The Aftermath of COVID-19: Exploring Long-Term Effects on the Organ Systems (preprint)

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) is a complicated disease that affects millions of people all over the world. Previous studies have shown that PASC impacts 10% of SARS-CoV-2 infected patients of which 50-70% are hospitalized. It has also been shown that 10-12% of those vaccinated against COVID-19 were affected with PASC and its complications. The severity and the later development of PASC symptoms is positively associated with the early intensity of the infection. Results: The generated health complications caused by PASC involve a vast variety of organ systems. Patients affected by PASC have been diagnosed with neuropsychiatric and neurological symptoms. Cardiovascular system also has been involved and several diseases such as myocarditis, pericarditis, and coronary artery diseases were reported. Chronic hematological problems such as thrombotic endothelialitis and hypercoagulability were described as a condition that could increase the risk of clotting disorders and coagulopathy in PASC patients. Chest pain, breathlessness, and cough in PASC patients were associated with respiratory system in long COVID-19 causing respiratory distress syndrome. The observed immune complications were notable, involving several diseases. Renal system also was impacted and result in raising the risk of diseases such as thrombotic issues, fibrosis, and sepsis. Endocrine gland malfunction can lead to diabetes, thyroiditis, and male infertility. Symptoms such as diarrhea, nausea, loss of appetite and taste were also among reported observations due to several gastrointestinal disorders. Skin abnormalities might be an indication of infection and long-term implications such as persistent cutaneous complaints were linked to PASC. Conclusions: Long COVID is a multidimensional syndrome with considerable public health implications, affecting several physiological systems and demanding thorough medical therapy as well as more study to address its underlying causes and long-term effects.

Real-world Nuvaxovid COVID-19 vaccine safety profile after first 100,000 doses in Australia, 2022-2023 (preprint)

Introduction Nuvaxovid became available in Australia from February 2022, a year later than the first COVID-19 vaccines were released. It was a much-anticipated alternative vaccine for people that had either suffered an adverse event to and/or were hesitant to receive one of the mRNA or adenovirus based COVID-19 vaccines. Although safety from clinical trials was reassuring, small trial population size, relatively low administration rates worldwide and limited post-licensure intelligence meant potential rare adverse events were underinformed. Methods We conducted a retrospective observational analysis of adverse events following immunisation (AEFI) spontaneously reported to SAFEVAC, the integrated vaccine safety surveillance system used by Victoria and Western Australia, Australia. Reports received from 14 Feb 2022 to 30 June 2023 were analysed by vaccinee demographics, reported reactions and COVID-19 vaccine dose received and compared as reporting rates (RR) per 100,000 doses administered. Results 356 AEFI reports were received, following 102,946 Nuvaxovid doses administered. Rates were higher post dose 1 than dose 2 (rate ratio 1.5, p=0.0008); primary series than booster (rate ratio 2.4, p<0.0001); in females than males (rate ratio 1.4, p<0.01), especially those aged 30-49 years (RR=1.6, p=0.002). Serious AEFI included 76 chest pain (RR=73.8), two myocarditis (RR=1.9) and 20 pericarditis (RR=19.4). No cases of Guillain Barre or thrombosis with thrombocytopaenia syndromes were reported and no deaths attributable to vaccination. Conclusion The shared SAFEVAC platform enables pooling of clinically reviewed data across jurisdictions, increasing the safety profile evidence base of novel vaccines like Nuvaxovid and improving the odds for identification and description of rare events across all vaccines.

Comparative safety and effectiveness of Pfizer BA.4-5 versus Sanofi during the spring 2023 COVID-19 booster vaccination programme in England: a matched cohort study in OpenSAFELY-TPP (preprint)

