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      Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19)

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      Author(s): 1 , , 1 , 1 , 2 , 1 , 1 , 1 , 3 , 3 , 3 , 4 , 5 , 6 , 5 , 6 , 7 , 6 , 8 , 9 , 9 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1
      Publication date (Electronic):
      Journal: Nature Communications
      Publisher: Nature Publishing Group UK
      Keywords: SARS-CoV-2, Viral infection, Translational research

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          Abstract

          Key questions in COVID-19 are the duration and determinants of infectious virus shedding. Here, we report that infectious virus shedding is detected by virus cultures in 23 of the 129 patients (17.8%) hospitalized with COVID-19. The median duration of shedding infectious virus is 8 days post onset of symptoms (IQR 5–11) and drops below 5% after 15.2 days post onset of symptoms (95% confidence interval (CI) 13.4–17.2). Multivariate analyses identify viral loads above 7 log 10 RNA copies/mL (odds ratio [OR] of 14.7 (CI 3.57-58.1; p < 0.001) as independently associated with isolation of infectious SARS-CoV-2 from the respiratory tract. A serum neutralizing antibody titre of at least 1:20 (OR of 0.01 (CI 0.003-0.08; p < 0.001) is independently associated with non-infectious SARS-CoV-2. We conclude that quantitative viral RNA load assays and serological assays could be used in test-based strategies to discontinue or de-escalate infection prevention and control precautions.

          Abstract

          Duration of infectious SARS-CoV-2 shedding is an important measure for improved disease control. Here, the authors use virus cultures of respiratory tract samples from COVID-19 patients and observe a median shedding duration of 8 days and a drop below 5% after 15,2 days post onset of symptoms.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Chaolin Huang, Yeming Wang, Xingwang Li … (2020)
          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            A Novel Coronavirus from Patients with Pneumonia in China, 2019

            Na Zhu, Dingyu Zhang, Wenling Wang … (2020)
            Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)
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              SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

              Markus Hoffmann, Hannah Kleine-Weber, Simon Schroeder … (2020)
              Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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                Author and article information

                Contributors
                Jeroen J. A. van Kampen: j.vankampen@erasmusmc.nl
                Journal
                Journal ID (nlm-ta): Nat Commun
                Journal ID (iso-abbrev): Nat Commun
                Title: Nature Communications
                Publisher: Nature Publishing Group UK (London )
                ISSN (Electronic): 2041-1723
                Publication date (Electronic): 11 January 2021
                Publication date PMC-release: 11 January 2021
                Publication date Collection: 2021
                Volume: 12
                Electronic Location Identifier: 267
                Affiliations
                [1 ]GRID grid.5645.2, ISNI 000000040459992X, Department of Viroscience, , Erasmus MC, ; Rotterdam, The Netherlands
                [2 ]GRID grid.416135.4, Department of Pediatrics, , Subdivision Infectious Diseases and Immunology, Erasmus MC - Sophia, ; Rotterdam, The Netherlands
                [3 ]GRID grid.5645.2, ISNI 000000040459992X, Department of Intensive Care, , Erasmus MC, ; Rotterdam, The Netherlands
                [4 ]GRID grid.5645.2, ISNI 000000040459992X, Department of Hematology, , Erasmus MC, ; Rotterdam, The Netherlands
                [5 ]GRID grid.5645.2, ISNI 000000040459992X, Department of Pulmonary Medicine, , Erasmus MC, ; Rotterdam, The Netherlands
                [6 ]GRID grid.5645.2, ISNI 000000040459992X, Erasmus MC Transplant Institute, ; Rotterdam, The Netherlands
                [7 ]GRID grid.5645.2, ISNI 000000040459992X, Department of Internal Medicine, Division of Nephrology and Transplantation, , Erasmus MC, ; Rotterdam, The Netherlands
                [8 ]GRID grid.5645.2, ISNI 000000040459992X, Department of Gastroenterology and Hepatology, , Erasmus MC, ; Rotterdam, The Netherlands
                [9 ]GRID grid.5645.2, ISNI 000000040459992X, Department of Medical Microbiology and Infectious Diseases, , Erasmus MC, ; Rotterdam, The Netherlands
                Author information
                http://orcid.org/0000-0001-6221-2015
                http://orcid.org/0000-0002-1431-4022
                http://orcid.org/0000-0002-2394-1079
                http://orcid.org/0000-0003-2165-3222
                http://orcid.org/0000-0002-5204-2312
                http://orcid.org/0000-0002-7678-314X
                Article
                Publisher ID: 20568
                DOI: 10.1038/s41467-020-20568-4
                PMC ID: 7801729
                PubMed ID: 33431879
                SO-VID: 13f448d1-15ec-4c50-ab41-f694d6eeeb54
                Copyright © © The Author(s) 2021
                License:

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 30 June 2020
                Date accepted : 1 December 2020
                Categories
                Subject: Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2021

                ScienceOpen disciplines: Uncategorized
                Keywords: sars-cov-2,viral infection,translational research
                Data availability:
                ScienceOpen disciplines: Uncategorized
                Keywords: sars-cov-2, viral infection, translational research

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