Seroprevalence of SARS-CoV-2 Antibodies in Denmark: Results of Two Nationwide Population-Based Surveys, February and May 2021.

Background: Seroprevalence studies can be used to measure the progression of national COVID-19 epidemics. The Danish National Seroprevalence Survey of SARS-CoV-2 infections (DSS) was conducted as five separate surveys between May 2020 and May 2021. Here, we present results from the two last surveys conducted in February and May 2021. Methods: Persons aged 12 or older were randomly selected from the Danish Population Register and those having received COVID-19 vaccination subsequently excluded. Invitations to have blood drawn in local test centers were sent by mail. Samples were analyzed for whole Immunoglobulin by ELISA. Seroprevalence was estimated by sex, age and geography. Comparisons to vaccination uptake and RT-PCR test results were made. Results: In February 2021, we found detectable antibodies in 7.2% (95% CI: 6.3-7.9%) of the invited participants (participation rate 25%) and in May 2021 in 8.6% (95% CI: 7.6-9.5%) of the invited (participation rate: 14%). Seroprevalence did not differ by sex, but by age group, generally being higher among the <50 than 50+ year-olds. In May 2021, levels of seroprevalence varied from an estimated 13% (95% CI: 12-15%) in the capital to 5.2% (95% CI: 3.4-7.4%) in rural areas. Combining seroprevalence results with vaccine coverage, estimates of protection against infection in May 2021 varied from 95% among 65+ year-olds down to 10-20% among 12-40 year-olds. In March-May 2021, an estimated 80% of all community SARS-CoV-2 infections were diagnosed by RT-PCR and captured by surveillance. Conclusion: Seroprevalence estimates doubled during the 2020-21 winter wave of SARS-CoV-2 infections and then stabilized as vaccinations were rolled out. The epidemic affected large cities and younger people the most. Denmark saw comparatively low infections rates, but high test coverage; an estimated four out of five infections were detected by RT-PCR in March-May 2021.

Effect of Influenza Vaccination on Risk of Coronavirus Disease 2019: A Prospective Cohort Study of 46†000 Healthcare Workers.

BACKGROUND: The purpose of this study was to assess whether influenza vaccination has an impact on the risk of coronavirus disease 2019 (COVID-19). METHODS: A cohort of 46 112 healthcare workers were tested for antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and filled in a survey on COVID-19 symptoms, hospitalization, and influenza vaccination. RESULTS: The risk ratio of hospitalization due to SARS-CoV-2 for influenza vaccinated compared with unvaccinated participants was 1.00 for the seasonal vaccination in 2019/2020 (confidence interval, .56-1.78, P = 1.00). Likewise, no clinical effect of influenza vaccination on development of antibodies against SARS-CoV-2 was found. CONCLUSIONS: The present findings indicate that influenza vaccination does not affect the risk of SARS-CoV-2 infection or COVID-19.

Prevalence of SARS-CoV-2 antibodies in Denmark: nationwide, population-based seroepidemiological study.

Seroprevalence studies have proven an important tool to monitor the progression of the coronavirus disease 2019 (COVID-19) pandemic. We present results of consecutive population-based seroprevalence surveys performed in Denmark in 2020. In spring, late summer and autumn/winter of 2020, invitation letters including a questionnaire covering symptoms were sent to representative samples of the population above 12 years and to parents of children below 18 years in the sample. Blood samples were analysed for total Ig and seroprevalence estimates per population segment were calculated and compared to other surveillance parameters. Based on 34 081 participants (participation rate 33%), seroprevalence estimates increased from 1.2% (95%CI: 0.3-1.9%) in May to 4.1% (95%CI: 3.1-4.9%) in December 2020. Seroprevalence estimates were roughly three times higher in those aged 12-29 years compared to 65 + and higher in metropolitan municipalities. By December 2020, 1.5% of the population had tested positive by RT-PCR. Infected individuals in older age groups were hospitalised several fold more often than in younger. Amongst seropositives, loss of taste/smell were the more specific symptoms, 32-56% did not report any symptoms. In more than half of seroconverted families, we did not see evidence of transmission between generations. Seroprevalence increased during 2020; adolescents were primarily infected in the autumn/winter. Denmark has a high per capita test rate; roughly one undiagnosed infection of SARS-CoV-2 were estimated to occur for each diagnosed case. Approximately half were asymptomatically infected. The epidemic appears to have progressed relatively modestly during 2020 in Denmark.

