Neutralizing Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 in Coronavirus Disease 2019 Inpatients and Convalescent Patients

This article has been Reviewed by the following groups

Read the full article See related articles

Abstract

Background

Coronavirus disease 2019 (COVID-19) is a pandemic with no specific antiviral treatments or vaccines. There is an urgent need for exploring the neutralizing antibodies from patients with different clinical characteristics.

Methods

A total of 117 blood samples were collected from 70 COVID-19 inpatients and convalescent patients. Antibodies were determined with a modified cytopathogenic neutralization assay (NA) based on live severe acute respiratory syndrome coronavirus 2 and enzyme-linked immunosorbent assay (ELISA). The dynamics of neutralizing antibody levels at different time points with different clinical characteristics were analyzed.

Results

The seropositivity rate reached up to 100.0% within 20 days since onset, and remained 100.0% till days 41–53. The total geometric mean titer was 1:163.7 (95% confidence interval [CI], 128.5–208.6) by NA and 1:12 441.7 (95% CI, 9754.5–15 869.2) by ELISA. The antibody level by NA and ELISA peaked on days 31–40 since onset, and then decreased slightly. In multivariate generalized estimating equation analysis, patients aged 31–45, 46–60, and 61–84 years had a higher neutralizing antibody level than those aged 16–30 years (β = 1.0470, P = .0125; β = 1.0613, P = .0307; β = 1.3713, P = .0020). Patients with a worse clinical classification had a higher neutralizing antibody titer (β = 0.4639, P = .0227).

Conclusions

The neutralizing antibodies were detected even at the early stage of disease, and a significant response was shown in convalescent patients.

Article activity feed

  1. SciScore for 10.1101/2020.04.15.20065623: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The protocol of the study was reviewed and approved by the Medical Ethical Committee of Beijing Youan Hospital, Capital Medical University (approval number LL-2020-041-K).
    Consent: Before enrollment, written informed consent was obtained from each enrolled patient.
    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
    The diluted serums were mixed with a virus suspension of 100 CCID50 in 96-well plates at a ratio of 1:1, followed by 2 hours incubation at 36.5°C in a 5% CO2 incubator. 1-2 X104 Vero cells were then added to the serum-virus mixture, and the plates were incubated for 5 days at 36.5°C in a 5% CO2 incubator.
    Vero
    suggested: None
    Software and Algorithms
    SentencesResources
    Analyses were conducted by SAS 9.4 (SAS Institute, Cary, NC, USA).
    SAS Institute
    suggested: (Statistical Analysis System, RRID:SCR_008567)

    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: We detected the following sentences addressing limitations in the study:
    Several limitations of this study should be noted. First, the involved patients were selected by convenient sampling instead of random sampling. So the representativeness is relatively insufficient, and the samples could only represent the general situation to a certain extent. Second, among 70 patients, only 12 of them were followed up more than twice, and the average follow-up period was relatively short, about only 14.3 days (range 3.0-36.0). Therefore, it is of value to follow up patients for a longer time. Third, the subjects were mainly mild or moderate by illness severity, and only 1 asymptomatic patient and 4 severe patients, whether a different antibody levels would have been observed with different severity patients cannot be determined. Hence, it’s important to evaluate antibody levels in asymptomatic infected and critical patients in future study. In conclusion, this study showed that all COVID-19 patients were seropositivity to SARS-CoV-2 even at the early stage of illness, and a significant neutralizing antibody response was observed in convalescent patients. Neutralizing antibody levels increased with days since onset of symptoms, elder age and the worsening of clinical classification. Changes on antibody levels ware individual specific.

    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.