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We present the case of a 56-year-old female admitted to our centre for hepatitis. She had recieved the first dose of the BNT162b2 vaccine against SARS-CoV-2 10 days before the admission. Etiologic study was negative. The patient was diagnosed with vaccine-induced hepatitis.

Importance: Data about the safety of vaccines against SARS-CoV-2 during pregnancy are limited., Objective: To examine the risk of adverse pregnancy outcomes after vaccination against SARS-CoV-2 during pregnancy., Design, Setting, and Participants: This registry-based retrospective cohort study included 157 521 singleton pregnancies ending after 22 gestational weeks from January 1, 2021, until January 12, 2022 (Sweden), or January 15, 2022 (Norway). The Pregnancy Register in Sweden and the Medical Birth Registry of Norway were linked to vaccination and other registries for identification of exposure and background characteristics., Exposures: Data on mRNA vaccines-BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)-and 1 viral vector vaccine-AZD1222 (AstraZeneca)-were collected from national vaccination registries., Main Outcomes and Measures: The risk of preterm birth and stillbirth was evaluated using Cox regression models, with gestational day as the time metric and vaccination as a time-dependent exposure variable. The risk of small for gestational age, low Apgar score, and neonatal care admission was evaluated using logistic regression. Random-effects meta-analysis was used to combine results between countries., Results: Among the 157 521 singleton births included in the study (103 409 in Sweden and 54 112 in Norway), the mean maternal age at the time of delivery was 31 years, and 28 506 (18%) were vaccinated against SARS-CoV-2 (12.9% with BNT162b2, 4.8% with mRNA-1273, and 0.3% with AZD1222) while pregnant. A total of 0.7%, 8.3%, and 9.1% of individuals delivering were vaccinated during the first, second, and third trimester, respectively. Vaccination against SARS-CoV-2 was not significantly associated with increased risk of preterm birth (6.2 vs 4.9 per 10 000 pregnancy days; adjusted hazard ratio [aHR], 0.98 [95% CI, 0.91 to 1.05]; I2 = 0%; P for heterogeneity = .60), stillbirth (2.1 vs 2.4 per 100 000 pregnancy days; aHR, 0.86 [95% CI, 0.63 to 1.17]), small for gestational age (7.8% vs 8.5%; difference, -0.6% [95% CI, -1.3% to 0.2%]; adjusted OR [aOR], 0.97 [95% CI, 0.90 to 1.04]), low Apgar score (1.5% vs 1.6%; difference, -0.05% [95% CI, -0.3% to 0.1%]; aOR, 0.97 [95% CI, 0.87 to 1.08]), or neonatal care admission (8.5% vs 8.5%; difference, 0.003% [95% CI, -0.9% to 0.9%]; aOR, 0.97 [95% CI, 0.86 to 1.10])., Conclusions and Relevance: In this population-based study conducted in Sweden and Norway, vaccination against SARS-CoV-2 during pregnancy, compared with no SARS-CoV-2 vaccination during pregnancy, was not significantly associated with an increased risk of adverse pregnancy outcomes. The majority of the vaccinations were with mRNA vaccines during the second and third trimesters of pregnancy, which should be considered in interpreting the findings.

To analyze the clinical presentation and outcomes of myocarditis after administration of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccine. Nine case series and 15 case reports (74 patients) of myocarditis after administration of the BNT162b2 or mRNA-1273 vaccine were reviewed from PubMed, Scopus, Embase, and Web of Science. We analyzed clinical manifestations, diagnostic findings, and outcomes. In addition, we performed a pooled analysis and investigated risk factors leading to admission to the intensive care unit and recovery with conservative care. Most patients were male (94.6%), and the median age (range) was 17.6 (14-70) years. Patients who received the BNT162b2 (n = 58, 78.4%) vaccine presented fewer systemic symptoms and left ventricular dysfunction than mRNA-1273 recipients. Although patients under 20 years experienced more fever and myalgia, they had better ejection fraction and less prominent myocardial inflammation in magnetic resonance imaging than older patients. The clinical course of all patients was favorable without mortality, and one-third of patients resolved with conservative care alone. Risk factor analyses revealed that patients with gastrointestinal symptoms required intensive care (odds ratio: 20.3, 95% confidence interval 1.90-217, p = 0.013). The risk of fatality in myocarditis subjected to mRNA vaccination seems to be low. However, patients with gastrointestinal symptoms received more intensive care, and a significant proportion of patients recovered with conservative management., (© 2021 Wiley Periodicals LLC.)

A tiny fraction of people immunized with lipid nanoparticle (LNP)-enclosed mRNA (LNP-mRNA) vaccines develop allergic symptoms following their first or subsequent vaccinations, including anaphylaxis. These reactions resemble complement (C) activation-related pseudoallergy (CARPA) to i.v. administered liposomes, for which pigs provide a naturally oversensitive model. Using this model, we injected i.v. the human vaccination dose (HVD) of BNT162b2 (Comirnaty, CMT) or its 2-fold (2x) or 5-fold (5x) amounts and measured the hemodynamic changes and other parameters of CARPA. We observed in 6 of 14 pigs transient pulmonary hypertension along with thromboxane A2 release into the blood and other hemodynamic and blood cell changes, including hypertension, granulocytosis, lymphopenia, and thrombocytopenia. One pig injected with 5x CMT developed an anaphylactic shock requiring resuscitation, while a repeat dose failed to induce the reaction, implying tachyphylaxis. These typical CARPA symptoms could not be linked to animal age, sex, prior immune stimulation with zymosan, immunization of animals with Comirnaty i.v., or i.m. 2 weeks before the vaccine challenge, and anti-PEG IgM levels in Comirnaty-immunized pigs. Nevertheless, IgM binding to the whole vaccine, used as antigen in an ELISA, was significantly higher in reactive animals compared to non-reactive ones. Incubation of Comirnaty with pig serum in vitro showed significant elevations of C3a anaphylatoxin and sC5b-9, the C-terminal complex. These data raise the possibility that C activation plays a causal or contributing role in the rare HSRs to Comirnaty and other vaccines with similar side effects. Further studies are needed to uncover the factors controlling these vaccine reactions in pigs and to understand their translational value to humans., (© 2022. The Author(s).)

