Detection, prevalence, and duration of humoral responses to SARS-CoV-2 under conditions of limited population exposure

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Abstract

We conducted an extensive serological study to quantify population-level exposure and define correlates of immunity against SARS-CoV-2. We found that relative to mild COVID-19 cases, individuals with severe disease exhibited elevated authentic virus-neutralizing titers and antibody levels against nucleocapsid (N) and the receptor binding domain (RBD) and the S2 region of spike protein. Unlike disease severity, age and sex played lesser roles in serological responses. All cases, including asymptomatic individuals, seroconverted by 2 weeks post-PCR confirmation. RBD- and S2-specific and neutralizing antibody titers remained elevated and stable for at least 2–3 months post-onset, whereas those against N were more variable with rapid declines in many samples. Testing of 5882 self-recruited members of the local community demonstrated that 1.24% of individuals showed antibody reactivity to RBD. However, 18% (13/73) of these putative seropositive samples failed to neutralize authentic SARS-CoV-2 virus. Each of the neutralizing, but only 1 of the non-neutralizing samples, also displayed potent reactivity to S2. Thus, inclusion of multiple independent assays markedly improved the accuracy of antibody tests in low seroprevalence communities and revealed differences in antibody kinetics depending on the viral antigen. In contrast to other reports, we conclude that immunity is durable for at least several months after SARS-CoV-2 infection.

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Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

Daniel Wrapp, Nianshuang Wang, Kizzmekia S. Corbett … (2020)

Structure of the nCoV trimeric spike The World Health Organization has declared the outbreak of a novel coronavirus (2019-nCoV) to be a public health emergency of international concern. The virus binds to host cells through its trimeric spike glycoprotein, making this protein a key target for potential therapies and diagnostics. Wrapp et al. determined a 3.5-angstrom-resolution structure of the 2019-nCoV trimeric spike protein by cryo–electron microscopy. Using biophysical assays, the authors show that this protein binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor. They also tested three antibodies known to bind to the SARS-CoV spike protein but did not detect binding to the 2019-nCoV spike protein. These studies provide valuable information to guide the development of medical counter-measures for 2019-nCoV. Science, this issue p. 1260

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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

Kelvin Kai-Wang To, Owen Tsang, Wai-Shing Leung … (2020)

Summary Background 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; R 2=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 (R 2>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.

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Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections

Quan-Xin Long, Xiao-Jun Tang, Qiu-Lin Shi … (2020)

The clinical features and immune responses of asymptomatic individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been well described. We studied 37 asymptomatic individuals in the Wanzhou District who were diagnosed with RT-PCR-confirmed SARS-CoV-2 infections but without any relevant clinical symptoms in the preceding 14 d and during hospitalization. Asymptomatic individuals were admitted to the government-designated Wanzhou People's Hospital for centralized isolation in accordance with policy1. The median duration of viral shedding in the asymptomatic group was 19 d (interquartile range (IQR), 15-26 d). The asymptomatic group had a significantly longer duration of viral shedding than the symptomatic group (log-rank P = 0.028). The virus-specific IgG levels in the asymptomatic group (median S/CO, 3.4; IQR, 1.6-10.7) were significantly lower (P = 0.005) relative to the symptomatic group (median S/CO, 20.5; IQR, 5.8-38.2) in the acute phase. Of asymptomatic individuals, 93.3% (28/30) and 81.1% (30/37) had reduction in IgG and neutralizing antibody levels, respectively, during the early convalescent phase, as compared to 96.8% (30/31) and 62.2% (23/37) of symptomatic patients. Forty percent of asymptomatic individuals became seronegative and 12.9% of the symptomatic group became negative for IgG in the early convalescent phase. In addition, asymptomatic individuals exhibited lower levels of 18 pro- and anti-inflammatory cytokines. These data suggest that asymptomatic individuals had a weaker immune response to SARS-CoV-2 infection. The reduction in IgG and neutralizing antibody levels in the early convalescent phase might have implications for immunity strategy and serological surveys.

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Author and article information

Journal

Journal ID (nlm-ta): medRxiv

Journal ID (publisher-id): MEDRXIV

Title: medRxiv

Publisher: Cold Spring Harbor Laboratory

Publication date (Electronic): 15 August 2020

Electronic Location Identifier: 2020.08.14.20174490

Affiliations

[1- ]Department of Immunobiology, University of Arizona College of Medicine – Tucson, Tucson, AZ, USA;

[2- ]University of Arizona Center on Aging, University of Arizona College of Medicine – Tucson, Tucson, AZ, USA;

[3 – ]Division of Biological and Biomedical Sciences, Washington University, St. Louis, MO, USA;

[4 – ]Department of Surgery, University of Arizona College of Medicine – Tucson, Tucson, AZ, USA;

[5 – ]Department of Cellular and Molecular Medicine, University of Arizona College of Medicine – Tucson, Tucson, AZ, USA;

[6 - ]Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Arizona College of Medicine – Tucson, Tucson, AZ, USA;

[7- ]Department of Medicine, University of Arizona-Phoenix, Phoenix, AZ;

[8- ]Department of Molecular and Cellular Biology, University of Arizona – Tucson, Tucson, AZ, USA;

[9- ]Functional Genomics Core, University of Arizona, Tucson, AZ;

[10- ]Department of Pathology, University of Arizona College of Medicine – Tucson, Tucson, AZ, USA;

[11 – ]Office of the Senior Vice-President for Health Sciences, University of Arizona, Tucson, USA;

[12- ]University of Arizona Genomics Core, University of Arizona, Tucson, AZ and the Arizona Research Labs, University of Arizona Genetics Core, University of Arizona, Tucson, AZ, USA;

[13- ]Division of Geriatrics, General Medicine and Palliative Care, Department of Medicine, University of Arizona College of Medicine-Tucson, Tucson, USA;

[14 – ]Department of Emergency Medicine, University of Arizona College of Medicine-Tucson, Tucson, USA;

[15- ]University of Arizona Health Sciences Biobank, University of Arizona, Tucson, USA;

[16- ]BIO5 Institute, University of Arizona, Tucson, USA.

Author notes

[*]

These authors contributed equally and are listed in alphabetical order;

[# -]

these authors contributed equally.

AUTHOR CONTRIBUTIONS:

T.J.R., J.L.U., M.W., R.W., R.S., J.N.Z., and D.B. designed the study. T.J.R., J.L.U., M.W., R.W., H.P., C.B., M.K., and R.S. performed experiments. T.J.R., J.L.U., M.W., R.W., A.C., C.S., M.K., T.E., R.S., J.N.Z., and D.B. analyzed the data. T.J.R., J.N.Z., and D.B. wrote the paper. All other authors participated in collection of samples and patient care for the study.

Address correspondence to Janko Nikolich-Žugich, at nikolich@ 123456arizona.edu ; or Deepta Bhattacharya, at deeptab@ 123456arizona.edu , or by mail at P.O. Box 249221, Department of Immunobiology, University of Arizona College of Medicine-Tucson, 1501 N. Campbell Ave., Tucson, AZ 85724

Article

DOI: 10.1101/2020.08.14.20174490

PMC ID: 7430613

PubMed ID: 32817969

SO-VID: 002925b1-5ba5-4f8e-bc03-f460453e68f8

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It is made available under a CC-BY-NC-ND 4.0 International license.

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Detection, prevalence, and duration of humoral responses to SARS-CoV-2 under conditions of limited population exposure

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Novel Coronavirus Disease COVID-19

Most cited references 56

Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

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

Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections

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