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

Identifieur interne : 000182 ( 2020/Analysis ); précédent : 000181; suivant : 000183

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

Auteurs : Kelvin Kai-Wang To [République populaire de Chine] ; Owen Tak-Yin Tsang [République populaire de Chine] ; Wai-Shing Leung [République populaire de Chine] ; Anthony Raymond Tam [République populaire de Chine] ; Tak-Chiu Wu [République populaire de Chine] ; David Christopher Lung [République populaire de Chine] ; Cyril Chik-Yan Yip [République populaire de Chine] ; Jian-Piao Cai [République populaire de Chine] ; Jacky Man-Chun Chan [République populaire de Chine] ; Thomas Shiu-Hong Chik [République populaire de Chine] ; Daphne Pui-Ling Lau [République populaire de Chine] ; Chris Yau-Chung Choi [République populaire de Chine] ; Lin-Lei Chen [République populaire de Chine] ; Wan-Mui Chan [République populaire de Chine] ; Kwok-Hung Chan [République populaire de Chine] ; Jonathan Daniel Ip [République populaire de Chine] ; Anthony Chin-Ki Ng [République populaire de Chine] ; Rosana Wing-Shan Poon [République populaire de Chine] ; Cui-Ting Luo [République populaire de Chine] ; Vincent Chi-Chung Cheng [République populaire de Chine] ; Jasper Fuk-Woo Chan [République populaire de Chine] ; Ivan Fan-Ngai Hung [République populaire de Chine] ; Zhiwei Chen [République populaire de Chine] ; Honglin Chen [République populaire de Chine] ; Kwok-Yung Yuen [République populaire de Chine]

Source :

RBID : PMC:7158907

Abstract

SummaryBackground

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.

Methods

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.

Findings

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.

Interpretation

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.

Funding

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.


Url:
DOI: 10.1016/S1473-3099(20)30196-1
PubMed: 32213337
PubMed Central: 7158907


Affiliations:


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PMC:7158907

Le document en format XML

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<name sortKey="Chan, Jasper Fuk Woo" sort="Chan, Jasper Fuk Woo" uniqKey="Chan J" first="Jasper Fuk-Woo" last="Chan">Jasper Fuk-Woo Chan</name>
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<name sortKey="Chen, Zhiwei" sort="Chen, Zhiwei" uniqKey="Chen Z" first="Zhiwei" last="Chen">Zhiwei Chen</name>
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<name sortKey="Chen, Honglin" sort="Chen, Honglin" uniqKey="Chen H" first="Honglin" last="Chen">Honglin Chen</name>
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<name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
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<title xml:lang="en" level="a" type="main">Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study</title>
<author>
<name sortKey="To, Kelvin Kai Wang" sort="To, Kelvin Kai Wang" uniqKey="To K" first="Kelvin Kai-Wang" last="To">Kelvin Kai-Wang To</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea>
<wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="aff2">Department of Clinical Microbiology and Infection Control, The University of Hong Kong–Shenzhen Hospital, Shenzhen, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Clinical Microbiology and Infection Control, The University of Hong Kong–Shenzhen Hospital, Shenzhen</wicri:regionArea>
<placeName>
<settlement type="city">Shenzhen</settlement>
<region type="province">Guangdong</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Tsang, Owen Tak Yin" sort="Tsang, Owen Tak Yin" uniqKey="Tsang O" first="Owen Tak-Yin" last="Tsang">Owen Tak-Yin Tsang</name>
<affiliation wicri:level="1">
<nlm:aff id="aff3">Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong Special Administrative Region, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong Special Administrative Region</wicri:regionArea>
<wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Leung, Wai Shing" sort="Leung, Wai Shing" uniqKey="Leung W" first="Wai-Shing" last="Leung">Wai-Shing Leung</name>
<affiliation wicri:level="1">
<nlm:aff id="aff3">Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong Special Administrative Region, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong Special Administrative Region</wicri:regionArea>
<wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Tam, Anthony Raymond" sort="Tam, Anthony Raymond" uniqKey="Tam A" first="Anthony Raymond" last="Tam">Anthony Raymond Tam</name>
<affiliation wicri:level="1">
<nlm:aff id="aff4">Department of Medicine, Queen Mary Hospital, Hong Kong Special Administrative Region, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medicine, Queen Mary Hospital, Hong Kong Special Administrative Region</wicri:regionArea>
<wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Wu, Tak Chiu" sort="Wu, Tak Chiu" uniqKey="Wu T" first="Tak-Chiu" last="Wu">Tak-Chiu Wu</name>
<affiliation wicri:level="1">
<nlm:aff id="aff5">Department of Medicine, Queen Elizabeth Hospital, Hong Kong Special Administrative Region, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medicine, Queen Elizabeth Hospital, Hong Kong Special Administrative Region</wicri:regionArea>
<wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Lung, David Christopher" sort="Lung, David Christopher" uniqKey="Lung D" first="David Christopher" last="Lung">David Christopher Lung</name>
<affiliation wicri:level="1">
<nlm:aff id="aff6">Department of Pathology, Queen Elizabeth Hospital, Hong Kong Special Administrative Region, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Pathology, Queen Elizabeth Hospital, Hong Kong Special Administrative Region</wicri:regionArea>
<wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Yip, Cyril Chik Yan" sort="Yip, Cyril Chik Yan" uniqKey="Yip C" first="Cyril Chik-Yan" last="Yip">Cyril Chik-Yan Yip</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea>
<wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Cai, Jian Piao" sort="Cai, Jian Piao" uniqKey="Cai J" first="Jian-Piao" last="Cai">Jian-Piao Cai</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea>
<wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Chan, Jacky Man Chun" sort="Chan, Jacky Man Chun" uniqKey="Chan J" first="Jacky Man-Chun" last="Chan">Jacky Man-Chun Chan</name>
<affiliation wicri:level="1">
<nlm:aff id="aff3">Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong Special Administrative Region, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong Special Administrative Region</wicri:regionArea>
<wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Chik, Thomas Shiu Hong" sort="Chik, Thomas Shiu Hong" uniqKey="Chik T" first="Thomas Shiu-Hong" last="Chik">Thomas Shiu-Hong Chik</name>
<affiliation wicri:level="1">
<nlm:aff id="aff3">Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong Special Administrative Region, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong Special Administrative Region</wicri:regionArea>
<wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Lau, Daphne Pui Ling" sort="Lau, Daphne Pui Ling" uniqKey="Lau D" first="Daphne Pui-Ling" last="Lau">Daphne Pui-Ling Lau</name>
<affiliation wicri:level="1">
<nlm:aff id="aff3">Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong Special Administrative Region, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong Special Administrative Region</wicri:regionArea>
<wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Choi, Chris Yau Chung" sort="Choi, Chris Yau Chung" uniqKey="Choi C" first="Chris Yau-Chung" last="Choi">Chris Yau-Chung Choi</name>
<affiliation wicri:level="1">
<nlm:aff id="aff3">Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong Special Administrative Region, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong Special Administrative Region</wicri:regionArea>
<wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Chen, Lin Lei" sort="Chen, Lin Lei" uniqKey="Chen L" first="Lin-Lei" last="Chen">Lin-Lei Chen</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea>
<wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Chan, Wan Mui" sort="Chan, Wan Mui" uniqKey="Chan W" first="Wan-Mui" last="Chan">Wan-Mui Chan</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea>
<wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Chan, Kwok Hung" sort="Chan, Kwok Hung" uniqKey="Chan K" first="Kwok-Hung" last="Chan">Kwok-Hung Chan</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea>
<wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Ip, Jonathan Daniel" sort="Ip, Jonathan Daniel" uniqKey="Ip J" first="Jonathan Daniel" last="Ip">Jonathan Daniel Ip</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea>
<wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Ng, Anthony Chin Ki" sort="Ng, Anthony Chin Ki" uniqKey="Ng A" first="Anthony Chin-Ki" last="Ng">Anthony Chin-Ki Ng</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea>
<wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Poon, Rosana Wing Shan" sort="Poon, Rosana Wing Shan" uniqKey="Poon R" first="Rosana Wing-Shan" last="Poon">Rosana Wing-Shan Poon</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea>
<wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Luo, Cui Ting" sort="Luo, Cui Ting" uniqKey="Luo C" first="Cui-Ting" last="Luo">Cui-Ting Luo</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea>
<wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Cheng, Vincent Chi Chung" sort="Cheng, Vincent Chi Chung" uniqKey="Cheng V" first="Vincent Chi-Chung" last="Cheng">Vincent Chi-Chung Cheng</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea>
<wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Chan, Jasper Fuk Woo" sort="Chan, Jasper Fuk Woo" uniqKey="Chan J" first="Jasper Fuk-Woo" last="Chan">Jasper Fuk-Woo Chan</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea>
<wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="aff2">Department of Clinical Microbiology and Infection Control, The University of Hong Kong–Shenzhen Hospital, Shenzhen, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Clinical Microbiology and Infection Control, The University of Hong Kong–Shenzhen Hospital, Shenzhen</wicri:regionArea>
<placeName>
<settlement type="city">Shenzhen</settlement>
<region type="province">Guangdong</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Hung, Ivan Fan Ngai" sort="Hung, Ivan Fan Ngai" uniqKey="Hung I" first="Ivan Fan-Ngai" last="Hung">Ivan Fan-Ngai Hung</name>
<affiliation wicri:level="1">
<nlm:aff id="aff7">Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea>
<wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Chen, Zhiwei" sort="Chen, Zhiwei" uniqKey="Chen Z" first="Zhiwei" last="Chen">Zhiwei Chen</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea>
<wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Chen, Honglin" sort="Chen, Honglin" uniqKey="Chen H" first="Honglin" last="Chen">Honglin Chen</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region</wicri:regionArea>
<wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
<affiliation wicri:level="3">
<nlm:aff id="aff2">Department of Clinical Microbiology and Infection Control, The University of Hong Kong–Shenzhen Hospital, Shenzhen, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Clinical Microbiology and Infection Control, The University of Hong Kong–Shenzhen Hospital, Shenzhen</wicri:regionArea>
<placeName>
<settlement type="city">Shenzhen</settlement>
<region type="province">Guangdong</region>
</placeName>
</affiliation>
</author>
</analytic>
<series>
<title level="j">The Lancet. Infectious Diseases</title>
<idno type="ISSN">1473-3099</idno>
<idno type="eISSN">1474-4457</idno>
<imprint>
<date when="2020">2020</date>
</imprint>
</series>
</biblStruct>
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<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<title>Summary</title>
<sec>
<title>Background</title>
<p>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.</p>
</sec>
<sec>
<title>Methods</title>
<p>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.</p>
</sec>
<sec>
<title>Findings</title>
<p>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 log
<sub>10</sub>
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;
<italic>R</italic>
<sup>2</sup>
=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 (
<italic>R</italic>
<sup>2</sup>
>0·9). No genome mutations were detected on serial samples.</p>
</sec>
<sec>
<title>Interpretation</title>
<p>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.</p>
</sec>
<sec>
<title>Funding</title>
<p>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.</p>
</sec>
</div>
</front>
<back>
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<li>République populaire de Chine</li>
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<li>Guangdong</li>
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<name sortKey="Chen, Lin Lei" sort="Chen, Lin Lei" uniqKey="Chen L" first="Lin-Lei" last="Chen">Lin-Lei Chen</name>
<name sortKey="Chen, Zhiwei" sort="Chen, Zhiwei" uniqKey="Chen Z" first="Zhiwei" last="Chen">Zhiwei Chen</name>
<name sortKey="Cheng, Vincent Chi Chung" sort="Cheng, Vincent Chi Chung" uniqKey="Cheng V" first="Vincent Chi-Chung" last="Cheng">Vincent Chi-Chung Cheng</name>
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<name sortKey="Choi, Chris Yau Chung" sort="Choi, Chris Yau Chung" uniqKey="Choi C" first="Chris Yau-Chung" last="Choi">Chris Yau-Chung Choi</name>
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<name sortKey="Ip, Jonathan Daniel" sort="Ip, Jonathan Daniel" uniqKey="Ip J" first="Jonathan Daniel" last="Ip">Jonathan Daniel Ip</name>
<name sortKey="Lau, Daphne Pui Ling" sort="Lau, Daphne Pui Ling" uniqKey="Lau D" first="Daphne Pui-Ling" last="Lau">Daphne Pui-Ling Lau</name>
<name sortKey="Leung, Wai Shing" sort="Leung, Wai Shing" uniqKey="Leung W" first="Wai-Shing" last="Leung">Wai-Shing Leung</name>
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<name sortKey="Luo, Cui Ting" sort="Luo, Cui Ting" uniqKey="Luo C" first="Cui-Ting" last="Luo">Cui-Ting Luo</name>
<name sortKey="Ng, Anthony Chin Ki" sort="Ng, Anthony Chin Ki" uniqKey="Ng A" first="Anthony Chin-Ki" last="Ng">Anthony Chin-Ki Ng</name>
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<name sortKey="Tam, Anthony Raymond" sort="Tam, Anthony Raymond" uniqKey="Tam A" first="Anthony Raymond" last="Tam">Anthony Raymond Tam</name>
<name sortKey="To, Kelvin Kai Wang" sort="To, Kelvin Kai Wang" uniqKey="To K" first="Kelvin Kai-Wang" last="To">Kelvin Kai-Wang To</name>
<name sortKey="Tsang, Owen Tak Yin" sort="Tsang, Owen Tak Yin" uniqKey="Tsang O" first="Owen Tak-Yin" last="Tsang">Owen Tak-Yin Tsang</name>
<name sortKey="Wu, Tak Chiu" sort="Wu, Tak Chiu" uniqKey="Wu T" first="Tak-Chiu" last="Wu">Tak-Chiu Wu</name>
<name sortKey="Yip, Cyril Chik Yan" sort="Yip, Cyril Chik Yan" uniqKey="Yip C" first="Cyril Chik-Yan" last="Yip">Cyril Chik-Yan Yip</name>
<name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
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