Changes in SARS-CoV-2 Spike versus Nucleoprotein Antibody Responses Impact the Estimates of Infections in Population-Based Seroprevalence Studies

SARS-CoV-2-specific antibody responses to the Spike (S) protein monomer, S protein native trimeric form or the nucleocapsid (N) proteins were evaluated in cohorts of individuals with acute infection (n=93) and in individuals enrolled in a post-infection seroprevalence population study (n=578) in Switzerland. Commercial assays specific for the S1 monomer, for the N protein and a newly developed Luminex assay using the S protein trimer were found to be equally sensitive in antibody detection in the acute infection phase samples. Interestingly, as compared to anti-S antibody responses, those against the N protein appear to wane in the post-infection cohort. Seroprevalence in a 'positive patient contacts' group (n=177) was underestimated by N protein assays by 10.9 to 32.2% and the 'random selected' general population group (n=311) was reduced up to 45% reduction relative to S protein assays. The overall reduction in seroprevalence targeting only anti-N antibodies for the total cohort ranged from 9.4 to 31%. Of note, the use of the S protein in its native trimer form was significantly more sensitive as compared to monomeric S proteins. These results indicate that the assessment of anti-S IgG antibody responses against the native trimeric S protein should be implemented to estimate SARS-CoV-2 infections in population-based seroprevalence studies.IMPORTANCE In the present study, we have determined SARS-CoV-2-specific antibody responses in sera of acute and post-infection phase subjects. Our results indicate that antibody responses against viral S and N proteins were equally sensitive in the acute phase of infection but that responses against N appear to wane in the post-infection phase while those against S protein persist over time. The most sensitive serological assay in both acute and post-infection phases used the native S protein trimer as binding antigen that has significantly greater conformational epitopes for antibody binding compared to the S1 monomer protein used in other assays. We believe that these results are extremely important in order to generate correct estimates of SARS-CoV-2 infections in the general population. Furthermore, the assessment of antibody responses against the trimeric S protein will be critical to evaluate the durability of the antibody response and for the characterization of a vaccine-induced antibody response

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

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COVID-19 Host Genetics Initiative. A first update on mapping the human genetic architecture of COVID-19

The COVID-19 pandemic continues to pose a major public health threat, especially in countries with low vaccination rates. To better understand the biological underpinnings of SARS-CoV-2 infection and COVID-19 severity, we formed the COVID-19 Host Genetics Initiative1. Here we present a genome-wide association study meta-analysis of up to 125,584 cases and over 2.5 million control individuals across 60 studies from 25 countries, adding 11 genome-wide significant loci compared with those previously identified2. Genes at new loci, including SFTPD, MUC5B and ACE2, reveal compelling insights regarding disease susceptibility and severity.</p