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Clinical Aspects

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21/05/2020 Original Article
Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors:
Maximilian Ackermann, Stijn E. Verleden, Mark Kuehnel, Axel Haverich, Tobias Welte, Florian Laenger, Arno Vanstapel, Christopher Werlein, Helge Stark, Alexandar Tzankov, William W. Li, Vincent W. Li, Steven J. Mentzer, Danny Jonigk

ABSTRACT

BACKGROUND Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (Covid-19) pandemic. Despite widespread interest in the pathophysiology of the disease, relatively little is known about the associated morphologic and molecular changes in the peripheral lung of patients who die from Covid-19.

METHODS We examined 7 lungs obtained during autopsy from patients who died from Covid-19 and compared them with 7 lungs obtained during autopsy from patients who died from acute respiratory distress syndrome (ARDS) secondary to influenza A(H1N1) infection and 10 age-matched, uninfected control lungs. The lungs were studied with the use of seven-color immunohistochemical analysis, micro–computed tomographic imaging, scanning electron microscopy, corrosion casting, and direct multiplexed measurement of gene expression.

RESULTS In patients who died from Covid-19–associated or influenza-associated respiratory failure, the histologic pattern in the peripheral lung was diffuse alveolar damage with perivascular T-cell infiltration. The lungs from patients with Covid-19 also showed distinctive vascular features, consisting of severe endothelial injury associated with the presence of intracellular virus and disrupted cell membranes. Histologic analysis of pulmonary vessels in patients with Covid-19 showed widespread thrombosis with microangiopathy. Alveolar capillary microthrombi were 9 times as prevalent in patients with Covid-19 as in patients with influenza (P<0.001). In lungs from patients with Covid-19, the amount of new vessel growth — predominantly through a mechanism of intussusceptive angiogenesis — was 2.7 times as high as that in the lungs from patients with influenza (P<0.001).

CONCLUSIONS In our small series, vascular angiogenesis distinguished the pulmonary pathobiology of Covid-19 from that of equally severe influenza virus infection. The universality and clinical implications of our observations require further research to define. (Funded by the National Institutes of Health and others.)

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20 /05/2020 Clinical Update
Olfactory Dysfunction in COVID-19 Diagnosis and Management

JAMA

Authors:
Katherine Lisa Whitcroft, Thomas Hummel

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18/05/2020 Review Article
Coronavirus disease 2019 (SARS-CoV-2) and colonization of ocular...

Coronavirus disease 2019 (SARS-CoV-2) and colonization of ocular tissues and secretions: a systematic review

EYE

Authors:
Francesco Aiello, Gabriele Gallo Afflitto, Raffaele Mancino, Ji-Peng Olivia Li, Massimo Cesareo, Clarissa Giannini, Carlo Nucci

ABSTRACT

Coronavirus disease 19 (COVID-19) has been described to potentially be complicated by ocular involvement. However, scant information is available regarding severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and ocular structures tropism. We conducted a systematic review of articles referenced in PubMed, Cochrane Library, Web of Science and Chinese Clinical Trial Register (ChiCTR) from December 20, 2019 to April 6, 2020, providing information on the presence of SARS-CoV-2 in cornea, conjunctiva, lacrimal sac, and tears. We excluded ongoing clinical studies as for unobtainable conclusive results. Of 2422 articles, 11 met the inclusion criteria for analysis and were included in the study. None of the studies were multinational. Among the 11 selected papers there were three original articles, one review, four letters, two editorials, and one correspondence letter. Globally, 252 SARS-CoV-2 infected patients were included in our review. The prevalence of ocular conjunctivitis complicating the course of COVID-19 was demonstrated to be as high as 32% in one study only. Globally, three patients had conjunctivitis with a positive tear-PCR, 8 patients had positive tear-PCR in the absence of conjunctivitis, and 14 had conjunctivitis with negative tear-PCR. The majority of the available data regarding SARS-CoV-2 colonization of ocular and periocular tissues and secretions have to be considered controversial. However, it cannot be excluded that SARS-CoV-2 could both infect the eye and the surrounding structures. SARS-CoV-2 may use ocular structure as an additional transmission route, as demonstrated by the COVID-19 patients’ conjunctival secretion and tears positivity to reverse transcriptase-PCR SARS-CoV-2-RNA assay.

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18/05/2020 Article
COVID-19 in persons with chronic myeloid leukaemia

LEUKEMIA

Authors:
Weiming Li, Danyu Wang, Jingming Guo, Guolin Yuan, Zhuangzhi Yang, Robert Peter Gale, Yong You, Zhichao Chen, Shiming Chen, Chucheng Wan, Xiaojian Zhu, Wei Chang, Lingshuang Sheng, Hui Cheng, Youshan Zhang, Qing Li, Jun Qin, Hubei Anti-Cancer Association, Li Meng, Qian Jiang

ABSTRACT

We studied by questionnaire 530 subjects with chronic myeloid leukaemia (CML) in Hubei Province during the recent SARS-CoV-2 epidemic. Five developed confirmed (N = 4) or probable COVID-19 (N = 1). Prevalence of COVID-19 in our subjects, 0.9% (95% Confidence Interval, 0.1, 1.8%) was ninefold higher than 0.1% (0, 0.12%) reported in normals but lower than 10% (6, 17%) reported in hospitalised persons with other haematological cancers or normal health-care providers, 7% (4, 12%). Co-variates associated with an increased risk of developing COVID-19 amongst persons with CML were exposure to someone infected with SARS-CoV-2 (P = 0.037), no complete haematologic response (P = 0.003) and co-morbidity(ies) (P = 0.024). There was also an increased risk of developing COVID-19 in subjects in advanced phase CML (P = 0.004) even when they achieved a complete cytogenetic response or major molecular response at the time of exposure to SARS-CoV-2. 1 of 21 subjects receiving 3rd generation tyrosine kinase-inhibitor (TKI) developed COVID-19 versus 3 of 346 subjects receiving imatinib versus 0 of 162 subjects receiving 2nd generation TKIs (P = 0.096). Other co-variates such as age and TKI-therapy duration were not significantly associated with an increased risk of developing COVID-19. Persons with these risk factors may benefit from increased surveillance of SARS-CoV-2 infection and possible protective isolation.

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18/05/2020 Correspondence
Silent COVID-19: what your skin can reveal

THE LANCET

Authors:
Claudio Guarneri, Emmanuele Venanzi Rullo, Piero Pavone, Massimiliano Berretta, Manuela Ceccarelli, Alfonso Natale, Giuseppe Nunnari

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18/05/2020 Features
How covid-19 is accelerating the threat of antimicrobial resistance

The BMJ

Authors:
Jeremy Hsu

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18/05/2020 Article
Detection of severe acute respiratory syndrome Coronavirus-2 in the tears of patients...

Detection of severe acute respiratory syndrome Coronavirus-2 in the tears of patients with Coronavirus disease 2019

NCBI

Authors:
Saeed Karimi, Amir Arabi,Toktam Shahraki, Sare Safi

ABSTRACT

Since there are few reports on the ocular involvement of coronavirus disease 2019 (COVID-19) patients, this study aimed to assess the presence of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) in the tears of patients with COVID-19.

Methods In this prospective case series, nasopharyngeal and tear sampling of 43 patients with severe COVID-19 were performed. The quantitative reverse transcription polymerase chain reaction (RT-PCR) was conducted to detect SARS-CoV-2. Ocular and systemic signs and symptoms were recorded from their medical history.

Results The mean age of patients was 56 ± 13 years. The average disease time from initiation of symptoms was 3.27 days, range: 1–7 days. Forty-one patients (95.3%) had fever at the time of sampling. Only one patient had conjunctivitis. Thirty (69.8%) nasopharyngeal and three (7%) tear samples were positive for SARS-CoV-2. The result of tear sample was positive in the patient with conjunctivitis. All patients with positive tear RT-PCR results had positive nasopharyngeal RT-PCR results.

Conclusions Ocular manifestation was rare in this series of severe COVID-19 patients, however, 7% of the patients had viral RNA in their conjunctival secretions. Therefore, possibility of ocular transmission should be considered even in the absence of ocular manifestations.

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16/05/2020 Review
Neurological manifestations and neuro‐invasive mechanisms of the severe acute...

Neurological manifestations and neuro‐invasive mechanisms of the severe acute respiratory syndrome coronavirus type 2

Wiley Online Library

Authors:
Kristl Vonck, Ieme Garrez, Veerle De Herdt, Dimitri Hemelsoet, Guy Laureys, Robrecht Raedt, Paul Boon

ABSTRACT

Introduction Infections with coronaviruses are not always confined to the respiratory tract and various neurological manifestations have been reported. The aim of this study was to perform a review to describe neurological manifestations in patients with COVID‐19 and possible neuro‐invasive mechanisms of Sars‐CoV‐2.

Methods Pubmed, WebOfScience and Covid‐dedicated databases were searched for the combination of COVID‐19 terminology and neurology terminology up to May 10th 2020. Social media channels were followed‐up between March 15th and May 10th 2020 for postings with the same scope. Neurological manifestations were extracted from the identified manuscripts and combined to provide a useful summary for the neurologist in clinical practice.

Results Neurological manifestations potentially related to COVID‐19 have been reported in large studies, case series and case reports and include acute cerebrovascular diseases, impaired consciousness, cranial nerve manifestations and auto‐immune disorders such as Guillain‐Barré Syndrome often present in patients with more severe COVID‐19. Cranial nerve symptoms such as olfactory and gustatory dysfunctions are highly prevalent in patients with mild‐to‐moderate COVID‐19 even without associated nasal symptoms and often present in an early stage of the disease.

Conclusion Physicians should be aware of the neurological manifestations in patients with COVID‐19, especially when rapid clinical deterioration occurs. The neurological symptoms in COVID‐19 patients may be due to direct viral neurological injury or indirect neuroinflammatory and autoimmune mechanisms. No antiviral treatments against the virus or vaccines for its prevention are available and the long‐term consequences of the infection on human health remain uncertain especially with regards to the neurological system.

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15/05/2020 Articles
The need to manage the risk of thromboembolism in COVID-19 patients

JVS

Authors:
Inayat Hussain Khan, Sugeevan Savarimuthu, Marco Shiu Tsun, Leung, Amer Harky

ABSTRACT

COVID-19 first presented in Wuhan, Hubei Province, China, in December 2019. Thought to be of zoonotic origin, it has been named SARS-CoV-2 (COVID-19) and has spread rapidly. As of April 20th, 2020, there have been more than 2.4 million cases recorded worldwide. The inflammatory process, cytokine storm, and lung injury that are associated with COVID-19 can put patients at an increased risk of thrombosis. It is uncertain what the total incidences of thrombotic events in COVID-19 patients is currently at. Those with more severe disease and with other risk factors, including increasing age, male sex, obesity, cancer, comorbidities, and intensive care unit admission, are at higher risk of these events. However, there is little international guidance on managing these risks in COVID-19 patients. In this paper, we explore the current evidence and theories surrounding thrombosis in these unique patients and reflect on experience from our center.

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13/05/2020 Articles
An outbreak of severe Kawasaki-like disease at the Italian epicentre of the...

An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study

The Lancet

Authors:
Lucio Verdoni, Angelo Mazza, Annalisa Gervasoni, Laura Martelli, Maurizio Ruggeri, Matteo Ciuffreda, Ezio Bonanomi, Lorenzo D’Antiga

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13/05/2020 Articles
Combination of four clinical indicators predicts the severe/critical symptom of...

Combination of four clinical indicators predicts the severe/critical symptom of patients infected COVID-19

ELSEVIER

Authors:
Liping Sun, Gang Liu, Fengxiang Song, Nannan Shi, Fengjun Liu, Shenyang Li, Ping Li, Weihan Zhang, Xiao Jiang, Yongbin Zhang, Lining Sun, Xiong Chen, Yuxin Shi

Background Despite the death rate of COVID-19 is less than 3%, the fatality rate of severe/critical cases is high, according to World Health Organization (WHO). Thus, screening the severe/critical cases before symptom occurs effectively saves medical resources.

Methods and materials In this study, all 336 cases of patients infected COVID-19 in Shanghai to March 12th, were retrospectively enrolled, and divided in to training and test datasets. In addition, 220 clinical and laboratory observations/records were also collected. Clinical indicators were associated with severe/critical symptoms were identified and a model for severe/critical symptom prediction was developed.

Results Totally, 36 clinical indicators significantly associated with severe/critical symptom were identified. The clinical indicators are mainly thyroxine, immune related cells and products. Support Vector Machine (SVM) and optimized combination of age, GSH, CD3 ratio and total protein has a good performance in discriminating the mild and severe/critical cases. The area under receiving operating curve (AUROC) reached 0.9996 and 0.9757 in the training and testing dataset, respectively. When the using cut-off value as 0.0667, the recall rate was 93.33% and 100% in the training and testing datasets, separately. Cox multivariate regression and survival analyses revealed that the model significantly discriminated the severe/critical cases and used the information of the selected clinical indicators.

