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Acquired hemophilia A (AHA) is a rare bleeding disorder (1.4 per million inhabitants per year) caused by neutralizing antibodies against factor VIII. Although uncommon, these autoantibodies can cause a high rate of morbidity and mortality. Several conditions are linked with AHA; based on an EACH2 study, 3.8% of AHA could be connected to infection. In the last four years, most humans have contracted the SARS-CoV-2 infection or have been vaccinated against it. Whether or not COVID-19 immunization might induce AHA remains controversial. This review aims to evaluate the evidence about this possible association. Overall, 18 manuscripts (2 case series and 16 case reports) were included. The anti-SARS-CoV-2 vaccination, as also happens with other vaccines, may stimulate an autoimmune response. However, older individuals with various comorbidities are both at risk of developing AHA and of COVID-19-related morbidity and mortality. Therefore, the COVID-19 vaccine must always be administered because the benefits still outweigh the risks. Yet, we should consider the rare possibility that the activation of an immunological response through vaccination may result in AHA. Detailed registries and prospective studies would be necessary to analyze this post-vaccine acquired bleeding disorder, looking for possible markers and underlying risk factors for developing the disease in association with vaccination. [ABSTRACT FROM AUTHOR]

There are varying data concerning the effect of prior anti-vector immunity on the T-cell response induced by immunisation with an identical vectored vaccine containing a heterologous antigen insert. To determine whether prior exposure to ChAdOx1-SARS-CoV2 immunisation (Vaxzevria®) impacts magnitudes of antigen-specific T-cell responses elicited by subsequent administration of the same viral vector (encoding HBV antigens, ChAdOx1-HBV), healthy volunteers that had received Vaxzevria® (n = 15) or the Pfizer or Moderna mRNA COVID-19 vaccine (n = 11) between 10 and 18 weeks prior were recruited to receive a single intramuscular injection of ChAdOx1-HBV. Anti-ChAdOx1-neutralising antibody titers were determined, and vector or insert-specific T-cell responses were measured by a gamma-interferon ELISpot and intracellular cytokine staining (ICS) assay using multiparameter flow cytometry. Participants were followed for three months after the ChAdOx1-HBV injection, which was well-tolerated, and no dropouts occurred. The baseline ChAdOx1 neutralisation titers were higher in the Vaxzevria® cohort (median of 848) than in the mRNA cohort (median of 25). T-cell responses to HBV antigens, measured by ELISpot, were higher on day 28 in the mRNA group (p = 0.013) but were similar between groups on day 84 (p = 0.441). By ICS, these differences persisted at the last time point. There was no clear correlation between the baseline responses to the adenoviral hexon and the subsequent ELISpot responses. As vaccination within 3 months using the same viral vector backbone affected the insert-specific T-cell responses, a greater interval after prior adenoviral immunisation using heterologous antigens may be warranted in settings in which these cells play critical roles. [ABSTRACT FROM AUTHOR]

Background: The emergence of the SARS-CoV-2 (COVID-19) pandemic has accelerated work on the creation of effective vaccines, both in terms of previously known vector vaccines and new-generation (mRNA) vaccines. The scientific research on vaccination against COVID-19 infection is limited; therefore, understanding how the immune system responds to vaccines is critical. In our study, we conducted a long-term analysis of the presence and persistence of the immune response via chemiluminescence, analyzing the level of IgG antibodies and neutralizing antibodies in subjects vaccinated with two types of mRNA (Comirnaty) and vector (Vaxzevria) vaccines. Materials and methods: Healthcare workers and a group of teachers were recruited for this study according to the 2021 government-launched vaccination calendar. They received two doses of the Comirnaty or Vaxzevria vaccine. SRBD (spike-receptor binding domain) IgG antibody levels were measured monthly for 6 consecutive months with a chemiluminescent assay (CLIA) and neutralizing antibodies for two periods—1 and 5 months from the completion of the vaccination course. Results: 168 people were recruited for this study: 135 people for the mRNA vaccine group and 33 people for the vector vaccine group. Comparing the serum IgG levels between the two types of vaccines, a significant difference in median values can be noted at all time points. In consecutive months, the mRNA-vaccinated group exhibited significantly higher SRBD levels compared to the vector group, with peak concentrations at one month after the complete vaccination cycle (745 AU/mL vs. 15.44 AU/mL; p < 0.001). Peak antibody concentration for the vector vaccine was observed one month later, at the third follow-up visit; however, the median IgG concentration was almost 7.7 times higher for the Comirnaty group. Both products were effective in stimulating neutralizing antibody production after vaccination. Higher median values were observed for the mRNA vaccines in both evaluations. At first evaluation, the median value for NA concentration in the Comirnaty group was 6 times higher than in the Vaxzevria group (median value 12.23 [IQR 27.3] vs. 1.7 [IQR 3.3]; p < 0.001. Conclusions: People vaccinated with the mRNA vaccine (Comirnaty) showed a stronger immune response to the vaccination than the group of people administered the vector vaccine (Vaxzevria). The Comirnaty group showed higher levels of IgG, including neutralizing antibodies, at all time points during the follow-up period, and this was independent of having had a SARS-CoV-2 infection. A natural decrease in antibody levels was seen within 6 months. A booster vaccination may be required. No serious side effects were observed in either group. [ABSTRACT FROM AUTHOR]

