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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]

Objective To investigate the association of immune response with vaccination adverse effects at peak anti–receptor-binding domain spike subunit 1 (anti-RBDS1) IgG after full vaccination with Comirnaty, Spikevax, or Vaxzevria. Methods Anti-RBDS1 IgG concentrations after vaccination were determined in healthy adults vaccinated with the Comirnaty, Spikevax, and Vaxzevria vaccines. The association of reactogenicity and peak antibody response after vaccination was tested. Results Anti-RBDS1 IgG values were significantly higher in the Comirnaty and Spikevax group, compared with the Vaxzevria group (P <.001). Fever and muscle pain were found to be significant independent predictors of peak anti-RBDS1 IgG in the Comirnaty and Spikevax groups (P =.03 and P =.02, respectively). The multivariate model, adjusted for covariates, showed that no association between reactogenicity and peak antibody concentrations was found in the Comirnaty, Spikevax, and Vaxzevria groups. Conclusions No association between reactogenicity and peak anti-RBDS1 IgG after vaccination with the Comirnaty, Spikevax, and Vaxzevria vaccine was found. [ABSTRACT FROM AUTHOR]

Mucosal antibodies play a key role in protection against breakthrough COVID‐19 infections and emerging viral variants. Intramuscular adenovirus‐based vaccination (Vaxzevria) only weakly induces nasal IgG and IgA responses, unless vaccinees have been previously infected. However, little is known about how Vaxzevria vaccination impacts the ability of mucosal antibodies to induce Fc responses, particularly against SARS‐CoV‐2 variants of concern (VoCs). Here, we profiled paired mucosal (saliva, tears) and plasma antibodies from COVID‐19 vaccinated only vaccinees (uninfected, vaccinated) and COVID‐19 recovered vaccinees (COVID‐19 recovered, vaccinated) who both received Vaxzevria vaccines. SARS‐CoV‐2 ancestral‐specific IgG antibodies capable of engaging FcγR3a were significantly higher in the mucosal samples of COVID‐19 recovered Vaxzevria vaccinees in comparison with vaccinated only vaccinees. However, when IgG and FcγR3a engaging antibodies were tested against a panel of SARS‐CoV‐2 VoCs, the responses were ancestral‐centric with weaker recognition of Omicron strains observed. In contrast, salivary IgA, but not plasma IgA, from Vaxzevria vaccinees displayed broad cross‐reactivity across all SARS‐CoV‐2 VoCs tested. Our data highlight that while intramuscular Vaxzevria vaccination can enhance mucosal antibodies responses in COVID‐19 recovered vaccinees, restrictions by ancestral‐centric bias may have implications for COVID‐19 protection. However, highly cross‐reactive mucosal IgA could be key in addressing these gaps in mucosal immunity and may be an important focus of future SARS‐CoV‐2 vaccine development. [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.

Intranasal (i.n.) vaccines can induce mucosal and systemic immunity against respiratory pathogens. Previously, we demonstrated that the recombinant vesicular stomatitis virus (rVSV)‐based COVID‐19 vaccine rVSV‐SARS‐CoV‐2, with poor immunogenicity via the intramuscular route (i.m.), is more suitable for i.n. administration in mice and nonhuman primates. Here, we found that the rVSV‐SARS‐CoV‐2 Beta variant was more immunogenic than the wild‐type strain and other variants of concern (VOCs) in golden Syrian hamsters. Furthermore, the immune responses elicited by rVSV‐based vaccine candidates via the i.n. route were significantly higher than those of two licensed vaccines: the inactivated vaccine KCONVAC delivered via the i.m. route and the adenovirus‐based Vaxzevria delivered i.n. or i.m. We next assessed the booster efficacy of rVSV following two i.m. doses of KCONVAC. Twenty‐eight days after receiving two i.m. doses of KCONVAC, hamsters were boosted with a third dose of KCONVAC (i.m.), Vaxzevria (i.m. or i.n.), or rVSVs (i.n.). Consistent with other heterologous booster studies, Vaxzevria and rVSV elicited significantly higher humoral immunity than the homogenous KCONVAC. In summary, our results confirmed that two i.n. doses of rVSV‐Beta elicited significantly higher humoral immune responses than commercial inactivated and adeno‐based COVID vaccines in hamsters. As a heterologous booster dose, rVSV‐Beta induced potent, persistent, and broad‐spectrum humoral and mucosal neutralizing responses against all VOCs, highlighting its potential to be developed into a nasal‐spray vaccine. [ABSTRACT FROM AUTHOR]

Within the first 4 months of the Western Australian COVID‐19 immunisation programme, 49 suspected anaphylaxis cases were reported to the vaccine safety surveillance system. Twelve reports met Brighton Collaboration case definition, corresponding to rates of 15.9 and 17.7 per million doses of Vaxzevria and Comirnaty administered respectively. [ABSTRACT FROM AUTHOR]

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.