Conclusion The model was robust and effective in predicting the severe/critical COVID cases.

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13/05/2020 Articles
Review article: COVID-19 and liver disease - what we know on 1st May 2020

WILEY ONLINE LIBRARY

Authors:
Sabel Garrido, Rodrigo Liberal, Guilherme Macedo

ABSTRACT

Background Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the causative pathogen of coronavirus disease 2019 (COVID‐19), became a global threat to human health. Liver impairment has been frequently reported as a common manifestation, although its clinical significance is still unclear, particularly in patients with underlying chronic liver disease (CLD).

Aims To summarize the changes in liver function tests during SARS‐CoV‐2 infection and the impact of COVID‐19 in patients with underlying CLD.

Methods A literature review using online database Pubmed was done using the search terms “SARS‐CoV‐2”, “COVID‐19”, “liver”, “cirrhosis” and “liver transplantation”.

Results COVID‐19 is frequently associated with different degrees of abnormal liver function tests, most notably transaminases, which are usually transitory and of mild degree. Available evidence suggests that liver injury may result from direct pathogenic effect by the virus, systemic inflammation or toxicity from commonly used drugs in this subset of patients. SARS‐CoV‐2 infection in children is associated with minimal or no increase in liver enzymes, thus the presence of abnormal liver function tests should trigger evaluation for underlying liver diseases. Although it seems that patients with CLD are not at greater risk for acquiring the infection, those with cirrhosis, hepatocellular carcinoma, non‐alcoholic fatty liver disease, autoimmune liver diseases or liver transplant may have a greater risk for severe COVID‐19.

Conclusions Abnormal liver function tests during the course of COVID‐19 are common, though clinically significant liver injury is rare. Further research is needed focusing on the effect of existing liver‐related comorbidities on treatment and outcome of COVID‐19.

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13/05/2020 Comment
Kawasaki-like disease: emerging complication during the COVID-19 pandemic

The Lancet

Authors:
Russell M Viner, Elizabeth Whittaker

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12/05/2020 Articles
Manifestations and prognosis of gastrointestinal and liver involvement in patients...

Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis

The Lancet

Authors:
Ren Mao, Yun Qiu, Jin-Shen He, Jin-Yu Tan, Xue-Hua Li, Jie Liang, Jun Shen, Liang-Ru Zhu, Yan Chen, Marietta Iacucci, Siew C Ng, Subrata Ghosh, Min-Hu Chen

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11/05/2020 Comment
Coagulation abnormalities and thrombosis in patients with COVID-19

The Lancet

Authors:
Marcel Levi, Jecko Thachil, Toshiaki Iba, Jerrold H Levy

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09/05/2020 Review
Impact of COVID-19 on the Cardiovascular System: A Review

JOURNAL OF CLINICAL MEDICINE

Authors:
Kensuke Matsushita, Benjamin Marchandot, Laurence Jesel, Patrick Ohlmann, Olivier Morel

ABSTRACT

The recent outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has been declared a public health emergency of international concern. COVID-19 may present as acute respiratory distress syndrome in severe cases, and patients with pre-existing cardiovascular comorbidities are reported to be the most vulnerable. Notably, acute myocardial injury, determined by elevated high-sensitivity troponin levels, is commonly observed in severe cases, and is strongly associated with mortality. Therefore, understanding the effects of COVID-19 on the cardiovascular system is essential for providing comprehensive medical care for critically ill patients. In this review, we summarize the rapidly evolving data and highlight the cardiovascular considerations related to COVID-19.

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08/05/2020 Comment
Diagnosing COVID-19-associated pulmonary aspergillosis

The Lancet

Authors:
Paul E Verweij, Jean-Pierre Gangneux, Matteo Bassetti, Roger J M Brüggemann, Oliver A Cornely, Philipp Koehler, Cornelia Lass-Flörl, Frank L van de Veerdonk, Arunaloke Chakrabarti, Martin Hoenigl, on behalf of the European Confederation of Medical Mycology, the International Society for Human and Animal Mycology, the European Society for Clinical Microbiology and Infectious Diseases Fungal Infection Study Group, and the ESCMID Study Group for Infections in Critically Ill Patients

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08/05/2020 Letter
High prevalence of olfactory and taste disorder during SARS‐CoV‐2 infection in outpatients

Wiley Online Library

Authors:
Andrea De Maria, Paola Varese, Chiara Dentone, Emanuela Barisione, Matteo Bassetti

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08/05/2020 Letter
The Italian Endo‐COVID‐19. Our response to the emergency

SPRINGER LINK

Authors:
A. M. Isidori, E. A. Jannini, A. Lenzi, E. Ghigo & the Board of Full Professors in Endocrinology, Directors of the Endocrinology, Metabolic Disorders Residency Program

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07/05/2020 Articles
Early experience in tracheostomy and tracheostomy tube management in Covid-19 patients

ELSEVIER

Authors:
Ottavio Piccin, Riccardo Albertini, Umberto Caliceti, Ottavio Cavicchi, Eleonora Cioccoloni, MarcoDemattè, Gian GaetanoFerri, Giovanni Macrì, Pietro Marrè, Irene Pelligra, Domenico Saggese, Patrizia Schiavon, Vittorio Sciarretta, Giovanni Sorrenti

ABSTRACT

In Italy, we have experienced Europe's first and largest coronavirus outbreak. Based on our preliminary experience, we discuss the challenges in performing tracheotomy and tracheostoma care in the setting of a new pathogen.

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07/05/2020 Case Report
COVID-19 in a 26-week preterm neonate

The Lancet

Authors:
Fiammetta Piersigilli, Katherine Carkeek, Catheline Hocq, Bénédicte van Grambezen, Corinne Hubinont, Olga Chatzis, Dimitri Van der Linden, Olivier Danhaive

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07/05/2020 Correspondence
Hyperinflammatoryshock in children during COVID-19 pandemic

The Lancet

Authors:
Shelley Riphagen, Xabier Gomez,Carmen Gonzalez-Martinez, Nick Wilkinson, Paraskevi Theocharis

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07/05/2020 Articles
Tropism, replication competence, and innate immune responses of the coronavirus...

Tropism, replication competence, and innate immune responses of the coronavirus SARS-CoV-2 in human respiratory tract and conjunctiva: an analysis in ex-vivo and in-vitro cultures

The Lancet

Authors:
Kenrie P Y Hui, Man-Chun Cheung, Ranawaka A P M Perera, Ka-Chun Ng, Christine H T Bui, John C W Ho, Mandy M T Ng, Denise I T Kuok, Kendrick C Shih, Sai-Wah Tsao, Leo L M Poon, Malik Peiris, John M Nicholls, Michael C W Chan

SUMMARY

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing a respiratory disease (coronavirus disease 2019, COVID-19) of varying severity in Wuhan, China, and subsequently leading to a pandemic. The transmissibility and pathogenesis of SARS-CoV-2 remain poorly understood. We evaluate its tissue and cellular tropism in human respiratory tract, conjunctiva, and innate immune responses in comparison with other coronavirus and influenza virus to provide insights into COVID-19 pathogenesis.

Methods We isolated SARS-CoV-2 from a patient with confirmed COVID-19, and compared virus tropism and replication competence with SARS-CoV, Middle East respiratory syndrome-associated coronavirus (MERS-CoV), and 2009 pandemic influenza H1N1 (H1N1pdm) in ex-vivo cultures of human bronchus (n=5) and lung (n=4). We assessed extrapulmonary infection using ex-vivo cultures of human conjunctiva (n=3) and in-vitro cultures of human colorectal adenocarcinoma cell lines. Innate immune responses and angiotensin-converting enzyme 2 expression were investigated in human alveolar epithelial cells and macrophages. In-vitro studies included the highly pathogenic avian influenza H5N1 virus (H5N1) and mock-infected cells as controls.

Findings SARS-CoV-2 infected ciliated, mucus-secreting, and club cells of bronchial epithelium, type 1 pneumocytes in the lung, and the conjunctival mucosa. In the bronchus, SARS-CoV-2 replication competence was similar to MERS-CoV, and higher than SARS-CoV, but lower than H1N1pdm. In the lung, SARS-CoV-2 replication was similar to SARS-CoV and H1N1pdm, but was lower than MERS-CoV. In conjunctiva, SARS-CoV-2 replication was greater than SARS-CoV. SARS-CoV-2 was a less potent inducer of proinflammatory cytokines than H5N1, H1N1pdm, or MERS-CoV.

Interpretation The conjunctival epithelium and conducting airways appear to be potential portals of infection for SARS-CoV-2. Both SARS-CoV and SARS-CoV-2 replicated similarly in the alveolar epithelium; SARS-CoV-2 replicated more extensively in the bronchus than SARS-CoV. These findings provide important insights into the transmissibility and pathogenesis of SARS-CoV-2 infection and differences with other respiratory pathogens.

Funding US National Institute of Allergy and Infectious Diseases, University Grants Committee of Hong Kong Special Administrative Region, China; Health and Medical Research Fund, Food and Health Bureau, Government of Hong Kong Special Administrative Region, China.

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06/05/2020 Comment
The immune system of children: the key to understanding SARS-CoV-2 susceptibility?

The Lancet

Authors:
Rita Carsetti, Concetta Quintarelli, Isabella Quinti, Eva Piano Mortari, Alimuddin Zumla, Giuseppe Ippolito, Franco Locatelli

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05/05/2020 Correspondence
Acute limb ischaemia in two young, non-atherosclerotic patients with COVID-19

The Lancet

Authors:
Paolo Perini, Bilal Nabulsi, Claudio Bianchini Massoni, Matteo Azzarone, Antonio Freyrie

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05/05/2020 Editorial
Understanding Observational Treatment Comparisons in the Setting of Coronavirus Disease 2019 (COVID-19)

JAMA

Authors:
Laine E. Thomas, Robert O. Bonow, Michael J. Pencina

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04/05/2020 Articles
Saliva is a non-negligible factor in the spread of COVID-19

WINLEY ONLINE LIBRARY

Authors:
Yuqing Li, Biao Ren, Xian Peng, Tao Hu, Jiyao Li, Tao Gong, Boyu Tang, Xin Xu, Xuedong Zhou

SUMMARY

SARS-CoV-2, a novel emerging coronavirus, has caused severe disease (COVID-19), and rapidly spread worldwide since the beginning of 2020. SARS-CoV-2 mainly spreads by coughing, sneezing, droplet inhalation, and contact. SARS-CoV-2 has been detected in saliva samples, making saliva a potential transmission route for COVID-19. The participants in dental practice confront a particular risk of SARS-CoV-2 infection due to close contact with the patients and potential exposure to saliva-contaminated droplets and aerosols generated during dental procedures. In addition, saliva-contaminated surfaces could lead to potential cross-infection. Hence, the control of saliva-related transmission in the dental clinic is critical, particularly in the epidemic period of COVID-19. Based on our experience of the COVID-19 epidemic, some protective measures that can help reduce the risk of saliva-related transmission are suggested, in order to avoid the potential spread of SARS-CoV-2 among patients, visitors, and dental practitioners.Accepted Article

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02/05/2020 Editorial
Asthma and COVID-19: is asthma a risk factor for severe outcomes?

WILEY ONLINE LIBRARY

Authors:
SEBASTIAN L. JOHNSON

ABSTRACT

When I first read the manuscript that accompanies this editorial, upon its online publication on February 19th 2020(1), COVID‐19 had already killed 2118 people in China, but only one person in Europe – an 80‐year‐old tourist from China, who died in France on the 15th February. I read the manuscript with grim fascination, as it was clear that SARS‐CoV‐2 had spread very rapidly in China which already had 74,576 cases and in South Korea which already had 58 cases, and that it was then invading Europe also, as France already had 12 cases, Germany 16, the UK 9, Italy 3, Spain 2 and other countries too.

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01/05/2020 Correspondence
Children with Covid-19 in Pediatric Emergency Departments in Italy

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors:
Niccolò Parri, Matteo Lenge, Danilo Buonsenso

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01/05/2020 Practice
Coagulopathy associated with COVID-19

CMAJ

Authors:
Stephanie G. Lee, Michael Fralick, Michelle Sholzberg

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30 /04/2020 Correspondence
An Italian programme for COVID-19 infection in multiple sclerosis

The Lancet

Authors:
MARIAPIA SORMANI

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30 /04/2020 Articles
Clinical Characteristics of Coronavirus Disease 2019 in China

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors:
W. Guan, Z. Ni, Yu Hu, W. Liang, C. Ou, J. He, L. Liu, H. Shan, C. Lei, D.S.C. Hui, B. Du, L. Li, G. Zeng, K.-Y. Yuen, R. Chen, C. Tang, T. Wang, P. Chen, J. Xiang, S. Li, Jin-lin Wang, Z. Liang, Y. Peng, L. Wei, Y. Liu, Ya-hua Hu, P. Peng, Jian-ming Wang, J. Liu, Z. Chen, G. Li, Z. Zheng, S. Qiu, J. Luo, C. Ye, S. Zhu, N. Zhong,

ABSTRACT

BACKGROUND Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients.