SARS-CoV-2 Antibody Responses Are Correlated to Disease Severity in COVID-19 Convalescent Individuals.

Globally, the COVID-19 pandemic has had extreme consequences for the healthcare system and has led to calls for diagnostic tools to monitor and understand the transmission, pathogenesis, and epidemiology, as well as to evaluate future vaccination strategies. In this study, we have developed novel, to our knowledge, flexible ELISA-based assays for specific detection of human SARS-CoV-2 Abs against the receptor-binding domain, including an Ag sandwich ELISA relevant for large population screening and three isotype-specific assays for in-depth diagnostics. Their performance was evaluated in a cohort of 350 convalescent participants with previous COVID-19 infection, ranging from asymptomatic to critical cases. We mapped the Ab responses to different areas on protein N and S and showed that the IgM, A, and G Ab responses against receptor-binding domain are significantly correlated to the disease severity. These assays and the data generated from them are highly relevant for diagnostics and prognostics and contribute to the understanding of long-term COVID-19 immunity.

Multilaboratory Comparison of Pneumococcal Multiplex Immunoassays Used in Immunosurveillance of Streptococcus pneumoniae across Europe.

Surveillance studies are required to estimate the impact of pneumococcal vaccination in both children and the elderly across Europe. The World Health Organization (WHO) recommends use of enzyme immunoassays (EIAs) as standard methods for immune surveillance of pneumococcal antibodies. However, as levels of antibodies to multiple serotypes are monitored in thousands of samples, a need for a less laborious and more flexible method has evolved. Fluorescent-bead-based multiplex immunoassays (MIAs) are suitable for this purpose. An increasing number of public health and diagnostic laboratories use MIAs, although the method is not standardized and no international quality assessment scheme exists. The EU Pneumo Multiplex Assay Consortium was initiated in 2013 to advance harmonization of MIAs and to create an international quality assessment scheme. In a multilaboratory comparison organized by the consortium, agreement among nine laboratories that used their own optimized MIA was assessed on a panel of 15 reference sera for 13 pneumococcal serotypes with the new WHO standard 007sp. Agreement was assessed in terms of assay accuracy, reproducibility, repeatability, precision, and bias. The results indicate that the evaluated MIAs are robust and reproducible for measurement of vaccine-induced antibody responses. However, some serotype-specific variability in the results was observed in comparisons of polysaccharides from different sources and of different conjugation methods, especially for serotype 4. On the basis of the results, the consortium has contributed to the harmonization of MIA protocols to improve reliability of immune surveillance of Streptococcus pneumoniaeIMPORTANCE Serology of Streptococcus pneumoniae is challenging due to existence of multiple clinically relevant serotypes and the introduction of multivalent vaccines in national immunization programs. Multiplex immunoassays (MIAs) are applied as high-throughput cost-effective methods for serosurveillance, and yet laboratories use their own protocols. The aims of this study were to assess the agreement of results generated by MIAs in different laboratories within the EU Pneumo Multiplex Assay Consortium, to analyze factors contributing to differences in outcome, and to create a harmonized protocol. The study demonstrated good agreement of results of MIAs performed by laboratories using controlled assays for determination of levels of vaccine-induced pneumococcal antibodies. The EU Pneumo Multiplex Assay Consortium is open to everyone working in public health services, and it aims to facilitate efforts by participants to run and maintain a cost-effective, reproducible, high-quality MIA platform.