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      SARS-CoV-2 shedding and infectivity

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      a , b , c , d
      Lancet (London, England)
      Elsevier

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          Abstract

          Fei Zhou and colleagues 1 estimated mean duration of viral shedding by assessing the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA in patient samples. Assessing potential infectivity is a labour-intensive process, but the presence of nucleic acid alone cannot be used to define viral shedding or infection potential, as the authors state is possible within their methods. For many viral diseases (SARS-CoV, Middle East respiratory syndrome coronavirus, influenza virus, Ebola virus, and Zika virus) it is well known that viral RNA can be detected long after the disappearance of infectious virus.2, 3, 4, 5, 6, 7 With measles virus, viral RNA can still be detected 6–8 weeks after the clearance of infectious virus. 8 The immune system can neutralise viruses by lysing their envelope or aggregating virus particles; these processes prevent subsequent infection but do not eliminate nucleic acid, which degrades slowly over time. We were surprised to note the absence of viral load data in this study. 1 Although the use of sensitive PCR methods offers value from a diagnostic viewpoint, caution is required when applying such data to assess the duration of viral shedding and infection potential because PCR does not distinguish between infectious virus and non-infectious nucleic acid. The timely publication of insightful data is paramount in responding to outbreaks of novel pathogens. However, the findings in this study should not be used to conclude prolonged viral shedding or provide rationale to amend isolation policies, as concluded by the authors; infectivity data are required to demonstrate these specific aspects.

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          Most cited references8

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

          Summary 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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            Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study

            Summary Background We investigated the temporal progression of the clinical, radiological, and virological changes in a community outbreak of severe acute respiratory syndrome (SARS). Methods We followed up 75 patients for 3 weeks managed with a standard treatment protocol of ribavirin and corticosteroids, and assessed the pattern of clinical disease, viral load, risk factors for poor clinical outcome, and the usefulness of virological diagnostic methods. Findings Fever and pneumonia initially improved but 64 (85%) patients developed recurrent fever after a mean of 8.9 (SD 3.1) days, 55 (73%) had watery diarrhoea after 7.5 (2.3) days, 60 (80%) had radiological worsening after 7.4 (2.2) days, and respiratory symptoms worsened in 34 (45%) after 8.6 (3.0) days. In 34 (45%) patients, improvement of initial pulmonary lesions was associated with appearance of new radiological lesions at other sites. Nine (12%) patients developed spontaneous pneumomediastinum and 15 (20%) developed acute respiratory distress syndrome (ARDS) in week 3. Quantitative reverse-transcriptase (RT) PCR of nasopharyngeal aspirates in 14 patients (four with ARDS) showed peak viral load at day 10, and at day 15 a load lower than at admission. Age and chronic hepatitis B virus infection treated with lamivudine were independent significant risk factors for progression to ARDS (p=0.001). SARS-associated coronavirus in faeces was seen on RT-PCR in 65 (97%) of 67 patients at day 14. The mean time to seroconversion was 20 days. Interpretation The consistent clinical progression, shifting radiological infiltrates, and an inverted V viral-load profile suggest that worsening in week 2 is unrelated to uncontrolled viral replication but may be related to immunopathological damage. Published online May 9, 2003 http://image.thelancet.com/extras/03art4432web.pdf
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              Is Open Access

              Detection of SARS Coronavirus in Patients with Suspected SARS

              Cases of severe acute respiratory syndrome (SARS) were investigated for SARS coronavirus (SARS-CoV) through RNA tests, serologic response, and viral culture. Of 537 specimens from patients in whom SARS was clinically diagnosed, 332 (60%) had SARS-CoV RNA in one or more clinical specimens, compared with 1 (0.3%) of 332 samples from controls. Of 417 patients with clinical SARS from whom paired serum samples were available, 92% had an antibody response. Rates of viral RNA positivity increased progressively and peaked at day 11 after onset of illness. Although viral RNA remained detectable in respiratory secretions and stool and urine specimens for >30 days in some patients, virus could not be cultured after week 3 of illness. Nasopharyngeal aspirates, throat swabs, or sputum samples were the most useful clinical specimens in the first 5 days of illness, but later in the illness viral RNA could be detected more readily in stool specimens.
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                Author and article information

                Contributors
                Journal
                Lancet
                Lancet
                Lancet (London, England)
                Elsevier
                0140-6736
                1474-547X
                15 April 2020
                15 April 2020
                Affiliations
                [a ]National Collection of Pathogenic Viruses, Public Health England, Salisbury, UK
                [b ]Directorate General for Disease Surveillance and Control, Ministry of Health, Muscat, Oman
                [c ]European Society for Clinical Microbiology and Infectious Diseases Task Force for Emerging Infections, Basel, Switzerland
                [d ]Institute for Clinical Medicine, Faculty of Health Sciences, University of Aarhus, 8200 Aarhus, Denmark
                Article
                S0140-6736(20)30868-0
                10.1016/S0140-6736(20)30868-0
                7159877
                8109bfb0-a8fd-4738-9445-00ed4dd2d86a
                .

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