There are varying data concerning the effect of prior anti-vector immunity on the T-cell response induced by immunisation with an identical vectored vaccine containing a heterologous antigen insert. To determine whether prior exposure to ChAdOx1-SARS-CoV2 immunisation (Vaxzevria®) impacts magnitudes of antigen-specific T-cell responses elicited by subsequent administration of the same viral vector (encoding HBV antigens, ChAdOx1-HBV), healthy volunteers that had received Vaxzevria® (n = 15) or the Pfizer or Moderna mRNA COVID-19 vaccine (n = 11) between 10 and 18 weeks prior were recruited to receive a single intramuscular injection of ChAdOx1-HBV. Anti-ChAdOx1-neutralising antibody titers were determined, and vector or insert-specific T-cell responses were measured by a gamma-interferon ELISpot and intracellular cytokine staining (ICS) assay using multiparameter flow cytometry. Participants were followed for three months after the ChAdOx1-HBV injection, which was well-tolerated, and no dropouts occurred. The baseline ChAdOx1 neutralisation titers were higher in the Vaxzevria® cohort (median of 848) than in the mRNA cohort (median of 25). T-cell responses to HBV antigens, measured by ELISpot, were higher on day 28 in the mRNA group (p = 0.013) but were similar between groups on day 84 (p = 0.441). By ICS, these differences persisted at the last time point. There was no clear correlation between the baseline responses to the adenoviral hexon and the subsequent ELISpot responses. As vaccination within 3 months using the same viral vector backbone affected the insert-specific T-cell responses, a greater interval after prior adenoviral immunisation using heterologous antigens may be warranted in settings in which these cells play critical roles.

Introduction: The COVID-19 pandemic has resulted in more than 6.5 million deaths worldwide yet. Vaccination against the SARS-CoV-2 virus is a reliable way out of the pandemic, however, vaccination rate reaches only 58% in the Slovak Republic. Concerns about the adverse reactions of vaccines are one of the reasons for the low vaccination rate. Objective: The aim of our analysis was to review reported suspicions of adverse reactions (ARs) of registered COVID-19 vaccines (Comirnaty, Vaxzevria, Spikevax), which State Institute for Drug Control received from healthcare professionals and patients in the period from 1 January 2021 to 31 May 2021. Methods: Data were collected from the State Institute for Drug Control database, a retrospective analysis was carried out focusing on trends in the number of all reports of suspicions of adverse reactions sent to the State Institute for Drug Control during the previously mentioned period. We analysed the Retrieved data were analysed with the usage of descriptive statistics and comparison to historical data on drug adverse reactions in Slovakia was performed. Results: During the evaluation period, 5,763 reported suspicions of adverse reactions were analysed, overall, there was a significant (p < 0.0001) increase in the number of reported adverse reactions fivefold. 93% of ARs (n = 5,346) were reported for COVID-19 vaccines. In comparison of the extentof all adverse reactions, there is clearly a statistically significant difference between all types of vaccines administered at that time (p ≤ 0.0001). No statistically significant difference (p ≤ 0.238) was identified between Spikevax and Comirnaty in the proportion of serious adverse reactions. However, a significantly higher (p ≤ 0.00001) proportion of reported suspicions of serious adverse reactions was observed after the administration of Vaxzevria. Conclusion: This is the first analysis conducted in Slovakia aimed to reported adverse reactions in relation to the administration of COVID-19 vaccines. The rate of spontaneously reported suspected adverse reactions has been insufficient in the past for a long time; during the period from January to May 2021 the reporting rate increased due active calls for adverse reactions reporting. In concordance with European data, Vaxzevria had a significantly higher ratio of reported suspicions of serious adverse reactions. [ABSTRACT FROM AUTHOR]