Purpose: To report a case of acute macular neuroretinopathy (AMN) following SARS-CoV-2 vaccination. Methods: Case report. Results: An otherwise healthy 28-year-old white woman presented to an ophthalmology department with complaints of black paracentral vision scotomata on both eyes that appeared 2 days after receiving the first dose of Vaxzevria vaccine. Fundus examination revealed bilateral red brown petaloid lesions around the fovea. On spectral domain optical coherence tomography, a hyperreflective plaque between the outer plexiform and outer nuclear layers along with disruption of ellipsoid zone/interdigitation zone was observed. A diagnosis of AMN was made. Conclusion: AMN may be an extremely rare adverse event of SARS-COV-2 vaccination, especially in patients with other risk factors. Synopsis: An otherwise healthy 28-year-old white woman was diagnosed with AMN 2 days after SARS-CoV-2 vaccination. [ABSTRACT FROM AUTHOR]

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.

To report two cases of acute macular neuroretinopathy (AMN) in young female patients following the administration of the adenovirus-based coronavirus disease 2019 (COVID-19) vaccine Vaxzevria (AstraZeneca). Spectral-domain optical coherence tomography and infrared imaging were used to confirm the diagnosis of AMN. Both patients showed a parafoveal hyperreflective band in the outer nuclear layer, disruption of the ellipsoid and interdigitation zones of the photoreceptor layers, and correlating hyporeflective areas on the near-infrared images. Both patients presented with flu-like fever and sudden onset of fortifications within 48 hours of vaccination. One patient showed altered flow in the deep capillary plexus and highly elevated thrombotic parameters. We report a possible association between immune-mediated AMN and the administration of adenovirus-based COVID-19 vaccine Vaxzevria. [ABSTRACT FROM AUTHOR]

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]

This case report describes a 59-year-old man with myelin oligodendrocyte glycoprotein (MOG)-positive longitudinal extensive transverse myelitis (LETM) after being vaccinated with the COVID-19 vaccine ChAdOx1 nCoV-19. He presented with urinary retention, gait disturbance, hypoesthesia and brisk reflexes in his lower extremities without paresis. Due to the ineffectiveness of high-dose intravenous methylprednisolone, therapeutic plasma exchange was performed, gradually improving the patient's condition. Vaccination as a trigger for an excessive immunological response seems plausible, though unspecific for the ChAdOx1 nCoV-19 vaccine. [ABSTRACT FROM AUTHOR]

• Studies conducted in real-world settings allow to address gaps in evidence from clinical trials. • This study evaluates two vaccine brands' effectiveness on the general population. • Comirnaty shows a 81% effectiveness 14 days after the scheduled second dose. • One dose of Vaxzevria showed an effectiveness of 63% after 7 weeks. • These results could help to promote the ongoing vaccination campaign. We estimated the effectiveness of Comirnaty and Vaxzevria vaccines among 371,423 residents in Lazio Region (Italy) vaccinated since 27/12/2020, and followed until diagnosis of SARS-CoV-2 infection or 25/4/2021, whichever came first. By the end of follow-up most of the Comirnaty-cohort (60%) had received the second dose at recommended time of 21 days (98%), while the Vaxzevria-cohort had received only one dose. Adjusted hazard ratios of SARS-CoV-2 infection at weekly intervals since the first dose were estimated through a Cox regression model using 0–13 days as reference time-interval. An increase in effectiveness with increasing time since administration was observed for Comirnaty (five-weeks = 81%, 95 %CI 71–88%; three-months = 94%, 95 %CI 84–98%). One dose of Vaxzevria showed an effectiveness of 63% (95 %CI 25–82%) after 7 weeks, although further analyses are needed after complete vaccination with two doses. These results could support the ongoing vaccination campaign by reinforcing evidence-based communication aimed at reducing vaccine hesitancy. [ABSTRACT FROM AUTHOR]

