Serologic responses to SARS-CoV-2 infection among hospital staff with mild disease in eastern France

Abstract

Background: The serologic response of individuals with mild forms of SARS-CoV-2 infection is poorly characterized.

Methods: Hospital staff who had recovered from mild forms of PCR-confirmed SARS-CoV-2 infection were tested for anti-SARS-CoV-2 antibodies using two assays: a rapid immunodiagnostic test (99.4% specificity) and the S-Flow assay (~99% specificity). The neutralizing activity of the sera was tested with a pseudovirus-based assay.

Findings: Of 162 hospital staff who participated in the investigation, 160 reported SARS-CoV-2 infection that had not required hospital admission and were included in these analyses. The median time from symptom onset to blood sample collection was 24 days (IQR: 21-28, range 13-39). The rapid immunodiagnostic test detected antibodies in 153 (95.6%) of the samples and the S-Flow assay in 159 (99.4%), failing to detect antibodies in one sample collected 18 days after symptom onset (the rapid test did not detect antibodies in that patient). Neutralizing antibodies (NAbs) were detected in 79%, 92% and 98% of samples collected 13-20, 21-27 and 28-41 days after symptom onset, respectively (P = 0.02).

Interpretation: Antibodies against SARS-CoV-2 were detected in virtually all hospital staff sampled from 13 days after the onset of COVID-19 symptoms. This finding supports the use of serologic testing for the diagnosis of individuals who have recovered from SARS-CoV-2 infection. The neutralizing activity of the antibodies increased overtime. Future studies will help assess the persistence of the humoral response and its associated neutralization capacity in recovered patients.

Fundings: The funders had no role in study design, data collection, interpretation, or the decision to submit the work for publication.

Keywords: Antibodies; Mild covid-19; Neutralization; Serology; sars-cov-2.

Conflict of interest statement

Declaration of Competing Interest SFK, YM, RG, LT, FA, PS, CSM, NC, AB, AV, NL, MM, NM, DR.., BH, JDS and AF have no competing interest to declare. PC is the founder and CSO of TheraVectys. LG, IS, TB, and OS are holder of a provisional patent on the S-Flow assay. Dr. Schwartz has a patent "Methods and products for serological analysis of SARS-COV-2 Infection" pending on the S-Flow assay. Dr. Rey reports grants and personal fees from Mylan, personal fees from ViiV Healthcare, grants from Gilead, grants from Abbvie, outside the submitted work.

Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

Figures

Fig. 1

Analysis of SARS-Cov-2 antibody response. (A) Sera from the 160 HCW were surveyed for anti-SARS-Cov-2 antibodies. S- Flow data are represented by the frequency of S+ cells (n = 160, left panel) and the median Fluorescence intensity (MFI) in positive samples (n = 159, middle panel). Historical pre-epidemic samples (pre) were included to determine backgrounds of S Flow (n = 140). Each dot represents a sample. Samples were grouped according to the number of days after symptom onset. Statistical analyses were performed using Kruskall-Wallis with Dunn's multiple comparisons test. * p < 0.005. n.a.: not applicable (B) Neutralizing activity of the 160 sera. The ability of each serum to neutralize lentiviral S- pseudotypes was assessed at a serum dilution of 1:100. Samples are grouped according to the number of days after symptom onset (left panel); * p < 0.005 using Kruskall-Wallis with Dunn's multiple comparisons test. For each time group, the frequencies of samples displaying a ID50 >100 (middle panel) or a ID80 >100 (right panel) were determined. Each dot represents a sample.; p-values obtained using the Chi-square test. (C) Relationship between serological measurement and neutralizing activity. The S-Flow MFI of samples displaying ID50 and ID80 above or below 100 are depicted. Each dot represents a sample. **** p < 0.0001 Unpaired t-test. The statistically significant differences are depicted.