METHODS We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death.

RESULTS The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission.

CONCLUSIONS During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)

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29/04/2020 Articles
Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases

WILEY ONLINE LIBRARY

Authors:
C. Galván Casas A. Català G. Carretero Hernández P. Rodríguez‐Jiménez D. Fernández Nieto A. Rodríguez‐Villa Lario I. Navarro Fernández R. Ruiz‐Villaverde D. Falkenhain M. Llamas Velasco J. García‐Gavín O. Baniandrés C. González‐Cruz V. Morillas‐Lahuerta X. Cubiró I. Figueras Nart G. Selda‐Enriquez J. Romaní X. Fustà‐Novell A. Melian‐Olivera M. Roncero Riesco P. Burgos‐Blasco J. Sola Ortigosa M. Feito Rodriguez I. García‐Doval

ABSTRACT

Background Cutaneous manifestations of COVID‐19 disease are poorly characterized.

Objectives To describe the cutaneous manifestations of COVID‐19 disease and to relate them to other clinical findings

Methods Nationwide case collection survey of images and clinical data. Using a consensus, we described 5 clinical patterns. We later described the association of these patterns with patient demographics, timing in relation to symptoms of the disease, severity, and prognosis.

Results Lesions may be classified as acral areas of erythema with vesicles or pustules (Pseudo‐chilblain) (19%), other vesicular eruptions (9%), urticarial lesions (19%), maculopapular eruptions (47%) and livedo or necrosis (6%). Vesicular eruptions appear early in the course of the disease (15% before other symptoms). The pseudo‐chilblain pattern frequently appears late in the evolution of the COVID‐19 disease (59% after other symptoms), while the rest tend to appear with other symptoms of COVID‐19. Severity of COVID‐19 shows a gradient from less severe disease in acral lesions to most severe in the latter groups. Results are similar for confirmed and suspected cases, both in terms of clinical and epidemiological findings. Alternative diagnoses are discussed but seem unlikely for the most specific patterns (pseudo‐chilblain and vesicular).

Conclusions We provide a description of the cutaneous manifestations associated with COVID‐19 infection. These may help clinicians approach patients with the disease and recognize paucisymptomatic cases.

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28/04/2020 Letter
Clinical determinants for fatality of 44,672 patients with COVID-19

NCBI

Authors:
Guangtong Deng, Mingzhu Yin, Xiang Chen and Furong Zeng

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28/04/2020 News
Covid-19: concerns grow over inflammatory syndrome emerging in children

BMJ

Authors:
Elisabeth Mahase

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28/04/2020 Articles
Facing COVID-19 in the ICU: vascular dysfunction, thrombosis, and dysregulated infammation

SPRINGER LINK

Authors:
Daniel E. Leisman, Clifford S. Deutschman & Matthieu Legrand

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28/04/2020 Correspondence
Reduced Rate of Hospital Admissions for ACS during Covid-19 Outbreak in Northern Italy

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors:
Ovidio De Filippo, Fabrizio D’Ascenzo, Filippo Angelini, Pier Paolo Bocchino, Federico Conrotto, Andrea Saglietto, Gioel Gabrio Secco, Gianluca Campo, Guglielmo Gallone, Roberto Verardi, et all

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24/04/2020 Correspondence
Co-infections: potentially lethal and unexplored in COVID-19

The Lancet

Authors:
Michael J Cox, Nicholas Loman, Debby Bogaert, Justin O’Grady

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24/04/2020Articles
Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors:
M.M. Arons, K.M. Hatfield, S.C. Reddy, A. Kimball, A. James, J.R. Jacobs, J. Taylor, K. Spicer, A.C. Bardossy, L.P. Oakley, S. Tanwar, J.W. Dyal, J. Harney, Z. Chisty, J.M. Bell, M. Methner, P. Paul, C.M. Carlson, H.P. McLaughlin, N. Thornburg, S. Tong, A. Tamin, Y. Tao, A. Uehara, J. Harcourt, S. Clark, C. Brostrom-Smith, L.C. Page, M. Kay, J. Lewis, P. Montgomery, N.D. Stone, T.A. Clark, M.A. Honein, J.S. Duchin, and J.A. Jernigan

ABSTRACT

BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can spread rapidly within skilled nursing facilities. After identification of a case of Covid-19 in a skilled nursing facility, we assessed transmission and evaluated the adequacy of symptom-based screening to identify infections in residents.

METHODS We conducted two serial point-prevalence surveys, 1 week apart, in which assenting residents of the facility underwent nasopharyngeal and oropharyngeal testing for SARS-CoV-2, including real-time reverse-transcriptase polymerase chain reaction (rRT-PCR), viral culture, and sequencing. Symptoms that had been present during the preceding 14 days were recorded. Asymptomatic residents who tested positive were reassessed 7 days later. Residents with SARS-CoV-2 infection were catego- rized as symptomatic with typical symptoms (fever, cough, or shortness of breath), symptomatic with only atypical symptoms, presymptomatic, or asymptomatic.

RESULTS Twenty-three days after the first positive test result in a resident at this skilled nurs- ing facility, 57 of 89 residents (64%) tested positive for SARS-CoV-2. Among 76 resi- dents who participated in point-prevalence surveys, 48 (63%) tested positive. Of these 48 residents, 27 (56%) were asymptomatic at the time of testing; 24 subsequently developed symptoms (median time to onset, 4 days). Samples from these 24 pre- symptomatic residents had a median rRT-PCR cycle threshold value of 23.1, and viable virus was recovered from 17 residents. As of April 3, of the 57 residents with SARS-CoV-2 infection, 11 had been hospitalized (3 in the intensive care unit) and 15 had died (mortality, 26%). Of the 34 residents whose specimens were sequenced, 27 (79%) had sequences that fit into two clusters with a difference of one nucleotide.

CONCLUSIONS Rapid and widespread transmission of SARS-CoV-2 was demonstrated in this skilled nursing facility. More than half of residents with positive test results were asymp- tomatic at the time of testing and most likely contributed to transmission. Infec- tion-control strategies focused solely on symptomatic residents were not sufficient to prevent transmission after SARS-CoV-2 introduction into this facility.

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24/04/2020 Articles
Mild or Moderate Covid-19

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors:
Rajesh T. Gandhi, John B. Lynch, M.P.H, Carlos del Rio

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23/04/2020 Rapid Communication
Clinical characteristics of coronavirus disease (COVID-19) early findings from...

Clinical characteristics of coronavirus disease (COVID-19) early findings from a teaching hospital in Pavia, North Italy, 21 to 28 February 2020

Eurosurveillance

Authors:
Marta Colaneri, Paolo Sacchi, Valentina Zuccaro, Simona Biscarini, Michele Sachs, Silvia Roda, Teresa Chiara Pieri, Pietro Valsecchi, Antonio Piralla, Elena Seminari, Angela Di Matteo, Stefano Novati, Laura Maiocchi, Layla Pagnucco, Marcello Tirani, Fausto Baldanti, Francesco Mojoli , Stefano Perlini, Raffaele Bruno

ABSTRACT

We describe clinical characteristics, treatments and outcomes of 44 Caucasian patients with coronavirus disease (COVID-19) at a single hospital in Pavia, Italy, from 21–28 February 2020, at the beginning of the outbreak in Europe. Seventeen patients developed severe disease, two died. After a median of 6 days, 14 patients were discharged from hospital. Predictors of lower odds of discharge were age > 65 years, antiviral treatment and for severe disease, lactate dehydrogenase > 300 mg/dL.

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23/04/2020 Clinical Picture
Myocarditis in a patient with COVID-19: a cause of raised troponin and ECG changes

The Lancet

Authors:
Denis Doyen, Pamela Moceri, Dorothée Ducreux, Jean Dellamonica

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23/04/2020 Articles
New understanding of the damage of SARS-CoV-2 infection outside the respiratory system

ELSEVIER

Authors:
Yuhao Zhanga,, Xiuchao Gengb,, Yanli Tana, Qiang Lic, Can Xua, Jianglong Xua, Liangchao Haoa, Zhaomu Zenga, Xianpu Luod, Fulin Liue, Hong Wanga

Since early December 2019, a number of pneumonia cases associated with unknown coronavirus infection were identified in Wuhan, China, and many additional cases were identified in other regions of China and in other countries within 3 months. Currently, more than 80,000 cases have been diagnosed in China, including more than 3000 deaths. The epidemic is spreading to the rest of the world, posing a grave challenge to prevention and control. On February 12, 2020, the International Committee on Taxonomy of Viruses and the World Health Organization officially named the novel coronavirus and associated pneumonia as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19), respectively. According to the recent research on SARS-CoV-2, the virus mainly infects the respiratory system but may cause damage to other systems. In this paper, we will systematically review the pathogenic features, transmission routes, and infection mechanisms of SARS-CoV-2, as well as any adverse effects on the digestive system, urogenital system, central nervous system, and circulatory system, in order to provide a theoretical and clinical basis for the diagnosis, classification, treatment, and prognosis assessment of SARS-CoV-2 infection.

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23/04/2020 Special Report
Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19

THE NEW ENGLAND JOURNAL OF MEDICINE

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

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22/04/2020 Letter
Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection

JAMA

Authors:
Giacomo Spinato, Cristoforo Fabbris, Jerry Polesel, Diego Cazzador, Daniele Borsetto, Claire Hopkins, MA(Oxon),Paolo Boscolo-Rizzo

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22/04/2020Articles
Dermatologists and SARS-CoV2 - The impact of the pandemic on daily practice

WILEY

Authors:
Gisondi P, Piaserico S, Conti A, Naldi L

ABSTRACT

Since the first case of “pneumonia of unknown aetiology” was diagnosed at the Wuhan Jinyintan Hospital in China on 30 December 2019, what was recognised thereafter as “severe acute respiratory syndrome coronavirus 2” (SARS‐CoV‐2) has spread over the four continents, causing the respiratory manifestations of Coronavirus disease‐19 (COVID‐ 19) and satisfying the epidemiological criteria for a label of “pandemic.” The ongoing SARS‐CoV‐2 pandemic is having a huge impact on dermatological practice including the marked reduction of face‐to‐face consultations in favour of teledermatology, the uncertainties concerning the outcome of COVID‐19 infection in patients with common inflammatory disorders such as psoriasis or atopic dermatitis receiving immunosuppressive/immunomodulating systemic therapies; the direct involvement of dermatologists in COVID‐19 care for patients assistance and new research needs to be addressed. It is not known yet, if skin lesions and derangement of the skin barrier could make it easier for SARS‐CoV‐2 to transmit via indirect contact; it remains to be defined if specific mucosal or skin lesions are associated with SARS‐CoV‐2 infection, although some unpublished observations indicate the occurrence of a transient varicelliform exanthema during the early phase of the infection. SARS‐CoV‐2 is a new pathogen for humans that is highly contagious, can spread quickly, and is capable of causing enormous health, economic and societal impacts in any setting. The consequences may continue long after the pandemic resolves, and new management modalities for dermatology may originate from the COVID‐19 disaster. Learning from experience may help to cope with future major societal changes.

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22/04/2020 ORIGINAL INVESTIGATION
Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients...

Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area

JAMA

Authors:
Safiya Richardson; Jamie S. Hirsch; Mangala Narasimhan, James M. Crawford, Thomas McGinn, Karina W. Davidson

ABSTRACT

IMPORTANCE There is limited information describing the presenting characteristics and outcomes of US patients requiring hospitalization for coronavirus disease 2019 (COVID-19).

OBJECTIVE To describe the clinical characteristics and outcomes of patients with COVID-19 hospitalized in a US health care system.

DESIGN, SETTING, AND PARTICIPANTS Case series of patients with COVID-19 admitted to 12 hospitals in New York City, Long Island, and Westchester County, New York, within the Northwell Health system. The study included all sequentially hospitalized patients between March 1, 2020, and April 4, 2020, inclusive of these dates.

EXPOSURES Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by positive result on polymerase chain reaction testing of a nasopharyngeal sample among patients requiring admission.

MAIN OUTCOMES AND MEASURES Clinical outcomes during hospitalization, such as invasive mechanical ventilation, kidney replacement therapy, and death. Demographics, baseline comorbidities, presenting vital signs, and test results were also collected.