Objective: To evaluate the safety and the serological response after two doses of mRNA-based SARS-CoV-2 vaccination in people with HIV (PWH)., Methods: Participants were evaluated 4 weeks after the second dose of mRNA-1273 or BNT162b2 vaccine. Tolerability was evaluated with a specific adverse event questionnaire. Patient's sera were analysed using LIAISON SARS-CoV-2 TrimericS IgG (DiaSorin)., Results: One-hundred PWH were included, 75% of them men, with a mean age of 44 ± 11 years old, all receiving antiretroviral treatment and mostly with controlled viral loads (98% with HIV RNA <50 copies/ml) and 96% had >200 CD4+/μl. All patients seroconverted after vaccination (antibody concentration ≥33.8 binding antibody units [BAU]/ml). Only 3% of the patients had a low antibody concentration (<520 BAU/ml), whereas 67% of them had concentrations above the assay's detection range (>2080 BAU/ml). Fifty-six patients had local or systemic symptoms, with mild arthromyalgia being the most common systemic symptom. No severe adverse events were reported., Conclusions: Vaccination with two doses of mRNA-1273 or BNT162b2 is well tolerated in PWH under effective antiretroviral treatment and it leads to a successful antibody response., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To investigate the relationship between COVID-19 full vaccination (two completed doses) and possible arthritis flare., Methods: Patients with rheumatoid arthritis (RA) were identified from population-based electronic medical records with vaccination linkage and categorised into BNT162b2 (mRNA vaccine), CoronaVac (inactive virus vaccine) and non-vaccinated groups. The risk of possible arthritis flare after vaccination was compared using a propensity-weighted cohort study design. We defined possible arthritis flare as hospitalisation and outpatient consultation related to RA or reactive arthritis, based on diagnosis records during the episode. Weekly prescriptions of rheumatic drugs since the launch of COVID-19 vaccination programme were compared to complement the findings from a diagnosis-based analysis., Results: Among 5493 patients with RA (BNT162b2: 653; CoronaVac: 671; non-vaccinated: 4169), propensity-scored weighted Poisson regression showed no significant association between arthritis flare and COVID-19 vaccination ((BNT162b2: adjusted incidence rate ratio 0.86, 95% Confidence Interval 0.73 to 1.01); CoronaVac: 0.87 (0.74 to 1.02)). The distribution of weekly rheumatic drug prescriptions showed no significant differences among the three groups since the launch of the mass vaccination programme (all p values >0.1 from Kruskal-Wallis test)., Conclusions: Current evidence does not support that full vaccination of mRNA or inactivated virus COVID-19 vaccines is associated with possible arthritis flare., Competing Interests: Competing interests: XL received research grants from Research Fund Secretariat of the Food and Health Bureau (HMRF, HKSAR), Research Grants Council Early Career Scheme RGC/ECS, HKSAR, Janssen and Pfizer; internal funding from the University of Hong Kong; consultancy fee from Merck Sharp & Dohme, unrelated to this work. CSLC has received grants from the Food and Health Bureau of the Hong Kong Government, Hong Kong Research Grant Council, Hong Kong Innovation and Technology Commission, Pfizer, IQVIA and Amgen; personal fee from Primevigilance Ltd.; outside the submitted work. FTTL has been supported by the RGC Postdoctoral Fellowship under the Hong Kong Research Grants Council, outside the submitted work. EYFW has received research grants from the Food and Health Bureau of the Government of the Hong Kong SAR, and the Hong Kong Research Grant Council, outside the submitted work. CKHW reports the receipt of General Research Fund, Research Grant Council, Government of Hong Kong SAR; EuroQol Research Foundation, all outside the submitted work. EWYC reports honorarium from Hospital Authority, supports from the Health and Medical Research Fund (HMRF), grants from Research Grants Council (RGC, Hong Kong), grants from National Natural Science Fund of China, grants from Wellcome Trust, grants from Bayer, grants from Bristol-Myers Squibb, grants from Pfizer, grants from Janssen, grants from Amgen, grants from Takeda, grants from Narcotics Division of the Security Bureau of HKSAR, grants from Innovation and Technology Commission of the Government of the HKSAR, all outside the submitted work. ICKW reports research funding outside the submitted work from Amgen, Bristol-Myers Squibb, Pfizer, Janssen, Bayer, GSK Novartis, the Hong Kong RGC, and the Hong Kong Health and Medical Research Fund, National Institute for Health Research in England, European Commission, National Health and Medical Research Council in Australia, and also received speaker fees from Janssen and Medice in the previous 3 years. He is also independent non-executive director of Jacobson Medical in Hong Kong., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The 2019 Coronavirus disease (Covid-19) has affected thousands of people worldwide. To date, vaccines appear to be the only method to prevent and reduce mortality. Four vaccinations have been outwardly approved by European Medicine Agency (EMA) in Europe: BNT162b2 (Comirnaty-BioNTech/Pfizer), mRNA-1273 (Spikevax-Moderna), ChAdOx1 (VaxzevriaAstrazeneca), and Ad26.COV2-S (Janssen-Johnson&Johnson). After vaccination, local and systemic adverse effects can occur. Cutaneous reactions like urticaria, local injection site pain, morbilliform rash have been documented after vaccination., Cases Presentation: We report four cases of oral erythema multiforme flare arising after BNT162b2 vaccination administration. All the patients denied previous erythema-like and herpetic manifestations history. Two of the reported cases (number 1 and 2) presented with both oral and cutaneous lesions, while cases 3 and 4 showed only oral manifestations. Three of the cases presented the erythema after the first vaccination dosage administration, only one case reported lesions after the second vaccination dosage administration. All the cases were treated with prednisone via oral administration and topical 0.05% clobetasol ointment., Conclusions: The present reports represent some of the few cases of erythema multiforme occurring as a side effect of the BNT162b2 COVID-19 vaccination. The causal role of the vaccine for the erythema multiforme has not been proven yet; nevertheless, it is not uncommon for medications to trigger this disease. The vaccine could surface a silent herpes virus infection, which would induce the erythema multiforme instead., (© 2022. The Author(s).)

