Fei Zhou1, Guohui Fan2, Zhibo Liu1, Bin Cao3. 1. Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100029, China. 2. Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100029, China; Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China. 3. Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100029, China; Department of Respiratory Medicine, Capital Medical University, Beijing, China; Tsinghua University School of Medicine, Beijing, China. Electronic address: caobin_ben@163.com.
We thank Barry Atkinson and Eskild Petersen for their comments on our Article describing the clinical course and risk factors for mortality of adult inpatients with coronavirus disease 2019 (COVID-19) in Wuhan, China. We agree that the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA in a respiratory specimen cannot be directly interpreted as a potential for disease transmission and infection.Although viral culture is an important method to evaluate viral infectivity and activity, it is unavailable in clinical practice because of its low sensitivity and long turn-around time for virus detection. Two negative SARS-CoV-2 RNA PCR tests, at least 24 h apart, was recommended by WHO as one of several criteria for discharge. Prolonged periods of detectable SARS-CoV-2 RNA suggest a sustained viral replication in some kinds of host cells in patients with COVID-19. A comparison has previously been made between viral shedding, as quantified by real time PCR (RT-PCR), and median tissue culture infectious dose (TCID50) in patients with influenza. The temporal changes in viral load by RT-PCR were similar to that of TCID50. For COVID-19, the association between viral load in respiratory tract specimens, quantified by RT-PCR, and viral culture needs evaluation.Viral activity is only one of various factors that might influence disease transmission. Epidemiology is the gold standard to measure transmission potential of patients who recover from COVID-19 yet are still positive for SARS-CoV-2 RNA. Further effort is urgently needed to evaluate the basic reproductive number in these patients.
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