RESULTS A total of 5700 patients were included (median age, 63 years [interquartile range {IQR}, 52-75; range, 0-107 years]; 39.7% female). The most common comorbidities were hypertension (3026; 56.6%), obesity (1737; 41.7%), and diabetes (1808; 33.8%). At triage, 30.7% of patients were febrile, 17.3% had a respiratory rate greater than 24 breaths/minute, and 27.8% received supplemental oxygen. The rate of respiratory virus co-infection was 2.1%. Outcomes were assessed for 2634 patients who were discharged or had died at the study end point. During hospitalization, 373 patients (14.2%) (median age, 68 years [IQR, 56-78]; 33.5% female) were treated in the intensive care unit care, 320 (12.2%) received invasive mechanical ventilation, 81 (3.2%) were treated with kidney replacement therapy, and 553 (21%) died. Mortality for those requiring mechanical ventilation was 88.1%. The median postdischarge follow-up time was 4.4 days (IQR, 2.2-9.3). A total of 45 patients (2.2%) were readmitted during the study period. The median time to readmission was 3 days (IQR, 1.0-4.5) for readmitted patients. Among the 3066 patients who remained hospitalized at the final study follow-up date (median age, 65 years [IQR, 54-75]), the median follow-up at time of censoring was 4.5 days (IQR, 2.4-8.1).

CONCLUSIONS AND RELEVANCE This case series provides characteristics and early outcomes of sequentially hospitalized patients with confirmed COVID-19 in the New York City area.

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21/04/2020 Letter
Eosinophil count in severe coronavirus disease 2019 (COVID-19)

OXFORD UNIVERSITY PRESS

Authors:
Giuseppe Lippi, Brandon M. Henry

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21/04/2020 Correspondence
Mediastinal lymphadenopathy in patients with severe COVID-19

The Lancet

Authors:
Xavier Valette, Damien du Cheyron, Suzanne Goursaud

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21/04/2020 Articles
Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang...

Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study

BMJ

Authors:
Shufa Zheng, Jian Fan, Fei Yu, Baihuan Feng, Bin Lou, Qianda Zou, Guoliang Xie, Sha Lin, Ruonan Wang, Xianzhi Yang, Weizhen Chen, Qi Wang, Dan Zhang, Yanchao Liu, Renjie Gong, Zhaohui Ma, Siming Lu, Yanyan Xiao, Yaxi Gu, Jinming Zhang, Hangping Yao, Kaijin ,Xiaoyang Lu,Guoqing Wei, Jianying Zhou,Qiang Fang, Hongliu Cai, Yunqing Qiu,Jifang Sheng, Yu Chen, Tingbo Liang

ABSTRACT

Objective To evaluate viral loads at different stages of disease progression in patients infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first four months of the epidemic in Zhejiang province, China.

Design Retrospective cohort study.

Setting A designated hospital for patients with covid-19 in Zhejiang province, China.

Participants 96 consecutively admitted patients with laboratory confirmed SARS-CoV-2 infection: 22 with mild disease and 74 with severe disease. Data were collected from 19 January 2020 to 20 March 2020. Main outcome measures Ribonucleic acid (RNA) viral load measured in respiratory, stool, serum, and urine samples. Cycle threshold values, a measure of nucleic acid concentration, were plotted onto the standard curve constructed on the basis of the standard product. Epidemiological, clinical, and laboratory characteristics and treatment and outcomes data were obtained through data collection forms from electronic medical records, and the relation between clinical data and disease severity was analysed.

Results 3497 respiratory, stool, serum, and urine samples were collected from patients after admission and evaluated for SARS-CoV-2 RNA viral load. Infection was confirmed in all patients by testing sputum and saliva samples. RNA was detected in the stool of 55 (59%) patients and in the serum of 39 (41%) patients. The urine sample from one patient was positive for SARS-CoV-2. The median duration of virus in stool (22 days, interquartile range 17-31 days) was significantly longer than in respiratory (18 days, 13-29 days; P=0.02) and serum samples (16 days, 11-21 days; P<0.001). The median duration of virus in the respiratory samples of patients with severe disease (21 days, 14-30 days) was significantly longer than in patients with mild disease (14 days, 10-21 days; P=0.04). In the mild group, the viral loads peaked in respiratory samples in the second week from disease onset, whereas viral load continued to be high during the third week in the severe group. Virus duration was longer in patients older than 60 years and in male patients.

Conclusion The duration of SARS-CoV-2 is significantly longer in stool samples than in respiratory and serum samples, highlighting the need to strengthen the management of stool samples in the prevention and control of the epidemic, and the virus persists longer with higher load and peaks later in the respiratory tissue of patients with severe disease. sequentially hospitalized patients with confirmed COVID-19 in the New York City area.

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20 /04/2020 Research Letters
Association Between Ages and Clinical Characteristics and Outcomes of Coronavirus Disease 2019

EUROPEAN RESPIRATORY JOURNAL

Authors:
Yang Liu, Bei Mao, Shuo Liang, Jia-wei Yang, Hai-wen Lu, Yan-hua Chai, Lan Wang, Li Zhang, Qiu- hong Li, Lan Zhao, Yan He, Xiao-long Gu, Xiao-bin Ji, Li Li, Zhi-jun Jie, Qiang Li, Xiang-yang Li, Hong-zhou Lu, Wen-hong Zhang, Yuan-lin Song, Jie-ming Qu, Jin-fu Xu

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20 /04/2020 Report
COVID-19 infection may cause ketosis and ketoacidosis

Diabetes, Obesity and Metabolism

Authors:
Juyi Li, Xiufang Wang, Jian Chen, Xiuran Zuo, Hongmei Zhang, Aiping Deng

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17/04/2020 Correspondence
Clinical Characteristics of Covid-19 in New York City

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors:
Parag Goyal, Justin J. Choi, Laura C. Pinheiro, Edward J. Schenck, Ruijun Chen, Assem Jabri, Michael J. Satlin, Thomas R. Campion, Musarrat Nahid

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17/04/2020 Correspondence
Clinical Characteristics of Pregnant Women with Covid-19 in Wuhan, China

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors:
Lian Chen, Qin Li, Danni Zheng, Hai Jiang, M.Yuan Wei

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17/04/2020 Editorial
Clinical features of covid-19

THE BMJ

Authors:
Pauline Vetter, Diem Lan Vu, Arnaud G L’Huillier, Manuel Schibler, Laurent Kaiser, Frederique Jacquerioz

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17/04/2020 Articles
Cytokine release syndrome in severe COVID-19

SCIENCE

Authors:
John B. Moore, Carl H. June

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17/04/2020 Articles
Well-aerated Lung on Admitting Chest CT to Predict Adverse Outcome in COVID-19 Pneumonia

RADIOLOGY

Authors:
Davide Colombi, Flavio C. Bodini, Marcello Petrini, Gabriele Maffi, Nicola Morell, Gianluca Milanese, Mario Silva, Nicola Sverzellati, Emanuele Michieletti,

Background Computed tomography (CT) of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease depicts the extent of lung involvement in COVID-19 pneumonia.

Purpose The aim of the study was to determine the value of quantification of the well-aerated lung obtained at baseline chest CT for determining prognosis in patients with COVID-19 pneumonia.

Materials and Methods Patients who underwent chest CT suspected for COVID-19 pneumonia at the emergency department admission between February 17 to March 10, 2020 were retrospectively analyzed. Patients with negative reverse-transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 in nasal-pharyngeal swabs, negative chest CT, and incomplete clinical data were excluded. CT was analyzed for quantification of well aerated lung visually (%V-WAL) and by open-source software (%S-WAL and absolute volume, VOL-WAL). Clinical parameters included demographics, comorbidities, symptoms and symptom duration, oxygen saturation and laboratory values. Logistic regression was used to evaluate relationship between clinical parameters and CT metrics versus patient outcome (ICU admission/death vs. no ICU admission/ death). The area under the receiver operating characteristic curve (AUC) was calculated to determine model performance.

Results The study included 236 patients (females 59/123, 25%; median age, 68 years). A %V-WAL<73% (OR, 5.4; 95% CI, 2.7-10.8; P<0.001), %S-WAL<71% (OR, 3.8; 95% CI, 1.9-7.5; P<0.001), and VOL-WAL<2.9 L (OR, 2.6; 95% CI, 1.2-5.8; P<0.01) were predictors of ICU admission/death. In comparison with clinical model containing only clinical parameters (AUC, 0.83), all three quantitative models showed higher diagnostic performance (AUC 0.86 for all models). The models containing %V-WAL<73% and VOL-WAL<2.9L were superior in terms of performance as compared to the models containing only clinical parameters (P=0.04 for both models).

Conclusion In patients with confirmed COVID-19 pneumonia, visual or software quantification the extent of CT lung abnormality were predictors of ICU admission or death.

Summary Visual and software-based quantification of well aerated lung parenchyma on admission chest CT were predictors of intensive care unit (ICU) admission or death in patients with COVID-19 pneumonia.

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28/04/2020 Articles
The trinity of COVID-19: immunity, inflammation and intervention

NATURE REVIEWS

Authors:
Matthew Zirui Tay, Chek Meng Poh, Laurent Rénia, Paul A. MacAry & Lisa F. P. Ng

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. Here, we provide an overview of the pathophysiology of SARS-CoV-2 infection. We describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. From nascent reports describing SARS-CoV-2, we make inferences on the basis of the parallel pathophysiological and immunological features of the other human coronaviruses targeting the lower respiratory tract — severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Finally, we highlight the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation.

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17/04/2020 Correspondence
Guillain–Barré Syndrome Associated with SARS-CoV-2

THE NEW ENGLAND JOUNAL OF MEDICINE

Authors:
Gianpaolo Toscano, Francesco Palmerini, Sabrina Ravaglia,Luigi Ruiz, Paolo Invernizzi,M. Giovanna Cuzzoni, Fausto Baldanti, Rossana Daturi, Paolo Postorino, Anna Cavallini, Giuseppe Micieli

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17/04/2020 Correspondence
ST-Segment Elevation in Patients

THE NEW ENGLAND JOUNAL OF MEDICINE

Authors:
Sripal Bangalore,Atul Sharma, Alexander Slotwiner, Leonid Yatskar, Rafael Harari, Binita Shah, Homam Ibrahim, Gary H. Friedman, Craig Thompson, Carlos L. Alviar, Hal L. Chadow, Glenn I. Fishman, Harmony R. Reynolds, Norma Keller, Judith S. Hochman

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16/04/2020 Letter
Panton-Valentine Leukocidin–Secreting Staphylococcus aureus Pneumonia Complicating COVID-19

CENTERS FOR DISEASE CONTROL AND PREVENTION

Authors:
Claire Duployez , Rémi Le Guern, Claire Tinez, Anne-Laure Lejeune, Laurent Robriquet, Sophie Six, Caroline Loïez, Frédéric Wallet

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15/04/2020 Correspondence
Neurologic Features in Severe SARS-CoV-2 Infection

THE NEW ENGLAND JOUNAL OF MEDICINE

Authors:
Julie Helms, Stéphane Kremer, Hamid Merdji, Raphaël Clere-Jehl, Malika Schenck, Christine Kummerlen, Olivier Collange,Clotilde Boulay, . Samira Fafi-Kremer, Mickaël Ohana, Mathieu Anheim, Ferhat Meziani

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15/04/2020 Letter
Rates of Co-infection Between SARS-CoV-2 and Other Respiratory Pathogens

JAMA

Authors:
David Kim, James Quinn, Benjamin Pinsky, Nigam H. Shah, Ian Brown

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15/04/2020 Letter
COVID-19 Pulmonary Involvement: Is Really an Interstitial Pneumonia?

NCBI

Authors:
Piero Boraschi

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15/04/2020 Correspondence
Smell and taste dysfunction in patients with COVID-19

The Lancet

Authors:
Michael S Xydakis, Puya Dehgani-Mobaraki, Eric H Holbrook, Urban W Geisthoff, Christian Bauer, Charlotte Hautefort, Philippe Herman, Geoffrey T Manley, ina M Lyon, Claire Hopkins

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15/04/2020 Letter
Rates of Co-infection Between SARS-CoV-2 and Other Respiratory Pathogens

JAMA

Authors:
David Kim, James Quinn, Benjamin Pinsky, Nigam H. Shah, Ian Brown,

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15/04/2020 Correspondence
Visualizing Speech-Generated Oral Fluid Droplets with Laser Light Scattering

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors:
Philip Anfinrud, Valentyn Stadnytskyi, Christina E. Bax, Adriaan Bax

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15/04/2020 Correspondence
Utility of hyposmia and hypogeusia for the diagnosis of COVID-19

The Lancet

Authors:
François Bénézit, Paul Le Turnier, Charles Declerck, Cécile Paillé, Matthieu Revest, Vincent Dubée, Pierre Tattevin

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14/04/2020 Editorial
The Spectrum of Neurologic Disease in the Severe Acute Respiratory Syndrome Coronavirus...