Small trials have suggested that heterologous vaccination with first-dose ChAdOx1 and second-dose BNT162b2 may generate a better immune response than homologous vaccination with two doses of ChAdOx1. In this cohort analysis, we use linked data from Catalonia (Spain), where those aged <60 who received a first dose of ChAdOx1 could choose between ChAdOx1 and BNT162b2 for their second dose. Comparable cohorts were obtained after exact-matching 14,325/17,849 (80.3%) people receiving heterologous vaccination to 14,325/149,386 (9.6%) receiving homologous vaccination by age, sex, region, and date of second dose. Of these, 464 (3.2%) in the heterologous and 694 (4.8%) in the homologous groups developed COVID-19 between 1st June 2021 and 5th December 2021. The resulting hazard ratio (95% confidence interval) is 0.66 [0.59-0.74], favouring heterologous vaccination. The two groups had similar testing rates and safety outcomes. Sensitivity and negative control outcome analyses confirm these findings. In conclusion, we demonstrate that a heterologous vaccination schedule with ChAdOx1 followed by BNT162b2 was more efficacious than and similarly safe to homologous vaccination with two doses of ChAdOx1. Most of the infections in our study occurred when Delta was the predominant SARS-CoV-2 variant in Spain. These data agree with previous phase 2 randomised trials., (© 2022. The Author(s).)

As more individuals were coronavirus disease 2019 (COVID-19) vaccinated, unexpected side effects appeared. Herein, we present the case of a 30-year-old man with myopathy in both extremities after the second dose of the Pfizer-BioNTech (BNT162b2) COVID-19 vaccine. Symptoms, swelling and pain, started from the proximal upper and lower extremities and extended to the distal parts. Although he underwent massive hydration, the muscle enzyme level continuously increased. He complained of dysphagia and dysarthria. Microscopically, muscle biopsy showed multifocal or scattered macrophage infiltration and degenerated myofibers. In contrast to general myopathy including inflammatory myositis and rhabdomyolysis, vaccine-induced inflammatory myositis shows a prolonged increase in muscle enzyme levels and multifocal macrophage infiltration with necrosis of the muscle fibers. Symptoms improved with glucocorticoid and immunosuppressive treatment. If vaccinated individuals experience severe and continuous muscle pain and swelling, clinicians should consider vaccine-induced inflammatory myositis, measure the muscle enzyme levels, and perform muscle biopsy for a definite diagnosis., Competing Interests: All authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Objective: To analyze the local and systemic reactions that appeared after the first and second dose of the BNT162b2 vaccine against COVID‑19 (Pfizer- BioNTech) in a sample of workers from a tertiary hospital, and to identify the  factors related to greater vaccine reactogenicity., Method: A self-administered questionnaire was used to interview 291 workers  from a tertiary hospital who received the BNT162b2 vaccine against COVID-19  between January and March 2021. The questionnaire included questions about  the sociodemographic variables of the participants, previous COVID-19  infection, and local and systemic reactions after the first and second dose of  the vaccine., Results: The most common adverse reaction was soreness at the injection site, which was reported more frequently after the first dose of the  vaccine. The systemic reactions evaluated were reported more frequently after the second dose of the vaccine. Women, younger adults, and  subjects with a prior COVID-19 infection reported increased reactogenicity. Furthermore, high reactogenicity after the first dose was found  to be related to a higher number of adverse reactions after the second dose of  the vaccine., Conclusions: The distribution of reactogenicity in the present study is consistent with the data reported in previous studies on the BNT162b2 vaccine, especially in terms of its association with the participants'  characteristics. These findings could facilitate the identification of people at a  higher risk of developing high reactogenicity to the vaccine, thereby making it  possible to anticipate the appearance of adverse reactions and plan for their  treatment., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Background: Despite high vaccine coverage, an increase in breakthrough coronavirus disease 2019 (COVID-19) infections, prompted administration of a third BNT162b2 dose to people aged >60 years in Israel since July 2021. Here, we report real-world immunogenicity following third dose., Methods: Overall, 208 healthcare workers aged >60 years were included. Paired pre- and post-second and/or third dose immunoglobulin G (IgG) and neutralizing antibody titers were compared. A subpopulation of low responders to the second dose was also tested for T-cell activation. For 25 paired serum samples, we tested neutralization of wild-type vs neutralization of Delta and Lambda variants, pre- and post-third dose. Active surveillance of vaccine adverse events was conducted through surveys., Results: A pronounced immune response was observed following the third dose, including a 33-fold and 51-fold increase in IgG and neutralizing antibody, respectively. The neutralizing antibody levels post-third dose were 9.34 times higher than post-second dose (geometric mean titer, 2598 [95% confidence interval {CI}, 2085-3237] vs 207 [95% CI, 126-339]). Nine previously low responders had a significant antibody increase post-third dose, and 7 of 9 showed increase in T-cell activation. Additionally, sera obtained post-third dose highly and comparably neutralized the wild-type and Delta and Lambda variants. Of 1056 responders to the adverse-event survey, none had serious events., Conclusions: We demonstrate a rapid and broad immune response to the third BNT162b2 dose in individuals >60 years of age., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: There are limited data directly comparing immune responses to vaccines and to natural infections with coronavirus disease 2019 (COVID-19). This study assessed the immunogenicity of the BNT162b2 and ChAdOx1 nCoV-19 vaccines over a 3-month period and compared the immune responses with those to natural infections., Method: We enrolled healthcare workers who received BNT162b2 or ChAdOx1 nCoV-19 vaccines and patients with confirmed COVID-19 and then measured S1 immunoglobulin (Ig) G