The protective effect of SARS-CoV-2 antibodies in Scottish healthcare workers

Discussion

In this observational study of health and social care workers, the SARS-CoV-2 seroprevalence rate was 14.5%. Importantly, the presence of antibodies was associated with clear protection against subsequent infection. This is important for our future understanding of risk for HCWs and the general population.

At the time of writing, Health Protection Scotland is leading a surveillance study for COVID-19 in Scotland on behalf of the Scottish Government [11]. Present data from this study demonstrate a comparative seroprevalence of 4.5%. Our data therefore suggest that health and social care workers are >3 times more likely to be positive for spike protein antibodies and thus are likely to have been infected with SARS-CoV-2.

Other HCW seroprevalence studies conducted in the rest of the UK have also reported higher seropositivity when compared to the general population, with seroprevalence rates of 24.4% [12], 25.4% [13] and 10.7% [14].

Our study was notable for the inclusion of dentistry staff, who had the highest seroprevalence rate at 26%. This was well above the average seroprevalence rate of 14.5% among our HCWs, although this higher rate should be interpreted with some caution given the lower number of dentistry staff enrolled (table 1). Dentistry staff are expected to be a higher risk group, given their focus of work is more likely to be aerosol generating and with close exposure to potentially infected mucosal surfaces [15]. Healthcare assistants, including such staff at nursing homes, had the second highest prevalence at 23%. The caring roles of these workers necessitate close patient contact and their increased risk was also reported in a recent Swedish study [16].

In other published HCW studies [12], domestic or housekeeping staff had the highest seroprevalence of antibodies. This was not evident in our study, where domestic staff had a below average seroprevalence rate of 13.1%. Other groups who had a seroprevalence rate above average were hospital porters and doctors. Doctors and porters are typically exposed to multiple patients in different working areas. By comparison, nurses typically care for up to six patients in a defined area during their working day. The variability in work location in a particular time period could be a factor in the increased infection rate we observed.

In our study, HCWs who worked in COVID-19 areas of the hospital had a slightly higher seroprevalence than those workers who did not. This finding is consistent with other studies, including HCW studies conducted in major urban areas where the community burden of COVID-19 was a significant source of exposure [17]. Working in COVID-19 areas of the hospital is one way to define high-risk exposure. Nevertheless, the majority of SARS-CoV-2 infections detected in this study occurred in staff who were not working directly with COVID-19 patients, and this group still had a significantly higher prevalence of SARS-CoV-2 antibodies than the general population. While a seroprevalence study cannot establish the source of infection, this strongly suggests transmission between healthcare staff within non-clinical environments, since many staff roles that did not involve direct contact with patients were still associated with an increased rate of antibody positivity. Therefore, while much media attention has focused on the importance of PPE for front-line staff, these data emphasise the importance of IPC measures in non-clinical areas within healthcare environments such as hospitals. The relative success of measures to protect high-risk front-line staff is illustrated by the low rate of antibody detection in critical care staff. All staff working in critical care areas wore PPE in accordance with Health Protection Scotland guidance on working in aerosol-generating procedures [18]. We found no significantly increased risk of infection for these staff. In the recently published study from Birmingham, UK [12], staff in intensive care had a significantly lower risk of seropositivity.

We asked our study participants to report if they thought they had had COVID-19 and list the symptoms they experienced. We describe that only one in four participants who thought they had contracted COVID-19 demonstrated serological evidence of infection. The heightened suspicion of infection is justified among HCWs, but perceived infection does not correlate well with actual infection. This has some potentially important implications when considering the issue of chronic symptoms in individuals who believe they have had COVID-19 infection [19]. However, we demonstrated in this study that certain symptoms are significantly more predictive of infection with SARS-CoV-2. Anosmia represented 12-fold increased odds of having serological evidence of infection. This particular symptom was also shown to be strongly predictive in similar analysis performed in other European studies [16, 20].

Our study demonstrates that approximately one-fifth (18.7%) of seropositive HCWs were completely asymptomatic. This is consistent with studies that only recruited asymptomatic HCWs [12] and indicates that a significant proportion of the healthcare workforce will attend work without knowing that they may potentially transmit the infection to their colleagues.

After the end of the recruitment period, we followed our study participants for up to 6 months from antibody positivity and up to 10 months from first PCR-confirmed SARS-CoV-2 infection. Winter 2020 coincided with the second wave of SARS-CoV-2 infections in Scotland and we had 39 new infections among our HCWs during this period. One of these infections (0.33% of the total study group) was a symptomatic re-infection in an HCW who had previously developed an antibody response from a previous infection. To our knowledge, this is the first reported case of laboratory-confirmed re-infection after the development and confirmed presence of natural antibodies.

97.4% of new infections were in HCWs who did not have previous antibodies. In our study, the presence of a natural antibody response was therefore 85% protective against re-infection with SARS-CoV-2 over a period of 6 months (May to December 2020).

Our results on antibody protection fit within the range of efficacy of vaccine-mediated immunity reported in the recently published SARS-CoV-2 vaccine trials [21, 22]. These results may have implications for the roll-out of vaccine programmes, since HCWs are often prioritised, but our results suggest HCWs with prior infection may be at low risk of future infection and may therefore be considered a lower priority.

This study has potential limitations, including potentially that individuals more likely to believe they have had a SARS-CoV-2-like illness would be more likely to volunteer for such a study. Nevertheless, we were successful in enrolling participants who had never experienced a symptomatic infection and demonstrate an increased seroprevalence even among this group. We enrolled patients up to September 2020 and therefore potentially up to 4–5 months post infection. This raises the possibility of antibodies waning over time [23]. This seems unlikely, as a prior study found no evidence of waning of the Siemens assay over 4 months [10], while a similar total spike protein antibody assay showed no waning over time in a study from Iceland [24]. Other studies have reported increased infection rates in the Black, Asian and minority ethnic populations [25–27]. We were unable to investigate this as NHS Tayside has a workforce that is 97% white. The patient population was representative of NHS Scotland staff. In 2019, the median age of staff employed across NHS Scotland was 46 years, and 77.4% of NHS Scotland employees were female. 9% were doctors, 0.4% dental staff, 42.6% nursing staff, 8.4% allied health professionals and 18.1% administrative staff. Our sample included 11.5% doctors, 29.2% nurses, 11.6% allied health professionals and 19.6% administrative staff. Our median age was 46 years and 81.7% of our cohort were female.