Sex and gender differences in adverse events following receipt of influenza and COVID-19 vaccination among healthcare workers (preprint)

IntroductionActive and passive surveillance studies have found that a greater proportion of females report adverse events (AE) following receipt of either the COVID-19 or seasonal influenza vaccine compared to males. We sought to determine the intersection of biological sex and sociocultural gender differences in prospective active reporting of vaccine outcomes, which remains poorly characterized. MethodsThis cohort study enrolled Johns Hopkins Health System healthcare workers (HCWs) who were recruited from the annual fall 2019-2022 influenza vaccine and the fall 2022 COVID-19 bivalent vaccine campaigns. Vaccine recipients were enrolled the day of vaccination and AE surveys were administered two days post-vaccination (DPV) for bivalent COVID-19 and Influenza vaccine recipients. Data were collected regarding the presence of a series of solicited local and systemic AEs. Open-ended answers about participants experiences with AEs also were collected for the COVID-19 vaccine recipients. ResultsFemales were more likely to report local AEs after influenza (OR=2.28, p=0.001) or COVID-19 (OR=2.57, p=0.008) vaccination compared to males, regardless of age or race. Males and females had comparable probabilities of reporting systemic AEs after influenza (OR=1.18, p=0.552) or COVID-19 (OR=0.96, p=0.907) vaccination. Exogenous hormones from birth control use did not impact the rates of reported AEs following COVID-19 vaccination among reproductive-aged female HCWs. Women reported more interruptions in their daily routine following COVID-19 vaccination than men and were more likely to seek out self-treatment. More women than men scheduled their COVID-19 vaccination before their days off in anticipation of AEs. ConclusionsOur findings highlight the need for sex- and gender-inclusive policies to inform more effective occupational health vaccination strategies. Further research is needed to evaluate the potential disruption of AEs on occupational responsibilities following mandated vaccination for healthcare workers and to more fully characterize the post-vaccination behavioral differences between men and women. KEY MESSAGEO_ST_ABSWhat is already known on this topicC_ST_ABS{Rightarrow} Among diversely aged adults 18-64 years, females report more AEs to vaccines, including the influenza and COVID-19 vaccines, than males. {Rightarrow}Vaccine AEs play a role in shaping vaccine hesitancy and uptake. {Rightarrow}Vaccine uptake related to influenza and COVID-19 are higher among men than women. {Rightarrow}Research that addresses both the sex and gender disparities of vaccine outcomes and behaviors is lacking. What this study adds{Rightarrow} This prospective active reporting study uses both quantitative and qualitative survey data to examine sex and gender differences in AEs following influenza or COVID-19 vaccination among a cohort of reproductive-aged healthcare workers. How this study might affect research, practice, or policy{Rightarrow} Sex and gender differences in AEs and perceptions relating to vaccination should drive the development of more equitable and effective vaccine strategies and policies in occupational health settings.

Enhancing social inclusion through the implementation of evidence-based digital health interventions for mental health and alcohol other drug use problems in the wake of COVID-19: A study protocol (preprint)

At any one time, over 900 million people globally experience a mental disorder (including alcohol/other drug use disorders, Whiteford et al., 2013), and this is increasing by about 3% each year (ABS, 2018). Adding to these challenges, the COVID-19 pandemic presents clear risks for a substantial decline in global mental health. Preliminary evidence points towards an overall rise in symptoms of anxiety and coping responses to stress (Holmes et al., 2020), including increased drug and alcohol use amongst the general population. The greatest mental health impacts of the COVID-19 pandemic will be felt, however, by those who are already most marginalised and people with pre-existing mental health and substance use disorders, who have a higher susceptibility to stress than the general population (Yao et al., 2020). eCliPSE is an online clinical portal developed by CI Professor Frances Kay-Lambkin in partnership with the research team and the NSW Ministry of Health to facilitate access to evidence-based ehealth treatments for mental health and alcohol/other drug [AOD] use problems. However, since the testing of eCliPSE in 2017, uptake of this tool via clinician referral has been low, and no clear models existed for digital treatment integration into health services (Batterham et al., 2015). There are very few examples in the available literature of successful implementation of digital interventions in clinical services, and many failures (Mohr et al., 2017). In response to this, our team has developed an evidence-informed Integrated Translation and Engagement Model (ITEM) to drive the uptake of digital therapeutics into mental health and alcohol/other drug services across NSW. Based on the latest evidence for effective implementation, a consideration of individual, social, environmental, and structural factors, the ITEM synthesises diverse theoretical approaches into a coherent, integrated model. The pandemic has highlighted (and exacerbated) social inequities in relation to the prevalence of mental illness, as well as treatment options. Technology has the potential to respond to this challenge, but Australia lags behind the rest of the world in implementing sustainable, effective digital tools into health service delivery. Additionally, no tool currently exists for the evaluation of dual diagnosis capability of digital programs.