and neutralizing antibodies and T-cell responses., Results: A total of 121 vaccinees and 26 patients with confirmed COVID-19 were analyzed. After the second dose, the BNT162b2 vaccine yielded S1 IgG antibody responses similar to those achieved with natural infections (mean IgG titer [standard deviation], 2241 [899] vs 2601 [5039]; P = .68) but significantly stronger than responses to the ChAdOx1 vaccine (174 [96]; P < .001). The neutralizing antibody titer generated by BNT162b2 was 6-fold higher than that generated by ChAdOx1 but lower than that by natural infection. T-cell responses persisted for 3 months with BNT162b2 and natural infection but decreased with ChAdOx1., Conclusions: Antibody responses after the second dose of BNT162b2 are higher than after the second dose of ChAdOx1 and like those occurring after natural infection. T-cell responses are maintained longer in BNT162b2 vaccinees than in ChAdOx1 vaccinees., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Data on the safety and efficacy of coronavirus disease 2019 (COVID-19) vaccination in people with a range of primary immunodeficiencies (PIDs) are lacking because these patients were excluded from COVID-19 vaccine trials. This information may help in clinical management of this vulnerable patient group., Objective: We assessed humoral and T-cell immune responses after 2 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in patients with PID and functional B-cell defects., Methods: A double-center retrospective review was performed of patients with PID who completed COVID-19 mRNA vaccination and who had humoral responses assessed through SARS-CoV-2 spike protein receptor binding domain (RBD) IgG antibody levels with reflex assessment of the antibody to block RBD binding to angiotensin-converting enzyme 2 (ACE2; hereafter referred to as ACE2 receptor blocking activity, as a surrogate test for neutralization) and T-cell response evaluated by an IFN-γ release assay. Immunization reactogenicity was also reviewed., Results: A total of 33 patients with humoral defect were evaluated; 69.6% received BNT162b2 vaccine (Pfizer-BioNTech) and 30.3% received mRNA-1273 (Moderna). The mRNA vaccines were generally well tolerated without severe reactions. The IFN-γ release assay result was positive in 24 (77.4%) of 31 patients. Sixteen of 33 subjects had detectable RBD-specific IgG responses, but only 2 of these 16 subjects had an ACE2 receptor blocking activity level of ≥50%., Conclusion: Vaccination of this cohort of patients with PID with COVID-19 mRNA vaccines was safe, and cellular immunity was stimulated in most subjects. However, antibody responses to the spike protein RBD were less consistent, and, when detected, were not effective at ACE2 blocking., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: Considering the concerns regarding the coronavirus disease-2019 (COVID-19) vaccine safety among pediatric patients with inflammatory rheumatic diseases (IRD) due to a lack of data, an urgent need for studies evaluating safety profiles of vaccines emerged., Methods: Among participants vaccinated by CoronaVac inactive SARS-CoV-2 or BNT162b2 messenger RNA (mRNA) COVID-19 (Pfizer-BioNTech) vaccine, healthy children under 18 and patients under 21 with an at least 1-year follow-up period in our department for a childhood-onset rheumatic disease were included into this cross-sectional study., Results: Overall, 246 subjects (141 [57.3%] females) (biologic group: 43, non-biologic group: 180, healthy control group: 23) were eligible for the study. The median age was 15.34 (12.02-20.92) years. The most common adverse events were fatigue (n = 68, 27.6%), headache (n = 44, 17.9%), myalgia (n = 38, 15.4%), arthralgia (n = 38, 15.4%), and fever (n = 35, 14.2%). Only 3 subjects (2 patients with familial Mediterranean fever, and one healthy child) were considered to experienced serious adverse events, since they required hospitalization. Local reactions were seen in 20 (8.13%), and 27 patients (12.1%) had disease flares within 1 month after the vaccines. Although it was significantly higher in those who received the BNT162b2 mRNA vaccine (P < .001), there was no significant relationship between adverse event frequency and age, gender, the existing diseases, ongoing treatment regimens and pre-vaccination COVID-19 histories., Conclusion: Although immunogenicity studies for efficacy of the vaccines and long-term follow-up studies for adverse events monitoring are required, our study indicates an acceptable safety profile of COVID-19 vaccines and encourages children with IRD to be vaccinated., (© 2022 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: BNT162b2 (Pfizer-BioNTech) is a nucleosidemodified mRNA vaccine formulated with lipid nanoparticles for the prevention of COVID-19 disease caused by SARSCoV-2 infection. In early December 2020, BNT162b2 received an emergency use authorization, initial efficacy and safety data have been released, consumer / patient information sheets for vaccines distributed in North America do not warn of Bell's palsy as a possible adverse effect. We reported the case of a patient who developed Bell's palsy on the right side in less than 3 hours after the application of the first dose of the Pfizer-BioNTech COVID-19 vaccine., Clinical Case: 32-year-old latina woman who developed right facial paralysis after receiving the first dose of the BNT162b2 mRNA vaccine on April 7, 2021; with right facial paresis, absence of forehead wrinkles, lip-buccal sulcus and nasolabial fold; spasms of the facial and periorbital muscles, laterocervical pain; possible etiologies were ruled out, prednisone, gabapentin and topiramate. CT without alterations, achieving gradual improvement; until full functional recovery after 15 days. With benign evolution, congruent with the natural history of the disease, classifying it as idiopathic Bell's palsy., Conclusions: Although a causal relationship cannot be established, the time and mode of appearance of the paralysis suggested a relationship with the application of the BNT162b2 vaccine. Given the recommendation of the health authorities to monitor the cases of Bell's palsy, and the surveillance of events supposedly attributable to vaccination (ESAVI) and as it is the first case reported in the literature, in the mexican population, we believe that this case should be shared with the scientific community in a timely manner., (© 2022 Revista Medica del Instituto Mexicano del Seguro Social.)

