Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study

Coronavirus disease 2019 (COVID-19) causes severe community and nosocomial outbreaks. Comprehensive data for serial respiratory viral load and serum antibody responses from patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not yet available. Nasopharyngeal and t...

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Published in:The Lancet infectious diseases Vol. 20; no. 5; pp. 565 - 574
Main Authors: To, Kelvin Kai-Wang, Tsang, Owen Tak-Yin, Leung, Wai-Shing, Tam, Anthony Raymond, Wu, Tak-Chiu, Lung, David Christopher, Yip, Cyril Chik-Yan, Cai, Jian-Piao, Chan, Jacky Man-Chun, Chik, Thomas Shiu-Hong, Lau, Daphne Pui-Ling, Choi, Chris Yau-Chung, Chen, Lin-Lei, Chan, Wan-Mui, Chan, Kwok-Hung, Ip, Jonathan Daniel, Ng, Anthony Chin-Ki, Poon, Rosana Wing-Shan, Luo, Cui-Ting, Cheng, Vincent Chi-Chung, Chan, Jasper Fuk-Woo, Hung, Ivan Fan-Ngai, Chen, Zhiwei, Chen, Honglin, Yuen, Kwok-Yung
Format: Journal Article
Language:English
Published: United States Elsevier Ltd 01.05.2020
Elsevier Limited
Subjects:
Adult
Aged
Antibodies
Antibodies, Viral - blood
Antiretroviral drugs
Antiviral agents
Antiviral drugs
Betacoronavirus - genetics
Betacoronavirus - immunology
Betacoronavirus - isolation & purification
Clinical Laboratory Techniques
Cohort analysis
Consultancy services
Coronavirus Infections - diagnosis
Coronavirus Infections - immunology
Coronavirus Infections - virology
Coronaviruses
COVID-19
COVID-19 Testing
Female
Gene sequencing
Genomes
Health care
Hospitals
Humans
Immunoglobulin G
Immunoglobulin M
Infectious diseases
Male
Middle Aged
Middle East respiratory syndrome
Mutation
Nosocomial infection
Observational studies
Pandemics
Patients
Pneumonia, Viral - diagnosis
Pneumonia, Viral - immunology
Pneumonia, Viral - virology
Rectum
Respiratory diseases
Ribonucleic acid
RNA
RNA-directed DNA polymerase
Saliva
Saliva - virology
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Severity of Illness Index
Spike protein
Studies
Viral diseases
Viral Load
Viruses
Whole genome sequencing
Hong Kong China
China
ISSN:1473-3099, 1474-4457, 1474-4457
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Summary:Coronavirus disease 2019 (COVID-19) causes severe community and nosocomial outbreaks. Comprehensive data for serial respiratory viral load and serum antibody responses from patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not yet available. Nasopharyngeal and throat swabs are usually obtained for serial viral load monitoring of respiratory infections but gathering these specimens can cause discomfort for patients and put health-care workers at risk. We aimed to ascertain the serial respiratory viral load of SARS-CoV-2 in posterior oropharyngeal (deep throat) saliva samples from patients with COVID-19, and serum antibody responses. We did a cohort study at two hospitals in Hong Kong. We included patients with laboratory-confirmed COVID-19. We obtained samples of blood, urine, posterior oropharyngeal saliva, and rectal swabs. Serial viral load was ascertained by reverse transcriptase quantitative PCR (RT-qPCR). Antibody levels against the SARS-CoV-2 internal nucleoprotein (NP) and surface spike protein receptor binding domain (RBD) were measured using EIA. Whole-genome sequencing was done to identify possible mutations arising during infection. Between Jan 22, 2020, and Feb 12, 2020, 30 patients were screened for inclusion, of whom 23 were included (median age 62 years [range 37–75]). The median viral load in posterior oropharyngeal saliva or other respiratory specimens at presentation was 5·2 log10 copies per mL (IQR 4·1–7·0). Salivary viral load was highest during the first week after symptom onset and subsequently declined with time (slope −0·15, 95% CI −0·19 to −0·11; R2=0·71). In one patient, viral RNA was detected 25 days after symptom onset. Older age was correlated with higher viral load (Spearman's ρ=0·48, 95% CI 0·074–0·75; p=0·020). For 16 patients with serum samples available 14 days or longer after symptom onset, rates of seropositivity were 94% for anti-NP IgG (n=15), 88% for anti-NP IgM (n=14), 100% for anti-RBD IgG (n=16), and 94% for anti-RBD IgM (n=15). Anti-SARS-CoV-2-NP or anti-SARS-CoV-2-RBD IgG levels correlated with virus neutralisation titre (R2>0·9). No genome mutations were detected on serial samples. Posterior oropharyngeal saliva samples are a non-invasive specimen more acceptable to patients and health-care workers. Unlike severe acute respiratory syndrome, patients with COVID-19 had the highest viral load near presentation, which could account for the fast-spreading nature of this epidemic. This finding emphasises the importance of stringent infection control and early use of potent antiviral agents, alone or in combination, for high-risk individuals. Serological assay can complement RT-qPCR for diagnosis. Richard and Carol Yu, May Tam Mak Mei Yin, The Shaw Foundation Hong Kong, Michael Tong, Marina Lee, Government Consultancy Service, and Sanming Project of Medicine.
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Contributed equally
ISSN:1473-3099
1474-4457
1474-4457
DOI:10.1016/S1473-3099(20)30196-1