Cardiac MRI in patients with COVID-19 infection.

OBJECTIVE: COVID-19 infection is a systemic disease with various cardiovascular symptoms and complications. Cardiac MRI with late gadolinium enhancement is the modality of choice for the assessment of myocardial involvement. T1 and T2 mapping can increase diagnostic accuracy and improve further management. Our study aimed to evaluate the different aspects of myocardial damage in cases of COVID-19 infection using cardiac MRI. METHODS: This descriptive retrospective study included 86 cases, with a history of COVID-19 infection confirmed by positive RT-PCR, who met the inclusion criteria. Patients had progressive chest pain or dyspnoea with a suspected underlying cardiac cause, either by an abnormal electrocardiogram or elevated troponin levels. Cardiac MRI was performed with late contrast-enhanced (LGE) imaging, followed by T1 and T2 mapping. RESULTS: Twenty-four patients have elevated hsTnT with a median hsTnT value of 133 ng/L (IQR: 102 to 159 ng/L); normal value < 14 ng/L. Other sixty-two patients showed elevated hsTnI with a median hsTnI value of 1637 ng/L (IQR: 1340 to 2540 ng/L); normal value < 40 ng/L. CMR showed 52 patients with acute myocarditis, 23 with Takotsubo cardiomyopathy, and 11 with myocardial infarction. Invasive coronary angiography was performed only in selected patients. CONCLUSION: Different COVID-19-related cardiac injuries may cause similar clinical symptoms. Cardiac MRI is the modality of choice to differentiate between the different types of myocardial injury such as Takotsubo cardiomyopathy and infection-related cardiomyopathy or even acute coronary syndrome secondary to vasculitis or oxygen-demand mismatch. KEY POINTS: • It is essential to detect early COVID-related cardiac injury using different cardiac biomarkers and cardiac imaging, as it has a significant impact on patient management and outcome. • Cardiac MRI is the modality of choice to differentiate between the different aspects of COVID-related myocardial injury.

A case of fulminant myocarditis associated with a novel coronavirus infection (preprint)

Background COVID-19 patients mainly have the high incidence and mortality of major cardiovascular diseases in the acute phase. However, fulminant myocarditis and cardiogenic shock are rare in the post-acute phase, and the prognosis is very poor.Case presentation Here, we report a case of a 43-year-old young man with fulminant myocarditis and cardiogenic shock in the acute phase after coronavirus infection, with timely extracorporeal membrane oxygenation and intra-aortic balloon application in respiratory failure, which improved the prognosis of fulminant myocarditis and saved the lives of COVID-19 patients. After active anti-shock, mechanical ventilation, anti-inflammation, and organ support and other treatments, the patient was discharged after a stable condition and stable vital signs. The patient was followed up weekly after discharge and showed good cardiopulmonary recovery.Conclusions In critically ill patients with severe myocarditis, cardiogenic shock, arrhythmia, respiratory and circulatory failure, ECMO and IABP in patients with explosive myocardial inflammatory cardiogenic shock have achieved better results.

Takotsubo syndrome in COVID-19 era: Is psychological distress the key?

