Introduction

SARS-CoV-2 has driven a pandemic crisis. Its hallmark is very high infectivity, pre-symptomatic transmission and asymptomatic prevalence which continue to fuel dramatic cumulative numbers of infections, hospitalizations, and deaths. To better understand the extent of undetected transmission, serological surveys in sampled cohorts identified antibodies from prior infection ranging from 57% prevalence in Bergamo—Italy’s epicenter [1], 20% in New York City [2], 5.2% in Kenya [3], down to 4.7% in Los Angeles County [4] and 2.8% in Santa Clara County [5], California.

While prevalence of antibodies among healthcare workers, presumed at high risk for infection, has also been increasingly studied, the prevalence, sample size, and sampling methodology greatly varies. Garcia-Basteiro, et al reports the cumulative prevalence (IgG, IgA, or current positive rRT-PCR) of SARS-CoV-2 infection of 11.2% among 578 subjects in a large hospital in Spain [6]. The study of 28,792 healthcare works from Denmark identified 2.81% prevalence for IgM and 2.67% for IgG, and found higher prevalence in front-line workers specifically working with COVID-19 patients, compared to other front-line workers [7]. It also found that subjects younger than 30 years had the highest seroprevalence compared to those who are 30 years or older. Another study found 13.7% IgG prevalence among 40,329 healthcare workers in the greater New York city area [8] similar to the community prevalence in New York State (14.0%) [9], and sero-positivity was strongly associated with self-reported suspicion of prior COVID-19 exposure and prior positive PCR testing.

Further determining such prevalence among healthcare workers in varied geographic areas and examining duration of antibody presence may help stratify the workforce for risk, establish better health place policies and procedures, and potentially better mitigate transmission across different healthcare settings.

This article reports on initial sero-surveillance conducted among 2,992 healthcare workers at Hoag Memorial Hospital Presbyterian, a regional hospital system in Orange County, California, United States, during May and June, 2020.

Methods

Results

Of an initial 2,992 samples recorded, subjects were excluded from analyses due to missing age (n = 3), gender (n = 14), race, (n = 31), occupation (n = 8), and symptoms (n = 12), resulting in a complete pool of 2,924 (Table 1).

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Table 1. Sample characteristics and group differences.

https://doi.org/10.1371/journal.pone.0240006.t001

Antibody testing identified 31 positive cases (2,893 negative), resulting in an observed prevalence of 1.06% (exact binomial 95% CI = 0.72% - 1.50%). Accounting for test sensitivity of 93.6% and specificity of 100%, an adjusted prevalence of 1.13% (95% CI = 0.78% - 1.58%) was calculated, indicating 33 positive cases (negative = 2,891) after adjustment.

Nonparametric tests for group differences were performed for demographics and five symptoms of COVID-19. Significant differences between observed negative and positive cases were found for age (z = 2.64, p = .008), race (p = .037), presence of fever (p < .001), and loss of smell (p < .001), but not for occupation (p = .710). Interestingly, of those with previously PCR confirmed diagnosis of COVID-19 (n = 11), 6 were antibody positive with 5 non-reactive. None of the non-reactive 5 had a history of hospitalization or severe illness.

Discussion

Our study found a significantly lower prevalence (1.06% observed prevalence) of SARS-CoV-2 antibody carriers among our healthcare workers compared to prior reports ranging from 2.6% to 13.7%. During this same period, prevalence of antibodies tested by physician order at our hospital laboratory was 3.87%.

One possible explanation for the low seroconversion rate in our work force is a relatively low overall regional estimated prevalence of infections (~4.4%), as further evidenced by an average 104 patients per day in ICU and 330 cumulative deaths in Orange County (total population of 3.18 million) at the time of our study [13]. This hypothesis is supported by the considerably higher prevalence in healthcare workers and even higher community prevalence in New York [9], indicating that geographic consideration needs to be given when evaluating the infection and transmission risks among healthcare workers.

Despite our relatively low community prevalence in the early stage of the pandemic, our institution had implemented stringent workforce education on personal hygiene, social distancing and appropriate PPE usage since January 2020 when we saw the first California and third US case, with hospital-wide protocols in patient triage and symptom surveillance. Such strategies may have heightened our healthcare workers’ awareness, urgency, and compliance with our policies, both at and outside work place, possibly contributing to the lower prevalence we have found in this study.

In addition, recent research indicates presence of innate and cross-reactive adaptive T cell mediated immunity, which may lower susceptibility to COVID-19 infection in some individuals. One might speculate that greater frequency of exposure to such agents occurs in healthcare workers vs. the general population. Several studies have reported that such innate T cell immunity exists [14] with documented cross-reactivity to related corona virus species [15–17]. One can speculate that workplace exposure is more frequent for health care workers to such various coronavirus pathogens. A combination of all of the above factors may explain our findings.

In our cohort, there were 11 cases with previously PCR confirmed diagnosis of COVID-19 with 5 non-reactive cases, which cannot be fully explained by antibody test sensitivity and specificity. Recent studies found a rapid decay of IgG antibody in patients with mild symptoms, with the possible span of 2–3 months [18, 19]. Of those 5 non-relative cases, 4 reported no or mild COVID-19 symptoms in the questionnaire, their confirmed COVID-19 results being up to 2 months prior to antibody tests. While this provides additional support for the recent findings [17, 18], further research in the larger cohort is needed, and whether such decrease in antibodies lowers immunity should be examined, given the extremely rare cases of re-infection being reported [20].

We will retest this same cohort at 8 weeks and 6 months, to better understand the dynamics of SARS-CoV-2 antibody prevalence and duration in healthcare workers.

Supporting information

Acknowledgments

We acknowledge our healthcare workers who have contributed to this study.