Study design and subjects

In May 2020, we asked the healthcare providers in Stockholm, Sweden to invite their employees to a study of past or present SARS-CoV-2 infections in the healthcare setting. The HCWs enrolled were from all professions within healthcare. The Stockholm Region is a relatively densely populated region in Sweden: the region has 2,34 million inhabitants, out of Sweden’s 10.23 million inhabitants (according to public data from 2019). The units who participated were 22 primary care centers, 2 care homes, and one palliative care unit representing approximately 1000 employees. Recruitment was carried out in June 2020. Healthcare staff on duty (hence without any disease symptoms) were eligible. To be included in the study, each study subject needed to provide a written informed consent form. For each unit included in the study, there also needed to be an approval by the operations manager. Staff members were excluded if they were absent from work or had an incomplete consent form. Among the included 839 individuals, swab samples for PCR were missing for 60 and invalid for 39 individuals. If one of the samples was present, the study subject was included in the study. If both samples were invalid or absent, the individual was excluded. Operations managers also reported measures taken to limit transmission of SARS-CoV-2 (S1 File).

Methods

Viral RNA detection and antibody detection methods were as described [10]. Briefly, viral RNA was extracted from throat swab samples using MGIEasy Magnetic Beads Virus DNA/RNA extraction kit and subjected to real-time PCR. Serological analysis (99.2% sensitivity and 99.8% specificity assay) was performed by IgG detection in inactivated serum. Antibodies were tested against three different variants of viral proteins (Spike trimers containing prefusion-stabilized spike glycoprotein ectodomain, Nucleocapsid protein and Spike S1 domain) and reactivity against at least two viral antigens was required for a sample to be assigned as IgG positive. SARS-CoV-2 testing results (PCR and serology) were reported as proportions by workplace, age, and sex. A one-sided Cochran Armitage test for trend was used to examine patterns in serology prevalence by age. The analyses were done in SAS 9.4, Cary NC, USA.

Ethics declaration

The approval of the study was granted by the National Ethical Review Agency of Sweden (Decision number 2020–01620 and 2020–01881). Trial registration number: ClinicalTrials.gov NCT04411576. All methods in the study were carried out in compliance with the Helsinki declaration.

Main findings

Our most important finding is that young HCWs in primary care, at homes and in palliative care, particularly young women, had frequently had SARS-CoV-2 infection, as demonstrated by the over 22% seroprevalence among female HCWs in ages 20–29. This is a significant finding because it suggests that young HCWs who are at the front line in primary care and other care settings outside hospitals may have been a source of nosocomial infections. We found a low prevalence of PCR positivity (1%) mostly coupled with serology positivity, suggesting that the PCR positivity was mostly post-symptomatic (the affected HCWs may have returned to work after symptoms have resolved). The finding of many more HCWs with past infection than with pre-symptomatic infection indicates that the study was performed at a time when the first wave of the epidemic was already subsiding in the region. Healthcare workers in primary care, in care homes and in palliative care are particularly responsible for and in close and frequent contact with older people and chronically ill patients with complex care needs who are vulnerable to COVID-19. During the first wave of the COVID-19 pandemic, in March to June 2020, in Sweden, protective measures for healthcare workers in Sweden were limited: postponing meetings that could wait, keeping a safe distance when possible, limit the time of close contact with care takers and to wear a surgical mask, a gown and gloves—but only if the patient had symptoms suggestive of COVID-19. Testing and contact tracing of patients with possible COVID-19 was not available for these settings during the first wave. These circumstances made it quite difficult for healthcare workers to effectively protect older and vulnerable people from COVID-19 –and to protect themselves. The data in the present study thus probably reflect a situation that would be close to a natural history setting.

The typical testing results found among subjects who will have symptomatic disease in the future (pre-symptomatic subjects; PCR positivity for high amounts of virus (CT value <27) and lack of antibodies) was found in only 2/839 subjects, considerably lower than in a major hospital in the same region tested a few weeks earlier (57/9449 subjects) [10] also implying that the number of new infections was declining at the time of the present study. The seroprevalence of SARS-CoV-2 specific antibodies varied substantially between units (0–29%). Hence, it is possible that cluster outbreaks may have occurred within units and is in line with previous literature on the spread of SARS-CoV-2 among HCWs [6, 12, 17, 18]. This finding is also in line with our result that the typical pattern of potential presymptomatic (“Superspreading”) HCWs was rare in our cohort.

Strengths of the study include the fact that it is a rather large study with a high attendance rate among HCWs in areas of healthcare that were of particular importance in the epidemic. Furthermore, PCR testing and serology testing was performed simultaneously with advanced technology. Weaknesses of the study include the fact that it was launched at a time when most of the first wave of the epidemic was already over. We did not query the participants regarding symptoms or risk factors for infection. However, guidelines were strict in that HCWs were not allowed to work in case of symptoms and it can thus be assumed that the participating HCWs were most likely asymptomatic.

Study findings in relation to previous research

The present study was performed in parallel with an identically designed study that tested almost 10,000 employees of the Karolinska University Hospital, also in Stockholm, Sweden [10]. The results were highly comparable. In particular, there was also a large variability in the proportion of seropositive subjects among HCWs working in different units of the hospital, with the highest risks for HCWs in emergency wards and acute care wards, and the lowest risks for staff without patient contact [17]. In agreement with our results, many studies have reported an increased risk of exposure to SARS-CoV-2 among HCWs [19], in elderly care homes [12, 15, 20], nursing facilities [16] as well as among the HCWs at hospitals [17, 18, 21]. Seropositivity was comparable to observational studies from hospitals in the same region and near in time [11, 18]. Participating in the active care of COVID-19 patients was a significant risk factor for being seropositive. A similar association between front line COVID-19 care and seropositivity has been observed in a Danish study, screening healthy HCWs, in April 2020 [22]. Occupational exposure to infection has also been found and illustrated as an increased risk of severe COVID-19 among HCWs [19, 23, 24]. In our study, there was a significant decrease of seropositivity with age, which can be due to the that staff with a higher age to a larger extent than otherwise have taken on other tasks than caring for patients with acute infections, during the COVID-19 epidemic. Our findings reveal that especially young HCWs in primary care, care homes and palliative care in Stockholm were highly exposed to SARS-CoV-2. Young individuals have a higher tendency to suffer SARS-CoV-2 infection as asymptomatic COVID-19 disease [25] and thus, young HCWs in primary care may have been a source population of nosocomial infections. The countries that most rapidly achieved a high vaccination coverage i.e. Israel and the UK found vaccination to protect against symptomatic and asymptomatic SARS-CoV-2 infection [26–28]. Asymptomatics and presymptomatics are of particular importance for transmission of SARS-CoV-2 in healthcare settings, as symptomatic HCWs should not be at work. Many countries have prioritized vaccination of HCWs and our data support that maintaining a high degree of immunity among HCWs is crucial to protect vulnerable populations and to safeguard occupational safety and health.