The Spectrum of Neurologic Disease in the Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic Infection Neurologists Move to the Frontlines

JAMA

Authors:
Samuel J. Pleasure, Ari J. Green, S. Andrew Josephson

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14/04/2020 Editorial
COVID-19 pneumonia: diferent respiratory treatments for diferent phenotypes?

SPRINGER LINK

Authors:
Luciano Gattinoni, Davide Chiumello, Pietro Caironi, Mattia Busana, Federica Romitti, Luca Brazzi, Luigi Camporota

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13/04/2020 Report
COVID‐19 outbreak in Italy: experimental chest X‐ray scoring system...

COVID‐19 outbreak in Italy: experimental chest X‐ray scoring system for quantifying and monitoring disease progression

RESEARCH SQUARE

Authors:
Andrea Borghesi, Roberto Maroldi

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new virus recently isolated from humans. SARS-CoV-2 was discovered to be the pathogen responsible for a cluster of pneumonia associated with severe respiratory disease occurred in December 2019 in China. This novel pulmonary infection, formally called coronavirus disease 2019 (COVID-19), has spread rapidly in China and beyond. On 8 March 2020, the number of Italians with SARS-CoV-2 infection was 7375 with a 48% hospitalization rate. At present, chest computed tomography imaging is considered the most effective method for detection of lung abnormalities in early-stage disease and for quantitative assessment of severity and progression of COVID-19 infection. Although chest x-ray (CXR) is considered not sensitive for the detection of pulmonary involvement in the early stage of disease, we believe that, in the current emergency setting, CXR can be a useful diagnostic tool for monitoring the rapid progression of lung abnormalities in infected patients, particularly in intensive care units. In this article we present our experimental CXR scoring system that we are applying in hospitalized patients with COVID-19 pneumonia to quantify and monitor the severity and progression of this new infectious disease. We also present the results of our preliminary validation study on a sample of 100 hospitalized patients with SARS-CoV-2 infection for whom the final outcome (recovery or death) was available.

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13/04/2020 Correspondence
Universal Screening for SARS-CoV-2 in Women Admitted for Delivery

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors:
Desmond Sutton, Karin Fuchs, Mary D’Alton, Dena Goffman

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10 /04/2020 Analysis
Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China

JAMA

Authors:
Ling Mao, Huijuan Jin, Mengdie Wang, Yu Hu, Shengcai Chen, Quanwei He, Jiang Chang, Candong Hong, AAVV

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08/04/2020 World Review
Sudden and Complete Olfactory Loss Function as a Possible Symptom of COVID-19

JAMA

Authors:
Michael Eliezer, Charlotte Hautefort, Anne-Laure Hamel, Benjamin Verillaud, Philippe Herman, Emmanuel Houdart, Corinne Eloit

Read More »

07/04/2020 Clinical Science
Ocular manifestations of a hospitalised patient with confirmed 2019 novel coronavirus disease

BMJ JOURNAL

Authors:
Lu Chen, Meizhou Liu, Zheng Zhang, Kun Qiao, Ting Huang, Miaohong Chen, Na Xin, Zuliang Huang, Lei Liu, Guoming Zhang, Jiantao Wang

ABSTRACT

Purpose To report the ocular characteristics and the presence of viral RNA of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in conjunctival swab specimens in a patient with confirmed 2019 novel coronavirus disease (COVID-19). Participant and methods A 30-year-old man with confirmed COVID-19 and bilateral acute conjunctivitis which occurred 13 days after illness onset. Based on detailed ophthalmic examination, reverse transcription PCR (RT-PCR) was performed to detect SARS-CoV-2 virus in conjunctival swabs. The ocular characteristics, presence of viral RNA and viral dynamics of SARS-CoV-2 in the conjunctival specimens were evaluated. Results Slit lamp examination showed bilateral acute follicular conjunctivitis. RT-PCR assay demonstrated the presence of viral RNA in conjunctival specimen 13 days after onset (cycle threshold value: 31). The conjunctival swab specimens remained positive for SARS-CoV-2 on 14 and 17 days after onset. On day 19, RT-PCR result was negative for SARS-CoV-2. Conclusion SARS-CoV-2 is capable of causing ocular complications such as viral conjunctivitis in the middle phase of illness. Precautionary measures are recommended when examining infected patients throughout the clinical course of the infection. However, conjunctival sampling might not be useful for early diagnosis because the virus may not appear initially in the conjunctiva.

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07/04/2020 Perspectives
Age, Complexity, and Crisis — A Prescription for Progress in Pandemic

The New England Journal of Medicine

Authors:
Louise Aronson

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07/04/2020 Perspectives
Between Scylla and Charybdis — Oncologic Decision Making in the Time of Covid-19

The New England Journal of Medicine

Authors:
Mark A. Lewis

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07/04/2020 Viewpoint
Understanding and Addressing Sources of Anxiety Among Health Care Professionals...

Understanding and Addressing Sources of Anxiety Among Health Care Professionals During the COVID-19 Pandemic

JAMA

Authors:
TAIT SHAFANETI - JONATHAN RIPP - MICKEY TROCKEL

Read More »

06/04/2020 Viewpoint
Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2...

Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy

JAMA

Authors:
Giacomo Grasselli, Alberto Zangrillo, Alberto Zanella, Massimo Antonelli, Luca Cabrini, Antonio Castelli, Danilo Cereda,

Read More »

06/04/2020 Editorial
Critical Illness in Patients With COVID-19 Mounting an Effective Clinical and Research Response

JAMA

Authors:
Deborah J. Cook, John C. Marshall, Robert A. Fowler

Read More »

06/04/2020 Viewpoint
The COVID-19 Pandemic in the US A Clinical Update

JAMA

Authors:
SAAD OMER - PREETI MALANI - CARLOS DEL RIO

Read More »

06/04/2020 Comment
Minimizing the risk of COVID-19 among patients on dialysis

Nature Review

Authors:
T. Alp Ikizler, ùAlan S. Kliger

Read More »

05/04/2020 Articles
Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2...

Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy

JAMA

Authors:
Giacomo Grasselli, Alberto Zangrillo, Alberto Zanella, Massimo Antonelli, Luca Cabrini, Antonio Castelli, Danilo Cereda, Antonio Coluccello, Giuseppe Foti, Roberto Fumagalli, Giorgio Iotti, Nicola Latronico, Luca Lorini, Stefano Merler, Giuseppe Natalini, Alessandra Piatti, Marco Vito Ranieri, Anna Mara Scandroglio, Enrico Storti, Maurizio Cecconi, Antonio Pesenti

ABSTRACT

IMPORTANCE
In December 2019, a novel coronavirus (severe acute respiratory syndrome coro- navirus 2 [SARS-CoV-2]) emerged in China and has spread globally, creating a pandemic. Informa- tion about the clinical characteristics of infected patients who require intensive care is limited.

OBJECTIVE
To characterize patients with coronavirus disease 2019 (COVID-19) requiring treatment in an intensive care unit (ICU) in the Lombardy region of Italy.

DESIGN, SETTING, AND PARTICIPANTS
Retrospective case series of 1591 consecutive patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinator center (Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network and treated at one of the ICUs of the 72 hospitals in this network between February 20 and March 18, 2020. Date of final follow-up was March 25, 2020.

EXPOSURES
SARS-CoV-2 infection confirmed by real-time reverse transcriptase–polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swabs.

MAIN OUTCOMES AND MEASURES
Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality. Data were recorded by the coordinator center on an electronic worksheet during telephone calls by the staff of the COVID-19 Lombardy ICU Network.

RESULTS
Of the 1591 patients included in the study, the median (IQR) age was 63 (56-70) years and 1304 (82%) were male. Of the 1043 patients with available data, 709 (68%) had at least 1 comorbidity and 509 (49%) had hypertension. Among 1300 patients with available respiratory support data, 1287 (99% [95% CI, 98%-99%]) needed respiratory support, including 1150 (88% [95% CI, 87%-90%]) who received mechanical ventilation and 137 (11% [95% CI, 9%-12%]) who received noninvasive ventilation. The median positive end-expiratory pressure (PEEP) was 14 (IQR, 12-16) cm H2O, and FIO2 was greater than 50% in 89% of patients. The median PaO2/FIO2 was 160 (IQR, 114-220). The median PEEP level was not different between younger patients (n = 503 aged 63 years) and older patients (n = 514 aged 64 years) (14 [IQR, 12-15] vs 14 [IQR, 12-16] cm H2O, respectively; median difference, 0 [95% CI, 0-0]; P = .94). Median FIO2 was lower in younger patients: 60% (IQR, 50%-80%) vs 70% (IQR, 50%-80%) (median difference, −10% [95% CI, −14% to 6%]; P = .006), and median PaO2/FIO2 was higher in younger patients: 163.5 (IQR, 120-230) vs 156 (IQR, 110-205) (median difference, 7 [95% CI, −8 to 22]; P = .02). Patients with hypertension (n = 509) were older than those without hypertension (n = 526) (median [IQR] age, 66 years [60-72] vs 62 years [54-68]; P < .001) and had lower PaO2/FIO2 (median [IQR], 146 [105-214] vs 173 [120-222]; median difference, −27 [95% CI, −42 to −12]; P = .005). Among the 1581 patients with ICU disposition data available as of March 25, 2020, 920 patients (58% [95% CI, 56%-61%]) were still in the ICU, 256 (16% [95% CI, 14%-18%]) were discharged from the ICU, and 405 (26% [95% CI, 23%-28%]) had died in the ICU. Older patients (n = 786; age 64 years) had higher mortality than younger patients (n = 795; age 63 years) (36% vs 15%; difference, 21% [95% CI, 17%-26%]; P < .001).

CONCLUSIONS AND RELEVANCE
In this case series of critically ill patients with laboratory-confirmed COVID-19 admitted to ICUs in Lombardy, Italy, the majority were older men, a large proportion required mechanical ventilation and high levels of PEEP, and ICU mortality was 26%.

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04/04/2020 Articles
Mortality Rates of Patients with Proximal Femoral Fracture in a Worldwide Pandemic

The Journal of Bone & Joint Surgery

Authors:
Josep Maria Muñoz Vives, Montsant Jornet-Gibert, J. Cámara-Cabrera, Pedro L. Esteban, Laia Brunet, Luis Delgado-Flores, P. Camacho-Carrasco, P. Torner and Francesc Marcano-Fernández

Read More »

04/04/2020 Articles
Clinical presentation and initial management critically ill patients with...

Clinical presentation and initial management critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Brescia, Italy

ELSEVIER

Authors:
Piva S, Filippini M, Turla F, Cattaneo S, Margola A, De Fulviis S, Nardiello I, Beretta A, Ferrari L, Trotta R, Erbici G, Focà E, Castelli F, Rasulo F, Lanspa MJ, Latronico N

Abstract An ongoing pandemic of COVID-19 that started in Hubei, China has resulted in massive strain on the healthcare infrastructure in Lombardy, Italy. The management of these patients is still evolving.

Materials and methods This is a single-center observational cohort study of critically ill patients infected with COVID-19. Bedside clinicians abstracted daily patient data on history, treatment, and short-term course. We describe management and a proposed severity scale for treatment used in this hospital.

Results 44 patients were enrolled; with incomplete information on 11. Of the 33 studied patients, 91% were male, median age 64; 88% were overweight or obese. 45% were hypertensive, 12% had been taking an ACE-inhibitor. Noninvasive ventilation was performed on 39% of patients for part or all or their ICU stay with no provider infection. Most patients received antibiotics for pneumonia. Patients also received lopinivir/ritonavir (82%), hydroxychloroquine (79%), and tocilizumab (12%) according to this treatment algorithm. Nine of 10 patients survived their ICU course and were transferred to the floor, with one dying in the ICU.

Conclusions ICU patients with COVID-19 frequently have hypertension. Many could be managed with noninvasive ventilation, despite the risk of aerosolization. The use of a severity scale augmented clinician management.

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02/04/2020 Comment
Cancer, COVID-19 and the precautionary principle: prioritizing treatment during a global pandemic

Nature Review

Authors:
Timothy P. Hanna, Gerald A. Evans, Christopher M. Booth

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03/04/2020 Articles
Covid-19 and immunomodulation in IBD

BMJ

Authors:
Markus F Neurath

ABSTRACT

The current coronavirus pandemic is an ongoing global health crisis due to covid-19, caused by severe acute respiratory syndrome coronavirus 2. Although covid-19 leads to little or mild flu-like symptoms in the majority of affected patients, the disease may cause severe, frequently lethal complications such as progressive pneumonia, acute respiratory distress syndrome and organ failure driven by hyperinflammation and a cytokine storm syndrome. This situation causes various major challenges for gastroenterology. In the context of IBD, several key questions arise. For instance, it is an important question to understand whether patients with IBD (eg, due to intestinal ACE2 expression) might be particularly susceptible to covid-19 and the cytokine release syndrome associated with lung injury and fatal outcomes. Another highly relevant question is how to deal with immunosuppression and immunomodulation during the current pandemic in patients with IBD and whether immunosuppression affects the progress of covid-19. Here, the current understanding of the pathophysiology of covid-19 is reviewed with special reference to immune cell activation. Moreover, the potential implications of these new insights for immunomodulation and biological therapy in IBD are discussed

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02/04/2020 News
Cancer guidelines during the COVID-19 pandemic

The Lancet

Authors:
Talha Khan Burki

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27/03/2020 Viewpoint
Potential Effects of Coronaviruses on the Cardiovascular System A Review

JAMA

Authors:
Mohammad Madjid, Payam Safavi-Naeini, Scott D. Solomon, Orly Vardeny, Pharm

IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19) has reached a pandemic level. Coronaviruses are known to affect the cardiovascular system. We review the basics of coronaviruses, with a focus on COVID-19, along with their effects on the cardiovascular system.

