ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
The COVID-19 pandemic has posed a tremendous challenge for the global community. We established a translational approach combining home blood sampling by finger-pricking with multiplexed serology to assess the exposure to the SARS-CoV-2 virus in a general population. The developed procedure determines the immune response in multiplexed assays against several spike (S, here denoted SPK), receptor binding domain (RBD) and nucleocapsid (NCP) proteins in eluates from dried capillary blood. The seroprevalence was then determined in two study sets by mailing 1000 blood sampling kits to random households in urban Stockholm during early and late April 2020, respectively. After receiving 55% (1097/2000) of the cards back within three weeks, 80% (878/1097) were suitable for the analyses of IgG and IgM titers. The data revealed diverse pattern of immune response, thus seroprevalence was dependent on the antigen, immunoglobulin class, stringency to include different antigens, as well as the required analytical performance. Applying unsupervised dimensionality reduction to the combined IgG and IgM data, 4.4% (19/435; 95% CI: 2.4%-6.3%) and 6.3% (28/443; 95% CI: 4.1%-8.6%) of the samples clustered with convalescent controls. Using overlapping scores from at least two SPK antigens, prevalence rates reached 10.1% (44/435; 95% CI: 7.3%-12.9%) in study set 1 and 10.8% (48/443; 95% CI: 7.9%-13.7%). Measuring the immune response against several SARS-CoV-2 proteins in a multiplexed workflow can provide valuable insights about the serological diversity and improve the certainty of the classification. Combining such assays with home-sampling of blood presents a viable strategy for individual-level diagnostics and towards an unbiased assessment of the seroprevalence in a population and may serve to improve our understanding about the diversity of COVID-19 etiology. One Sentence SummaryA multiplexed serology assay was developed to determine antibodies against SARS-CoV-2 proteins in home-sampled dried blood spots collected by finger pricking.