Introduction: The spring 2023 COVID-19 booster vaccination programme in England used both Pfizer BA.4-5 and Sanofi vaccines. All people aged 75 years or over and the clinically vulnerable were eligible to receive a booster dose. Direct comparisons of the effectiveness of these two vaccines in boosting protection against severe COVID-19 events have not been made in trials or observational data. Methods With the approval of NHS England, we used the OpenSAFELY-TPP database to compare effectiveness of the Pfizer BA.4-5 and Sanofi vaccines during the spring 2023 booster programme, between 1 April and 30 June 2023. We investigated two cohorts separately: those aged 75 or over (75+); and those aged 50 or over and clinically vulnerable (CV). In each cohort, vaccine recipients were matched on date of vaccination, COVID-19 vaccine history, age, and other characteristics. Effectiveness outcomes were COVID-19 hospital admission, COVID-19 critical care admission, and COVID-19 death up to 16 weeks after vaccination. Safety outcomes were pericarditis and myocarditis up to 4 weeks after vaccination. We report the cumulative incidence of each outcome, and compare safety and effectiveness using risk differences (RD), relative risks (RR), and incidence rate ratios (IRRs). Results 492,642 people were 1-1 matched in the CV cohort, and 673,926 in the 75+ cohort, contributing a total of 7,423,251 and 10,173,230 person-weeks of follow-up, respectively. The incidence of COVID-19 hospital admission was higher for Sanofi than for Pfizer BA.4-5. In the CV cohort, 16-week risks per 10,000 people were 22.3 (95%CI 20.4 to 24.3) for Pfizer BA.4-5 and 26.4 (24.4 to 28.7) for Sanofi, with an IRR of 1.19 (95%CI 1.06 to 1.34). In the 75+ cohort, these were 17.5 (16.1 to 19.1) for Pfizer BA.4-5 and 20.4 (18.9 to 22.1) for Sanofi, with an IRR of 1.18 (1.05-1.32). These findings were similar across all pre-specified subgroups. More severe COVID-19 related outcomes (critical care admission and death), and safety outcomes at 4 weeks, were rare in both vaccines so we could not reliably compare effectiveness of the two vaccines. Conclusion This observational study comparing effectiveness of Pfizer BA.4-5 and Sanofi vaccine during the spring 2023 programme in England in the two main eligible cohorts - people aged 75 and over and in clinically vulnerable people - found some evidence of superior effectiveness against COVID-19 hospital admission for Pfizer BA.4-5 compared with Sanofi within 16 weeks after vaccination.

Myocarditis and Pericarditis Following the COVID-19 Vaccination: A Single-Centre Case Seriese (preprint)

The Surveillance of rare adverse events following vaccination, particularly related to COVID-19 vaccines, requires thorough examination. This paper investigates vaccine-associated myocarditis and/or pericarditis (VAMPS), presenting insights into clinical manifestations, management, and outcomes. Conducted at the Prince Sultan Cardiac Center in Saudi Arabia from March 2021 to May 2022, this retrospective case series comprises 20 patients with an average age of 27.9 ± 14.0 years, predominantly males (70%). Pfizer-BioNTech, AstraZeneca, and Moderna vaccines were administered in 74%, 21%, and 5% of cases, respectively, with 53% receiving the second dose, 26% the booster, and 21% the initial dose. Common symptoms included shortness of breath (60%), chest pain (50%), palpitations (40%), premature ventricular contractions (35%), and fever (25%). Cardiac magnetic resonance imaging revealed preserved left ventricular function (80%), subepicardial and/or mid-wall late gadolinium enhancement (65%), and lateral (39%), anterolateral (15%), inferolateral (15%), and anteroseptal (15%) segments affected. Myocarditis, pericarditis, and myopericarditis were diagnosed in 40%, 20%, and 40% of cases, respectively. C-reactive protein was elevated in two-thirds of patients. Recovery was achieved with anti-inflammatory medications, primarily colchicine (72%), aspirin(39%), and ibuprofen (33%). While no fatalities occurred, 30% experienced severe complications, and 15% had minor complications. In conclusion, VAMPS exhibits distinct characteristics and may lead to serious complications. Cardiologists should consider VAMPS in the differential diagnosis for symptomatic patients recently vaccinated against COVID-19, emphasizing the importance of ongoing surveillance and understanding of rare adverse events.