OBSERVATIONS Coronavirus disease 2019 can cause a viral pneumonia with additional extrapulmonary manifestations and complications. A large proportion of patients have underlying cardiovascular disease and/or cardiac risk factors. Factors associated with mortality include male sex, advanced age, and presence of comorbidities including hypertension, diabetes mellitus, cardiovascular diseases, and cerebrovascular diseases. Acute cardiac injury determined by elevated high-sensitivity troponin levels is commonly observed in severe cases and is strongly associated with mortality. Acute respiratory distress syndrome is also strongly associated with mortality.

CONCLUSIONS AND RELEVANCE Coronavirus disease 2019 is associated with a high inflammatory burden that can induce vascular inflammation, myocarditis, and cardiac arrhythmias. Extensive efforts are underway to find specific vaccines and antivirals against SARS-CoV-2. Meanwhile, cardiovascular risk factors and conditions should be judiciously controlled per evidence-based guidelines.

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12/03/2020 Correspondence
Detection of Covid-19 in Children in Early January 2020 in Wuhan, China

The New England Journal of Medicine

Authors:
Weiyong Liu, Qi Zhang, Junbo Chen, Rong Xiang, Huijuan Song, Sainan Shu, Ling Chen, Lu Liang, Jiaxin Zhou, Lei You, Peng Wu, Bo Zhang, Yanjun Lu, Liming Xia, Lu Huang, Yang Yang, Fang Liu,Malcolm G. Semple, Benjamin J. Cowling, Ke Lan, Ziyong Sun, Hongjie Yu, Yingle Liu

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01/04/2020 Review
Insight into 2019 novel coronavirus...

Insight into 2019 novel coronavirus — An updated interim review and lessons from SARS-CoV and MERS-CoV

SCIENCE

Authors:
Mingxuan Xiea, Qiong Chena

ABSTRACT

Background: The rapid spread of the coronavirus disease 2019 (COVID-19), caused by a zoonotic beta- coronavirus entitled 2019 novel coronavirus (2019-nCoV), has become a global threat. Awareness of the biological features of 2019-nCoV should be updated in time and needs to be comprehensively summarized to help optimize control measures and make therapeutic decisions.

Methods: Based on recently published literature, official documents and selected up-to-date preprint studies, we reviewed the virology and origin, epidemiology, clinical manifestations, pathology and treatment of 2019-nCoV infection, in comparison with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) infection.

Results: The genome of 2019-nCoV partially resembled SARS-CoV and MERS-CoV, and indicated a bat origin. The COVID-19 generally had a high reproductive number, a long incubation period, a short serial interval and a low case fatality rate (much higher in patients with comorbidities) than SARS and MERS. Clinical presentation and pathology of COVID-19 greatly resembled SARS and MERS, with less upper respiratory and gastrointestinal symptoms, and more exudative lesions in post-mortems. Potential treatments included remdesivir, chloroquine, tocilizumab, convalescent plasma and vaccine immuniza- tion (when possible).

Conclusion: The initial experience from the current pandemic and lessons from the previous two pandemics can help improve future preparedness plans and combat disease progression.

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12/03/2020 Articles
Dynamic and explainable machine learning prediction of mortality in patients...

Dynamic and explainable machine learning prediction of mortality in patients in the intensive care unit: a retrospective study of high-frequency data in electronic patient records

The Lancet Journal

Authors:
Hans-Christian Thorsen-Meyer, Annelaura B Nielsen, Anna P Nielsen, Benjamin Skov Kaas-Hansen, Palle Toft, Jens Schierbeck, Thomas Strøm, Piotr J Chmura, Marc Heimann, Lars Dybdahl, Lasse Spangsege, Patrick Hulsen, Kirstine Belling, Søren Brunak, Anders Perner

Background Many mortality prediction models have been developed for patients in intensive care units (ICUs); most are based on data available at ICU admission. We investigated whether machine learning methods using analyses of time-series data improved mortality prognostication for patients in the ICU by providing real-time predictions of 90-day mortality. In addition, we examined to what extent such a dynamic model could be made interpretable by quantifying and visualising the features that drive the predictions at different timepoints.

Methods Based on the Simplified Acute Physiology Score (SAPS) III variables, we trained a machine learning model on longitudinal data from patients admitted to four ICUs in the Capital Region, Denmark, between 2011 and 2016. We included all patients older than 16 years of age, with an ICU stay lasting more than 1 h, and who had a Danish civil registration number to enable 90-day follow-up. We leveraged static data and physiological time-series data from electronic health records and the Danish National Patient Registry. A recurrent neural network was trained with a temporal resolution of 1 h. The model was internally validated using the holdout method with 20% of the training dataset and externally validated using previously unseen data from a fifth hospital in Denmark. Its performance was assessed with the Matthews correlation coefficient (MCC) and area under the receiver operating characteristic curve (AUROC) as metrics, using bootstrapping with 1000 samples with replacement to construct 95% CIs. A Shapley additive explanations algorithm was applied to the prediction model to obtain explanations of the features that drive patient-specific predictions, and the contributions of each of the 44 features in the model were analysed and compared with the variables in the original SAPS III model.

Findings From a dataset containing 15615 ICU admissions of 12616 patients, we included 14190 admissions of 11492 patients in our analysis. Overall, 90-day mortality was 33⋅1% (3802 patients). The deep learning model showed a predictive performance on the holdout testing dataset that improved over the timecourse of an ICU stay: MCC 0⋅29 (95% CI 0⋅25–0⋅33) and AUROC 0⋅73 (0⋅71–0⋅74) at admission, 0⋅43 (0⋅40–0⋅47) and 0⋅82 (0⋅80–0⋅84) after 24 h, 0⋅50 (0⋅46–0⋅53) and 0⋅85 (0⋅84–0⋅87) after 72 h, and 0⋅57 (0⋅54–0⋅60) and 0⋅88 (0⋅87–0⋅89) at the time of discharge. The model exhibited good calibration properties. These results were validated in an external validation cohort of 5827 patients with 6748 admissions: MCC 0⋅29 (95% CI 0⋅27–0⋅32) and AUROC 0⋅75 (0⋅73–0⋅76) at admission, 0⋅41 (0⋅39–0⋅44) and 0⋅80 (0⋅79–0⋅81) after 24 h, 0⋅46 (0⋅43–0⋅48) and 0⋅82 (0⋅81–0⋅83) after 72 h, and 0⋅47 (0⋅44–0⋅49) and 0⋅83 (0⋅82–0⋅84) at the time of discharge.

Interpretation The prediction of 90-day mortality improved with 1-h sampling intervals during the ICU stay. The dynamic risk prediction can also be explained for an individual patient, visualising the features contributing to the prediction at any point in time. This explanation allows the clinician to determine whether there are elements in the current patient state and care that are potentially actionable, thus making the model suitable for further validation as a clinical tool.

Funding Novo Nordisk Foundation and the Innovation Fund Denmark.

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27/03/2020 Articles
Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19)

JAMA

Authors:
Tao Guo, Yongzhen Fan, Ming Chen, Xiaoyan Wu, Lin Zhang, Tao He, Hairong Wang, Jing Wan, Xinghuan Wang, Zhibing Lu



ABSTRACT

IMPORTANCE
 Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents. Information regarding the impact of cardiovascular complication on fatal outcome is scarce.

OBJECTIVE
To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.

DESIGN, SETTING, AND PARTICIPANTS
This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020. Analysis began February 25, 2020.

MAIN OUTCOMES AND MEASURES
Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels.

RESULT
Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died. The mean (SD) age was 58.50 (14.66) years. Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels. The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs. Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]). Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro–brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001). Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16). During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (41 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels. The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 25.6% (43 of 168).

CONCLUSIONS AND RELEVANCE
Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable. Myocardial injury is associated with cardiac dysfunction and arrhythmias. Inflammation may be a potential mechanism for myocardial injury. Aggressive treatment may be considered for patients at high risk of myocardial injury.

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31/03/2020 Comment
Protecting the psychological health of children through effective communication about COVID-19

The Lancet

Authors:
Louise Dalton, Elizabeth Rapa, Alan Stein

Read More »

26/03/2020 Analysis
Managing mental health challenges faced by healthcare workers during covid-19 pandemic

the BMJ

Authors:
Neil Greenberg, Mary Docherty , Sam Gnanapragasam, Simon Wessely

Read More »

12/03/2020 Articles
First known person-to-person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the USA

The Lancet Journal

Authors:
Isaac Ghinai, Tristan D McPherson, Jennifer C Hunter, Hannah L Kirking, Demian Christiansen, Kiran Joshi, Rachel Rubin, Shirley Morales-Estrada, Stephanie R Black, Massimo Pacilli, Marielle J Fricchione, Rashmi K Chugh, Kelly A Walblay, N Seema Ahmed, William C Stoecker, Nausheen F Hasan, Deborah P Burdsall, Heather E Reese, Megan Wallace, Chen Wang, Darcie Moeller, Jacqueline Korpics, Shannon A Novosad, Isaac Benowitz, Max W Jacobs, Vishal S Dasari, Megan T Patel, Judy Kauerauf, E Matt Charles, Ngozi O Ezike, Victoria Chu, Claire M Midgley, Melissa A Rolfes, Susan I Gerber, Xiaoyan Lu, Stephen Lindstrom, Jennifer R Verani, Jennifer E Layden

Background Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first detected in China in December, 2019. In January, 2020, state, local, and federal public health agencies investigated the first case of COVID-19 in Illinois, USA. Methods Patients with confirmed COVID-19 were defined as those with a positive SARS-CoV-2 test. Contacts were people with exposure to a patient with COVID-19 on or after the patient’s symptom onset date. Contacts underwent active symptom monitoring for 14 days following their last exposure. Contacts who developed fever, cough, or shortness of breath became persons under investigation and were tested for SARS-CoV-2. A convenience sample of 32 asymptomatic health-care personnel contacts were also tested.

Findings Patient 1—a woman in her 60s—returned from China in mid-January, 2020. One week later, she was hospitalised with pneumonia and tested positive for SARS-CoV-2. Her husband (Patient 2) did not travel but had frequent close contact with his wife. He was admitted 8 days later and tested positive for SARS-CoV-2. Overall, 372 contacts of both cases were identified; 347 underwent active symptom monitoring, including 152 community contacts and 195 health-care personnel. Of monitored contacts, 43 became persons under investigation, in addition to Patient 2. These 43 persons under investigation and all 32 asymptomatic health-care personnel tested negative for SARS-CoV-2.

Interpretation Person-to-person transmission of SARS-CoV-2 occurred between two people with prolonged, unprotected exposure while Patient 1 was symptomatic. Despite active symptom monitoring and testing of symptomatic and some asymptomatic contacts, no further transmission was detected.

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17/03/2020 Comment
Clinical course and mortality risk of severe COVID-19

The Lancet Journal

Authors:
Paul Weiss, David R Murdoch

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26/02/2020 Articles
Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases

Radiology Society of North America

Authors:
Tao Ai MD, Zhenlu Yang, Hongyan Hou, Chenao Zhan, Chong Chen, Wenzhi Lv, Qian Tao, Ziyong Sun, Liming Xia

Background:
Chest CT is used for diagnosis of 2019 novel coronavirus disease (COVID-19), as an important complement to the reverse-transcription polymerase chain reaction (RT-PCR) tests.

Purpose:
To investigate the diagnostic value and consistency of chest CT as compared with comparison to RT-PCR assay in COVID-19.

Methods
From January 6 to February 6, 2020, 1014 patients in Wuhan, China who underwent both chest CT and RT-PCR tests were included. With RT-PCR as reference standard, the performance of chest CT in diagnosing COVID-19 was assessed. Besides, for patients with multiple RT-PCR assays, the dynamic conversion of RT-PCR results (negative to positive, positive to negative, respectively) was analyzed as compared with serial chest CT scans for those with time-interval of 4 days or more.

