ABSTRACT
Diagnostic assays currently used to monitor the efficacy of COVID-19 vaccines measure levels of antibodies to the receptor-binding domain of ancestral SARS-CoV-2 (RBDwt). However, the predictive value for protection against new variants of concern (VOCs) has not been firmly established. Here, we used bead-based arrays and flow cytometry to measure binding of antibodies to spike proteins and receptor-binding domains (RBDs) from VOCs in 12,000 sera. Effects of sera on RBD-ACE2 interactions were measured as a proxy for neutralizing antibodies. The samples were obtained from healthy individuals or patients on immunosuppressive therapy who had received two to four doses of COVID-19 vaccines and from COVID-19 convalescents. The results show that anti-RBDwt titers correlate with the levels of binding- and neutralizing antibodies against the Alpha, Beta, Gamma, Delta, Epsilon and Omicron variants. The benefit of multiplexed analysis lies in the ability to measure a wide range of anti-RBD titers using a single dilution of serum for each assay. The reactivity patterns also yield an internal reference for neutralizing activity and binding antibody units per milliliter (BAU/ml). Results obtained with sera from vaccinated healthy individuals and patients confirmed and extended results from previous studies on time-dependent waning of antibody levels and effects of immunosuppressive agents. We conclude that anti-RBDwt titers correlate with levels of neutralizing antibodies against VOCs and propose that our method may be implemented to enhance the precision and throughput of immunomonitoring.
ABSTRACT
BackgroundThe Omicron variant of SARS-CoV-2 is now overtaking the Delta variant in many countries. Results showing that sera from double vaccinated individuals have minimal neutralizing activity against Omicron may indicate that the higher rate of transmission is due to evasion from vaccine-induced immunity. However, there is little information about activation of recall responses to Omicron in vaccinated individuals. MethodsWe measured inflammatory mediators, antibodies to the SARS-CoV-2 spike and nucleocapsid proteins, and spike peptide-induced release of interferon gamma in whole blood in 51 vaccinated individuals infected with Omicron, in 14 infected with Delta, and in 18 healthy controls. The median time points for the first and second samples were 7 and 14 days after symptom onset, respectively. FindingsInfection with Omicron or Delta led to a rapid and similar increase in antibodies to the SARS-CoV-2 spike and nucleocapsid proteins and spike peptide-induced interferon gamma in whole blood. Both the Omicron and the Delta infected patients had a mild and transient increase in inflammatory parameters. InterpretationThe results suggest that vaccine-induced immunological memory yields similar coverage for the Omicron and Delta variants.
ABSTRACT
Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of a well-characterized cohort of 3,260 COVID-19 patients with respiratory failure and 12,483 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen (HLA) region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a highly pleiotropic [~]0.9-Mb inversion polymorphism and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.
ABSTRACT
BackgroundThe risk factors for SARS-CoV-2 transmission are not well characterised in Western populations. We sought to identify potential risk factors for transmission and actionable information to prevent for SARS-CoV-2. MethodsIndividuals tested for SARS-CoV-2 at four major laboratories were invited. In addition, participants were sampled by convenience after a media campaign. Self-reported test results were compared with laboratory results, demographic data and behavioural facts were collected using a digital platform. In a cross-sectional design positive cases were compared with negative and untested control groups. FindingsApproximately 14 days after a countrywide lockdown in Norway, 116,678 participants were included. Median age was 46 years, 44% had children in preschool or in school; 18% were practicing health professionals. International flights, contact with infected, and gatherings of more than 50 people, were associated with high risk. Health professionals who used public transport were at higher risk of testing positive than those who did not. Having undergone light infections, the last six months was strongly associated with lower odds ratio of SARS-CoV-2 positivity. Contact with children, use of hand sanitiser and use of protective gloves in private were also associated with lower odds ratio of testing positive for SARS-CoV-2. InterpretationFurther research is needed to explore if being a parent or looking after children is associated with lower risk of SARS-CoV-2 positivity in the next phases of the pandemic. Immunological research should be done to determine the effects of prior trivial infections on SARS-CoV-2 infection. We confirm that large gatherings during the pandemic should be avoided and those who are infected, or under suspicion thereof, posed very high risks to others this population.