Background: The emergence of the SARS-CoV-2 (COVID-19) pandemic has accelerated work on the creation of effective vaccines, both in terms of previously known vector vaccines and new-generation (mRNA) vaccines. The scientific research on vaccination against COVID-19 infection is limited; therefore, understanding how the immune system responds to vaccines is critical. In our study, we conducted a long-term analysis of the presence and persistence of the immune response via chemiluminescence, analyzing the level of IgG antibodies and neutralizing antibodies in subjects vaccinated with two types of mRNA (Comirnaty) and vector (Vaxzevria) vaccines. Materials and methods: Healthcare workers and a group of teachers were recruited for this study according to the 2021 government-launched vaccination calendar. They received two doses of the Comirnaty or Vaxzevria vaccine. SRBD (spike-receptor binding domain) IgG antibody levels were measured monthly for 6 consecutive months with a chemiluminescent assay (CLIA) and neutralizing antibodies for two periods—1 and 5 months from the completion of the vaccination course. Results: 168 people were recruited for this study: 135 people for the mRNA vaccine group and 33 people for the vector vaccine group. Comparing the serum IgG levels between the two types of vaccines, a significant difference in median values can be noted at all time points. In consecutive months, the mRNA-vaccinated group exhibited significantly higher SRBD levels compared to the vector group, with peak concentrations at one month after the complete vaccination cycle (745 AU/mL vs. 15.44 AU/mL; p < 0.001). Peak antibody concentration for the vector vaccine was observed one month later, at the third follow-up visit; however, the median IgG concentration was almost 7.7 times higher for the Comirnaty group. Both products were effective in stimulating neutralizing antibody production after vaccination. Higher median values were observed for the mRNA vaccines in both evaluations. At first evaluation, the median value for NA concentration in the Comirnaty group was 6 times higher than in the Vaxzevria group (median value 12.23 [IQR 27.3] vs. 1.7 [IQR 3.3]; p < 0.001. Conclusions: People vaccinated with the mRNA vaccine (Comirnaty) showed a stronger immune response to the vaccination than the group of people administered the vector vaccine (Vaxzevria). The Comirnaty group showed higher levels of IgG, including neutralizing antibodies, at all time points during the follow-up period, and this was independent of having had a SARS-CoV-2 infection. A natural decrease in antibody levels was seen within 6 months. A booster vaccination may be required. No serious side effects were observed in either group.

Introduction: The COVID-19 pandemic has resulted in more than 6.5 million deaths worldwide yet. Vaccination against the SARS-CoV-2 virus is a reliable way out of the pandemic, however, vaccination rate reaches only 58% in the Slovak Republic. Concerns about the adverse reactions of vaccines are one of the reasons for the low vaccination rate.Objective: The aim of our analysis was to review reported suspicions of adverse reactions (ARs) of registered COVID-19 vaccines (Comirnaty, Vaxzevria, Spikevax), which State Institute for Drug Control received from healthcare professionals and patients in the period from 1 January 2021 to 31 May 2021.Methods: Data were collected from the State Institute for Drug Control database, a retrospective analysis was carried out focusing on trends in the number of all reports of suspicions of adverse reactions sent to the State Institute for Drug Control during the previously mentioned period. We analysed the Retrieved data were analysed with the usage of descriptive statistics and comparison to historical data on drug adverse reactions in Slovakia was performed.Results: During the evaluation period, 5,763 reported suspicions of adverse reactions were analysed, overall, there was a significant (p < 0.0001) increase in the number of reported adverse reactions fivefold. 93% of ARs (n = 5,346) were reported for COVID-19 vaccines. In comparison of the extentof all adverse reactions, there is clearly a statistically significant difference between all types of vaccines administered at that time (p ≤ 0.0001). No statistically significant difference (p ≤ 0.238) was identified between Spikevax and Comirnaty in the proportion of serious adverse reactions. However, a significantly higher (p ≤ 0.00001) proportion of reported suspicions of serious adverse reactions was observed after the administration of Vaxzevria.Conclusion: This is the first analysis conducted in Slovakia aimed to reported adverse reactions in relation to the administration of COVID-19 vaccines. The rate of spontaneously reported suspected adverse reactions has been insufficient in the past for a long time; during the period from January to May 2021 the reporting rate increased due active calls for adverse reactions reporting. In concordance with European data, Vaxzevria had a significantly higher ratio of reported suspicions of serious adverse reactions.

On February 9, 2021, the Italian Ministry of Health made the "Covid-19 vaccine AstraZeneca" (now "Vaxzevria") available for use in the anti-COVID-19 vaccination campaign. However, in early March, the media reported that five people died a few days after receiving the vaccine. The reaction among both those already vaccinated and the vaccine candidates was one of near panic. The subsequent events have had long-lasting consequences, as 10-20% of vaccine candidates have since refused vaccination with the AstraZeneca vaccine, so in addition to the delay in vaccination, ~200,000 doses of it were not administered. The goal of the vaccination campaign in Italy, when operating at full capacity, was to administer 500,000 doses per day, for a total of 3,500,000 doses per week. In this large amount of people, it is statistically certain that a certain number of subjects will develop non-vaccine related health problems or even die from causes unrelated to having been vaccinated. At this time in history, press reports must be inspired by a strong sense of responsibility and awareness of the potential consequences of misinformation; this is particularly true, especially because also the social media get inevitably involved. [ABSTRACT FROM AUTHOR]

