Abstract
Autoantibodies against platelet glycoproteins (anti-GP) are found in the majority of patients with autoimmune thrombocytopenia (AITP) as well as in thrombocytopenia associated with systemic lupus erythematosus (SLE). Some of these patients may have anti-phospholipid antibodies (anti-PL). To evaluate the pathogenetic significance of anti-PL and anti-GP antibodies in AITP and SLE patients, we investigated anti-cardiolipin (anti-CL), anti-phosphatidylserine (anti-PS) and anti-GP antibodies (anti-GPIIb-IIIa and anti-GPIb-IX) in 71 patients with AITP and 3 thrombocytopenic patients with SLE. Anti-GP antibodies were detected in 52 (70%) patients. Fifty-six (73%) patients showed anti-PL antibodies. Seven patients (6 AITP, 1 SLE) with both anti-GPIIb-IIIa and IgG anti-PL antibodies were followed during treatment with corticosteroids. Antibodies were measured before treatment and at the time of platelet-peak. Anti-GPIIb-IIIa antibodies decreased in all or became undetectable in five. In contrast, IgG anti-PS and IgG anti-CL antibodies decreased only moderately or remained positive. Adsorption experiments, using gelfiltered platelets, erythrocyte (Ec)-inside-out-vesicles and purified GPIIb-IIIa, showed that anti-GP and anti-PL antibodies have distinct specificities and do not crossreact. We conclude that anti-PL and anti-GP antibodies may be present simultaneously in some patients with immune mediated thrombocytopenia. Although anti-PS as well as anti-CL antibodies may be responsible for thrombocytopenia, we speculate that anti-GPIIb-IIIa antibodies are more related to the severity of thrombocytopenia.
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Introduction
As the first wave of the ongoing COVID-19 pandemic swept across the northern hemisphere in the spring of 2020, most countries adopted wide-ranging measures to limit the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1. Most measures, however, imposed little or no restrictions on ‘essential’ workers—whose occupations are deemed indispensable for the provision of crucial services, including healthcare, transportation, food production, social work, among others. Depending on the nature of their function, workers may be exposed to infectious, often asymptomatic5, members of the public and/or colleagues, increasing their risk of infection compared with individuals working from home—and beyond the risk of household transmission6,7. Cumulating evidence indicates that healthcare workers in hospitals face an increased risk of infection, although the risk may be department-specific or associated to social rather than professional activities, whilst some studies have found no increased risk. Some evidence shows that healthcare workers in nonhospital settings, such as nursing homes, are also at increased risk. Less is known about occupations outside healthcare settings, though evidence from RT-PCR testing indicates that public-facing workers such as waiters, social workers, and transport drivers may be at increased risk17,18. As the second or third waves of the pandemic spread across the world and mass vaccination starts, there remains an urgent need to better characterize the risk of SARS-CoV-2 infection among workers who are mobilized during lockdowns in order to better guide public health policy to both limit the spread of the virus and protect exposed workers, including in vaccine prioritization.
The canton of Geneva in Switzerland reported its first confirmed COVID-19 case on February 26, 2020, and by April 26, 2021, 54,964 confirmed cases (110.0 per 1000 inhabitants) and 729 deaths had been reported19. Lockdown measures—similar to those implemented regionally or nationally across Europe and North America—were imposed on March 16, 2020 from which only essential businesses remained operational and the population was encouraged to stay home; progressive lifting of restrictions took place from April 27, 2020 until June 6, 2020.To understand the SARS-CoV-2 infection risk among workers from key sectors that remained operational during the lockdown, we established the SEROCoV-WORK + serology study, using the same testing procedure as in our SEROCoV-POP population-based seroprevalence study20,21, whose representative sample can serve as comparison.
Results
We included 10,513 participants in our analytical sample (55.6% women; mean age [standard deviation]: 43.0 years [10.7]) after excluding 69 participants with missing data or outside the target age range (18–65 years). About 48% had a tertiary education, while 8.3% had only a primary education. Most participants were non-smokers (58.3% versus 25.9% current smokers), 32.0% were overweight and 12.0% were obese. Participants represented 16 activity sectors, ranging from 1668 in healthcare (15.9%), 1185 in transportation (11.3%), and 1102 in nursing homes (10.5%) to 182 in construction (1.7%), 166 in media (1.6%) and 97 in agriculture (0.9%) (Table 1).