Covid-19 pandemic, starting from Wuhan, China spread all over the world and Italy was one of the most affected countries, especially in Lombardy, where, on February 20, the first confirmed case was detected. Italian Government ordered a national lockdown on the 9 th March 2020, forcing the population to severe restrictive isolation measures. The burden on mental health of the medical emergency related to COVID19 is progressively been revealed. Takotsubo syndrome (TTS), is estimated to represent 1-3% of patients admitted with suspected STEMI, mostly affecting elderly women with emotional stress and/or acute illness preceding the presentation. Comparing patients hospitalised from February to May 2020 with those of the corresponding period in 2019 we observed a significantly increased number of TTS diagnosis in 2020 (11 patients vs 3 in 2019), especially during the first period of lockdown. The only two males were patients with COVID-19 and were the only two who died in hospital. At psychological examination all patients enrolled report to have lived a particularly stressful experience at IES-R in the last year, without presenting the symptoms of a post-traumatic stress disorder. Most patients were positive to the allostatic overload. Only one patient showed a clinical cut-off for HADS and no one for the Fear COVID-19 scale. We finally concluded that subjects with pre-pandemic psychological distress may have experienced additional psychological overload, opening the door to TTS by a series of physiological alterations as the secretion of cortisol and catecholamines, making the subject more vulnerable to the onset of TTS.

Epidemiology, Pathophysiology, Diagnosis, and Principles of Management of Takotsubo Cardiomyopathy: A Review.

Takotsubo cardiomyopathy, also known as stress-induced cardiomyopathy, is a reversible syndrome commonly found among patients presenting for acute coronary syndromes, especially women. With the COVID-19 pandemic, the incidence of takotsubo cardiomyopathy was dramatically increased. However, this clinical cardiac entity remains underdiagnosed, largely due to the interplay with acute coronary syndrome. The pathophysiology of takotsubo cardiomyopathy is miscellaneous, including coronary vasospasm, microcirculatory dysfunction, catecholamine surge, and sympathetic overdrive. Diagnosing takotsubo cardiomyopathy requires a high index of clinical suspicion and multimodality tests. To date, there are no guidelines for the management of takotsubo cardiomyopathy. Thus, available data are derived from case series, retrospective analyses, and experts' opinions. Heart failure medicines were investigated in takotsubo cardiomyopathy patients. Evidence supports the benefits of angiotensin-converting enzyme inhibitors and angiotensin receptors blockers use on mortality and recurrence rates, while results from use of beta-blockers are controversial. In complicated cases, inotropes are preferred over vasopressors, except in the presence of left ventricular outflow tract obstruction, in which medical therapy is limited to fluids administration and beta-blockers. Use of oral vitamin K antagonist can benefit patients at high thrombo-embolic risk for up to 3 months. Mechanical supports are reserved for refractory hemodynamically unstable cases. This review aims to provide an update on the epidemiology, diagnosis, and outcomes of takotsubo cardiomyopathy, and an extended discussion on the management of complicated and non-complicated cases.

Takotsubo syndrome in COVID-19: a case series study.

BACKGROUND: Takotsubo syndrome is a clinical syndrome characterized by an acute and transient left ventricular systolic dysfunction related to an emotional or physical stressful event. CASE PRESENTATION: During the Covid-19 pandemic, five cases of Takotsubo syndrome in hospitalized, mechanically ventilated patients due critical SARS-CoV-2 infection have been identified at our institution. Here we present the electrocardiographic, echocardiographic and angiographic characteristics of this case series. All cases were initially suspected by echocardiography performed due an abnormal electrocardiogram, troponin elevation or clinical deterioration. CONCLUSION: A high index of suspicion should be sought to identify Takotsubo syndrome and other cardiac complications associated with SARS-CoV-2 infection.

Takotsubo Syndrome Occurring after mRNA COVID-19 Vaccination in a Patient with Graves' Disease.