On 11 June 2021, the Italian Ministry of Health authorized the heterologous vaccination schedule. The goals of our retrospective study were to (a) evaluate the undesirable effects after the administration of Vaxzevria and Comirnaty vaccines; (b) evaluate the antibody response after 28 days from the administration of the second dose; and (c) compare the antibody responses after the homologous and heterologous vaccination regimens. The undesirable effects were collected using a survey; IgG Spike was quantified using the electrochemiluminescence method; the comparison between the antibody responses was carried out using the sample of a homologous vaccine schedule previously analyzed. Pain at the injection site is the most common undesirable effect after the administration of both vaccines (62.1% after Vaxzevria vs. 82.75% after Comirnaty); swelling at the injection site is more frequent after the administration of Vaxzevria than after the administration of Comirnaty: (15.52% vs. 5.17%); headache is more frequent in women than in men for both the vaccination types (p < 0.05); 49.09% of the sample reported IgG Spike ≥ 12,500 U/mL; the antibody titer of the heterologous schedule is higher than that of the homologous vaccination. Our study demonstrated that the undesirable effects after the administration of the second dose are less frequent and less severe than after the administration of the first dose, and that the immunogenicity of the heterologous vaccinations is higher than that of the homologous ones. [ABSTRACT FROM AUTHOR]

We assessed the non-inferiority of homologous boosting compared with heterologous boosting with the recombinant protein vaccine, SCB-2019, in adults previously immunized with different COVID-19 vaccines. Three equal cohorts (N ~ 420) of Philippino adults (18-80 years) previously immunized with Comirnaty, CoronaVac or Vaxzevria COVID-19 vaccines were randomized 1:1 to receive homologous or heterologous (SCB-2019) boosters. Neutralizing antibodies against prototype SARS-CoV-2 (Wuhan-Hu-1) were measured in all participants and against Delta variant and Omicron sub-lineages in subsets (30‒50 per arm) 15 days after boosting. Participants recorded solicited adverse events for 7 days and unsolicited and serious adverse events until Day 60. Prototype SARS-CoV-2 neutralizing responses on Day 15 after SCB-2019 were statistically non-inferior to homologous Vaxzevria boosters, superior to CoronaVac, but lower than homologous Comirnaty. Neutralizing responses against Delta and Omicron BA.1, BA.2, BA.4 and BA.5 variants after heterologous SCB-2019 were higher than homologous CoronaVac or Vaxzevria, but lower than homologous Comirnaty. Responses against Omicron BF.7, BQ.1.1.3, and XBB1.5 following heterologous SCB-2019 were lower than after homologous Comirnaty booster but significantly higher than after Vaxzevria booster. SCB-2019 reactogenicity was similar to CoronaVac or Vaxzevria, but lower than Comirnaty; most frequent events were mild/moderate injection site pain, headache and fatigue. No vaccine-related serious adverse events were reported. Heterologous SCB-2019 boosting was well tolerated and elicited neutralizing responses against all tested SARS-COV-2 viruses including Omicron BA.1, BA.2, BA.4, BA.5, BF.7, BQ.1.1.3, and XBB1.5 sub-lineages that were non-inferior to homologous boosting with CoronaVac or Vaxzevria, but not homologous Comirnaty booster.

Cases that experienced COVID-19 postvaccination-related thrombosis have been reported after the first dose of ChAdOx1 nCov-19 (Vaxzevria, AstraZeneca) or Ad26.COV2.S (Johnson & Johnson/Janssen) vaccine. These rare thrombotic events were observed within the expected vaccine-induced seroconversion period and could be attributed to platelet-activating (auto)antibodies against platelet factor 4 (PF4). Newly, vaccine-induced, cross-reactive anti-PF4 antibodies could explain this observation. An in-silico analysis using the Basic Local Alignment Search Tool was used to identify sequence similarity between PF4 and antigens contained in or encoded by ChAdOx1 nCov-19 or Ad26.COV2.S vaccines. Only one sequence within the signaling peptide of the SARS-CoV-2 spike protein exhibited a high percent identity (85.71%) with PF4. This sequence overlaps with a proven immunogenic peptide recognized from convalescent COVID-19 sera and could be responsible for the formation of platelet-activating immunocomplexes in susceptible patients. Manipulation of the immunogenicity of this particular sequence within the encoded SARS-CoV-2 spike protein signaling peptide may eliminate this iatrogenic severe adverse effect.