Background: Case reports of carditis after BNT162b2 vaccination are accruing worldwide., Objective: To examine the association of BNT162b2 and CoronaVac (Sinovac) vaccination with carditis., Design: Case-control study with hospital control participants., Setting: Territory-wide, public health care database with linkage to population-based vaccination records in Hong Kong., Patients: Inpatients aged 12 years or older first diagnosed with carditis were selected as case patients. All other hospitalized patients without carditis were treated as control participants. Ten control participants were randomly matched with each case patient by age, sex, and admission date., Intervention: Vaccination with BNT162b2 or CoronaVac., Measurements: Incident diagnosis of carditis based on the International Classification of Diseases, Ninth Revision, and elevated troponin levels., Results: A total of 160 case patients and 1533 control participants were included. Incidence of carditis per 100 000 doses of CoronaVac and BNT162b2 administered was estimated to be 0.31 (95% CI, 0.13 to 0.66) and 0.57 (CI, 0.36 to 0.90), respectively. Multivariable analyses showed that recipients of the BNT162b2 vaccine had higher odds of carditis (adjusted odds ratio [OR], 3.57 [CI, 1.93 to 6.60]) than unvaccinated persons. Stratified by sex, the OR was 4.68 (CI, 2.25 to 9.71) for males and 2.22 (CI, 0.57 to 8.69) for females receiving the BNT162b2 vaccine. The ORs for adults and adolescents receiving the BNT162b2 vaccine were 2.41 (CI, 1.18 to 4.90) and 13.79 (CI, 2.86 to 110.38), respectively. Subanalysis showed an OR of 9.29 (CI, 3.94 to 21.91) for myocarditis and 1.06 (CI, 0.35 to 3.22) for pericarditis associated with BNT162b2. The risk was mainly seen after the second dose of BNT162b2 rather than the first. No association between CoronaVac and carditis with a magnitude similar to that for BNT162b2 was seen., Limitation: Limited sample size, absence of electrocardiography and other clinical investigative data, and unrecorded overseas vaccination exposure., Conclusion: Despite a low absolute risk, there is an increased risk for carditis associated with BNT162b2 vaccination. This elevated risk should be weighed against the benefits of vaccination., Primary Funding Source: Health and Medical Research Fund.

Leukocytoclastic vasculitis (LCV) is the vasculitis of small vessels. In this report, we describe a 38-year-old male patient who presented to our outpatient clinic with a 1-week history of rash on his lower extremities that had started 4 days after receiving the Pfizer-BioNTech SARS-CoV-2 vaccine. A diagnosis of LCV was made based on clinical and histopathological findings. The patient was treated with antihistamines and prednisolone, after which improvement was observed in the lesions. With this paper, we aim to raise awareness concerning the possibility of LCV development after COVID-19 vaccination., (© 2021 Wiley Periodicals LLC.)

Evans syndrome presents as concurrent autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). Systemic lupus erythematosus (SLE) is the most frequent autoimmune disorder associated with Evans syndrome. We herein report a case of new-onset Evans syndrome associated with SLE after BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccination in a 53-year-old woman. Blood examination at diagnosis showed hemolytic anemia with a positive Coombs test and thrombocytopenia. Hypocomplementemia and the presence of lupus anticoagulant indicated a strong association with SLE. Prednisolone administration rapidly restored hemoglobin level and platelet count. This case suggests that mRNA COVID-19 vaccination may cause an autoimmune disorder. Physicians should be aware of this adverse reaction by mRNA COVID-19 vaccination and should consider the benefits and risks of vaccination for each recipient., (© 2021. Japanese Society of Hematology.)