Long-term cardiovascular safety of COVID-19 vaccination according to brand, dose and combinations: Cohort study of 46 million adults in England (preprint)

Using longitudinal health records from 45.7 million adults in England followed for a year, our study compared the incidence of thrombotic and cardiovascular complications after first, second and booster doses of brands and combinations of COVID-19 vaccines used during the first two years of the UK vaccination program with the incidence before or without the corresponding vaccination. The incidence of common arterial thrombotic events (mainly acute myocardial infarction and ischaemic stroke) was generally lower after each vaccine dose, brand and combination. Similarly, the incidence of common venous thrombotic events, (mainly pulmonary embolism and lower limb deep venous thrombosis) was lower after vaccination. There was a higher incidence of previously reported rare harms after vaccination: vaccine-induced thrombotic thrombocytopenia after first ChAdOx1 vaccination, and myocarditis and pericarditis after first, second and transiently after booster mRNA vaccination (BNT-162b2 and mRNA- 1273) These findings support the wide uptake of future COVID-19 vaccination programs.

COVID-related Constrictive Pericarditis Requiring Pericardiectomy: A Case Report (preprint)

Background The COVID-19 pandemic was primarily considered a respiratory malady in the early phases of the outbreak. However, as more patients suffer from this illness, a myriad of symptoms emerge in organ systems separate from the lungs. Among those patients with cardiac involvement, myocarditis, pericarditis, myocardial infarction, and arrhythmia were among the most common manifestations. Pericarditis with pericardial effusion requiring medical or interventional treatments has been previously reported in the acute setting. Notably, chronic pericarditis with pericardial thickening resulting in constriction requiring sternotomy and pericardiectomy has not been published to date.Case Presentation A patient with COVID-19-associated constrictive pericarditis three years after viral infection requiring pericardiectomy was reported. The COVID-19 infection originally manifested as anosmia and ageusia. Subsequently, the patient developed dyspnea, fatigue, right-sided chest pressure, bilateral leg edema, and abdominal fullness. Following recurrent right pleural effusions and a negative autoimmune work-up, the patient was referred for cardiothoracic surgery for pericardiectomy when radiographic imaging and hemodynamic assessment were consistent with constrictive pericarditis. Upon median sternotomy, the patient’s pericardium was measured to be 8 mm thick. Descriptions of the clinical, diagnostic, and therapeutic features are provided. Within the first week after the operation, the patient’s dyspnea resolved; one month later, leg edema and abdominal bloating were relieved.Conclusions Although an association between COVID-19 and cardiac complications has been established, this case adds another element of virus severity and chronic manifestations. The need for sternotomy and pericardiectomy to treat COVID-19-related constrictive pericarditis is believed to be the first reported diagnosis.

Clinical Characteristics and Outcomes of Children and Adolescents with cancer infected with SARS-CoV2 at a Tertiary Care Medical Center in Jordan. (preprint)

Background: Our knowledge about SARS-CoV2 infection is still evolving, its effects and complications on children and adolescents with cancer need to be studied more. The aim of this study is to present our experience with SARS-CoV2 infection in this population and to highlight specific complications and outcomes. Methods: This is a retrospective and prospective observational study, involved 21 cancer patients below the age of 18 years in north Jordan. Data regarding age, sex, cancer type, phase of treatment, duration between infection and chemotherapy and others were collected and reviewed. Results: A total of 21 patients with malignancy were included. Mean age of 8.5 years. Two patients (9.5%) had died; 4.7% is COVID related mortality and 4.7% related to cancer progression. Four patients had disease progression following SARS-CoV2 infection. Six cases developed hematological malignancy weeks to months after SARS-CoV2 infection and one patient was diagnosed with malignancy concomitantly with COVID-19 infection. Out of 15 patients with pre-existing malignancy, 1 patient (7%) developed pulmonary embolism, 4 (27%) patients were diagnosed with pneumonia and one patient was diagnosed with pericarditis (7%), 2 (13%) patients were admitted to pediatric intensive care unit. Regarding oxygen requirements; a total of 3 (20%) patients required some form of Oxygen supplementation. Conclusion: Diagnosis of COVID19 should not distract physicians from investigating new malignancy or relapse as they may come together or may be the result of COVID-19 infection. More studies and investigations are needed to identify the contribution of corona virus in pathogenesis of cancer.