Myocarditis in response to COVID-19 vaccination has been reported since early 2021. In particular, young male individuals have been identified to exhibit an increased risk of myocardial inflammation following the administration of mRNA-based vaccines. Even though the first epidemiological analyses and numerous case reports investigated potential relationships, endomyocardial biopsy (EMB)-proven cases are limited. Here, we present a comprehensive histopathological analysis of EMBs from 15 patients with reduced ejection fraction (LVEF = 30 (14–39)%) and the clinical suspicion of myocarditis following vaccination with Comirnaty® (Pfizer-BioNTech) (n = 11), Vaxzevria® (AstraZenica) (n = 2) and Janssen® (Johnson & Johnson) (n = 2). Immunohistochemical EMB analyses reveal myocardial inflammation in 14 of 15 patients, with the histopathological diagnosis of active myocarditis according the Dallas criteria (n = 2), severe giant cell myocarditis (n = 2) and inflammatory cardiomyopathy (n = 10). Importantly, infectious causes have been excluded in all patients. The SARS-CoV-2 spike protein has been detected sparsely on cardiomyocytes of nine patients, and differential analysis of inflammatory markers such as CD4+ and CD8+ T cells suggests that the inflammatory response triggered by the vaccine may be of autoimmunological origin. Although a definitive causal relationship between COVID-19 vaccination and the occurrence of myocardial inflammation cannot be demonstrated in this study, data suggest a temporal connection. The expression of SARS-CoV-2 spike protein within the heart and the dominance of CD4+ lymphocytic infiltrates indicate an autoimmunological response to the vaccination. [ABSTRACT FROM AUTHOR]

Summary: Background: Aging influences COVID-19 severity and response to vaccination, but previous vaccine effectiveness (VE) analyzes lack the power to evaluate its role in subgroups within the elderly age group. Here we analyzed the impact of age on viral vector and inactivated virus vaccines' effectiveness, the main platforms used in low- and middle-income countries. Methods: We report a retrospective longitudinal study of 75,919,840 Brazilian vaccinees from January 18 to July 24, 2021, evaluating documented infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19-related hospitalisation, ICU admission, and death. Negative binomial regression models adjusted for sociodemographic characteristics were used for VE estimation. Findings: The overall analyzes of full vaccination showed VE against hospitalisation, ICU admission, and death of 91·4% (95%CI:90·1–92·5), 91·1% (95%CI:88·9–92·9) and 92·3% (95%CI:90·5–93·7) for Vaxzevria and 71·2% (95%CI:70·0–72·4), 72·2% (95%CI:70·2–74·0) and 73·7% (95%CI:72·1–75·2) for CoronaVac, respectively. VE for all outcomes is progressively lower with age. In fully-Vaxzevria-vaccinated individuals aged

On 11 June 2021, the Italian Ministry of Health authorized the heterologous vaccination schedule. The goals of our retrospective study were to (a) evaluate the undesirable effects after the administration of Vaxzevria and Comirnaty vaccines; (b) evaluate the antibody response after 28 days from the administration of the second dose; and (c) compare the antibody responses after the homologous and heterologous vaccination regimens. The undesirable effects were collected using a survey; IgG Spike was quantified using the electrochemiluminescence method; the comparison between the antibody responses was carried out using the sample of a homologous vaccine schedule previously analyzed. Pain at the injection site is the most common undesirable effect after the administration of both vaccines (62.1% after Vaxzevria vs. 82.75% after Comirnaty); swelling at the injection site is more frequent after the administration of Vaxzevria than after the administration of Comirnaty: (15.52% vs. 5.17%); headache is more frequent in women than in men for both the vaccination types (p < 0.05); 49.09% of the sample reported IgG Spike ≥ 12,500 U/mL; the antibody titer of the heterologous schedule is higher than that of the homologous vaccination. Our study demonstrated that the undesirable effects after the administration of the second dose are less frequent and less severe than after the administration of the first dose, and that the immunogenicity of the heterologous vaccinations is higher than that of the homologous ones.

La anemia hemolítica autoinmune (AHAI) inducida por fármacos es un trastorno hematológico en cual se produce una destrucción inmnunitaria de los glóbulos rojos por anticuerpos. Los agentes mas asociados son antibióticos y algunos quimioterápicos, pero también se han comunicado casos asociados con diferentes vacunas, incluido tras las vacunas frente a la COVID 19. Presentamos un caso de AHAI cuyo probable desencadenante fue la vacuna COVID 19 Vaxzevria.

Several European countries suspended or changed recommendations for the use of Vaxzevria (AstraZeneca) for suspected adverse effects due to atypical blood-clotting. This research aims to identify a reference point towards the number of thrombotic events expected in the Italian population over 50 years of age who received Vaxzevria from 22 January to 12 April 2021. The venous thromboembolism (VT) and immune thrombocytopenia (ITP) event rates were estimated from a population-based cohort. The overall VT rate was 1.15 (95% CI 0.93–1.42) per 1000 person-years, and the ITP rate was 2.7 (95% CI 0.7–11) per 100,000 person-years. These figures translate into 83 and two expected events of VT and ITP, respectively, in the 15 days following the first administration of Vaxzevria. The number of thrombotic events reported from the Italian Medicines Agency does not appear to have increased beyond that expected in individuals over 50 years of age.