Overall, 9.8% of individuals (1026/10513) tested positive for SARS-CoV-2 anti-S1 IgG antibodies (Table 1), roughly the same seropositivity rate (7.9% [95% CrI: 6.8–8.9]) as the general working-age population of Geneva over a similar time period21. Older participants (≥50 years) had a lower risk of being seropositive (RR: 0.70; 95% CrI: 0.56–0.83) compared with 18–34-year-old participants. Relative to participants with a doctorate, the risk of being seropositive was lower among participants with an apprenticeship (RR: 0.54; 95% CrI: 0.35–0.76) and among those with up to secondary education (RR: 0.65; 95% CrI: 0.45–0.90). Compared with non-smokers, smokers and ex-smokers had a reduced risk of being seropositive (RR: 0.45, 95% CrI: 0.30–0.57; RR: 0.72, 95% CrI: 0.55–0.88, respectively).
Seropositivity rate varied widely across sectors, from as high as 14.3% in the nursing home sector to as low as 4.2% in media. Seropositivity rate reached 12.1% in the homecare sector, 11.1% in healthcare, 11.0% in pharmacy and 10.1% in the food industry. Relative to healthcare sector participants, those in the public security sector (RR: 0.53; 95% CrI: 0.22–0.93) and early childhood education sector (RR: 0.37; 95% CrI: 0.09–0.84) were at lower risk of being seropositive. Participants who were fully confined during the lockdown were more likely to be seropositive (RR: 1.27; 95% CrI: 1.03–1.56), compared with mobilized participants. In line with this finding, participants with at least one out-of-work exposure to a confirmed COVID-19 case were more likely to be seropositive (RR: 2.29; 95% CrI: 1.93–2.74) compared with their counterparts without any exposure.
A large heterogeneity in seropositivity rate was observed across participating facilities within every sector (Fig. ). For example, it ranged from 0 to 31.4% across 21 nursing homes, and from 2.6 to 24.6% across 8 public administration facilities. Furthermore, occupations within facilities and sectors also showed varying degrees of seropositivity rate. Across the 32 occupations, seropositivity rate was as high as 15.0% among kitchen staff and 14.4% among nurses/nurse assistants, and as low as 5.4% among domestic care workers and 2.8% among journalists.
Sensitivity analyses excluding participants who were confined during the lockdown yielded similar results (Supplementary figs. 1–2; Supplementary table 3). Disaggregating seropositivity rates by out-of-work exposure showed that participants with at least one out-of-work exposure to a confirmed COVID-19 case generally had twice the seropositivity rate compared with their same-sector or same-occupation counterparts with no out-of-work exposure (Supplementary tables 4–5). Further adjusting relative risk estimates for known out-of-work exposures, however, showed no appreciable change from the main results (Supplementary table ).
Discussion
In this large sample of workers from 16 sectors who were mobilized during the spring 2020 Swiss lockdown, we observed that the proportion of workers having developed anti-SARS-CoV-2 antibodies after the first COVID-19 wave varied widely across sectors, across facilities within sectors and across occupations within sectors. With few important exceptions, our findings do not show a pattern of increased risk of SARS-CoV-2 infection among sectors and occupations of workers who were mobilized during the lockdown, the overall seropositivity rate of this sample being only slightly higher than that of the general working-age population during the spring 202021. Yet, there was considerable variability across sectors and occupations.
While nursing home workers exhibited the highest seropositivity rate relative to that of the working-age population, reflecting evidence from Spain14, Sweden15, and the UK16, it differed widely across nursing home facilities; this intra-sector variability, which was observed in almost all sectors, may reflect overdispersion, a well-known characteristic of SARS-CoV-2 transmission dynamics22,23. Whether the degree of adherence to preventive measures within facilities and in private life may also help explain this heterogeneity will be elucidated in further studies. It is also possible that most infections had occurred before strict measures were implemented. Healthcare sector workers showed a generally higher seropositivity rate than the general population, consistent with extensive evidence from many countries.