Background:  In January 2021, the Dutch vaccination program against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was started. Clinical studies have shown that systemic reactions occur in up to 50% of vaccine recipients. Therefore, COVID-19 vaccination could affect anticoagulation control, potentially leading to an increased risk of thrombotic events and bleeding complications., Aims:  This article investigates whether the BNT162b2 vaccine affects anticoagulation control in outpatients using vitamin K antagonists (VKAs)., Methods:  A case-crossover study was performed in a cohort of outpatient VKA users from four Dutch anticoagulation clinics who received a BNT162b2 vaccine. International normalized ratio (INR) results and VKA dosages before the first vaccination, the reference period, were compared with those after the first and second vaccination., Results:  A total of 3,148 outpatient VKA users were included, with a mean age (standard deviation) of 86.7 (8.7) years, of whom 43.8% were male, 67.0% used acenocoumarol, and 33.0% phenprocoumon. We observed a decrease of 8.9% of INRs within range in the standard intensity group (target INR 2.0-3.0). There was both an increased risk of supratherapeutic (odds ratio [OR] = 1.34 [95% confidence interval [CI] 1.08-1.67]) and subtherapeutic levels (OR = 1.40 [95% CI 1.08-1.83]) after first vaccination. In the high-intensity group (target INR 2.5-3.5), the risk of a supratherapeutic INR was 2.3 times higher after first vaccination (OR = 2.29 [95% CI 1.22-4.28]) and 3.3 times higher after second vaccination (OR = 3.25 [95% CI 1.06-9.97])., Conclusion:  BNT162b2 was associated with an immediate negative effect on anticoagulation control in patients treated with VKAs, so it is advisable to monitor the INR shortly after vaccination, even in stable patients., Competing Interests: C.V., J.S.B., M.C.N., F.J..v.d.M., A.J.W.G., Y.C.F.M., S.C.C., and W.M.L. have no conflicts of interest to declare. M.J.H.A.K. has received unrestricted grants paid to the department for research outside this work from Bayer and Daiichi Sankyo, and has received a speaker's fee paid to the department from Bayer., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Vaccination against coronavirus 2019 (COVID-19) has created new challenges. Lymphadenopathy with increased uptake in patients undergoing PET/CT may mislead to unnecessary further evaluation. We have analyzed routinely performed PET/CT studies after Pfizer-BioNTech vaccination to familiarize ourselves with the PET/CT appearance of various PET tracers and to prevent the consequences of misinterpretation. Methods: We analyzed 1,018 PET/CT studies performed between January 1, 2021, and February 15, 2021. Information about the dates and sites of vaccination was collected. Visual and semiquantitative analysis of axillary-neck lymphadenopathy and arm uptake was correlated with immunization data. Results: Increased uptake in axillary lymphadenopathy was observed unilaterally in 66% of vaccinated patients, in 55% of patients vaccinated once, and in 69% of those vaccinated twice. The intensity of uptake decreased over time. Fifty-four of 274 patients (20%) had simultaneous increased activity in the posterior arm and ipsilateral axillary lymphadenopathy (double sign [DS]). The sensitivity, specificity, positive predictive value, and negative predictive value were 55.4%, 83.6%, 86.7%, 49.2%, respectively, for axillary lymphadenopathy and 38.6%, 100%, 100%, and 66.1%, respectively, for DS. No DS was observed later than 10 and 21 d after the first and the second vaccinations, respectively. None of the nonvaccinated patients had arm uptake or DS. Conclusion: Vaccination against COVID-19 frequently causes nonspecific axillary lymphadenopathy with increased PET tracer activity. In one fifth of our study population, this lymphadenopathy was associated with increased uptake at the vaccination site, DS. DS was 100% specific, with a 100% positive predictive value for postvaccination lymphadenopathy, hence enabling avoidance of misinterpretation of PET/CT studies and further unnecessary evaluation., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Several countries restricted the administration of ChAdOx1 to older age groups in 2021 over safety concerns following case reports and observed versus expected analyses suggesting a possible association with cerebral venous sinus thrombosis (CVST). Large datasets are required to precisely estimate the association between Coronavirus Disease 2019 (COVID-19) vaccination and CVST due to the extreme rarity of this event. We aimed to accomplish this by combining national data from England, Scotland, and Wales., Methods and Findings: We created data platforms consisting of linked primary care, secondary care, mortality, and virological testing data in each of England, Scotland, and Wales, with a combined cohort of 11,637,157 people and 6,808,293 person years of follow-up. The cohort start date was December 8, 2020, and the end date was June 30, 2021. The outcome measure we examined was incident CVST events recorded in either primary or secondary care records. We carried out a self-controlled case series (SCCS) analysis of this outcome following first dose vaccination with ChAdOx1 and BNT162b2. The observation period consisted of an initial 90-day reference period, followed by a 2-week prerisk period directly prior to vaccination, and a 4-week risk period following vaccination. Counts of CVST cases from each country were tallied, then expanded into a full dataset with 1 row for each individual and observation time period. There was a combined total of 201 incident CVST events in the cohorts (29.5 per million person years). There were 81 CVST events in the observation period among those who a received first dose of ChAdOx1 (approximately 16.34 per million doses) and 40 for those who received a first dose of BNT162b2 (approximately 12.60 per million doses). We fitted conditional Poisson models to estimate incidence rate ratios (IRRs). Vaccination with ChAdOx1 was associated with an elevated risk of incident CVST events in the 28 days following vaccination, IRR = 1.93 (95% confidence interval (CI) 1.20 to 3.11). We did not find an association between BNT162b2 and CVST in the 28 days following vaccination, IRR = 0.78 (95% CI 0.34 to 1.77). Our study had some limitations. The SCCS study design implicitly controls for variables that are constant over the observation period, but also assumes that outcome events are independent of exposure. This assumption may not be satisfied in the case of CVST, firstly because it is a serious adverse event, and secondly because the vaccination programme in the United Kingdom prioritised the clinically extremely vulnerable and those with underlying health conditions, which may have caused a selection effect for individuals more prone to CVST. Although we pooled data from several large datasets, there was still a low number of events, which may have caused imprecision in our estimates., Conclusions: In this study, we observed a small elevated risk of CVST events following vaccination with ChAdOx1, but not BNT162b2. Our analysis pooled information from large datasets from England, Scotland, and Wales. This evidence may be useful in risk-benefit analyses of vaccine policies and in providing quantification of risks associated with vaccination to the general public., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests. AS is a member of the Scottish Government Chief Medical Officer’s COVID-19 Advisory Group and the New and Emerging Respiratory Virus Threats (NERVTAG) Risk Stratification Subgroup and AstraZeneca’s COVID-19 Thrombocytopenia Taskforce; all roles are remunerated to AS or his institution. AS and SS are members of the editorial board of PLOS Medicine. CRS declares funding from the MRC, NIHR, CSO and New Zealand Ministry for Business, Innovation and Employment and Health Research Council during the conduct of this study. SVK is co-chair of the Scottish Government’s Expert Reference Group on COVID-19 and ethnicity, is a member of the Scientific Advisory Group on Emergencies (SAGE) subgroup on ethnicity and acknowledges funding from a NRS Senior Clinical Fellowship, MRC and CSO. CR is a member of the Scottish Government Chief Medical Officer’s COVID-19 Advisory Group, SPI-M, MHRA Vaccine Benefit and Risk Working Group. HRS is an advisor to the Scottish Parliament’s COVID-19 Committee. RKO is a member of the National Institute for Health and Care Excellence (NICE) Technology Appraisal Committee. DB is employed by Queen’s University Belfast, the Public Health Agency and the Department of Health (Northern Ireland). DB is a member of several Northern Ireland and UK government COVID-19 advisory boards, including the Scientific Pandemic Influenza Group on Modelling and the UK Vaccine Effectiveness Expert Panel, and has represented Northern Ireland on the UK Scientific Advisory Group for Emergencies and its subgroups. SdeL through his University holds grants from AstraZeneca, Eli-Lilly, GSK, MSD, Sanofi and Seqirus. He has been advisory board members for Astra Zeneca, Sanofi and Seqirus. MW is a member of UK government COVID-19 advisory group, SPI-M, and a member of Scottish Government COVID-19 Advisory Group. All other authors report no conflicts of interest.

