ABSTRACT
Throughout the SARS-CoV-2 pandemic, Germany lacked an adaptive population panel for epidemic diseases and a modelling platform to rapidly incorporate panel estimates. We evaluated how a cross-sectional analysis of 9922 participants of the MuSPAD study in June/July 2022 combined with a newly developed modelling platform could bridge the gap and analyzed antibody levels, neutralizing serum activity and interferon-gamma release response of serum samples. We categorized the population into four groups with differing protection against severe course of disease (validated by neutralizing serum activity), and found that 30% were in the group with highest protection, and 85% in either the highest categories or second highest group regarding protection level. Estimated hospitalizations due to SARS-CoV-2 were predicted to be between 30 to 300% of the peak in 02/2021 dependent on assumed variant characteristics. We showed the feasibility of a rapid epidemic panel able to evaluate complex endpoints for SARS-CoV-2 and inform scenario modelling.
Subject(s)
Encephalitis, ArbovirusABSTRACT
Background: SARS-CoV-2 variants accumulating immune escape mutations provide a significant risk to vaccine-induced protection. The novel variant of concern Omicron (B.1.1.529) has to date the largest number of amino acid alterations in its Spike protein. Thus, it may efficiently escape recognition by neutralizing antibodies, allowing breakthrough infections in convalescent and vaccinated individuals. Aims: We analysed neutralization activity after vaccination with all mRNA-, vector- or heterologous immunization schemes currently available in Europe at peak response and in a longitudinal follow-up with BNT162b2 vaccinees to define immune escape potential of the Omicron VoC. Methods: We tested sera by in vitro neutralization assay towards SARS-CoV-2 B.1, Omicron, Beta and Delta pseudotypes Results: All vaccines apart from Ad26.CoV2.S showed high levels of responder rates (93.3-100%) towards SARS-CoV-2 wild-type, but some reductions in neutralizing Beta and Delta VoC pseudotypes. The novel Omicron variant had the biggest impact, both in terms of response rates and neutralization titres among responders. Only mRNA-1273 showed a 100% response rate to Omicron and induced the highest titres of neutralizing antibodies, followed by heterologous prime-boost approaches. Homologous BNT162b2 vaccination or vector-based formulations with AZD1222 or Ad26.CoV2.S performed less well with peak responder rates of 33%, 50% and 9%, respectively. However, Omicron responder rates in BNT162b2 recipients were maintained in our six month longitudinal follow-up and even slightly increased to 47%, indicating cross-protection against Omicron is maintained over time. Conclusions: Overall, our data strongly argues for urgent booster doses in individuals who were previously vaccinated with BNT162b2, or a vector-based immunization scheme.
Subject(s)
COVID-19 , Breakthrough PainABSTRACT
Background While SARS-CoV-2 vaccinations were successful in decreasing COVID-19 caseloads, recent increases in SARS-CoV-2 infections have led to questions about duration and quality of the subsequent immune response. While numerous studies have been published on immune responses triggered by vaccination, these often focused on the initial peak response generated in specific population subgroups (e.g. healthcare workers or immunocompromised individuals) and have often only examined the effects of one or two different immunisation schemes. Methods and Findings We analysed serum samples from participants of a large German seroprevalence study (MuSPAD) who had received all available vaccines and dose schedules (mRNA-1273, BNT162b2, AZD1222, Ad26.CoV2S.2 or a combination of AZD1222 plus either mRNA-1273 or BNT162b2). Antibody titers against various SARS-CoV-2 antigens and ACE2 binding inhibition against SARS-CoV-2 wild-type and the Alpha, Beta, Gamma and Delta variants of concern were analysed using a previously published multiplex immunoassay MULTICOV-AB and an ACE2-RBD competition assay. Among the different vaccines and their dosing regimens, homologous mRNA-based or heterologous prime-boost vaccination produced significantly higher antibody responses than vector-based homologous vaccination. Ad26.CoV2S.2 performance was significantly reduced, even compared to AZD1222, with 91.67% of samples being considered non-responsive forACE2 binding inhibition. mRNA-based vaccination induced a higher ratio of RBD- and S1-targeting antibodies than vector-based vaccination, which resulted in an increased proportion of S2-targeting antibodies. Previously infected individuals had a robust immune response once vaccinated, regardless of which vaccine they received. When examining antibody kinetics post-vaccination after homologous immunisation regimens, both titers and ACE2 binding inhibition peaked approximately 28 days post-vaccination and then decreased as time increased. Conclusions As one of the first and largest population-based