Cardiovascular events such as myocarditis following mRNA COVID-19 vaccination are increasing. We present a 67-year-old postmenopausal woman with Takotsubo Syndrome and Graves' disease after mRNA COVID-19 vaccination. She developed chest pain and shortness of breath one week after vaccination. An electrocardiogram revealed ST elevation in the precordial leads. Coronary angiography revealed the absence of obstructive coronary artery disease, and the left ventriculography showed a typical feature with apical ballooning. Laboratory workup showed the elevation of free T4 and thyrotropin receptor antibodies. It was presumed that Takotsubo Syndrome and Graves' disease were probably related to the COVID-19 mRNA vaccination. The patient was treated with low-dose bisoprolol, diuretics, carbimazole, and steroid and discharged uneventfully. The mRNA COVID-19 vaccination is still safe and effective to defend against COVID-19 pandemic. However, clinicians should be aware of the possible cardiovascular adverse events other than myocarditis following vaccination.

COVID-19 With Stress Cardiomyopathy Mortality and Outcomes Among Patients Hospitalized in the United States: A Propensity Matched Analysis Using the National Inpatient Sample Database.

Takotsubo syndrome (stress cardiomyopathy) has become a well-known complication of COVID-19 infections, with limited large-scale studies evaluating outcomes. We used the National Inpatient Sample (NIS) database to compare COVID-19 patients with and without stress cardiomyopathy. A total of 1,659,040 patients were included in the study: COVID-19 with stress cardiomyopathy (n = 1665, 0.1%) and COVID-19 without stress cardiomyopathy (n = 1657, 375, and 99.9%). The primary outcome was in-hospital mortality, with secondary analysis with propensity matching performed to confirm results from traditional multivariate analysis. COVID-19 patients with stress cardiomyopathy had significantly increased in-hospital mortality compared to COVID-19 patients without stress cardiomyopathy (32.8% vs 14.6%, adjusted OR [aOR]: 2.3 [95% CI, 1.2-4.5], P = 0.01) along with significantly increased mechanical ventilation and vasopressor support, hospitalization charge, acute kidney injury requiring hemodialysis, cardiogenic shock, and cardiac arrest. These results emphasize the need for more research to reduce worse outcomes with COVID-19-related stress cardiomyopathy patients.

In-Hospital Outcomes of Takotsubo Cardiomyopathy During the COVID-19 Pandemic: Propensity Matched National Cohort.

Takotsubo Cardiomyopathy (TTS) is an acute reversible left ventricular dysfunction with regional ballooning secondary to various physical or psychological triggers, including COVID-19. The impact of TTS on outcomes in COVID-19 patients is not well studied. The Nationwide in-patient sample database from 2019 to 2020 was utilized to identify TTS patients with and without COVID-19. Clinical Modification (ICD-10-CM) codes U07.1 and I51.81 were used as disease identifiers for COVID-19 and TTS, respectively. Multivariate logistic regression was performed to report adjusted odds ratios (aOR) and propensity score match (PSM) was done to compare outcomes among TTS patients with and without COVID. The primary outcome was in-hospital mortality. A total of 83,215 TTS patients for the period 2019-2020 were included in our study, of which 1665 (2%) had COVID-19. COVID-19 with TTS group had higher adjusted odds of in-hospital mortality (aOR 7.23, PSM 32.7% vs 10.16%, p = <0.001), cardiogenic shock; (aOR 2.32, PSM 16.7% vs 9.5%, P < 0.001) and acute kidney injury; (aOR 2.30, PSM 47.5% vs 33.1%, P< 0.001) compared to TTS without COVID-19. TTS hospitalizations with COVID-19 were associated with longer lengths of stay (12 ± 12 vs 7 ± 9 days) and higher total cost ($47,702 ± $67,940 vs $26,957 ± $44,286) compared to TTS without COVID. TTS with COVID-19 group had a higher proportion of males compared to TTS without COVID-19 group (37.8% vs 18.5%). TTS with COVID-19 group had a greater proportion of non-white race. The proportion of Blacks, Hispanics, and Asian/Pacific Islander was higher in the COVID-19 TTS group compared to TTS without COVID-19 group (12.9% vs 8.4%, 20.4% vs 6.5%, 5 vs 2.2%, respectively). TTS in the setting of COVID-19 illness has worse outcomes in terms of in-hospital mortality, cardiogenic shock, and acute kidney injury. Male sex and non-white race were more likely to be affected by TTS in the setting of COVID-19. The out-of-hospital morbidity and mortality in patients who suffered TTS during COVID-19 illness need further study. Studies are needed to provide mechanistic insights into the interaction between COVID-19 and TTS.

