Monitoring the SARS-CoV-2 Pandemic: Prevalence of Antibodies in a Large, Repetitive Cross-Sectional Study of Blood Donors in Germany-Results from the SeBluCo Study 2020-2022.

SARS-CoV-2 serosurveillance is important to adapt infection control measures and estimate the degree of underreporting. Blood donor samples can be used as a proxy for the healthy adult population. In a repeated cross-sectional study from April 2020 to April 2021, September 2021, and April/May 2022, 13 blood establishments collected 134,510 anonymised specimens from blood donors in 28 study regions across Germany. These were tested for antibodies against the SARS-CoV-2 spike protein and nucleocapsid, including neutralising capacity. Seroprevalence was adjusted for test performance and sampling and weighted for demographic differences between the sample and the general population. Seroprevalence estimates were compared to notified COVID-19 cases. The overall adjusted SARS-CoV-2 seroprevalence remained below 2% until December 2020 and increased to 18.1% in April 2021, 89.4% in September 2021, and to 100% in April/May 2022. Neutralising capacity was found in 74% of all positive specimens until April 2021 and in 98% in April/May 2022. Our serosurveillance allowed for repeated estimations of underreporting from the early stage of the pandemic onwards. Underreporting ranged between factors 5.1 and 1.1 in the first two waves of the pandemic and remained well below 2 afterwards, indicating an adequate test strategy and notification system in Germany.

Differences in Immunogenicity of Three Different Homo- and Heterologous Vaccination Regimens against SARS-CoV-2.

Background: Due to findings on adverse reactions and clinical efficacy of different vaccinations against SARS-CoV-2, the administration of vaccination regimens containing both adenoviral vector vaccines and mRNA-based vaccines has become common. Data are still needed on the direct comparison of immunogenicity for these different regimens. Methods: We compared markers for immunogenicity (anti-S1 IgG/IgA, neutralizing antibodies, and T-cell response) with three different vaccination regimens (homologous ChAdOx1 nCoV-19 (n = 103), or mixture of ChAdOx1 nCoV-19 with mRNA-1273 (n = 116) or BNT162b2 (n = 105)) at two time points: the day of the second vaccination as a baseline and 14 days later. Results: All examined vaccination regimens elicited measurable immune responses that were significantly enhanced after the second dose. Homologous ChAdOx1 nCoV-19 was markedly inferior in immunogenicity to all other examined regimens after administration of the second dose. Between the heterologous regimens, mRNA-1273 as second dose induced greater antibody responses than BNT162b2, with no difference found for neutralizing antibodies and T-cell response. Discussion: While these findings allow no prediction about clinical protection, from an immunological point of view, vaccination against SARS-CoV-2 with an mRNA-based vaccine at one or both time points appears preferable to homologous vaccination with ChAdOx1 nCoV-19. Whether or not the demonstrated differences between the heterologous regimens are of clinical significance will be subject to further research.

B-cell responses to vaccination with BNT162b2 and mRNA-1273 6 months after second dose.

OBJECTIVES: To examine the state of B-cell immunity 6 months after the second vaccination against SARS-CoV-2 in comparison to the state observed 2 weeks after vaccination. METHODS: Sera of 439 participants, whose immune responses to two doses of an mRNA-based vaccine (BNT162b2 or mRNA-1273) were previously characterized, was examined for anti-S1 IgG and IgA, anti-NCP IgG and neutralizing antibodies (nAb), and antinuclear antibodies (ANA). RESULTS: Levels of all examined markers decreased significantly from 2 weeks to 6 months after second vaccination (anti-S1 IgG: 3744 ± 2571.4 vs. 253 ± 144 binding antibody units (BAU)/mL; anti-S1 IgA: 12 ± 0 vs. 1.98 ± 1.75 optical density (OD) ratio; nAb: 100% ± 0% vs. 82% ± 19.3%), the vast majority of participants retaining reactive levels of anti-S1 IgG (436/439) and anti-S1 IgA (334/439) at 6 months. Immune responses were stronger for mRNA-1273 compared with BNT162b2 (anti-S1 IgG: 429 ± 289 vs. 243 ± 143 BAU/mL; anti-S1 IgA: 5.38 ± 3.91 vs. 1.89 ± 1.53 OD ratio; nAb: 90.5% ± 12.6% vs. 81% ± 19.3%). There was no meaningful influence of sex and age on the examined markers. There was a strong correlation between anti-S1 IgG and the surrogate neutralization assay (rho = 0.91, p <0.0001), but not for for IgA and the surrogate neutralization assay (rho = 0.52, p <0.0001). There was a ceiling effect for the association between anti-S1 IgG titres and the inhibition of binding between S1 and ACE2. ANA prevalence was unchanged from 2 weeks to 6 months after the second vaccination (87/498 vs. 77/435), as were the median ANA titres (1:160 vs. 1:160). DISCUSSION: Although the clinical consequences of decreasing anti-SARS-CoV-2 antibody titres cannot be estimated with certainty, a lowered degree of clinical protection against SARS-CoV-2 is possible. Persistently stronger responses to mRNA-1273 suggest that it might confer greater protection than BNT162b2, even 6 months after the second vaccination. Neither examined vaccinations induced ANA within the examined time frame.