Background and Objectives: Cerebral venous sinus thrombosis (CVST) as a part of the thrombosis and thrombocytopenia syndrome is a rare adverse drug reaction of severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) vaccination. Estimated background rate of CVST with thrombocytopenia is 0.1 per million per month. We assessed the age-stratified risk of CVST with and without thrombocytopenia after SARS-CoV-2 vaccination., Methods: We estimated the absolute risk of CVST with and without thrombocytopenia within 28 days of a first dose of 4 SARS-CoV-2 vaccinations using data from the European Medicines Agency's EudraVigilance database (until June 13, 2021). As a denominator, we used data on vaccine delivery from 31 European countries. For 22.8 million adults from 25 countries, we estimated the absolute risk of CVST after the first dose of ChAdOx1 nCov-19 per age category., Results: The absolute risk of CVST within 28 days of first-dose vaccination was 7.5 (95% confidence interval [CI] 6.9-8.3), 0.7 (95% CI 0.2-2.4), 0.6 (95% CI 0.5-0.7), and 0.6 (95% CI 0.3-1.1) per million of first doses of ChAdOx1 nCov-19, Ad26.COV2.S, BNT162b2, and mRNA-1273, respectively. The absolute risk of CVST with thrombocytopenia within 28 days of first dose vaccination was 4.4 (95% CI 3.9-4.9), 0.7 (95% CI 0.2-2.4), 0.0 (95% CI 0.0-0.1), and 0.0 (95% CI 0.0-0.2) per million of first doses of ChAdOx1 nCov-19, Ad26.COV2.S, BNT162b2, and mRNA-1273, respectively. In recipients of ChAdOx1 nCov-19, the absolute risk of CVST, both with and without thrombocytopenia, was the highest in the 18- to 24-year-old group (7.3 per million, 95% CI 2.8-18.8 and 3.7 per million, 95% CI 1.0-13.3, respectively). The risk of CVST with thrombocytopenia in ChAdOx1 nCov-19 recipients was the lowest in the age group ≥70 years (0.2, 95% CI 0.0-1.3). Age <60 years compared to ≥60 years was a predictor for CVST with thrombocytopenia (incidence rate ratio 5.79, 95% CI 2.98-11.24, p < 0.001)., Discussion: The risk of CVST with thrombocytopenia within 28 days of first-dose vaccination with ChAdOx1 nCov-19 was higher in younger age groups. The risk of CVST with thrombocytopenia was slightly increased in patients receiving Ad26.COV2.S compared with the estimated background risk. The risk of CVST with thrombocytopenia was not increased in recipients of SARS-CoV-2 mRNA vaccines., (© 2021 American Academy of Neurology.)

Objective: Pregnancy is a known risk factor for severe Coronavirus disease 2019. It is important to develop safe vaccines that elicit strong maternal and fetal antibody responses., Methods: Registries (ClinicalTrials.gov, the WHO Clinical Trial Registry, and the European Union Clinical Trial Registry) and databases (MEDLINE, ScienceDirect, Cochrane Library, Proquest, Springer, medRxiv, and bioRxiv) were systematically searched in June 20-22, 2021, for research articles pertaining to Covid-19 and pregnancy. Manual searches of bioRxiv and medRxiv were also conducted. Inclusion criteria were studies that focused on Covid-19 vaccination among pregnant women, while review articles and non-human studies were excluded. Infection rate, maternal antibody response, transplacental antibody transfer, and adverse events were described., Results: There were 13 observational studies with a total of 48,039 pregnant women who received mRNA vaccines. Of those, three studies investigated infection rate, six studies investigated maternal antibody response, seven studies investigated antibody transfer, three studies reported local adverse events, and five studies reported systemic adverse events. The available data suggested that the mRNA-based vaccines (Pfizer-BioNTech and Moderna) can prevent future SARS-CoV-2 infection. These vaccines did not show clear harm in pregnancy. The most commonly encountered adverse reactions were pain at the injection site, fatigue, and headache, but these were transient. Antibody responses were rapid after the first vaccine dose. After the booster, antibody responses were stronger and associated with better transplacental antibody transfer. Longer intervals between first vaccination dose and delivery were also associated with higher antibody fetal IgG and a better antibody transfer ratio., Conclusions: The SARS-CoV-2 mRNA vaccines are encouraged for pregnancy. These vaccines can be a safe option for pregnant women and their fetuses. Two vaccine doses are recommended for more robust maternal and fetal antibody responses. Longer latency is associated with higher fetal antibody responses. Further research about its long-term effect on pregnancy is needed., Systematic Review Registration: PROSPERO (CRD42021261684)., Competing Interests: The authors have declared that no competing interests exist.

