Background Heterologous COVID-19 vaccination regimens combining vector- and mRNA-based vaccines are already administered, but data on solicited adverse reactions, immunological responses and elicited protection are limited. Methods To evaluate the reactogenicity and humoral as well as cellular immune responses towards most prevalent SARS-CoV-2 variants after a heterologous ChAdOx1 nCoV-19 BNT162b2 prime-boost vaccination, we analysed a cohort of 26 clinic employees aged 25-46 (median 30.5) years who received a ChAdOx1 nCoV-19 prime followed by a BNT162b2 boost after an 8-week interval. Serological data were compared to a cohort which received homologous BNT162b2 vaccination with a 3-week interval (14 individuals aged 25-65, median 42). Findings Self-reported solicited symptoms after ChAdOx1 nCoV-19 prime were in line with previous reports and more severe than after the BNT162b2 boost. Antibody titres increased significantly over time resulting in strong neutralization titres two weeks after the BNT162b2 boost and subsequently slightly decreased over the course of 17 weeks. At the latest time point measured, all analysed sera retained neutralizing activity against the currently dominant Delta (B.1.617.2) variant. Two weeks post boost, neutralizing activity against the Alpha (B.1.1.7) and immune-evading Beta (B.1.351) variant was ∼4-fold higher than in individuals receiving homologous BNT162b2 vaccination. No difference was observed in neutralization of Kappa (B.1.617.1). In addition, heterologous vaccination induced CD4 + and CD8 + T cells reactive to SARS-CoV-2 spike peptides of all analysed variants; Wuhan-Hu-1, Alpha, Beta, Gamma (P.1), and Delta. Interpretation In conclusion, heterologous ChAdOx1 nCoV-19 / BNT162b2 prime-boost vaccination is not associated with serious adverse events and induces potent humoral and cellular immune responses. The Alpha, Beta, Delta, and Kappa variants of spike are potently neutralized by sera from all participants and reactive T cells recognize spike peptides of all tested variants. These results suggest that this heterologous vaccination regimen is at least as immunogenic and protective as homologous vaccinations and also offers protection against current variants of concern. Funding This project has received funding from the European Union's Horizon 2020 research and innovation programme, the German Research Foundation, the BMBF, the Robert Koch Institute (RKI), the Baden-Württemberg Stiftung, the county of Lower Saxony, the Ministry for Science, Research and the Arts of Baden-Württemberg, Germany, and the National Institutes of Health.

Highly sensitive and specific platforms for the detection of anti-SARS-CoV-2 antibodies are becoming increasingly important for (1) evaluating potential SARS-CoV-2 convalescent plasma donors, (2) studying the spread of SARS-CoV-2 infections and (3) identifying individuals with seroconversion. This study provides a comparative validation of four anti-SARS-CoV-2 platforms. Unique feature of this study is the use of a representative cohort of COVID-19-convalescent patients with mild-to-moderate disease course. All platforms showed significant correlations with a SARS-CoV-2 plaque-reduction-neutralization test, with highest sensitivities for the Euroimmun and the Roche platforms, suggesting their preferential use for screening of persons at increased risk of SARS-CoV-2 infections.

Background Heterologous prime-boost schedules with vector- and mRNA-based COVID-19 vaccines are already administered, but immunological responses and elicited protection have not been reported. Methods We here analyzed a cohort of 26 individuals aged 25-46 (median 30.5) years that received a ChAdOx1 nCoV-2019 prime followed by a BNT162b2 boost after an 8-week interval for reactogenicity, antibody responses and T cell reactivity. Results Self-reported solicited symptoms after ChAdOx1 nCoV-2019 prime were in line with previous reports and less severe after the BNT162b2 boost. Antibody titers increased significantly over time resulting in strong neutralization titers 2 weeks after the BNT162b2 boost. Neutralizing activity against the prevalent strain B.1.1.7 was 3.9-fold higher than in individuals receiving homologous BNT162b2 vaccination, only 2-fold reduced for variant of concern B.1.351, and similar for variant B.1.617. In addition, CD4+ and CD8+ T cells reacted to SARS-CoV-2 spike peptide stimulus 2 weeks after the full vaccination. Conclusions The heterologous ChAdOx1 nCoV-2019 / BNT162b2 prime-boost vaccination regimen is not associated with serious adverse events and results in a potent humoral immune response and elicits T cell reactivity. Variants of concern B.1.1.7, B.1.351 and B.1.617 are potently neutralized by sera of all participants. These results suggest that this heterologous vaccination regimen is at least as immunogenic and protective as homologous vaccinations.

