We conducted this multicenter prospective cohort study among frontline HCWs to investigate SARS-CoV-2 infection in HCWs during the first COVID-19 epidemic wave in Paris, France. We report a 5.8% baseline (early phase) SARS-CoV-2 seroprevalence rate together with a 3-month 14.6% rate of laboratory-confirmed SARS-CoV-2 infection (end of first wave). Most infections occurred very early, that is, diagnosed at M1. Among the identified risk factors was the working department, infectious disease units being at highest risk at the very early phase, then emergency departments during the epidemic peak, with the same level of risk for both at the end of the wave and intensive care units with an intermediate risk, with the virology laboratory staff as reference. Active smokers were at reduced risk. Demographics, other job-related characteristics, adherence to PPE, and use of public transportation were not significantly associated with SARS-CoV-2 infection. To our knowledge, our study is the largest reporting the longitudinal evolution of anti–SARS-CoV-2 antibodies in HCWs over a 3-month period.
The seroprevalence in the general population estimated in the SAPRIS study12 in the same geographical area (Greater Paris) in May 2020, corresponding to M1 in the SEROCOV study, was significantly lower than in the SEROCOV first-line HCWs: 6.4% in the 20- to 59-year-old population of the SAPRIS study (using a similar anti-nucleoprotein assay and considering weak positive as positive as in SEROCOV) versus 13.3% in SEROCOV (p<0.0001). Previous published HCW surveys reported seroprevalence ranging from 3.4–13.7%. However, the heterogeneity in type of HCW tested, type of assay used, period of testing and countries with incomparable SARS-CoV-2 epidemic burden precludes a face-to-face comparison. In a multicenter cross-sectional study in the New York city area, Moscola et al. reported a 13.7% prevalence (95%CI [13.4; 14.0]) of SARS-CoV-2 antibodies in 40,329 HCWs, a rate similar to that among adults randomly tested in New York state (14.0%). 3 However, in another cross-sectional study in Roslyn, New York, in one hospital, employees had a significantly lower serology-positive rate than the general population (9.9% vs 16.7%, P < 0.001).4 Stubblefield et al. reported a 7.6% seroprevalence among 249 frontline HCWs during the first month of epidemic in Nashville, Tennessee, whereas Jespersen et al. reported a 3.4% seroprevalence (95% CI [2.5; 3.8]) among 17,971 HCWs, administrative personnel, pre-hospital services and specialist practitioner clinics in Denmark, with high geographical seroprevalence variation (from 1.2–11.9%). 6,7 In the United States, in a Multistate Hospital Network, Self et al. reported 6.0% positive serology in front-line HCWs.5 Among the 194 participants with positive results, 56 (29%) reported no symptoms in the previous weeks. In our study, this asymptomatic proportion was 50% among participants with positive serology at inclusion. Conversely, we confirm that anosmia and/or ageusia during the epidemic wave was a discriminative clinical sign, although with low sensitivity. This result confirms the Belgian monocentric study findings reporting of anosmia associated with an OR for positive serology of 7.78 ([95%CI [5.22; 11.53]). 2
Most HCW contaminations occurred very early during the epidemic wave, almost half documented at baseline (positive serology: 5.9%, 95% CI [4.7; 7.5]) and 12.9% at M1 (corresponds to infections during the ascendant phase of the epidemic wave as shown in Figure 2). The kinetics of these infections probably reflects both infections in the private sphere, following the epidemic curve of the general population, but also the effectiveness of better adherence to protective measures in professional activity related to an enforcement of PPE and standard measures as the epidemic progressed. The family and friends or professional origin of HCW contamination is still debated.13 In a single center study in Belgium of 3,056 HCWs (tested with an IgG/IgM rapid lateral flow assay), the OR for positive serology was 3.15 (95% CI [2.33; 4.25]) when reporting household contact with a suspected or confirmed COVID-19 case. 2 Conversely, a large study in Denmark of 17,971 hospital staff (based on the adjusted seroprevalence according to living and working places) found risk of SARS-CoV-2 positive serology associated with workplace rather than place of living. 7
Recently, a large survey of HCWs in the United Kingdom reported anti-spike or anti-nucleocapsid IgG antibodies associated with substantially reduced risk of SARS-CoV-2 reinfection and highlighted that individual HCWs middle-/long-term protection by post-COVID self-immunization is a major concern.14 Our data support the persistence of SARS-CoV-2 antibodies at 3 months: only 11 (8%) participants with positive serology had later negative results. Controversial results were reported by Patel et al. for 249 HCWs with a positive serology rate decreasing from 7.6% at baseline to 3.2% at 60 days, whereas Gudbjartsson et al. showed no decline in anti–SARS-CoV-2 antibodies at 4 months after COVID-19 diagnosis. 15,16
