RESUMO
Self-sampled blood provided valuable information about the COVID-19 seroprevalence in the general population. To enable an even deeper understanding of pathophysiological processes following SARS-CoV-2 infections, 276 circulating proteins were quantified by proximity extension assays in dried blood spots (DBS). Samples from undiagnosed individuals collected during the first wave of the pandemic were selected based on their serological immune response and matched on self-reported symptoms. We stratified these as seropositive (IgM+IgG+; N = 41) or seronegative (IgM-IgG-; N = 37), and to represent the acute (IgM+IgG-; N = 26) and convalescent phases (IgM-IgG+; N = 40). This revealed proteins from a variety of clinical processes including inflammation and immune response (MBL2, MMP3, IL2RA, FCGR2A, CCL5), haemostasis (GP1BA, VWF), stress response (ANG), virus entry (SDC4) or nerve regeneration (CHL1). The presented approach complements clinical surveys and enables a deep molecular and population-wide analysis of COVID-19 from blood specimens collected outside a hospital setting.
RESUMO
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.
