The elicited anti-SARS-CoV-2 immunity is becoming increasingly complex with individuals receiving a different number of vaccine doses paired with or without recovery from breakthrough infections with different variants. Here we analyze the immunity of individuals that initially received two doses of mRNA vaccine and either received a booster vaccination, recovered from a breakthrough infection, or both. Our data suggest that two vaccine doses and delta breakthrough infection or three vaccine doses and optionally omicron or delta infection provide better B cell immunity than the initial two doses of mRNA vaccine with or without alpha breakthrough infection. A particularly potent B cell response against the currently circulating omicron variant (B. 1.1.529) was observed for thrice vaccinated individuals with omicron breakthrough infection; a 46-fold increase in plasma neutralization compared to two vaccine doses (p < 0.0001). The T cell response after two vaccine doses is not significantly influenced by additional antigen exposures. Of note, individuals with hybrid immunity show better correlated adaptive immune responses compared to those only vaccinated. Taken together, our data provide a detailed insight into SARS-CoV-2 immunity following different antigen exposure scenarios.

Background The ongoing global SARS-CoV-2 pandemic has caused over 4.7 million infections greatly challenging healthcare workers (HCW) and medical institutions worldwide. The SARS-CoV-2 pandemic has shown to significantly impact mental and physical health of HCW. Thus, implementation of testing facilities supporting HCW are urgently needed. Methods A low-threshold SARS-CoV-2 testing facility was introduced at the University Hospital Bonn, Germany, in March 2020. Irrespective of clinical symptoms employees were offered a voluntary and free SARS-CoV-2 test. Furthermore, employees returning from SARS-CoV-2 risk regions and employees after risk contact with SARS-CoV-2 infected patients or employees were tested for SARS-CoV-2 infection. Pharyngeal swabs were taken and reverse transcription polymerase chain reaction for detection of SARS-CoV-2 was performed, test results being available within 24 hours. Profession, symptoms and reason for SARS-CoV-2 testing of employees were recorded. Results Between 9th March and 30th April 2020, a total of 1,510 employees were tested for SARS-CoV-2 infection. 1,185 employees took advantage of the low-threshold testing facility. One percent (n=11) were tested positive for SARS-CoV-2 infection, 18% being asymptomatic, 36% showing mild and 36% moderate/severe symptoms (missing 10%). Furthermore, of 56 employees returning from SARS-CoV-2 risk regions, 18% (10/56) were tested SARS-CoV-2 positive. After risk contact tracking by the hospital hygiene 6 patient-to-employee transmissions were identified in 163 employees with contact to 55 SARS-CoV-2 positive patients. Conclusion In the absence of easily accessible public SARS-CoV-2 testing facilities low-threshold SARS-CoV-2 testing facilities in hospitals with rapid testing resources help to identify SARS-CoV-2 infected employees with absent or mild symptoms, thus stopping the spread of infection in vulnerable hospital environments. High levels of professional infection prevention training and implementation of specialized wards as well as a perfectly working hospital hygiene network identifying and tracking risk contacts are of great importance in a pandemic setting.

BackgroundWorldwide vaccination campaigns significantly reduced mortality caused by SARS-CoV-2 infection and diminished the devastating effects of the pandemic. The first approved vaccines are based on novel mRNA technology and elicit potent immune responses offering high levels of protection from severe disease.MethodsHere we longitudinally assessed adaptive immune responses during a 12-month follow-up period after the initial immunization with 2 doses of mRNA vaccines and after the booster dose in blood and saliva.ResultsOur findings demonstrate a rapid waning of the anti-spike IgG titers between months 3 and 6 after the initial vaccination (1.7- and 2.5-fold decrease in plasma and saliva, respectively; P&lt;0.0001). Conversely, the frequency of spike-specific memory B cells increased during this period (2.4-fold increase; P&lt;0.0001) while the frequency of spike-specific CD4+ and CD8+ T cells remained stable for all assessed functions: cytotoxicity, IFNγ, IL-2, and TNFα expression. Booster vaccination significantly improved the antibody response in plasma and saliva, with the most profound changes observed in the neutralization capacity against the currently circulating omicron variant (25.6-fold increase; P&lt;0.0001). The positive effect of booster vaccination was also evident for spike-specific IgG+ memory B cell (2.4-fold increase; P&lt;0.0001) and cytotoxic CD4+ and CD8+ T cell responses (1.7- and 1.9-fold increase respectively; P&lt;0.05).ConclusionsCollectively, our findings offer a detailed insight into the kinetics of adaptive immune response following SARS-CoV-2 vaccination and underline the beneficial effects of a booster vaccination.

Rabies post-exposure prophylaxis (R-PEP) including wound treatment, vaccination and application of rabies immunoglobulin is essential in preventing rabies mortality. Today, Germany is officially declared free from terrestrial rabies and rabies is only found in bats. However, physicians in A&E Departments are frequently consulted on the need for R-PEP. We retrospectively analysed patients who received R-PEP at the A&E Department of the University Hospital Bonn between 01.01.2013 and 30.06.2019. Demographic data, travel history, clinical and laboratory findings, previous rabies vaccinations and R-PEP vaccination regimen were recorded. During the study period, 90 patients received R-PEP at the University Hospital Bonn, in 10 cases without indication for R-PEP. Altogether, we found deviations from R-PEP guidelines in 51% (n=41/80). Infiltration of rabies immunoglobulin (RIG) was missed in 12 patients and incorrectly administrated in 24 patients. Furthermore, vaccination scheme was incorrect in 11 patients. Correct wound washing and documentation of tetanus status was missing in 14% and 63% of patients, respectively. Despite rabies elimination in Germany patients frequently seek advice for R-PEP, the majority returning from foreign travel. Our data show that there is a high need for education on indication for R-PEP before and after travel and for implementation of precise R-PEP guidelines in daily clinical practice.

The elicited anti-SARS-CoV-2 immunity worldwide is becoming increasingly complex with individuals receiving a different amount of vaccine doses paired with or without recovery from breakthrough infections with different variants. To understand the variety of anti-SARS-CoV-2 immunity we analyzed the adaptive immune responses of individuals that initially received 2 doses of mRNA vaccine and either received a booster vaccination, recovered from a breakthrough infection, or both. Our data suggest that two vaccine doses and delta breakthrough infection or three vaccine doses and optionally omicron or delta infection provide better B cell immunity than the initial 2 doses of mRNA vaccine with or without alpha breakthrough infection. A particularly potent humoral response against the currently circulating omicron variant was observed for the thrice vaccinated individuals with omicron breakthrough infection; a 46-fold increase in neutralization compared to 2 vaccine doses (P < 0.0001). The same group also had the highest titer of spike-specific antibodies in saliva and highest frequency of spike-specific memory B cells in peripheral blood; 9.5-fold (P < 0.001) and 3.5-fold (P < 0.05) increase compared to 2 vaccine doses. The T cell response after two vaccine doses was not significantly influenced by additional immunizations. Of note, individuals with hybrid immunity showed better coordination of the adaptive immune response compared to those only vaccinated. Taken together, our data provide a detailed insight into the SARS-CoV-2 immunity following different immunization scenarios.