SARS-CoV-2 is localized in cardiomyocytes: a postmortem biopsy case.

A 72-year-old patient was admitted to the intensive care unit due to acute respiratory distress syndrome caused by COVID-19. On day 20, the patient experienced shock. The electrocardiogram showed ST segment elevation in leads V3-V6 and severe left ventricular dysfunction with an ejection fraction of 35%-40%. The left ventricle showed basal hypokinesis and apical akinesis, while the creatine kinase level was normal, indicating Takotsubo cardiomyopathy. On day 24, the patient died of multiple organ failure. In post-mortem biopsy, SARS-CoV-2 antigen was detected in cardiomyocytes by immunostaining. Moreover, SARS-CoV-2 RNA was detected in heart tissue. We need to further analyse the direct link between SARS-CoV-2 and cardiomyocytes.

Potential risk polarization for acute myocardial infarction during the COVID-19 pandemic: Single-center experiences in Osaka, Japan (preprint)

This study compared the time course and outcomes of acute myocardial infarction, including mechanical complications and hospital mortality, before and after the coronavirus disease 2019 (COVID-19) pandemic at a regional core hospital in South Osaka, Japan. Moreover, it identified predictors for hospital mortality and mechanical complications. In total, 503 patients who underwent emergency percutaneous coronary intervention between January 2011 and December 2021 at our institution were examined retrospectively. The time course of acute myocardial infarction, mechanical complications, and mortality rate before and after the COVID-19 emergency declaration were compared. Overall, 426 patients with ST-segment elevation myocardial infarction and 77 patients with non-ST-segment elevation myocardial infarction were identified. For patients with ST-segment elevation myocardial infarction, the onset-to-door time was longer (181 vs. 156 min, P = 0.001) and mechanical complications were worse (7.8% vs. 2.6%, P = 0.025) after the emergency declaration of COVID-19 than before the pandemic. Age, low ejection fraction, out-of-hospital cardiac arrest, and mechanical complications were identified as independent risk factors for hospital mortality among patients with ST-segment elevation myocardial infarction, using multivariable analysis. Post-declaration, age, walk-ins, referrals, and intra-aortic balloon pump use were independent predictors of mechanical complications among patients with ST-segment elevation myocardial infarction. Onset-to-door time and mechanical complication rate increased after the COVID-19 declaration among patients with ST-segment elevation myocardial infarction. Arrival by walk-in and a referral that caused treatment delay were identified as independent risk factors for mechanical complication, in addition to age, use of intra-aortic balloon pump, and post-declaration of COVID-19. Therefore, the risks posed by the COVID-19 pandemic might have a polarization tendency resulting from the relief or worsening of cardiac symptoms.

Quality and Audience Engagement of Takotsubo Syndrome-Related Videos on TikTok: Content Analysis.