Adverse Events Following SARS-CoV-2 mRNA Vaccination in Adolescents: A Norwegian Nationwide Register-Based Study (preprint)

BackgroundVaccination of older adolescents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started in the spring of 2021 and continued with younger adolescents throughout the summer and fall. We assessed risks of adverse events following immunization (AEFI) in adolescents aged 12-19 years following SARS-CoV-2 vaccination with a messenger RNA (mRNA) vaccine in Norway. Materials and MethodsThe study sample included 496,432 adolescents born in 2002-2009, residing in Norway, and unvaccinated against SARS-CoV-2 at the beginning of the age-specific waves of vaccination in 2021. The exposures under study were first- and second-dose SARS-CoV-2 mRNA vaccinations vs. no dose. We applied Poisson regression and self-controlled case series (SCCS) analysis to estimate incidence rate ratios (IRRs) of 17 preselected outcomes, with associated 95% confidence intervals (CIs), between vaccinated and unvaccinated subjects using predefined post-vaccination risk windows. ResultsMost outcome-specific numbers of cases were low. There were no statistically significant associations between first-dose vaccination and any of the outcomes. In the main Poisson regression, second-dose vaccination was associated with increased risks of anaphylactic reaction (adjusted IRR [aIRR]: 10.05; 95% CI: 1.22-82.74), lymphadenopathy (aIRR: 2.33; 95% CI: 1.46-3.72), and myocarditis and pericarditis (aIRR: 5.27; 95% CI: 1.98-14.05). We also observed increased incidence of acute appendicitis outside the 14-day risk window. When expanding the risk window to 42 days in a post-hoc analysis, there was increased incidence of acute appendicitis following both first-dose vaccination (aIRR: 1.39; 95% CI: 1.09-1.78) and second-dose vaccination (aIRR: 1.43; 95% CI: 1.07-1.91). Results of the SCCS analysis were similar to the Poisson regression. ConclusionsIn general, potential AEFI were rare among adolescents. We found increased risks of anaphylactic reaction, lymphadenopathy, and myocarditis and pericarditis following second-dose vaccination. There were also indications of increased acute appendicitis risk when applying longer risk windows.

Safety of Monovalent BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and NVX-CoV2373 (Novavax) COVID-19 Vaccines in US Children Aged 6 months to 17 years (preprint)

Importance Active monitoring of health outcomes after COVID-19 vaccination provides early detection of rare outcomes that may not be identified in prelicensure trials. Objective To conduct near-real-time monitoring of health outcomes following COVID-19 vaccination in the United States (US) pediatric population aged 6 months to 17 years. Design We evaluated 21 pre-specified health outcomes; 15 were sequentially tested through near-real-time surveillance, and 6 were monitored descriptively within a cohort of vaccinated children. We tested for increased rate of each outcome following vaccination compared to a historical comparator cohort. Setting This population-based study was conducted under the US Food and Drug Administration public health surveillance mandate using three commercial claims databases. Participants Children aged 6 months to 17 years were included if they received a monovalent COVID-19 vaccine dose before early 2023 and had continuous enrollment in a medical health insurance plan from the start of an outcome-specific clean window to the COVID-19 vaccination dose. Exposure Exposure was defined as receipt of a monovalent BNT162b2, mRNA-1273, or NVX-CoV2373 COVID-19 vaccine dose. The primary analysis evaluated dose 1 and dose 2 combined, and secondary analyses evaluated each dose separately. Follow-up time was censored at death, disenrollment, end of risk window, end of study period, or a subsequent dose administration. Main Outcomes Twenty-one prespecified health outcomes. Results The study included 4,102,016 enrollees aged 6 months to17 years. Thirteen of 15 outcomes sequentially tested did not meet the threshold for a statistical signal. In the primary analysis, myocarditis or pericarditis signals were detected following BNT162b2 vaccine in children aged 12-17 years old and seizures/convulsions signals were detected following vaccination with BNT162b2 and mRNA-1273 in children aged 2-4/5 years. However, in a post-hoc sensitivity analysis, the seizures/convulsions signal was sensitive to background rates selection and was not observed when 2022 background rates were selected instead of 2020 rates. Conclusions and Relevance Of the two signaled outcomes, the myocarditis or pericarditis signals are consistent with previously published reports. The new signal detected for seizures/convulsions among younger children should be further investigated in a robust epidemiological study with better confounding adjustment.

