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.

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.