studies to examine vaccine responses for all currently available immunisation schemes in Germany, we found that homologous mRNA or heterologous vaccination elicited the highest immune responses. The high percentage of non-responders for Ad26.CoV2.S requires further investigation and suggests that a booster dose with an mRNA-based vaccine may be necessary. The high responses seen in recovered and vaccinated individuals could aid future dose allocation, should shortages arise for certain manufacturers. Given the role of RBD- and S1-specific antibodies in neutralising SARS-CoV-2, their relative over-representation after mRNA vaccination may explain why mRNA vaccines have an increased efficacy compared to vector-based formulations. Further investigation on these differences will be of particular interest for vaccine development and efficacy, especially for the next-generation of vector-based vaccines.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
Prevalence of SARS-CoV-2 antibodies is an essential indicator to guide measures. Few population-based estimates are available in Germany. We determine seroprevalence allowing comparison between regions, time points, socio-demographic and health-related factors. MuSPAD is a sequential multi-local seroprevalence study. We randomly recruited adults in five counties with differing cumulative SARS-CoV-2 incidence July 2020 - February 2021. Serostatus was determined using Spike S1-specific IgG ELISA. We determined county-wise proportions of seropositivity. We assessed underestimation of infections, county and age specific infection fatality risks, and association of seropositivity with demographic, socioeconomic and health factors. We found seroprevalence of 2.4 % (95%CI: 1.8-3.1%) for Reutlingen in June 2020 (stage 1) which increased to 2.9% (95%CI: 2.1-3.8%) in October (stage 2), Freiburg stage 1 1.5% (95% CI: 1.1-2.1%) vs. 2.5% (95%CI: 1.8-3.4%), Aachen stage 1 2.3% (95% CI: 1.7-3.1%) vs. 5.4% (95%CI: 4.4-6.6%), Osnabrück 1.3% (95% CI: 1.0-1.9%) and Magdeburg in Nov/Dec 2020. 2.4% (95%CI 1.9-3.1%). Number needed to quarantine to have one infected person quarantined was 8.2. The surveillance detection ratio (SDR) between number of infections based on our results and number reported to health authorities ranged from 2.5-4.5. Participants aged 80+ had lower SDR. Infection fatality estimates ranged from 0.2-2.4%. Lower education was associated with higher, smoking with lower seropositivity. Seroprevalence remained low until December 2020 with high underdetection. The second wave from November 2020 to February 2021 resulted in additional 2-5% of the population being infected. Detected age specific differences of SDR should be taken into account in modelling and forecasting COVID-19 morbidity. Highlights Evidence before this study Seroepidemiological surveys on SARS-CoV-2 are a useful tool to track the transmission during the epidemic. We searched PubMed/the pre-print server medRxiv and included web-based reports from German health organizations using the keywords “seroprevalence”, “SARS-CoV-2”, “Germany” and similar other English and German terms in the period from January 1st, 2020 until March 2021. We identified 30 published studies in Germany which mostly report low SARS-CoV-2 seroprevalence (<5%). Most of these surveys were so-called hotspot studies which assessed seroprevalence after localized outbreaks or examined seroprevalence of specific population groups such as e.g. medical staff. Few studies are either population-based or blood donor-based, but do not allow comparisons between regions. To date, we only consider the Corona sub-study of the Rhineland study similar to MuSPAD. It reports a low SARS-CoV-2 seroprevalence (46/4755; 0.97%; 95% CI: 0.72−1.30). Based on this, almost the entire German population remained susceptible to a SARS-CoV-2 infection by the end of 2020. Added value of this study We provide the first comprehensive, high-precision multi-region population-based SARS-CoV-2 seroprevalence study with representative sampling following the WHO protocol in Germany. By measuring SARS-CoV-2 IgG, we explore immunity at regional and national level over time. We also assess risk factors and sample each region twice, which permits to monitor seroprevalence progression throughout the epidemic in different exemplary German regions. Implications of all the available evidence Our results show low seroprevalence (<3%) until Mid-December 2020 in all regions. While estimates in Reutlingen, Aachen, Freiburg and Osnabrück reflect low seroprevalence mostly after the first wave, the survey in Magdeburg cumulatively already represents the beginning of the second wave. The number needed to quarantine to ensure one infected person was quarantined was 8.2 in our study. We also show that for the first wave reported infections reflected overall around 25% of those actually infected rising to 40-50% in the second wave. A slightly raised infection risk could be shown for persons with lower education.