Results
Of 1014 patients, 59% (601/1014) had positive RT-PCR results, and 88% (888/1014) had positive chest CT scans. The sensitivity of chest CT in suggesting COVID-19 was 97% (95%CI, 95-98%, 580/601 patients) based on positive RT-PCR results. In patients with negative RT-PCR results, 75% (308/413) had positive chest CT findings; of 308, 48% were considered as highly likely cases, with 33% as probable cases. By analysis of serial RT-PCR assays and CT scans, the mean interval time between the initial negative to positive RT-PCR results was 5.1 ± 1.5 days; the initial positive to subsequent negative RT-PCR result was 6.9 ± 2.3 days). 60% to 93% of cases had initial positive CT consistent with COVID-19 prior (or parallel) to the initial positive RT-PCR results. 42% (24/57) cases showed improvement in follow-up chest CT scans before the RT-PCR results turning negative.

Conclusion
Chest CT has a high sensitivity for diagnosis of COVID-19. Chest CT may be considered as a primary tool for the current COVID-19 detection in epidemic areas.

2019-nCoV pneumonia,reverse transcription polymerase chain reaction, chest CT imaging, diagnostic value, positive rate

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30 /03/2020 Correspondence
Dementia care during COVID-19

The Lancet

Authors:
Huali Wang, Tao Li, Paola Barbarino, Serge Gauthier, Henry Brodaty, José Luis Molinuevo, Hengge Xie, Yongan Sun, Enyan Yu, Yanqing Tang, Wendy Weidner, Xin Yu, Show less

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26/03/2020 Editorial
Can SARS-CoV-2 Infection Be Acquired In Utero? More Definitive Evidence Is Needed

JAMA

Authors:
David W. Kimberlin, Sergio Stagno

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20 /03/2020 Articles
Eleven Faces of Coronavirus Disease 2019

Wiley Online Library

Authors:
Xiang Dong, Yi-yuan Cao, Xiao-xia Lu, Jin-jin Zhang, Hui Du, You-qin Yan, Cezmi A. Akdis, Ya-dong Gao

Background and aims: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has recently spread worldwide and been declared a pandemic. We aim to describe here the various clinical presentations of this disease by examining eleven cases. Methods: Electronic medical records of 11 patients with COVID-19 were collected and demographics, clinical manifestations, outcomes, key laboratory results, and radiological images are discussed. Results: The clinical course of the eleven cases demonstrated the complexity of the COVID-19 profile with different clinical presentations. Clinical manifestations range from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Laboratory detection of the viral nucleic acid can yield false-negative results, and serological testing of virus specific IgG and IgM antibodies should be used as an alternative for diagnosis. Patients with common allergic diseases did not develop distinct symptoms and severe courses. Cases with a pre-existing condition of chronic obstructive pulmonary disease or complicated with a secondary bacterial pneumonia were more severe.
Conclusion: All different clinical characteristics of COVID-19 should be taken into consideration to identify patients that need to be in strict quarantine for the efficient containment of the pandemic.

coronavirus disease 2019, SARS-CoV-2, case reports, clinical characteristics, allergic diseases

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12/03/2020 Correspondence
Real estimates of mortality following COVID-19 infection

The Lancet Journal

Authors:
David Baud, Xiaolong Qi, Karin Nielsen-Saines, Didier Musso, Léo Pomar, Guillaume Favre

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17/03/2020 Analysis
COVID-19 can present with a rash and be mistaken for dengue

JAAD

Authors:
Beuy Joob and Viroj Wiwanitkit

Read More »

23/03/2020 Review
Should COVID-19 Concern Nephrologists? Why and to What Extent?...

Should COVID-19 Concern Nephrologists? Why and to What Extent? The Emerging Impasse of Angiotensin Blockade

NCBI

Authors:
Luca Perico, Ariela Benigni, Giuseppe Remuzzi

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18/03/2020 Articles
Clinical characteristics and outcomes of patients undergoing surgeries...

Clinical characteristics and outcomes of patients undergoing surgeries during the incubation period of COVID-19 infection

ELSEVIER

Authors:
Shaoqing Lei, Fang Jiang, Wating Su, Chang Chen, Jingli Chen, Wei Mei, Li-Ying Zhan, Yifan Jia, Liangqing Zhang, Danyong Liu, Zhong-Yuan Xia, Zhengyuan Xia

ABSTRACT

Background:
The outbreak of 2019 novel coronavirus disease (COVID-19) in Wuhan, China, has spread rapidly worldwide. In the early stage, we encountered a small but meaningful number of patients who were uninten- tionally scheduled for elective surgeries during the incubation period of COVID-19. We intended to describe their clinical characteristics and outcomes.

Methods:
We retrospectively analyzed the clinical data of 34 patients underwent elective surgeries during the incubation period of COVID-19 at Renmin Hospital, Zhongnan Hospital, Tongji Hospital and Central Hospital in Wuhan, from January 1 to February 5, 2020.

Findings:
Of the 34 operative patients, the median age was 55 years (IQR, 4363), and 20 (58¢8%) patients were women. All patients developed COVID-19 pneumonia shortly after surgery with abnormal findings on chest computed tomographic scans. Common symptoms included fever (31 [91¢2%]), fatigue (25 [73¢5%]) and dry cough (18 [52¢9%]). 15 (44¢1%) patients required admission to intensive care unit (ICU) during disease progression, and 7 patients (20¢5%) died after admission to ICU. Compared with non-ICU patients, ICU patients were older, were more likely to have underlying comorbidities, underwent more difficult surgeries, as well as more severe laboratory abnormalities (eg, hyperleukocytemia, lymphopenia). The most common complications in non-survivors included ARDS, shock, arrhythmia and acute cardiac injury. Interpretation: In this retrospective cohort study of 34 operative patients with confirmed COVID-19, 15 (44¢1%) patients needed ICU care, and the mortality rate was 20¢5%.

Funding:
National Natural Science Foundation of China.

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25/02/2020 Review
Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory...

Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths 

Science Direct

Authors:
Chih-Cheng Lai, Yen Hung Liu, Cheng-Yi Wang, Ya-Hui Wang, Shun-Chung Hsueh, Muh-Yen Yen, Wen-Chien Ko, Po-Ren Hsueh

ABSTRACT

Since the emergence of coronavirus disease 2019 (COVID-19) (formerly known as the 2019 novel coronavirus [2019-nCoV]) in Wuhan, China in December 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more than 75,000 cases have been reported in 32 countries/regions, resulting in more than 2000 deaths worldwide. Despite the fact that most COVID-19 cases and mortalities were reported in China, the WHO has declared this outbreak as the sixth public health emergency of international concern. The

COVID-19 can present as an asymptomatic carrier state, acute respiratory disease, and pneu- monia. Adults represent the population with the highest infection rate; however, neonates,children, and elderly patients can also be infected by SARS-CoV-2. In addition, nosocomial infection of hospitalized patients and healthcare workers, and viral transmission from asymp- tomatic carriers are possible. The most common finding on chest imaging among patients with pneumonia was ground-glass opacity with bilateral involvement. Severe cases are more likely to be older patients with underlying comorbidities compared to mild cases. Indeed, age and disease severity may be correlated with the outcomes of COVID-19. To date, effective treat- ment is lacking; however, clinical trials investigating the efficacy of several agents, including remdesivir and chloroquine, are underway in China. Currently, effective infection control intervention is the only way to prevent the spread of SARS-CoV-2.

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11/03/2020 Correspondence
Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?Testing

The Lancet

Authors:
Lei Fang, George Karakiulakis, Michael Roth

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18/03/2020 Correspondence
SARS-CoV-2 Infection in Children

The New England Journal of Medicine

Authors:
Xiaoxia Lu, Liqiong Zhang, Hui Du, Jingjing Zhang, Yuan Y. Li, Jingyu Qu, Wenxin Zhang, Youjie Wang, Shuangshuang Bao, Ying Li, Chuansha Wu, Hongxiu Liu, Di Liu, Jianbo Shao, Xuehua Peng, Yonghong Yang, hisheng Liu, Yun Xiang, Furong Zhang, Rona M. Silva, Kent E. Pinkerton, Kunling Shen, Han Xiao, Shunqing Xu, Gary W.K. Wong

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through ACE2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, while also causing acute myocardial injury and chronic damage to the cardiovascular system. Therefore, particular attention should be given to cardiovascular protection during treatment for COVID-19.

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16/03/2020 Articles
Clinical characteristics of refractory COVID-19 pneumonia in Wuhan, China

Oxford University Press

Authors:
Pingzheng Mo, Yuanyuan Xing, Yu Xiao, Liping Deng, Qiu Zhao, Hongling Wang, Yong Xiong, Zhenshun Cheng, Shicheng Gao, Ke Liang, Mingqi Luo, Tielong Chen, Shihui Song, Zhiyong Ma, Xiaoping Chen, Ruiying Zheng, Qian Cao, Fan Wang, Yongxi Zhang"

Background:
Since December 2019, novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19) occurred in Wuhan, and rapidly spread throughout China. This study aimed to clarify the characteristics of patients with refractory COVID-19. Methods: In this retrospective single-center study, we included 155 consecutive patients with confirmed COVID-19 in Zhongnan Hospital of Wuhan University from January 1st to February 5th. The cases were divided into general and refractory COVID-19 groups according to the clinical efficacy after hospitalization, and the difference between groups were compared.
Results:
Compared with general COVID-19 patients (45.2%), refractory patients had an older age, male sex, more underlying comorbidities, lower incidence of fever, higher levels of maximum temperature among fever cases, higher incidence of breath shortness and anorexia, severer disease assessment on admission, high levels of neutrophil, aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and C-reactive protein, lower levels of platelets and albumin, and higher incidence of bilateral pneumonia and pleural effusion (P<0.05). Refractory COVID-19 patients were more likely to receive oxygen, mechanical ventilation, expectorant, and adjunctive treatment including corticosteroid, antiviral drugs and immune enhancer (P<0.05). After adjustment, those with refractory COVID-19 were also more likely to have a male sex and manifestations of anorexia and fever on admission, and receive oxygen, expectorant and adjunctive agents (P<0.05) when considering the factors of disease severity on admission, mechanical ventilation, and ICU transfer. Conclusion: Nearly 50% COVID-19 patients could not reach obvious clinical and radiological remission within 10 days after hospitalization. The patients with male sex, anorexia and no fever on admission predicted poor efficacy.

COVID-19, SARS-CoV-2, clinical efficacy, predictors

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25/02/2020 Review
Understanding of COVID‐19 based on current evidence

Wiley Online Library

Authors:
Pengfei Sun, Xiaosheng Lu, Chao Xu, Wenjuan Sun, Bo Pan

Since December 2019, a series of unexplained pneumonia cases have been reported in Wuhan, China. On 12 January 2020, the World Health Organization (WHO) temporarily named this new virus as the 2019 novel coronavirus (2019‐nCoV). On 11 February 2020, the WHO officially named the disease caused by the 2019‐nCoV as coronavirus disease (COVID‐19). The COVID‐19 epidemic is spreading all over the world, especially in China. Based on the published evidence, we systematically discuss the characteristics of COVID‐19 in the hope of providing a reference for future studies and help for the pre- vention and control of the COVID‐19 epidemic.

2019‐nCoV, coronavirus, COVID‐19, epidemiology, pneumonia, SARS‐CoV‐2

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27/03/2020 Editorial
Association of Coronavirus Disease 2019 (COVID-19) With Myocardial Injury and Mortality

JAMA

Authors:
Robert O. Bonow, Gregg C. Fonarow, Patrick T.O’Gara, Clyde W. Yancy

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18/03/2020 Perspectives
Infuenza and obesity: its odd relationship and the lessons for COVID‐19 pandemic

Springer

Authors:
Livio Luzi, Maria Grazia Radaelli

ABSTRACT

Aims Analyze the relationship between obesity and infuenza. Methods Basal hormone milieu, defective response of both innate and adaptive immune system and sedentariness are major determinants in the severity of infuenza viral infection in obese patients. Being overweight not only increases the risk of infection and of complications for the single obese person, but a large prevalence of obese individuals within the popula- tion might increase the chance of appearance of more virulent viral strain, prolongs the virus shedding throughout the total population and eventually might increase overall mortality rate of an infuenza pandemic.

Results

Waiting for the development of a vaccination against COVID-19, isolation of positive cases and social distancing are the primary interventions. Nonetheless, evidence from previous infuenza pandemics suggests the following interven- tions aimed at improving immune response: (1) lose weight with a mild caloric restriction; (2) include AMPK activators and PPAR gamma activators in the drug treatment for obesity associated with diabetes; and (3) practice mild-to-moderate physical exercise.

Conclusions

Due to prolonged viral shedding, quarantine in obese subjects should likely be longer than nor mal weight individuals.