BACKGROUND: The incidence of Takotsubo syndrome (TTS), also known as the broken heart syndrome or stress cardiomyopathy, is increasing worldwide. The understanding of its prognosis has been progressively evolving and currently appears to be poorer than previously thought, which has attracted the attention of researchers. An attempt to recognize the awareness of this condition among the general population drove us to analyze the dissemination of this topic on TikTok, a popular short-video-based social media platform. We found a considerable number of videos on TTS on TikTok; however, the quality of the presented information remains unknown. OBJECTIVE: The aim of this study was to analyze the quality and audience engagement of TTS-related videos on TikTok. METHODS: Videos on the TikTok platform were explored on August 2, 2021 to identify those related to TTS by using 6 Chinese keywords. A total of 2549 videos were found, of which 80 met our inclusion criteria and were evaluated for their characteristics, content, quality, and reliability. The quality and reliability were rated using the DISCERN instrument and the Journal of the American Medical Association (JAMA) criteria by 2 reviewers independently, and a score was assigned. Descriptive statistics were generated, and the Kruskal-Wallis test was used for statistical analysis. Multiple linear regression was performed to evaluate the association between audience engagement and other factors such as video content, video quality, and author types. RESULTS: The scores assigned to the selected video content were low with regard to the diagnosis (0.66/2) and management (0.34/2) of TTS. The evaluated videos were found to have an average score of 36.93 out of 80 on the DISCERN instrument and 1.51 out of 4 per the JAMA criteria. None of the evaluated videos met all the JAMA criteria. The quality of the relayed information varied by source (All P<.05). TTS-related videos made by health care professionals accounted for 28% (22/80) of all the evaluated videos and had the highest DISCERN scores with an average of 40.59 out of 80. Multiple linear regression analysis showed that author types that identified as health professionals (exponentiated regression coefficient 17.48, 95% CI 2.29-133.52; P=.006) and individual science communicators (exponentiated regression coefficient 13.38, 95% CI 1.83-97.88; P=.01) were significant and independent determinants of audience engagement (in terms of the number of likes). Other author types of videos, video content, and DISCERN document scores were not associated with higher likes. CONCLUSIONS: We found that the quality of videos regarding TTS for patient education on TikTok is poor. Patients should be cautious about health-related information on TikTok. The formulation of a measure for video quality review is necessary, especially when the purpose of the published content is to educate and increase awareness on a health-related topic.

[Reverse Takotsubo ou myocardite fulminante ? Succès de VA ECMO chez une patiente ayant une atteinte cardiaque liée COVID 19]. / Reverse TakoTsubo or Fulminant myocarditis ? Life saving VA ECMO in a COVID 19 patient.

A 45 years old female patient was admitted to our facility for COVID -19 infection complicated by fulminant cardiac injury and refractory cardiogemic shock. She had echographic findings of reverse takotsubo cardiomyopathy. She was successfully treated by VA-ECMO allowing complete revocery of the left ventricule function and weaning from support.

Reverse Takotsubo Cardiomyopathy After Casirivimab-Imdevimab Therapy in a Patient with COVID-19: A Case Report.

BACKGROUND Takotsubo cardiomyopathy, also referred to as apical ballooning syndrome (ABS), stress cardiomyopathy, or broken heart syndrome, initially described in Japan, is characterized by transient wall motion abnormalities involving the apical segment. Several variants have been described, including reverse type, mid-ventricular type, and the focal type. In the reverse type, there is basal hypokinesis and apical hyperkinesis. Stress cardiomyopathy is most likely to occur in middle-aged women and the underlying etiology is believed to be related to catecholamine release due to intense stress. CASE REPORT We report an extremely rare case of reverse takotsubo cardiomyopathy (rTTC) in a young woman with COVID-19 who was treated with Casirivimab-Imdevimab therapy. Our report is the second to reveal rTTC in a patient with COVID-19 in which obstructive coronary artery disease was definitively ruled out by coronary CT angiography. CONCLUSIONS Cardiovascular involvement in COVID-19 has been linked to increased morbidity and mortality rates. Recent reports have suggested the occasional occurrence of TTC and the rare occurrence of reverse takotsubo cardiomyopathy (rTTC) in patients with COVID-19. In fact, to the best of our knowledge, this is only the fifth reported case of rTTC in a patient with COVID-19; importantly, 3 out of the 4 of the previous reported cases lacked definitive ischemic work-up to rule out obstructive coronary artery disease due to the critical condition of the patients.

Takotsubo Syndrome during COVID-19 Pandemic in the Veneto Region, Italy.