Kinetics of the Antibody Response to Boostering With Three Different Vaccines Against SARS-CoV-2.

BACKGROUND: Heterologous vaccinations against SARS-CoV-2 with ChAdOx1 nCoV-19 and a second dose of an mRNA-based vaccine have been shown to be more immunogenic than homologous ChAdOx1 nCoV-19. In the current study, we examined the kinetics of the antibody response to the second dose of three different vaccination regimens (homologous ChAdOx1 nCoV-19 vs. ChAdOx1 nCoV-19 + BNT162b2 or mRNA-1273) against SARS-CoV-2 in a longitudinal manner; whether there are differences in latency or amplitude of the early response and which markers are most suitable to detect these responses. METHODS: We performed assays for anti-S1 IgG and IgA, anti-NCP IgG and a surrogate neutralization assay on serum samples collected from 57 participants on the day of the second vaccination as well as the following seven days. RESULTS: All examined vaccination regimens induced detectable antibody responses within the examined time frame. Both heterologous regimens induced responses earlier and with a higher amplitude than homologous ChAdOx1 nCoV-19. Between the heterologous regimens, amplitudes were somewhat higher for ChAdOx1 nCoV-19 + mRNA-1273. There was no difference in latency between the IgG and IgA responses. Increases in the surrogate neutralization assay were the first changes to be detectable for all regimens and the only significant change seen for homologous ChAdOx1 nCoV-19. DISCUSSION: Both examined heterologous vaccination regimens are superior in immunogenicity, including the latency of the response, to homologous ChAdOx1 nCoV-19. While the IgA response has a shorter latency than the IgG response after the first dose, no such difference was found after the second dose, implying that both responses are driven by separate plasma cell populations. Early and steep increases in surrogate neutralization levels suggest that this might be a more sensitive marker for antibody responses after vaccination against SARS-CoV-2 than absolute levels of anti-S1 IgG.

"Clinical characteristics of headache after vaccination against COVID-19 (coronavirus SARS-CoV-2) with the BNT162b2 mRNA vaccine: A multicentre observational cohort study": Erratum

Reports an error in "Clinical characteristics of headache after vaccination against COVID-19 (coronavirus SARS-CoV-2) with the BNT162b2 mRNA vaccine: A multicentre observational cohort study" by Carl H. Gobel, Axel Heinze, Sarah Karstedt, Mascha Morscheck, Lilian Tashiro, Anna Cirkel, Qutayba Hamid, Rabih Halwani, Mohamad-Hani Temsah, Malte Ziemann, Siegfried Gorg, Thomas Munte and Hartmut Gobel (Brain Communications, 2021[Jul][23], Vol 3[3][fcab169]). In the originally published version of this manuscript, the video abstract was missing. The video abstract is now available online. (The following abstract of the original article appeared in record 2021-82839-001). The novel coronavirus SARS-CoV-2 causes the infectious disease COVID-19. Newly developed mRNA vaccines can prevent the spread of the virus. Headache is the most common neurological symptom in over 50% of those vaccinated. Detailed information about the clinical characteristics of this form of headache has not yet been described. The aim of the study is to examine in detail the clinical characteristics of headaches occurring after vaccination against COVID-19 with the BNT162b2 mRNA COVID-19 vaccine for the first time. In a multicentre observational cohort study, data on the clinical features and corresponding variables were recorded using a standardized online questionnaire. The questionnaire was circulated to 12 000 residential care homes of the elderly as well as tertiary university hospitals in Germany and the United Arab Emirates. The primary outcomes of this study are the clinical features of headache after vaccination. Comorbidities, treatment with medication and sociodemographic variables are also analysed. A total of 2349 participants reported headaches after vaccination with the BNT162b2 mRNA COVID-19 vaccine. Headaches occur an average of 18.0 +/- 27.0 h after vaccination and last an average duration of 14.2 +/- 21.3 h. Only 9.7% of those affected also report headaches resulting from previous vaccinations. In 66.6% of the participants, headache occurs as a single episode. A bilateral location is indicated by 73.1% of the participants. This is most often found on the forehead (38.0%) and temples (32.1%). A pressing pain character is indicated by 49.2% and 40.7% report a dull pain character. The pain intensity is most often moderate (46.2%), severe (32.1%) or very severe (8.2%). The most common accompanying symptoms are fatigue (38.8%), exhaustion (25.7%) and muscle pain (23.4%). Headaches after COVID-19 vaccination show an extensive complex of symptoms. The constellation of accompanying symptoms together with the temporal and spatial headache characteristics delimit a distinctive headache phenotype. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

The temporal course of T- and B-cell responses to vaccination with BNT162b2 and mRNA-1273.