A 66-year-old white female presented with a generalized, erythematous, and itchy eruption for 3 days after. She reported having fever on the first day of eruption, complaints of asthenia, and anorexia with no other systemic symptoms. She received her first dose of Vaxzevria (AstraZeneca, Cambridge, UK) against COVID-19 three weeks prior. The eruption started on the right arm at the vaccine injection site and then spread progressively throughout the entire body. We noticed multiform erythema-like patches with three or four concentric circles with different shades of redness. Anatomopathological analysis indicated a lichenoid histological pattern compatible with adverse event of vaccine. Degressive general corticotherapy was prescribed with an improvement of the symptomatology and complete healing in ten days. Physicians should be aware if this rare adverse event. Drug-induced lichenoid exanthema is considered a non-severe reaction and does not contraindicate the readministration of essential drugs. In this case, the patient refused the second injection of Vaxzevria. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has resulted in more than 6.2 million deaths worldwide. Despite advances in the treatment of this disease over the last 2 years, the only way out of the pandemic is vaccination against the SARS-CoV-2 virus, which is constantly confronted with considerable mistrust and fears of adverse reactions (ADRs) in Slovakia. The aim of this study is to analyse reported suspicions of ADRs of registered COVID-19 vaccines (Comirnaty, Vaxzevria, Spikevax), which the State Institute for Drug Control received from health care professionals and patients between 1 January and 31 May 2021. The program R (version 3.6.3), a language and environment for statistical calculations, GNU GPL license was used for data analysis. During the evaluation period, 5,763 reported suspicions of ADRs were analysed. Overall, there was a significant (p < .0001) fivefold increase in the number of reported ADRs. Ninety-three percent of ADRs (n = 5,346) were reported for COVID-19 vaccines. No statistically significant difference (p = .238) was identified between Spikevax and Comirnaty in the proportion of serious ADRs. However, a significantly higher (p = .00001) proportion of reported suspicions of severe ADRs was observed with Vaxzevria. There is a significant difference in the ratio of serious ADRs between the sexes for all COVID-19 vaccines (p < .00001); in women this ratio is in all cases significantly higher than in men (p < .0001). ADRs were most often reported by patients (p < .0001). In Slovakia, the rate of spontaneous reporting of suspected ADRs has been low for a long time; in the period between January and May 2021, however, the rate increased as a result of active calls for ADR reporting, most often from patients. According to European data, Vaxzevria has a significantly higher ratio of reported suspicions of serious ADRs. For all vaccines, the incidence of severe ADRs is significantly higher in women. [ABSTRACT FROM AUTHOR]

Cases that experienced COVID-19 postvaccination-related thrombosis have been reported after the first dose of ChAdOx1 nCov-19 (Vaxzevria, AstraZeneca) or Ad26.COV2.S (Johnson & Johnson/Janssen) vaccine. These rare thrombotic events were observed within the expected vaccine-induced seroconversion period and could be attributed to platelet-activating (auto)antibodies against platelet factor 4 (PF4). Newly, vaccine-induced, cross-reactive anti-PF4 antibodies could explain this observation. An in-silico analysis using the Basic Local Alignment Search Tool was used to identify sequence similarity between PF4 and antigens contained in or encoded by ChAdOx1 nCov-19 or Ad26.COV2.S vaccines. Only one sequence within the signaling peptide of the SARS-CoV-2 spike protein exhibited a high percent identity (85.71%) with PF4. This sequence overlaps with a proven immunogenic peptide recognized from convalescent COVID-19 sera and could be responsible for the formation of platelet-activating immunocomplexes in susceptible patients. Manipulation of the immunogenicity of this particular sequence within the encoded SARS-CoV-2 spike protein signaling peptide may eliminate this iatrogenic severe adverse effect.

Kawasaki disease (KD) is a medium-vessel vasculitis that is typically presented during childhood; fewer than 100 cases of KD have been reported worldwide in adult patients who met the criteria according to the American College of Rheumatology. This study presents the case of an 18-year-old patient with no previous history of any disease, who presented atypical KD with liver and kidney dysfunction, with a good response to intravenous immunoglobulin therapy. The symptoms began 22 days after the application of the COVID-19 vaccine (nonreplicating viral vector Vaxzevria), and other conditions were ruled out. The term Adverse Events Following Immunization (AEFI)encompasses all the reactions that follow the application of any vaccine with no necessary causal relationship and can be due to the vaccine product, quality of the vaccine, immunization errors, or anxiety or just happen to be coincident events. These reactions should be reported so that clinicians can identify compatible cases and consider that the presentation of this disease, despite being atypical, can be manifested in adult patients. Likewise, case reports are an important basis for the pharmacovigilance of vaccines. [ABSTRACT FROM AUTHOR]

