: a word of caution

The Lancet

Authors
Brandon Michael Henry

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10/03/2020 Articles
A systematic review on the efficacy and safety of chloroquine for the ...

A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19

ELSEVIER

Authors
Andrea Cortegiani, Giulia Ingoglia, Mariachiara Ippolito, Antonino Giarratano, Sharon Einav

Purpose:
COVID-19 (coronavirus disease 2019) is a public health emergency of international concern. As of this time, there is no known effective pharmaceutical treatment, although it is much needed for patient contracting the severe form of the disease. The aim of this systematic review was to summarize the evidence regarding chlo- roquine for the treatment of COVID-19.

Methods:
PubMed, EMBASE, and three trial Registries were searched for studies on the use of chloroquine in pa- tients with COVID-19.

Results:
We included six articles (one narrative letter, one in-vitro study, one editorial, expert consensus paper, two national guideline documents) and 23 ongoing clinical trials in China. Chloroquine seems to be effective in limiting the replication of SARS-CoV-2 (virus causing COVID-19) in vitro.

Conclusions:
There is rationale, pre-clinical evidence of effectiveness and evidence of safety from long-time clin- ical use for other indications to justify clinical research on chloroquine in patients with COVID-19. However, clin- ical use should either adhere to the Monitored Emergency Use of Unregistered Interventions (MEURI) framework or be ethically approved as a trial as stated by the World Health Organization. Safety data and data from high-quality clinical trials are urgently needed.

SARS-CoV-2, COVID-19, Chloroquine, Pneumonia, Coronavirus

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06/03/2020 Articles
Patients of COVID-19 may benefit from sustained lopinavir-combined reg...

Patients of COVID-19 may benefit from sustained lopinavir-combined regimen...

JAMA

Authors
Fang Liu, Aifang Xu, Yan Zhang, Weiling Xuan, Tingbo Yan, Kenv Pan, Wenyan Yu, Jun Zhang

Abstract

Objectives
To explore the epidemiological information, clinical characteristics, therapeutic outcomes and temporal progression of laboratory findings in 2019-coronavirus disease (COVID-19) patients exposed to lopinavir.

Methods
We collected data from ten COVID-19 patients admitted between January 22, 2020 and February 11, 2020 at Xixi hospital in Hangzhou, China.

Results
Of ten patients, secondary, tertiary and quartus patients emerged, the incubation period was 3–7 days. Mainly initial symptoms were cough and low fever (37.3–38.0 ℃). An asymptomatic case presented normal radiography, the others existed ground glass opacities. All cases (three transferred, seven discharged) exposed to lopinavir on initial hospitalization. Three patients stopped lopinavir using because of adverse effect, two of them deteriorated, one hospitalized longer than others who with sustained lopinavir using. Levels of potassium, albumin, lymphocyte were low, but increased persistently after treatment. Eosinophil values were low on initial hospitalization, then all returned to normal before discharge. Viral load of SARS-CoV-2, radiography and eosinophil improved continuously in 3–14, 6–8 and 7–9 days, respectively.

Conclusions
Increasing eosinophils may be an indicator of COVID-19 improvement. The COVID-19 patients may benefit from sustained lopinavir using. More researches on a larger scale are needed to verify these points.

Keywords
2019-Coronavirus disease / Lopinavir / Asymptomatic infection /Eosinophil

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05/03/2020 Editorial
Remdesivir as a possible therapeutic option for the COVID-19

ELSEVIER

Authors
Al-Tawfiq JA, Al-Homoud AH, Memish ZA

Read More »

05/03/2020 Correspondence
Respiratory support for patients with COVID-19 infection

The Lancet

Authors
Silvio A &Ntilde;amendys-Silva

Read More »

04/03/2020 Press Release
Chloroquine and hydroxychloroquine as available weapons to fight COVID...

Chloroquine and hydroxychloroquine as available weapons to fight COVID-19

ELSEVIER

Authors
Philippe Colson, Jean-Marc Rolain, Jean-Christophe Lagier, Philippe Brouqui, Didier Raoult

Read More »

01/03/2020 Articles
COVID-19 Drug Therapy — Potential Options

ELSEVIER

Authors
Tim Smith, Tony Prosser

Read More »

14/02/2020 Short Communication
Case of the Index Patient Who Caused Tertiary Transmission of Coronavi...

Case of the Index Patient Who Caused Tertiary Transmission of Coronavirus Disease 2019 in Korea...

JKMS

Authors
Jaegyun Lim ,Seunghyun Jeon ,Hyun-Young Shin ,Moon Jung Kim ,Yu Min Seong ,Wang Jun Lee ,Kang-Won Choe ,Yu Min Kang ,Baeckseung Lee, Sang-Joon Park

Abstract:
Since mid-December of 2019, coronavirus disease 2019 (COVID-19) has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, β-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.

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11/02/2020 Correspondence
On the use of corticosteroids for 2019-nCoV pneumonia

The Lancet

Authors
Lianhan Shang, Jianping Zhao, Yi Hu, Ronghui Du, Bin Cao

Read More »

29/05/2019 Articles
High-Throughput Screening and Identification of Potent Broad-Spectrum ...

High-Throughput Screening and Identification of Potent Broad-Spectrum Inhibitors of Coronaviruses

American Society for Microbiology - Journal of Virology

Authors
Liang Shen, Junwei Niu, Chunhua Wang, Baoying Huang, Wenling Wang, Na Zhu, Yao Deng, Huijuan Wang, Fei Ye, Shan Cen, Wenjie Tana

Coronaviruses (CoVs) act as cross-species viruses and have the potential to spread rapidly into new host species and cause epidemic diseases. Despite the severe public health threat of severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome CoV (MERS-CoV), there are currently no drugs available for their treatment; therefore, broad-spectrum inhibitors of emerging and endemic CoVs are urgently needed. To search for effective inhibitory agents, we per- formed high-throughput screening (HTS) of a 2,000-compound library of approved drugs and pharmacologically active compounds using the established genetically en- gineered human CoV OC43 (HCoV-OC43) strain expressing Renilla luciferase (rOC43- ns2Del-Rluc) and validated the inhibitors using multiple genetically distinct CoVs in vitro. We screened 56 hits from the HTS data and validated 36 compounds in vitro using wild-type HCoV-OC43. Furthermore, we identified seven compounds (lycorine, emetine, monensin sodium, mycophenolate mofetil, mycophenolic acid, phenazo- pyridine, and pyrvinium pamoate) as broad-spectrum inhibitors according to their strong inhibition of replication by four CoVs in vitro at low-micromolar concentra- tions. Additionally, we found that emetine blocked MERS-CoV entry according to pseudovirus entry assays and that lycorine protected BALB/c mice against HCoV- OC43-induced lethality by decreasing viral load in the central nervous system. This represents the first demonstration of in vivo real-time bioluminescence imaging to monitor the effect of lycorine on the spread and distribution of HCoV-OC43 in a mouse model. These results offer critical information supporting the development of an effective therapeutic strategy against CoV infection.

IMPORTANCE
Currently, there is no approved therapy to treat coronavirus infection; therefore, broad-spectrum inhibitors of emerging and endemic CoVs are needed. Based on our high-throughput screening assay using a compound library, we identi- fied seven compounds with broad-spectrum efficacy against the replication of four CoVs in vitro. Additionally, one compound (lycorine) was found to protect BALB/c mice against HCoV-OC43-induced lethality by decreasing viral load in the central nervous system. This inhibitor might offer promising therapeutic possibilities for combatting novel CoV infections in the future.

Coronaviruses, bioluminescence imaging, broad-spectrum, high-throughput screening, inhibitor, mice

Read More »

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