In light of the decreasing immune protection against symptomatic SARS-CoV-2 infection after initial vaccinations and the now dominant immune-evasive Omicron variants, ‘booster’ vaccinations are regularly performed to restore immune responses. Many individuals have received a primary heterologous prime-boost vaccination with long intervals between vaccinations, but the resulting long-term immunity and the effects of a subsequent ‘booster’, particularly against Omicron BA.1, have not been defined. We followed a cohort of 23 young adults, who received a primary heterologous ChAdOx1 nCoV-19 BNT162b2 prime-boost vaccination, over a 7-month period and analysed how they responded to a BNT162b2 ‘booster’. We show that already after the primary heterologous vaccination, neutralization titers against Omicron BA.1 are recognizable but that humoral and cellular immunity wanes over the course of half a year. Residual responsive memory T cells recognized spike epitopes of the early SARS-CoV-2 B.1 strain as well as the Delta and BA.1 variants of concern (VOCs). However, the remaining antibody titers hardly neutralized these VOCs. The ‘booster’ vaccination was well tolerated and elicited both high antibody titers and increased memory T cell responses against SARS-CoV-2 including BA.1. Strikingly, in this young heterologously vaccinated cohort the neutralizing activity after the ‘booster’ was almost as potent against BA.1 as against the early B.1 strain. Our results suggest that a ‘booster’ after heterologous vaccination results in effective immune maturation and potent protection against the Omicron BA.1 variant in young adults.

Zusammenfassung Hintergrund Pflegeeinrichtungen sind Belastungen der COVID-19-Pandemie gegenüber besonders exponiert, sowohl in personellen wie strukturellen Bereichen. Ziel der Arbeit Prospektive Querschnittsstudie zum punktuellen Infektionsgeschehen, zu psychosozialen Belastungen und zum Umgang der Einrichtungen mit der COVID-19-Pandemie. Material und Methoden Systematische Datenerhebung zwischen dem 27.07.2020 und dem 25.08.2020 in 7 Pflegeeinrichtungen in Baden-Württemberg. Dies beinhaltete für Bewohner/Mitarbeiter einen Fragebogen, eine SARS-CoV-2-PCR und Antikörpertestung. Die Einrichtungen wurden auf Umgang und Präventionsmaßnahmen befragt. Ergebnisse Von insgesamt 829 SARS-CoV-2-PCR-Tests waren 100 % negativ. 2 Probanden hatten SARS-CoV-2-Antikörper, allerdings ohne positive Anamnese. Keiner der Probanden mit positiver PCR in der Anamnese (n = 6) hatte nachweisbare Antikörper. Mitarbeiter hatten Angst, Mitmenschen, v. a. Heimbewohner, (54,4 %) anzustecken, weniger sich selbst (27,2 %). Als pandemieassoziierte Belastungen wurden in 17,1 % Erschöpfung, 16 % finanzielle Ängste und 13,1 % Schlafstörungen angegeben. Die Bewältigungsstrategien umfassten einen moderaten Anstieg schädlichen Konsumverhaltens (+3,3 % Alkohol, +4,3 % Nikotin). Wesentlich kritischer war dies bei unter 35-Jährigen (+13 % Alkohol, +12,7 % Nikotin). Frauen gaben eine Zunahme des Medikamentengebrauchs um 2,4 % an. 49,8 % der Befragten reduzierten ihre Sozialkontakte, 76,8 % veränderten ihr Hygieneverhalten. Die Einrichtungen waren eingeschränkt auf die COVID-19-Pandemie vorbereitet. Diskussion Trotz der niedrigen Punktprävalenz zum Zeitpunkt der Erhebung belastete die COVID-19-Pandemie die Pflegeeinrichtungen in vielfachen Aspekten. Aus den entstandenen Belastungen bei Mitarbeitern müssen Bewältigungs- und Präventionskonzepte resultieren.

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The practical course in macroscopic (gross) anatomy is an essential component of medical studies. The dynamic situation with high SARS-CoV-2 infection rates prior to the winter semester (02.11.2020 until 01.03.2021) confronted university institutions with the difficult question of how or whether essential practical courses in medical schools can be conducted in presence. The gross anatomy course at Ulm University took place with a comprehensive hygiene concept and accompanied by a longitudinal study. This included in particular SARS-CoV-2 pathogen detection (swab with RT-PCR) at neuralgic time points, as well as antibody testing at the beginning and at the end of the semester for both students and teaching staff. The first SARS-CoV-2 RT-PCR test prior to the gross anatomy course revealed two asymptomatic SARS-CoV-2 positive individuals of 327 students. All institute and student staff of this course tested negative at semester start (n=75). Antibodies to SARS-CoV-2 were detected in 6.4% of the anatomy course students (22 out of 345). The second SARS-CoV-2 RT-PCR test after the Christmas break was negative in all participants, including teaching staff (n=429). At the end of the course in mid-February 2021, seroconversion after infection was detected in only two students of the anatomy course who participated in both tests (0.6%, n=325). Also other semester cohorts of the first three years of study in human medicine and dentistry were invited. No further active SARS-CoV-2 infections at the start of the semester and seven seroconversions after infection (n=335) were detected after the semester in these cohorts. The data illustrate the likely preventive effect from the interaction of hygiene concepts, regular information on the pandemic and testing. Thus, this study demonstrates ways in which face-to-face teaching can be implemented for selected courses at universities, even with high national incidence rates.