Shedding of infectious SARS-CoV-2 by hospitalized COVID-19 patients in relation to serum antibody responses

  1. Hedvig Glans
  2. Sara Gredmark-Russ
  3. Mikaela Olausson
  4. Sara Falck-Jones
  5. Renata Varnaite
  6. Wanda Christ
  7. Kimia T. Maleki
  8. Maria Lind Karlberg
  9. Sandra Broddesson
  10. Ryan Falck-Jones
  11. Max Bell
  12. Niclas Johansson
  13. Anna Färnert
  14. Anna Smed-Sörensen
  15. Jonas Klingström
  16. Andreas Bråve

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Abstract

Background

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic. The understanding of the transmission and the duration of viral shedding in SARS-CoV-2 infection is still limited.

Objectives

To assess the timeframe and potential risk of SARS-CoV-2 transmission from hospitalized COVID-19 patients in relation to antibody response.

Method

We performed a cross-sectional study of 36 COVID-19 patients hospitalized at Karolinska University Hospital. Patients with more than 8 days of symptom duration were sampled from airways, for PCR analysis of SARS-CoV-2 RNA and in vitro culture of replicating virus. Serum SARS-CoV-2-specific immunoglobulin G (IgG) and neutralizing antibodies titers were assessed by immunofluorescence assay (IFA) and microneutralization assay.

Results

SARS-CoV-2 RNA was detected in airway samples in 23 patients (symptom duration median 15 days, range 9–53 days), whereas 13 patients were SARS-CoV-2 RNA negative (symptom duration median 21 days, range 10–37 days). Replicating virus was detected in samples from 4 patients at 9–16 days. All but two patients had detectable levels of SARS-CoV-2-specific IgG in serum, and SARS-CoV-2 neutralizing antibodies were detected in 33 out of 36 patients. Total SARS-CoV-2-specific IgG titers and neutralizing antibody titers were positively correlated. High levels of both total IgG and neutralizing antibody titers were observed in patients sampled later after symptom onset and in patients where replicating virus could not be detected.

Conclusions

Our data suggest that the presence of SARS-Cov-2 specific antibodies in serum may indicate a lower risk of shedding infectious SARS-CoV-2 by hospitalized COVID-19 patients.

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  1. Version published to 10.1186/s12879-021-06202-8
  2. ScreenIT

    SciScore for 10.1101/2020.09.11.20191940: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementConsent: Patients included in the study provided written informed consent.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    For the virus cultures, 100 µL sample from nasopharyngeal swabs (NPS) and 100 µL tracheal secretion or sputum collected from a total of 37 patients, the positive control patient included, were inoculated in duplicate on Vero-E6 cells.
    Vero-E6
    suggested: None
    Briefly, SARS-CoV-2-infected Vero cells mixed with uninfected Vero cells were used as target cells.
    Vero
    suggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)
    After incubation, 100 µL of the mixtures were added to Vero E6 cells seeded on 96-well plates and incubated at 37 °C 5% CO2.
    Vero E6
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2020.09.11.20191940 on medRxiv