Several European countries suspended or changed recommendations for the use of Vaxzevria (AstraZeneca) for suspected adverse effects due to atypical blood-clotting. This research aims to identify a reference point towards the number of thrombotic events expected in the Italian population over 50 years of age who received Vaxzevria from 22 January to 12 April 2021. The venous thromboembolism (VT) and immune thrombocytopenia (ITP) event rates were estimated from a population-based cohort. The overall VT rate was 1.15 (95% CI 0.93–1.42) per 1000 person-years, and the ITP rate was 2.7 (95% CI 0.7–11) per 100,000 person-years. These figures translate into 83 and two expected events of VT and ITP, respectively, in the 15 days following the first administration of Vaxzevria. The number of thrombotic events reported from the Italian Medicines Agency does not appear to have increased beyond that expected in individuals over 50 years of age. [ABSTRACT FROM AUTHOR]

A 76 year-old female came to our observation one week after the vaccination with ChAdOx1 nCoV-19 AZD1222 for the onset of purpuric rash on her gluteal and legs regions associated with coxalgia and episodes of macrohaematuria. Henoch-Schönlein purpura (HSP) was diagnosed on the basis of the revised criteria developed by the European League Against Rheumatism, the Paediatric Rheumatology International Trials Organization, and the Paediatric Rheumatology European Society (EULAR/PRINTO/PRES). HSP is a common IgA-mediated small vessel vasculitis, typical of childhood, that affects several systems and is characterized by a tetrad of dermatological, abdominal, joint, and renal manifestations. The Etiology of HSP is not completely understood, but it was observed following upper respiratory tract infections, medications, vaccinations, and malignancies. HSP has previously been reported following immunization with various vaccines, mostly within 12 weeks post, suggesting a possible correlation. To our knowledge, this is the first report of the possible association between COVID-19 ChAdOx1 nCoV-19 AZD1222 and the onset of HSP in a previously healthy woman. No similar cases were reported amongst 23.848 participants in the ChAdOx1 nCoV-19 AZD1222 trial. [ABSTRACT FROM AUTHOR]

To assess vaccine immunogenicity in non-infected and previously infected individuals in a real-world scenario, SARS-CoV-2 antibody responses were determined during follow-up 2 (April 2021) of the population-based Tirschenreuth COVID-19 cohort study comprising 3378 inhabitants of the Tirschenreuth county aged 14 years or older. Seronegative participants vaccinated once with Vaxzevria, Comirnaty, or Spikevax had median neutralizing antibody titers ranging from ID50 = 25 to 75. Individuals with two immunizations with Comirnaty or Spikevax had higher median ID50s (of 253 and 554, respectively). Regression analysis indicated that both increased age and increased time since vaccination independently decreased RBD binding and neutralizing antibody levels. Unvaccinated participants with detectable N-antibodies at baseline (June 2020) revealed a median ID50 of 72 at the April 2021 follow-up. Previously infected participants that received one dose of Vaxzevria or Comirnaty had median ID50 to 929 and 2502, respectively. Individuals with a second dose of Comirnaty given in a three-week interval after the first dose did not have higher median antibody levels than individuals with one dose. Prior infection also primed for high systemic IgA levels in response to one dose of Comirnaty that exceeded IgA levels observed after two doses of Comirnaty in previously uninfected participants. Neutralizing antibody levels targeting the spike protein of Beta and Delta variants were diminished compared to the wild type in vaccinated and infected participants.

Background: Aging influences COVID-19 severity and response to vaccination, but previous vaccine effectiveness (VE) analyzes lack the power to evaluate its role in subgroups within the elderly age group. Here we analyzed the impact of age on viral vector and inactivated virus vaccines' effectiveness, the main platforms used in low- and middle-income countries., Methods: We report a retrospective longitudinal study of 75,919,840 Brazilian vaccinees from January 18 to July 24, 2021, evaluating documented infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19-related hospitalisation, ICU admission, and death. Negative binomial regression models adjusted for sociodemographic characteristics were used for VE estimation., Findings: The overall analyzes of full vaccination showed VE against hospitalisation, ICU admission, and death of 91·4% (95%CI:90·1-92·5), 91·1% (95%CI:88·9-92·9) and 92·3% (95%CI:90·5-93·7) for Vaxzevria and 71·2% (95%CI:70·0-72·4), 72·2% (95%CI:70·2-74·0) and 73·7% (95%CI:72·1-75·2) for CoronaVac, respectively. VE for all outcomes is progressively lower with age. In fully-Vaxzevria-vaccinated individuals aged <60 years, VE against death was 96.5% (95%CI:82.1-99.3) versus 68·5% (95%CI:40·0-83·4) in those ≥90 years. Among fully-CoronaVac-vaccinated individuals, VE against death was 84.8% (95%CI:77.1-89.9) in those <60 years compared to 63.5 (95%CI 58.7-67.7) for vaccinees aged 80-89 years and 48·6%; (95%CI:35·0-59·3) for individuals aged ≥90 years. Post-vaccination daily cumulative incidence curves for all outcomes showed increased risk from younger to elder decades of life. There was no increase in the incidence of hospitalisation for individuals <60 years vaccinated during the same period as those aged ≥90 years., Interpretation: Although both vaccines have been effective in protecting against infection, hospitalization and death; Vaxzevria and CoronaVac demonstrated high effectiveness against severe outcomes for individuals up to 79 years of age. Our results reinforce the idea that booster doses should be carefully considered in elders., Funding: This study was partially supported by a donation from the "Fazer o bem faz bem" program., Competing Interests: VO, VB, MB, and MB-N are employees of Fiocruz, a federal public institution, which manufactures Vaxzevria in Brazil, through a full technology transfer agreement with AstraZeneca. Fiocruz allocates all manufactured products to the Brazilian Ministry of Health for public health service (SUS) use. All other authors report no potential competing interests., (© 2021 The Author(s).)