Keywords

Obese subjects / COVID-19 / Infuenza / Immune-modulation

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17/03/2020 Articles
Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study

The BMJ

Authors:
Tao Chen, Di Wu, Huilong Chen, Weiming Yan, Danlei Yang, Guang Chen, Ke Ma, Dong Xu, Haijing Yu, Hongwu Wang, Tao Wang, Wei Guo, Jia Chen, Chen Ding, Xiaoping Zhang, Jiaquan Huang, Meifang Han, Shusheng Li, Xiaoping Luo, Jianping Zhao, Qin Ning

ABSTRACT

OBJECTIVE

To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died.

DESIGN

Retrospective case series.

SETTING

Tongji Hospital in Wuhan, China.

PARTICIPANTS

Among a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed. Data were collected until 28 February 2020.

MAIN OUTCOME MEASURES

Clinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms.

RESULTS

The median age of deceased patients (68 years) was significantly older than recovered patients (51 years). Male sex was more predominant in deceased patients (83; 73%) than in recovered patients (88; 55%). Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)). Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)). The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days. Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively. Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113; 100%), type I respiratory failure (18/35; 51%), sepsis (113; 100%), acute cardiac injury (72/94; 77%), heart failure (41/83; 49%), alkalosis (14/35; 40%), hyperkalaemia (42; 37%), acute kidney injury (28; 25%), and hypoxic encephalopathy (23; 20%). Patients with cardiovascular comorbidity were more likely to develop cardiac complications. Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients.

CONCLUSION

Severe acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk. Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.

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20/ 02/2020 Articles
2019-novel Coronavirus severe adult respiratory distress syndrome in two cases in Italy: An uncommon radiological presentation

ELSEVIER

Authors:
Fabrizio Albarello, Elisa Pianura, Federica Di Stefano, Massimo Cristofaro, Ada Petrone, Luisa Marchioni, Claudia Palazzolo, Vincenzo Schininà, Emanuele Nicastri, Nicola Petrosillo, Paolo Campioni, Petersen Eskild, Alimuddin Zumla, Giuseppe Ippolito

Introduction:
Several recent case reports have described common early chest imaging findings of lung pathology caused by 2019 novel Coronavirus (SARS-COV2) which appear to be similar to those seen previously in SARS-CoV and MERS-CoV infected patients.

Objective:
We present some remarkable imaging findings of the first two patients identified in Italy with COVID-19 infection travelling from Wuhan, China. The follow-up with chest X-Rays and CT scans was also included, showing a progressive adult respiratory distress syndrome (ARDS).

Results:
Moderate to severe progression of the lung infiltrates, with increasing percentage of high-density infiltrates sustained by a bilateral and multi-segmental extension of lung opacities, were seen. During the follow-up, apart from pleural effusions, a tubular and enlarged appearance of pulmonary vessels with a sudden caliber reduction was seen, mainly found in the dichotomic tracts, where the center of a new insurgent pulmonary lesion was seen. It could be an early alert radiological sign to predict initial lung deterioration. Another uncommon element was the presence of mediastinal lymphadenopathy with short-axis oval nodes.

Conclusions:
Although only two patients have been studied, these findings are consistent with the radiological pattern described in literature. Finally, the pulmonary vessels enlargement in areas where new lung infiltrates develop in the follow-up CT scan, could describe an early predictor radiological sign of lung impairment.

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11/03/2020 Comment
Implications of COVID-19 for patients with pre-existing digestive diseases

The Lancet

Authors:
Ren Mao, Jie Liang, Jun Shen, Subrata Ghosh, Liang-Ru Zhu, Hong Yang, Kai-Chun Wu, Min-Hu Chen

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27/03/2020 Brief Report
Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19)

JAMA

Authors:
Riccardo M. Inciardi, Laura Lupi, Gregorio Zaccone, Leonardo Italia, Michela Raffo, Daniela Tomasoni, Dario S. Cani, Manuel Cerini, Davide Farina, Emanuele Gavazzi, Roberto Maroldi, Marianna Adamo, Enrico Ammirati, Gianfranco Sinagra, Carlo M. Lombardi, Marco Metra

ABSTRACT

IMPORTANCE Virus infection has been widely described as one of the most common causes of myocarditis. However, less is known about the cardiac involvement as a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

OBJECTIVE To describe the presentation of acute myocardial inflammation in a patient with coronavirus disease 2019 (COVID-19) who recovered from the influenzalike syndrome and developed fatigue and signs and symptoms of heart failure a week after upper respiratory tract symptoms.

DESIGN, SETTING, AND PARTICIPANT This case report describes an otherwise healthy 53-year-old woman who tested positive for COVID-19 and was admitted to the cardiac care unit in March 2020 for acute myopericarditis with systolic dysfunction, confirmed on cardiac magnetic resonance imaging, the week after onset of fever and dry cough due to COVID-19. The patient did not show any respiratory involvement during the clinical course.

EXPOSURE Cardiac involvement with COVID-19.

MAIN OUTCOMES AND MEASURES Detection of cardiac involvement with an increase in levels of N-terminal pro–brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T, echocardiography changes, and diffuse biventricular myocardial edema and late gadolinium enhancement on cardiac magnetic resonance imaging.

RESULTS An otherwise healthy 53-year-old white woman presented to the emergency department with severe fatigue. She described fever and dry cough the week before. She was afebrile but hypotensive; electrocardiography showed diffuse ST elevation, and elevated high-sensitivity troponin T and NT-proBNP levels were detected. Findings on chest radiography were normal. There was no evidence of obstructive coronary disease on coronary angiography. Based on the COVID-19 outbreak, a nasopharyngeal swab was performed, with a positive result for SARS-CoV-2 on real-time reverse transcriptase– polymerase chain reaction assay. Cardiac magnetic resonance imaging showed increased wall thickness with diffuse biventricular hypokinesis, especially in the apical segments, and severe left ventricular dysfunction (left ventricular ejection fraction of 35%). Short tau inversion recovery and T2-mapping sequences showed marked biventricular myocardial interstitial edema, and there was also diffuse late gadolinium enhancement involving the entire biventricular wall. There was a circumferential pericardial effusion that was most notable around the right cardiac chambers. These findings were all consistent with acute myopericarditis. She was treated with dobutamine, antiviral drugs (lopinavir/ritonavir), steroids, chloroquine, and medical treatment for heart failure, with progressive clinical and instrumental stabilization.

CONCLUSIONS AND RELEVANCE This case highlights cardiac involvement as a complication associated with COVID-19, even without symptoms and signs of interstitial pneumonia.

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11/03/2020 Correspondence
Sex difference and smoking predisposition in patients with COVID-19

The Lancet Journal

Authors:
Hua Cai

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11/03/2020 Articles
Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

The Lancet Journal

 

Authors:
Fei Zhou, Ting Yu, Ronghui Du, Guohui Fan, Ying Liu, Zhibo Liu, Jie Xiang, Yeming Wang, Bin Song, Xiaoying Gu, Lulu Guan, Yuan Wei, Hui Li, Xudong Wu, Jiuyang Xu, Shengjin Tu, Yi Zhang, Hua Chen, Bin Cao

Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.

Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory- confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been

discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.
Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

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11/03/2020 Comment
Diabetes and COVID-19

The Lancet

Authors:
Zachary T. Bloomgarden

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13/02/2020 Articles
Estimation of the asymptomatic ratio of novel coronavirus infections (COVID-19)

International Journal of Infectious Diseases

Authors:
Hiroshi Nishiura, Tetsuro Kobayashi, Ayako Suzuki, Sung-Mok Jung, Katsuma Hayashi, Ryo Kinoshita, Yichi Yang, Baoyin Yuan, Andrei R. Akhmetzhanov, Natalie M. Linton

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12/02/2020 Articles
Chest CT for Typical 2019-nCoV Pneumonia: Relationship to Negative RT-PCR Testing

Radiology Society of North America

Authors:
Xingzhi Xie, Zheng Zhong ,Wei Zhao, Chao Zheng, Fei Wang, Jun Liu

Some patients with positive chest CT findings may present with negative results of real time reverse-transcription–polymerase chain- reaction (RT-PCR) for 2019 novel coronavirus (2019-nCoV). In this report, we present chest CT findings from five patients with 2019-nCoV infection who had initial negative RT-PCR results. All five patients had typical imaging findings, including ground-glass opacity (GGO) (5 patients) and/or mixed GGO and mixed consolidation (2 patients). After isolation for presumed 2019-nCoV pneumonia, all patients were eventually confirmed with 2019-nCoV infection by repeated swab tests. A combination of repeated swab tests and CT scanning may be helpful when for individuals with high clinical suspicion of nCoV infection but negative RT-PCR screening

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09/03/2020 Correspondence
Comorbidities and multi-organ injuries in the treatment of COVID-19

The Lancet Journal

Authors:
Tianbing Wang, Zhe Du, Fengxue Zhu, Zhaolong Cao, Youzhong An, Yan Gao, Baoguo Jiang

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05/03/2020 Comment
COVID-19 and the cardiovascular system

Nature Review

Authors:
Ying-Ying Zheng, Yi-Tong Ma, Jin-Ying Zhang, Xiang Xie

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through ACE2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, while also causing acute myocardial injury and chronic damage to the cardiovascular system. Therefore, particular attention should be given to cardiovascular protection during treatment for COVID-19.

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02/02/2020 Articles
Bacterial and fungal co-infection in individuals with coronavirus: A rapid review...

Bacterial and fungal co-infection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing

OXFORD ACADEMY

Authors:
Timothy M Rawson, Luke S P Moore, Nina Zhu, Nishanthy Ranganathan, Keira Skolimowska, Mark Gilchrist, Giovanni Satta, Graham Cooke, Alison Holmes

ABSTRACT

Background: To explore and describe the current literature surrounding bacterial/fungal co-infection in patients with coronavirus infection.

Methods: MEDLINE, EMBASE, and Web of Science were searched using broad based search criteria relating to coronavirus and bacterial co-infection. Articles presenting clinical data for patients with coronavirus infection (defined as SARS-1, MERS, SARS-COV-2, and other coronavirus) and bacterial/fungal co-infection reported in English, Mandarin, or Italian were included. Data describing bacterial/fungal co-infections, treatments, and outcomes were extracted. Secondary analysis of studies reporting antimicrobial prescribing in SARS-COV-2 even in the absence of co-infection was performed.

Results: 1007 abstracts were identified. Eighteen full texts reported bacterial/fungal co-infection were included. Most studies did not identify or report bacterial/fungal coinfection (85/140;61%). 9/18 (50%) studies reported on COVID-19, 5/18 (28%) SARS-1, 1/18 (6%) MERS, and 3/18 (17%) other coronavirus. For COVID-19, 62/806 (8%) patients were reported as experiencing bacterial/fungal co-infection during hospital admission. Secondary analysis demonstrated wide use of broad-spectrum antibacterials, despite a paucity of evidence for bacterial coinfection. On secondary analysis, 1450/2010 (72%) of patients reported received antimicrobial therapy. No antimicrobial stewardship interventions were described. For non-COVID-19 cases bacterial/fungal co-infection was reported in 89/815 (11%) of patients. Broad-spectrum antibiotic use was reported.

Conclusions: Despite frequent prescription of broad-spectrum empirical antimicrobials in patients with coronavirus associated respiratory infections, there is a paucity of data to support the association with respiratory bacterial/fungal co-infection. Generation of prospective evidence to support development of antimicrobial policy and appropriate stewardship interventions specific for the COVID-19 pandemic are urgently required.

Keywords: SARS-COV-2, antimicrobial stewardship, antimicrobial resistance

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29/02/2020 Articles
Similarity in Case Fatality Rates (CFR) of COVID-19/SARS-COV-2 in Italy and China

The Journal of Infection in Developing Countries

Authors:
Rossella Porcheddu, Caterina Serra, David Kelvin, Nikki Kelvin, Salvatore Rubino

As of 28 February 2020, Italy had 888 cases of SARS-CoV-2 infections, with most cases in Northern Italy in the Lombardia and Veneto regions. Travel-related cases were the main source of COVID-19 cases during the early stages of the current epidemic in Italy. The month of February, however, has been dominated by two large clusters of outbreaks in Northern Italy, south of Milan, with mainly local transmission the source of infections. Contact tracing has failed to identify patient zero in one of the outbreaks. As of 28 February 2020, twenty-one cases of COVID-19 have died. Comparison between case fatality rates in China and Italy are identical at 2.3. Additionally, deaths are similar in both countries with fatalities in mostly the elderly with known comorbidities. It will be important to develop point-of-care devices to aid clinicians in stratifying elderly patients as early as possible to determine the potential level of care they will require to improve their chances of survival from COVID-19 disease.

Novel coronavirus COVID-19, outbreak, Italy, Case Fatality Rates SARS-CoV-19

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Link
NEW: Coronavirus disease (COVID-19) Formerly known as 2019 novel coronavirus (2019-nCoV)

Eurosurveillance

 

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