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      Upper respiratory viral load in asymptomatic individuals and mildly symptomatic patients with SARS-CoV-2 infection

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          Abstract

          Background

          Asymptomatic individuals with SARS-CoV-2 infection have viable viral loads and have been linked to several transmission cases. However, data on the viral loads in such individuals are lacking. We assessed the viral loads in asymptomatic individuals with SARS-CoV-2 infection in comparison with those in symptomatic patients with COVID-19.

          Methods

          Study participants were recruited from a community facility designated for the isolation of patients with mild COVID-19 in South Korea. The presence of symptoms was evaluated with a questionnaire-based survey. Viral loads in the upper respiratory tract were measured with real-time reverse transcription-PCR (RT-PCR) targeting the E, RdRp and N genes of SARS-CoV-2, with a cycle threshold (Ct) value of 40 for determining positivity.

          Results

          In 213 patients with SARS-CoV-2 infection, 41 (19%) had remained asymptomatic from potential exposure to laboratory confirmation and admission; of them, 39 (95%) underwent follow-up RT-PCR testing after a median 13 days. In 172 symptomatic patients, 144 (84%) underwent follow-up RT-PCR testing. Twenty-one (54%) asymptomatic individuals and 92 (64%) symptomatic patients tested positive for SARS-CoV-2 at follow-up. Asymptomatic individuals and symptomatic patients did not show any significant differences in the mean Ct values of the E (31.15 vs 31.43; p>0.99), RdRp (32.26 vs 32.93; p=0.92) and N (33.05 vs 33.28; p>0.99) genes.

          Conclusion

          Approximately one-fifth of the individuals without severe symptoms were asymptomatic, and their viral loads were comparable to those in symptomatic patients. A large proportion of mildly symptomatic patients with COVID-19 or asymptomatic individuals with SARS-CoV-2 showed persistent positive upper respiratory RT-PCR results at follow-up.

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          Most cited references 14

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          Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention

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            A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster

            Summary Background An ongoing outbreak of pneumonia associated with a novel coronavirus was reported in Wuhan city, Hubei province, China. Affected patients were geographically linked with a local wet market as a potential source. No data on person-to-person or nosocomial transmission have been published to date. Methods In this study, we report the epidemiological, clinical, laboratory, radiological, and microbiological findings of five patients in a family cluster who presented with unexplained pneumonia after returning to Shenzhen, Guangdong province, China, after a visit to Wuhan, and an additional family member who did not travel to Wuhan. Phylogenetic analysis of genetic sequences from these patients were done. Findings From Jan 10, 2020, we enrolled a family of six patients who travelled to Wuhan from Shenzhen between Dec 29, 2019 and Jan 4, 2020. Of six family members who travelled to Wuhan, five were identified as infected with the novel coronavirus. Additionally, one family member, who did not travel to Wuhan, became infected with the virus after several days of contact with four of the family members. None of the family members had contacts with Wuhan markets or animals, although two had visited a Wuhan hospital. Five family members (aged 36–66 years) presented with fever, upper or lower respiratory tract symptoms, or diarrhoea, or a combination of these 3–6 days after exposure. They presented to our hospital (The University of Hong Kong-Shenzhen Hospital, Shenzhen) 6–10 days after symptom onset. They and one asymptomatic child (aged 10 years) had radiological ground-glass lung opacities. Older patients (aged >60 years) had more systemic symptoms, extensive radiological ground-glass lung changes, lymphopenia, thrombocytopenia, and increased C-reactive protein and lactate dehydrogenase levels. The nasopharyngeal or throat swabs of these six patients were negative for known respiratory microbes by point-of-care multiplex RT-PCR, but five patients (four adults and the child) were RT-PCR positive for genes encoding the internal RNA-dependent RNA polymerase and surface Spike protein of this novel coronavirus, which were confirmed by Sanger sequencing. Phylogenetic analysis of these five patients' RT-PCR amplicons and two full genomes by next-generation sequencing showed that this is a novel coronavirus, which is closest to the bat severe acute respiatory syndrome (SARS)-related coronaviruses found in Chinese horseshoe bats. Interpretation Our findings are consistent with person-to-person transmission of this novel coronavirus in hospital and family settings, and the reports of infected travellers in other geographical regions. Funding The Shaw Foundation Hong Kong, Michael Seak-Kan Tong, Respiratory Viral Research Foundation Limited, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited, Marina Man-Wai Lee, the Hong Kong Hainan Commercial Association South China Microbiology Research Fund, Sanming Project of Medicine (Shenzhen), and High Level-Hospital Program (Guangdong Health Commission).
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              Virological assessment of hospitalized patients with COVID-2019

              Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 20191,2. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses3. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung2,4; the same receptor tropism is thought to have determined the pathogenicity-but also aided in the control-of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission6-8. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 108 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples-in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19.
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                Author and article information

                Journal
                Thorax
                Thorax
                thoraxjnl
                thorax
                Thorax
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                0040-6376
                1468-3296
                August 2020
                28 August 2020
                Affiliations
                [1 ] departmentDepartment of Infectious Diseases , Asan Medical Center , Songpa-gu, Seoul, Republic of Korea
                [2 ] departmentClinical Research Center, Asan Institute for Life Sciences , Asan Medical Center , Songpa-gu, Seoul, Republic of Korea
                [3 ] departmentHealth Screening & Promotion Center , Asan Medical Center , Songpa-gu, Seoul, Republic of Korea
                Author notes
                [Correspondence to ] Professor Sung-Han Kim, Department of Infectious Diseases, Asan Medical Center, Songpa-gu, Seoul, Korea (the Republic of); kimsunghanmd@ 123456hotmail.com
                Article
                thoraxjnl-2020-215042
                10.1136/thoraxjnl-2020-215042
                7462047
                © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

                This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

                Product
                Funding
                Funded by: Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea;
                Award ID: HI16C0272
                Categories
                Respiratory Infection
                2474
                2313
                Original research
                Custom metadata
                free

                Surgery

                viral infection

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