Background: During the COVID-19 pandemic, the risk of SARS-CoV-2 infection, the public health measures of social distancing, the freedom limitations, quarantine, and the enforced homeworking under the lockdown period, as well as medical causes including COVID-19 infection per se, may have caused major emotional distress, especially in the most vulnerable patients. We aimed to evaluate the variations in the number of admissions due to Takotsubo syndrome (TTS) during the COVID-19 pandemic in the Veneto region. Methods: We retrospectively reviewed and analyzed the number of admissions because of TTS in 13 Divisions of Cardiology located in the Veneto region, the northeastern area of Italy, covering a population of more than 2.5 million inhabitants, during the two major pandemic waves of COVID-19 (the first between 15 March and 30 April 2020 and the second between 15 November and 30 December 2020) that occurred in 2020. Results: In total, 807 acute coronary syndromes were admitted in the 13 enrolling hospitals. Among these, 3.9% had TTS. Compared to the corresponding 2018 and 2019 time periods, we observed a significant increase in the number of TTS cases (+15.6%, p = 0.03 and +12.5%, p = 0.04, comparing 2018 to 2020 and 2019 to 2020, respectively). Geographical distribution of the TTS cases reflected the broad spread of the SARS-CoV-2 infection with a significant direct relationship between TTS incidence and the number of COVID-19 infections according to Pearson's correlation (r = 0.798, p < 0.001). Conclusions: The higher incidence of TTS during the 2020 COVID-19 pandemic waves, especially in the areas that were hit hardest in terms of morbidity and mortality by the SARS-CoV-2 infection, suggest a strong direct and/or indirect role of COVID-19 in the pathogenesis of TTS.

Cohort monitoring of 29 Adverse Events of Special Interest prior to and after COVID-19 vaccination in four large European electronic healthcare data sources (preprint)

Setting Primary and/or secondary health care data from four European countries: Italy, the Netherlands, the United Kingdom, Spain Participants Individuals with complete data for the year preceding enrollment or those born at the start of observation time. The cohort comprised 25,720,158 subjects. Interventions First and second dose of Pfizer, AstraZeneca, Moderna, or Janssen COVID-19 vaccine. Main outcome measures 29 adverse events of special interest (AESI): acute aseptic arthritis, acute coronary artery disease, acute disseminated encephalomyelitis (ADEM), acute kidney injury, acute liver injury, acute respiratory distress syndrome, anaphylaxis, anosmia or ageusia, arrhythmia, Bells’ palsy, chilblain-like lesions death, erythema multiforme, Guillain Barré Syndrome (GBS), generalized convulsion, haemorrhagic stroke, heart failure, ischemic stroke, meningoencephalitis, microangiopathy, multisystem inflammatory syndrome, myo/pericarditis, myocarditis, narcolepsy, single organ cutaneous vasculitis (SOCV), stress cardiomyopathy, thrombocytopenia, thrombotic thrombocytopenia syndrome (TTS) venous thromboembolism (VTE) Results 12,117,458 individuals received at least a first dose of COVID-19 vaccine: 54% with Comirnaty (Pfizer), 6% Spikevax (Moderna), 38% Vaxzevria (AstraZeneca) and 2% Janssen Covid-19 vaccine. AESI were very rare <10/100,000 PY in 2020, only thrombotic and cardiac events were uncommon. After adjustment for factors associated with severe COVID, 10 statistically significant associations of pooled incidence rate ratios remained based on dose 1 and 2 combined. These comprised anaphylaxis after AstraZeneca vaccine, TTS after both AstraZeneca and Janssen vaccine, erythema multiforme after Moderna, GBS after Janssen vaccine, SOCV after Janssen vaccine, thrombocytopenia after Janssen and Moderna vaccine and VTE after Moderna and Pfizer vaccines. The pooled rate ratio was more than two-fold increased only for TTS, SOCV and thrombocytopenia. Conclusion We showed associations with several AESI, which remained after adjustment for factors that determined vaccine roll out. Hypotheses testing studies are required to establish causality.