Prevalence and incidence of anti-SARS-CoV-2 antibodies among healthcare workers in Belgian hospitals before vaccination: a prospective cohort study

Abstract

Objectives: To describe prevalence and incidence of anti-SARS-CoV-2 antibodies among Belgian hospital healthcare workers (HCW) in April-December 2020.

Design: Prospective cohort study. Follow-up was originally planned until September and later extended.

Setting: Multicentre study, 17 hospitals.

Participants: 50 HCW were randomly selected per hospital. HCW employed beyond the end of the study and whose profession involved contact with patients were eligible. 850 HCW entered the study in April-May 2020, 673 HCW (79%) attended the September visit and 308 (36%) the December visit.

Outcome measures: A semiquantitative ELISA was used to detect IgG against SARS-CoV-2 in serum (Euroimmun) at 10 time points. In seropositive samples, neutralising antibodies were measured using a virus neutralisation test. Real-time reverse transcription PCR (RT-qPCR) was performed to detect SARS-CoV-2 on nasopharyngeal swabs. Participant characteristics and the presence of symptoms were collected via an online questionnaire.

Results: Among all participants, 80% were women, 60% nurses and 21% physicians. Median age was 40 years. The seroprevalence remained relatively stable from April (7.7% (95% CI: 4.8% to 12.1%) to September (8.2% (95% CI: 5.7% to 11.6%)) and increased thereafter, reaching 19.7% (95% CI: 12.0% to 30.6%) in December 2020. 76 of 778 initially seronegative participants seroconverted during the follow-up (incidence: 205/1000 person-years). Among all seropositive individuals, 118/148 (80%) had a positive neutralisation test, 83/147 (56%) presented or reported a positive RT-qPCR, and 130/147 (88%) reported COVID-19-compatible symptoms at least once. However, only 46/73 (63%) of the seroconverters presented COVID-19-compatible symptoms in the month prior to seroconversion.

Conclusions: The seroprevalence among hospital HCW was slightly higher than that of the general Belgian population but followed a similar evolution, suggesting that infection prevention and control measures were effective and should be strictly maintained. After two SARS-CoV-2 waves, 80% of HCW remained seronegative, justifying their prioritisation in the vaccination strategy.

Trial registration number: NCT04373889.

Keywords: COVID-19; epidemiology; immunology; infection control; public health.

Figure 1

Estimated prevalence of SARS-CoV-2 seropositivity among healthcare workers in Belgian hospitals over a period of 8 months. Individuals with one positive Euroimmun test result are considered to be seropositive for anti-SARS-CoV-2 IgG antibodies. The estimates are based on a cohort of 850 healthcare workers followed up over time and are corrected for the two-stage cluster sampling design. In the period between the dashed grey lines, the 17 selected hospitals participated in the study. Before the first dashed line, not all hospitals had started recruitment (two hospitals joined the study on the second time point and one hospital on the third time point). After the second dashed line, five hospitals dropped out of the study.

Figure 2

Kaplan-Meier curve showing the probability of becoming seropositive over time. The Kaplan-Meier analysis includes 778 healthcare workers who were seronegative at baseline. The solid line indicates the probability of becoming seropositive over time. The shaded area represents the 95% confidence bands.

Figure 3

Timeline indicating symptoms, RT-qPCR, ELISA and neutralisation test results of three selected participants who seroconverted during follow-up. Grey colour indicates absence of symptoms or negative test results. Blue colour indicates presence of symptoms (prior to a study visit) and positive test results (on the day of a study visit). Participant A had a confirmed molecular diagnosis of SARS-CoV-2 infection and consistent serological response. Participant B presented a consistent serological response but had no molecular proof of SARS-CoV-2 infection. Participant C had an unexpected pattern of results (discordant ELISA and neutralisation test results, waning antibody response, and puzzling timing of events). The timelines of 15 participants with unexpected patterns are available in online supplemental file 4. NTAb, virus neutralisation test; RT-qPCR, real-time reverse transcription PCR.