The current SARS-CoV-2 pandemic diffused worldwide has encouraged the rapid development of vaccines to counter the spread of the virus. At present in Italy, 75.01% of the population completed the vaccination course (AIFA.gov.it) and very few adverse events have been recorded by now. Side-effects related to a theoretical over-reaction of the immune system in response to vaccines administration have been described, and the possibility that an autoimmune or a hyperinflammatory condition may occur was recently observed. Herein, we report four cases of hyperinflammatory syndrome with features indicative of Adult-onset Still's disease (AOSD) and macrophage activation syndrome (MAS), occurred after anti-SARS-CoV-2 vaccine injection and seen at our Unit between March and May 2021. Since interleukin (IL)-1 is one of the pivotal cytokines involved in AOSD pathogenesis, the inhibition of IL-1 is crucial in ameliorating the clinical symptoms of those patients. Moreover, it has been highlighted the central role of IL-1 as a hallmark of the hyperinflammatory status elicited by SARS-CoV-2 infection. In this case series, we successfully employed the IL-1 receptor antagonist anakinra to curb the cytokine release likely unleashed by the vaccine stimulation in potentially predisposed subjects. We also made a literature search to detect other patients with hyperinflammation temporally related to vaccines injection who benefited from IL-1 inhibition, while other AOSD/MAS-like described syndromes improved with other immunomodulatory strategies.

The immunogenicity and safety of Pfizer-BioNTech BNT162b2 mRNA vaccine in allogeneic haematopoietic stem cell transplantation (HSCT) recipients are unknown. We prospectively followed 152 HSCT recipients who were at least six months following transplantation and with no active acute graft-versus-host disease (GVHD). Blood samples were taken 2-4 weeks after the second vaccination and analyzed for receptor-binding domain (RBD) antibodies and neutralizing antibodies (NA). 272 immunocompetent healthcare workers served as controls. At a median of 28 days after the second vaccination, 118 patients (77·6%) developed RBD immunoglobulin G (IgG) with a geometric mean titre (GMT) of 2·61 [95% CI (confidence interval), 2·16-3·16]. In the control group 269/272 (98·9%) developed RBD IgG, with a GMT of 5·98 (95% CI 5·70-6·28), P < 0·0001. The GMT of NA in HSCT recipients and controls was 116·0 (95% CI 76·5-175·9), and 427·9 (95% CI 354·3-516·7) respectively (P < 0001). Multivariate logistic regression analysis revealed that HSCT recipients with no chronic GVHD and no immunosuppressive therapy at the time of vaccination had significantly higher levels of NA following the second vaccination. Adverse events were minimal and were less common than in healthy controls. In conclusion; the BNT162b2 mRNA vaccination is safe and effective in HSCT recipients, especially those who are immunosuppression-free. A significant fraction developed protecting NA., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Background: COVID-19 and some anti-SARS-CoV-2 vaccines trigger a humoral autoimmune response against a broad range of endogenous components, which may affect recipients' prognosis in predisposed individuals. Autoantibodies directed against apolipoprotein A-1 (AAA1 IgG) the major protein fraction of High Density Lipoprotein have been shown to be raised in COVID-19 and in rheumatoid arthritis (RA) patients and other populations where they have been associated with poorer outcomes. We wanted to assess the impact of anti-SARS-CoV-2 mRNA-based vaccination on AAA1 autoimmune biomarkers in RA patients., Methods: 20 healthy controls and 77 RA mRNA-based vaccinated patients were collected at baseline, 3 weeks after the first vaccination, 2 and 8 weeks after the second vaccination. AAA1 and SARS-CoV-2 serologies were measured by immunoassays. Systemic and local symptoms occurring during the vaccination protocol were recorded., Results: mRNA-based vaccination induced a significant increase in median AAA1 IgG levels in both healthy controls and RA patients overtime. However, in both populations, these medians trend did not translate into significant increase in AAA1 IgG seropositivity rates despite evolving from 5 to 10% in healthy controls, and from 9 to 12.9% in RA patients. No associations were retrieved between AAA1 IgG and symptoms of any kind during the vaccination protocol., Conclusions: mRNA-based vaccination seems to induce a light AAA1 IgG response in immunocompetent individuals within 2 months after the last injection. Although we did not observe any warning signs, the formal demonstration of the harmlessness of such biological warrants further studies., (© 2021 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Competing Interests: YA declares receiving research grants from Pfizer, outside the scope of this work. AS is partially supported by the Israeli Council for Higher Education via the Weizmann Data Science Research Center, and by a research grant from the Estate of Tully and Michele Plesser. IW reports speaker fees and fees for consultancy from Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Beyond Air, AstraZeneca, and Novartis; contracts or research funding from Roche, Novatis, Beyond Air, and Merck Sharp & Dohme; participation on a data safety monitoring board or advisory board of Merck Sharp & Dohme and AstraZeneca; participation in committee of Israeli Cancer Association; and stock options in Breath of life. All other authors declare no competing interests. COVI3 study investigators are listed at the appendix (p 4).