OBJECTIVES: To investigate the response of the immune system (and its influencing factors) to vaccination with BNT162b2 or mRNA-1273. METHODS: 531 vaccinees, recruited from healthcare professionals, donated samples before, in between, and after the administration of the two doses of the vaccine. T- and B-cell responses were examined via interferon-γ (IFN-γ) release assay, and antibodies against different epitopes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (S1 and NCP) were detected via ELISA and surrogate neutralization assay. Results were correlated with influencing factors such as age, sex, prior infection, vaccine received (BNT162b2 or mRNA-1273), and immunosuppression. Furthermore, antinuclear antibodies (ANAs) were measured to screen for autoimmune responses following vaccination with an mRNA vaccine. RESULTS: No markers of immunity against SARS-CoV-2 were found before the first vaccination. Two weeks after it, specific responses against SARS-CoV-2 were already measurable (median ± median absolute deviation (MAD): anti-S1 IgG 195.5 ± 172.7 BAU/mL; IgA 6.7 ± 4.9 OD; surrogate neutralization 39 ± 23.7%), and were significantly increased two weeks after the second dose (anti-S1 IgG 3744 ± 2571.4 BAU/mL; IgA 12 ± 0 OD; surrogate neutralization 100 ± 0%, IFN-γ 1897.2 ± 886.7 mIU/mL). Responses were stronger for younger participants (this difference decreasing after the second dose). Further influences were previous infection with SARS-CoV-2 (causing significantly stronger responses after the first dose compared to unexposed individuals (p ≤ 0.0001)) and the vaccine received (significantly stronger reactions for recipients of mRNA-1273 after both doses, p < 0.05-0.0001). Some forms of immunosuppression significantly impeded the immune response to the vaccination (with no observable immune response in three immunosuppressed participants). There was no significant induction of ANAs by the vaccination (no change in qualitative ANA results (p 0.2592) nor ANA titres (p 0.08) from pre-to post-vaccination. CONCLUSIONS: Both vaccines elicit strong and specific immune responses against SARS-CoV-2 which become detectable one week (T-cell response) or two weeks (B-cell response) after the first dose.

Headache Attributed to Vaccination Against COVID-19 (Coronavirus SARS-CoV-2) with the ChAdOx1 nCoV-19 (AZD1222) Vaccine: A Multicenter Observational Cohort Study.

INTRODUCTION: The most frequently reported neurological adverse event of ChAdOx1 nCoV-19 (AZD1222) vaccine is headache in 57.5%. Several cases of cerebral venous thrombosis (CVT) have developed after vaccination. Headache is the leading symptom of CVT. For the differential diagnosis of headaches attributed to this vaccine and headaches attributed to CVT, it is of central clinical importance whether and, if so, how the phenotypes and course of these headaches can be differentiated. The study aims to examine in detail the phenotype of headache attributed to this vaccine. METHODS: Data on the clinical features and corresponding variables were recorded using a standardized online questionnaire in this multicenter observational cohort study. The primary outcomes of this study are the clinical features of headaches after vaccination. FINDINGS: A total of 2464 participants reported headaches after vaccination with the ChAdOx1 nCoV-19 (AZD1222) vaccine. On average, headaches occurred 14.5 ± 21.6 h after vaccination and lasted 16.3 ± 30.4 h. A bilateral location was described by 75.8% of participants. This is most often found on the forehead (40.0%) and temples (31.4%); 50.4% reported a pressing and 37.7% a dull pain character. Headache intensity was most often severe (38.7%), moderate (35.2%), or very severe (15.5%). Accompanying symptoms were most commonly fatigue (44.8%), chills (36.1%), exhaustion (34.9%), and fever (30.4%). CONCLUSION: Headaches attributed to COVID-19 vaccination with the ChAdOx1 nCoV-19 (AZD1222) vaccine demonstrate an extensive and characteristic complex of symptoms. The findings have several important clinical implications for the differentiation of post-vaccinal headache and other primary as well as secondary headaches.