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Treatment

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

TOCIVID-19 è il primo e più ampio studio sul tocilizumab autorizzato dall’Agenzia Italiana del Farmaco (AIFA).

ISTITUTO NAZIONALE TUMORI DI NAPOLI

Authors:
ISTITUTO NAZIONALE TUMORI DI NAPOLI

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11/05/2020 Pharmacological Research
Compassionate remdesivir treatment of severe Covid-19 pneumonia in intensive care unit (ICU)...

Compassionate remdesivir treatment of severe Covid-19 pneumonia in intensive care unit (ICU) and Non-ICU patients: Clinical outcome and differences in post treatment hospitalisation status

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 Original Investigation
Association of Treatment With Hydroxychloroquine or Azithromycin...

Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State

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

EMA

Authors:
EUROPEAN MEDICINES AGENCY

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

The Lancet

Authors:
Sophie Cousins

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

Tocilizumab for Treatment of Severe COVID-19 Patients: Preliminary Results from SMAtteo COvid19 REgistry (SMACORE)

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

SCIENCE

Authors:
Barney S. Graham

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07/05/2020 Letter
Baseline use of hydroxychloroquine in systemic lupus erythematosus does not...

Baseline use of hydroxychloroquine in systemic lupus erythematosus does not preclude SARS-CoV-2 infection and severe COVID-19

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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07/05/2020 Articles
Interleukin-1 blockade with high-dose anakinra in patients with COVID-19...

Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study

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

Coronavirus (COVID-19) related deaths by ethnic group, England and Wales: 2 March 2020 to 10 April 2020

Office for National Statistics

Authors:
Office for National Statistics

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07/05/2020 Articles
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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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 Review
Continuous hydroxychloroquine or colchicine therapy does not prevent infection with...

Continuous hydroxychloroquine or colchicine therapy does not prevent infection with SARS-CoV-2: Insights from a large healthcare database analysis

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

Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: A retrospective analysis of 1061 cases in Marseille, France

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 Ramírez-Santana, Juan C. Díaz-Coronado, Rubén 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 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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05/05/2020 Letter
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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04/05/2020 Editorial
Developing a vaccine for covid-19

THE BMJ

Authors:
Sarah Caddy

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

Assessment of QT Intervals in a Case Series of Patients With Coronavirus Disease 2019 (COVID-19) Infection Treated With Hydroxychloroquine Alone or in Combination With Azithromycininan Intensive Care Unit

JAMA

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

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

JAMA

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

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

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

U.S. Food and Drug Administration

Authors:
U.S. Food and Drug Administration

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

Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19)

JAMA

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

Read More »

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 COVID-19

JAMA

Authors:
Rita Rubin

Read More »

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

Nature

Authors:
Ewen Callaway

Read More »

29/04/2020 Articles
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, placebo-controlled, multicentre trial

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.

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

BMJ

Authors:
Elisabeth Mahase

Read More »

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

Repurposing Antiviral Protease Inhibitors Using Extracellular Vesicles for Potential Therapy of COVID-19

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

The Current and Future State of Vaccines, Antivirals and Gene Therapies Against Emerging Coronaviruses

FRONTIERS IN MICROBIOLOGY

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

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24/04/2020 Editorial
Caution Needed on the Use of Chloroquine and Hydroxychloroquine for Coronavirus Disease 2019

JAMA

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

Read More »

24/04/2020 Letter
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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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 Articles
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. Müller, Christian Drosten, Stefan Pöhlmann

Read More »

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

The Lancet

Authors:
Richard Lane

Read More »

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

AMERICAN COLLEGE OF CARDIOLOGY

Authors:
Messerli FH, Siontis GC, Rexhaj E.

Read More »

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

THE BMJ

Authors:
Abi Rimmer , Emma Wilkinson

Read More »

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

Weak Induction of Interferon Expression by SARS-CoV-2 Supports Clinical Trials of Interferon Lambda to Treat Early COVID-19

OXFORD ACADEMY

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

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16/04/2020 Editorial
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 Ramón-García, N. Regina Rabinovich

Read More »

13/04/2020 Review
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

Read More »

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

The Lancet

Authors:
Susan Jaffe

Read More »

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’Arminio Monforte, S. Ismail, Kato, G. Lapadula, E. L’Her, T. Maeno, S. Majumder, M. Massari, AA.VV.

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09/04/2020 Comment
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

Read More »

07/04/2020 Research
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

Read More »

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 human airway epithelial cell cultures and multiple coronaviruses in mice

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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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 Review
Prediction models for diagnosis and prognosis of covid-19 infection...

Prediction models for diagnosis and prognosis of covid-19 infection: systematic review and critical appraisal

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 »

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:
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

Read More »

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
Microneedle array delivered recombinant coronavirus vaccines...

Microneedle array delivered recombinant coronavirus vaccines: Immunogenicity and rapid translational development

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

AIFA

Authors:
AIFA

Read More »

04/2020 News
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

Read More »

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

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 »

30 /03/2020 Special Report
Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19

The New England Journal of Medicine

Authors:
Muthiah Vaduganathan, Orly Vardeny, Thomas Michel, John J.V. McMurray, Marc A. Pfeffer, Scott D. Solomon

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

Read More »

27/03/2020 Preliminary Communication
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.

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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

Read More »

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

Urgent Guidance for Navigating and Circumventing the QTc Prolonging and Torsadogenic Potential of Possible Pharmacotherapies for COVID-19 

Mayo Clinic Proceedings

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

Read More »

24/03/2020 Viewpoint
Potential inhibitors against 2019-nCoV coronavirus M protease from clinically approved medicines

JAMA

Authors:
Andre C. Kalil

Read More »

20 /03/2020 Articles
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 Press Release
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 »

20 /03/2020 Articles
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.

Read More »

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 »

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

Springer Nature

Authors:
Shibo Jiang

Read More »

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

The Lancet

Authors:
Oriol Mitjà, Bonaventura Clotet

Read More »

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.

Read More »

18/03/2020 Research Articles
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.

Read More »

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

Springer Nature

Authors:
Anne Catherine Cunningham, Hui Poh Goh, David Koh

Read More »

15/03/2020 Review
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

Read More »

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

The Lancet

Authors:
Brandon Michael Henry

Read More »

13/02/2020 Editorial
Potential inhibitors against 2019-nCoV coronavirus M protease from clinically approved medicines

Elsevier

Authors:
Xin Liu, Xiu-Jie Wang

Read More »

14/02/2020 Short Communication
Case of the Index Patient Who Caused Tertiary Transmission of Coronavirus Disease 2019 in Korea...

Case of the Index Patient Who Caused Tertiary Transmission of Coronavirus Disease 2019 in Korea: the Application of Lopinavir/Ritonavir for the Treatment of COVID-19 Pneumonia Monitored by Quantitative RT-PCR 

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.

Read More »

10/03/2020 Articles
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

Read More »

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 »

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

Patients of COVID-19 may benefit from sustained lopinavir-combined regimen and the increase of eosinophil may predict the outcome of COVID-19 progression

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

Read More »

29/05/2019 Articles
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

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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 Ñamendys-Silva

Read More »

03/2020 Editorial
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.

Objectives
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 »

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

ELSEVIER

Authors:
Tim Smith, Tony Prosser

Read More »

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