Journal Article

Virological assessment of hospitalized patients with COVID-2019

Rothe, Camilla, Drosten, Christian, Corman, Victor M., Seilmaier, Michael, Niemeyer, Daniela, Bleicker, Tobias, Müller, Marcel A., Zwirglmaier, Katrin, Jones, Terry C., Ehmann, Rosina, Guggemos, Wolfgang, Hoelscher, Michael, Schneider, Julia, Zange, Sabine, Wendtner, Clemens, Wölfel, Roman, Brünink, Sebastian, Vollmar, Patrick

2020

Overview

Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 2019 1 , 2 . Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses 3 . This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung 2 , 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 2003 5 . 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 transmission 6 – 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 × 10 8  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. Detailed virological analysis of nine cases of coronavirus disease 2019 (COVID-19) provides proof of active replication of the SARS-CoV-2 virus in tissues of the upper respiratory tract.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/1 / 631/326/596/4130 / 692/308/174 / 692/699/255/2514 / Analysis / Antibodies, Viral - analysis / Antibodies, Viral - immunology / Base Sequence / Betacoronavirus - genetics / Betacoronavirus - immunology / Betacoronavirus - isolation & purification / Betacoronavirus - pathogenicity / Blood - virology / Clinical Laboratory Techniques / Containment / Coronavirus Envelope Proteins / Coronavirus Infections - diagnosis / Coronavirus Infections - immunology / Coronavirus Infections - virology / Coronaviruses / COVID-19 / COVID-19 Testing / Diagnostic tests / Disease transmission / Feces - chemistry / Feces - virology / Hospital patients / Hospitalization / Humanities and Social Sciences / Humans / Immunoglobulin G - analysis / Immunoglobulin G - immunology / Immunoglobulin M - analysis / Immunoglobulin M - immunology / Infections / Infectivity / Influenza / Intermediates / Laboratories / Lung - virology / Lungs / Medical examination / Medical virology / multidisciplinary / Nucleotide sequence / Pandemics / Pathogenicity / Pathogens / Patients / Pharynx / Pharynx - virology / Pneumonia, Viral - diagnosis / Pneumonia, Viral - immunology / Pneumonia, Viral - virology / Polymorphism, Single Nucleotide - genetics / Receptors / Replication / Respiratory diseases / Respiratory tract / Respiratory tract diseases / Ribonucleic acid / RNA / RNA viruses / RNA, Viral - analysis / SARS-CoV-2 / Science / Science (multidisciplinary) / Seroconversion / Severe acute respiratory syndrome / Severe acute respiratory syndrome coronavirus 2 / Signs and symptoms / Sputum / Sputum - virology / Throats / Tropism / Urine - virology / Viral diseases / Viral Envelope Proteins - genetics / Viral infections / Viral Load - immunology / Virus Replication / Virus Shedding / Viruses