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Current SARS-CoV-2 serological assays generate discrepant results, and the longitudinal characteristics of antibodies targeting various antigens after asymptomatic to mild COVID-19 are yet to be established. This longitudinal cohort study including 1965 healthcare workers, of which 381 participants exhibited antibodies against the SARS-CoV-2 spike antigen at study inclusion, reveal that these antibodies remain detectable in most participants, 96%, at least four months post infection, despite having had no or mild symptoms. Virus neutralization capacity was confirmed by microneutralization assay in 91% of study participants at least four months post infection. Contrary to antibodies targeting the spike protein, antibodies against the nucleocapsid protein were only detected in 80% of previously anti-nucleocapsid IgG positive healthcare workers. Both anti-spike and anti-nucleocapsid IgG levels were significantly higher in previously hospitalized COVID-19 patients four months post infection than in healthcare workers four months post infection (p=2*10-23 and 2*10-13 respectively). Although the magnitude of humoral response was associated with disease severity, our findings support a durable and functional humoral response after SARS-CoV-2 infection even after no or mild symptoms. We further demonstrate differences in antibody kinetics depending on the antigen, arguing against the use of the nucleocapsid protein as target antigen in population-based SARS-CoV-2 serological surveys.
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BackgroundPre-symptomatic subjects are spreaders of SARS-CoV-2 infection, and strategies that could identify these subjects, particularly in hospital settings, are needed. MethodsWe tested a cohort of 9449 employees at work at the Karolinska University Hospital, Stockholm, Sweden for SARS-CoV-2 RNA and antibodies, linked the screening results to sick leave records and examined the association between screening results and past or future sick leave using multinomial logistic regression. ResultsWe found that healthcare workers with high amounts of SARS-CoV-2 virus, as indicated by the Cycle threshold (Ct) value in the PCR, had the highest risk for sick leave in the two weeks after testing (OR 11{middle dot}97 (CI 95% 6{middle dot}29-22{middle dot}80)) whereas subjects with low amounts of virus had the highest risk for sick leave in the past three weeks before testing (OR 6{middle dot}31 (4{middle dot}38-9{middle dot}08)). Only 2{middle dot}5% of employees were SARS-CoV-2 positive while 10{middle dot}5% were positive by serology and 1{middle dot}2% were positive in both tests. Serology-positive subjects were not at excess risk for future sick leave (OR 1{middle dot}06 (95% CI, 0{middle dot}71-1{middle dot}57)), but virus-positive subjects had a 7{middle dot}23 fold (95% CI, 4{middle dot}52-11{middle dot}57)) increased risk for sick leave within two weeks post testing. ConclusionsScreening of asymptomatic healthcare workers for high amounts of SARS-CoV-2 virus using Ct values will identify pre-symptomatic subjects who will develop disease in the next few weeks. Identification of potentially contagious, pre-symptomatic subjects is likely critical for protecting patients and healthcare workers. Main pointHealthy healthcare workers with low amounts of SARS-CoV-2 nucleic acids will previously have had the disease. Presence of a high amount of SARS-CoV-2 nucleic acids predicts future symptomatic disease.
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Background: The extent that antibodies to SARS-CoV-2 may protect against future virus-associated disease is unknown. Method: We analyzed 12928 healthy hospital employees for SARS-CoV-2 antibodies and compared results to participant sick leave records (Clinical trial registration: ClinicalTrials.gov NCT04411576). Results: Subjects with viral serum antibodies were not at excess risk for future sick leave (Odds Ratio (OR): 0.85 (95% Confidence Interval (CI) (0.85 (0.43-1.68)). By contrast, subjects with antibodies had an excess risk for sick leave in the past weeks (OR: 3.34 (2.98-3.74)). Conclusion: Presence of viral antibodies marks past disease and protection against excess risk of future disease.
RESUMO
BackgroundSARS-CoV-2 may pose an occupational health risk to health care workers, but the prevalence of infections in this population is unknown. We examined the seroprevalence of SARS-CoV-2 antibodies among health care workers at a large acute care hospital in Stockholm, Sweden. We determined correlations between seroprevalence, self-reported symptoms and occupational exposure to SARS-CoV-2. Methods and findingsAll employees at Danderyd Hospital (n=4375) were invited to participate in a cross-sectional study. 2149 employees from all hospital departments were enrolled in the study between April 14th and May 8th 2020. Study participants completed a questionnaire consisting of symptoms compatible with SARS-CoV-2 infection since January 2020 and occupational exposure to patients infected with SARS-CoV-2. IgG antibodies against SARS-CoV-2 were analyzed using a multiplex assay evaluated to have 99.4% sensitivity and 99.1% specificity. The over-all seroprevalence among 2149 participants was 19.1% (n=410). There was no difference in age or sex between seropositive and seronegative participants. The symptoms with the strongest correlation to seroprevalence were anosmia and ageusia, with odds ratios of 28.4 (p=2.02*10^-120) and 19.2 (p=1.67*10^-99) respectively. Seroprevalence was strongly associated with patient-related work (OR 2.9, p=4.24*10^-8), covid-19 patient contact (OR 1.43, p=0.003), and occupation as assisting nurse (OR 3.67, p=2.16*10^-9). ConclusionThese results demonstrate that anosmia and ageusia should be included in screening guidance and in the recommendations of self-isolation to reduce further spread of SARS-CoV-2. The results furthermore imply an occupational health risk for SARS-CoV-2 infection among hospital workers. Continued measures are warranted to assure healthcare worker safety and reduce transmission from health care settings to the community during the covid-19 outbreak.