Objectives: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a new and rare syndrome resulting from the largest vaccination campaign against SARS-CoV-2 in the history of mankind. The aim of this review is to clarify underlying mechanisms, pathology, diagnosis, and therapy, with the related clinical implications. Methods: We performed a comprehensive literature review in order to collect the clinical and treatment data about patients suffering from VITT. PubMed, Ovid Medline, Ovid EMBASE, Scopus, and Web of Science were screened regarding patients who developed VITT. Last search was launched on June 30th 2021. Results: Abdominal and/or neurological symptoms develop between 5 and 20 days after vaccine administration and do not involve the lower extremities. VITT is suspected if the platelet count is lower than 100.000/mm3 and D-dimer is higher than the age-adjusted range. Medical treatment is mainly based on intravenous immunoglobulins, corticosteroids, and anticoagulant drugs with a short plasma half-life, but the complete avoidance of low molecular weight heparin is recommended. Endovascular treatment and/or decompressive craniectomy might be an option in a minority of cases. Conclusion: Due to widespread vaccination concerns, the vascular specialist and phlebologist are increasingly consulted to prevent or diagnose VITT. The latter has peculiar and completely different localizations, symptoms, and treatment compared to the common pictures of venous thrombosis. [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.

The amazing effort of vaccination against COVID-19, with more than 2 billion vaccine doses administered all around the world as of 16 June 2021, has changed the history of this pandemic, drastically reducing the number of severe cases or deaths in countries were mass vaccination campaign have been carried out. However, the people's rising enthusiasm has been blunted in late February 2021 by the report of several cases of unusual thrombotic events in combination with thrombocytopenia after vaccination with ChAdOx1 nCov-19 (Vaxzevria), and a few months later also after Ad26.COV2. S vaccines. Of note, both products used an Adenovirus-based (AdV) platform to deliver the mRNA molecule - coding for the spike protein of SARS-CoV-2. A clinical entity characterized by cerebral and/or splanchnic vein thrombosis, often associated with multiple thromboses, with thrombocytopenia and bleeding, and sometimes disseminated intravascular coagulation (DIC), was soon recognized as a new syndrome, named vaccine-induced immune thrombotic thrombocytopenia (VITT) or thrombosis with thrombocytopenia syndrome (TTS). VITT was mainly observed in females under 55 years of age, between 4 and 16 days after receiving only Adenovirus-based vaccine and displayed a seriously high fatality rate. This prompted the Medicine Regulatory Agencies of various countries to enforce the pharmacovigilance programs, and to provide some advices to restrict the use of AdV-based vaccines to some age groups. This point-of view is aimed at providing a comprehensive review of epidemiological issues, pathogenetic hypothesis and treatment strategies of this rare but compelling syndrome, thus helping physicians to offer an up-to dated and evidence-based counseling to their often alarmed patients. [ABSTRACT FROM AUTHOR]

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.

Objective: To investigate the association of immune response with vaccination adverse effects at peak anti-receptor-binding domain spike subunit 1 (anti-RBDS1) IgG after full vaccination with Comirnaty, Spikevax, or Vaxzevria., Methods: Anti-RBDS1 IgG concentrations after vaccination were determined in healthy adults vaccinated with the Comirnaty, Spikevax, and Vaxzevria vaccines. The association of reactogenicity and peak antibody response after vaccination was tested., Results: Anti-RBDS1 IgG values were significantly higher in the Comirnaty and Spikevax group, compared with the Vaxzevria group (P < .001). Fever and muscle pain were found to be significant independent predictors of peak anti-RBDS1 IgG in the Comirnaty and Spikevax groups (P = .03 and P = .02, respectively). The multivariate model, adjusted for covariates, showed that no association between reactogenicity and peak antibody concentrations was found in the Comirnaty, Spikevax, and Vaxzevria groups., Conclusions: No association between reactogenicity and peak anti-RBDS1 IgG after vaccination with the Comirnaty, Spikevax, and Vaxzevria vaccine was found., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To present a case of branch retinal vein occlusion (BRVO) following ChAdOx1 nCoV-19 (Oxford-AstraZeneca) Vaccine., Methods: Case report., Results: A 60-year old otherwise healthy Caucasian male, presented to the ophthalmology emergency clinic complaining of sudden, painless vision loss in his right eye of 24 h" duration. The patient had received Vaxveria seven days prior. The clinical and fundus examination of the right eye established the diagnosis of BRVO., Conclusion: The present case descibes the occurrence of BRVO soon after the vaccination with the Oxford-AstraZeneca vaccine. The close temporal relationship between the BRVO incidence and the vaccination is reinforced by the lack of othe subjective cause to justify the episode.

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]