Workers in first-line clinical departments (infectious diseases, emergency, intensive care unit) were at higher risk of laboratory-confirmed SARS-CoV-2 infection as compared with virology laboratory staff (Table 3). In a large study in Denmark, Jespersen et al. reported the highest adjusted seroprevalence in emergency departments: 29.7% (95% CI [23.1; 37.6]); departments with no or limited patient contact had the lowest seroprevalence: 1.79% (0.31; 3.90).7 From January to mid-March 2020, infectious disease departments and intensive care units directly admitted patients with suspected COVID-19 from home or the general practitioner’s office, bypassing the emergency department, and were therefore initially more exposed to SARS-CoV-2 than emergency department workers. This situation may explain the association of SARS-CoV-2 positive serology with working in intensive care units (OR 1.2 [95%CI (0.47; 3.51)]) and especially infectious diseases units (6.61, [2.64; 16.54]) at inclusion versus emergency departments (Table 3). Virology laboratory staff, although handling numerous SARS-CoV-2–contaminated samples, are probably more concerned and stricter about PPE enforcement to prevent contamination and had no staff with positive serology at inclusion, together with the lowest seroprevalence rate at 3 months. Similarly, as compared with emergency department staff, intensive care unit staff were at intermediate risk, which could be explained by a more usual concern about the risk of pathogen transmission (particularly during highly resistant bacteria outbreaks).
At M0 and M3 and in the analysis restricted to high-risk HCWs and accounting for adherence to PPE measures, being an active smoker reduced the risk of laboratory-confirmed SARS-CoV-2 infection (OR 0.36, 95% CI [0.21; 0.63]). An increasing number of studies have reported this reduced risk of SARS-CoV-2 infection in active smokers in different contexts (cross-sectional studies in the general population; cross-sectional, case–control or control studies in different populations).17–22 Our results from a large multicenter prospective study in a young population of HCWs with 26.9% active smokers support the role of use of tobacco substances as protective against SARS-CoV-2 infection, which may act through the nicotine pathway.23–26 This result should not encourage smoking to limit the risk of COVID-19; indeed, 78,000 deaths per year are due to smoking in France.27 However, the nicotinic hypothesis is of interest, even in the era of an anti-SARS-CoV-2 vaccine, and is being investigating for prevention of COVID-19 (NCT04583410).
The professional category was not a risk factor for laboratory-confirmed SARS-CoV-2 infection, even if medical students exhibited high prevalence as compared with senior physicians (23.5%, 95% CI [20.8-26.4] vs 14.2% [12.2-16.5]) (Table 2). This result may be explained by an insufficient practice or experience with PPE recommendations in medical students or confounded by age. Similarly, reporting high compliance with PPE was not protective (Table 4 and supplementary table 1). However, reported adherence to PPE was very good in the SEROCOV population. Regardless, two studies highlighted greater prevalence of SARS-CoV-2 positive serology in HCWs reporting not systematically wearing PPEs in general or covering the face during clinical encounters than in HCWs fully compliant (15.8% vs 4.3%, p=0.07, and 9% vs 6% p=0.012). 5,6 The questionnaire on PPE compliance completed only at the end of follow-up in our study may explain in part this discrepancy due to a potential memory bias in addition to social desirability bias.
The strengths of the study are the prospective design, the recruitment in the early phase of the first epidemic wave; the multicenter, multi-department and multi-professional recruitment of the study; the large sample size; the 3-point serology testing; the centralization of serology assays; and the criteria retained for laboratory-confirmed SARS-CoV-2 infection (rather than seroprevalence alone, which is exposed to negativation). As limitations, first, 11.7% HCWs were lost to follow-up at M3, but missing serology results were handled by multiple imputations. Second, compliance with PPE and standard recommendations were queried only at the end of the study and not weekly, as for the clinical signs, with therefore a potential risk of memory bias and social desirability bias. Finally, the serology assay we used (targeting the viral nucleoprotein) is less sensitive than anti-spike assays.8,12 Therefore, the reported incidence rate of documented SARS-CoV-2 infection in the SEROCOV study may be slightly underestimated. However, we accounted for this issue in the comparison with seroprevalence data available in the general population.
In summary, in this study of frontline HCWs in Paris, France, we report a 14.6% SARS-CoV-2 cumulative incidence rate at the end of the first COVID-19 wave, with a seroprevalence in May 2020 significantly higher than in the general population. The study of risk factors for laboratory-confirmed SARS-CoV-2 infection argues for a significant part of professional (together with household) contaminations and highlights smoker status as an independent protective factor. At the era of anti-SARS-CoV2 vaccination, our results represent an argument to include HCWs in the first-line target population.