An increased risk of developing severe infections has been evidenced in rheumatic disease (RD) patients, and anti-COVID-19 vaccination is strictly recommended for RD patients. However, up to now, no data are available on safety, immunogenicity and efficacy of COVID-19 vaccinations in RD patients. The possible development of adverse events (AEs), including the flare-up of underlying RD, represents a matter of growing importance. The aim of our study is to assess, in RD patients, the safety profile of different types of approved vaccines and the possible influence of immunosuppressive therapies and clinical or demographic characteristics of RD patients on development of AEs. Participants (n = 185; 30.7%) received anti-COVID-19 vaccinations, 137 with autoimmune/chronic inflammatory RD (Au/cIn-RD) and 48 with nonautoimmune/chronic inflammatory RD (no-Au/cIn-RD). AEs were recorded in 42% of patients after the first dose of vaccine, and in 26% of patients after the second dose. The most common reported AEs after anti-COVID 19 vaccines were site injection pain (17%), headache (12%), fever (12%), myalgia (10%) and fatigue (10%). Relapses of the underlying Au/c-In-RD were recorded in 2.2% of patients after the first dose of vaccine. In Au/c-In-RD the risk of developing AEs after the first dose of vaccine was lower in older patients (OR = 0.95; p = 0.001), and in the group of patients with complete control of RD (OR: 0.2; p = 0.010). A lower percentage of AEs was observed in patients with complete control of their Au/cIn-RD (29%) compared to those with low (57%) or moderate-high disease activity (63%) (p = 0.002 and p = 0.006 respectively). In this study all types of COVID-19 vaccines in use in Italy seemed safe in RD patients. The results of this study might provide reassuring information for Au/cIn RD patients and clinicians and could strengthen the data on vaccine safety to guide the use of COVID-19 vaccines in Au/cIn-RD on immunosuppressive agents. [ABSTRACT FROM AUTHOR]

Vaccination with the adenoviral-vector-based AstraZeneca ChAdOx1 nCov-19 (Vaxzevria) vaccine is efficient and safe. However, in rare cases vaccinated individuals developed life-threatening thrombotic complications, including thrombosis in cerebral sinus and splanchnic veins. Monitoring of the applied vector in vivo represents an important precondition to study the molecular mechanisms underlying vaccine-driven adverse effects now referred to as vaccine-induced immune thrombotic thrombocytopenia (VITT). We previously have shown that digital PCR (dPCR) is an excellent tool to quantify transgene copies in vivo . Here, we present a highly sensitive dPCR for in situ quantification of ChAdOx1 nCoV-19 copies. Using this method, we quantified vector copies in human plasma 24, 72, and 168 h post vaccination and in a variety of murine tissues in an experimental vaccination model 30 min post injection. We describe a method for high-sensitivity quantitative detection of ChAdOx1 nCoV-19 with possible implications to elucidate the mechanisms of severe ChAdOx1 nCov-19 vaccine complications., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s).)

Thrombosis with thrombocytopenia (TTS) has been identified as a rare adverse event following COVID-19 vaccination with Vaxzevria. We modelled the benefits and risks of Vaxzevria distribution from May to September 2021 in metropolitan France where other vaccines are available, considering French hospitalisation data and European data on TTS. Across different scenarios, benefits of Vaxzevria distribution in people 55 years and older exceeded the risk of death from COVID-19. In young adults, risks were at least of similar magnitude as benefits.

We investigated a COVID-19 outbreak of the SARS-CoV-2 Delta variant of concern in a London care home, where 8/21 residents and 14/21 staff had received a single dose of Vaxzevria (ChAdOx1-S; AstraZeneca) vaccine. We identified 24 SARS-CoV-2 infections (16 residents, 8 staff) among 40 individuals (19 residents, 21 staff); four (3 residents, 1 staff) were hospitalised, and none died. The attack rate after one vaccine dose was 35.7% (5/14) for staff and 81.3% (13/16) for residents.