Global Safety Assessment of Adverse Events of Special Interest Following 2 Years of Use and 772 Million Administered Doses of mRNA-1273 (preprint)

Background: The large-scale use of mRNA COVID-19 vaccines during the pandemic was associated with enhanced safety monitoring to ensure accurate and timely review of safety. We reviewed the mRNA-1273 (original strain) safety profile following 2 years of use (>772 million administered doses), primarily focusing upon predefined safety topics (ie, adverse events of special interest [AESI]) proposed in advance of COVID-19 vaccine use. Methods: Cumulative mRNA-1273 safety data from spontaneous adverse event (AE) cases reported to the Moderna, Inc., global safety database (GSDB) between December 18, 2020, and December 17, 2022, were included. Reporting rates of AESI were calculated per 1 million doses of mRNA-1273 administered. Observed-to-expected (OE) ratios were computed by comparing observed rates of AESI to the background/expected rate for these events to evaluate potential associations with mRNA-1273. Results: There were 658,767 identified case reports, associated with 2,517,669 AEs. Most AEs were non-serious (83.4%); 0.7% were fatal. AESI represented 13.7% of all AEs, with reporting rates for most AESI below the expected background incidence. Exceptions included anaphylaxis (OE ratio 3 days after vaccination, 2.19 [95% CI, 2.02-2.37]), myocarditis (OE ratio 7 days after vaccination, 1.41 [1.32-1.51]; among men aged 12-40 years, 9.75 [7.74-12.3]; and individuals aged 12-40 years, 3.51 [3.19-3.86]), and pericarditis (OE ratio 7 days after vaccination in individuals aged 12-40 years, 2.54 [2.16-2.99]). Conclusions: With the exceptions of anaphylaxis, myocarditis, and pericarditis, this safety analysis of mRNA-1273 did not find evidence to suggest an increased risk for AESI identified for enhanced monitoring ahead of COVID-19 vaccine use.

The role of COVID-19 vaccines in preventing post COVID-19 thromboembolic and cardiovascular complications: a multinational cohort study (preprint)

ImportanceThe overall effects of vaccination on the risk of cardiac, and venous and arterial thromboembolic complications following COVID-19 remain unclear. ObjectiveWe studied the association between COVID-19 vaccination and the risk of acute and subacute COVID-19 cardiac and thromboembolic complications. DesignMultinational staggered cohort study, based on national vaccination campaign rollouts. SettingNetwork study using electronic health records from primary care records from the UK, primary care data linked to hospital data from Spain, and national insurance claims from Estonia. ParticipantsAll adults with a prior medical history of [≥]180 days, with no history of COVID-19 or previous COVID-19 vaccination at the beginning of vaccine rollout were eligible. ExposureVaccination status was used as a time-varying exposure. Vaccinated individuals were classified by vaccine brand according to the first dose received. Main OutcomesPost COVID-19 complications including myocarditis, pericarditis, arrhythmia, heart failure (HF), venous (VTE) and arterial thromboembolism (ATE) up to 1 year after SARS-CoV-2 infection. MeasuresPropensity Score overlap weighting and empirical calibration based on negative control outcomes were used to minimise bias due to observed and unobserved confounding, respectively. Fine-Gray models were fitted to estimate sub-distribution Hazard Ratios (sHR) for each outcome according to vaccination status. Random effect meta-analyses were conducted across staggered cohorts and databases. ResultsOverall, 10.17 million vaccinated and 10.39 million unvaccinated people were included. Vaccination was consistently associated with reduced risks of acute (30-day) and subacute post COVID-19 VTE and HF: e.g., meta-analytic sHR 0.34 (95%CI, 0.27-0.44) and 0.59 (0.50-0.70) respectively for 0-30 days, sHR 0.58 (0.48 - 0.69) and 0.71 (0.59 - 0.85) respectively for 90-180 days post COVID-19. Additionally, reduced risks of ATE, myocarditis/pericarditis and arrhythmia were seen, but mostly in the acute phase (0-30 days post COVID-19). ConclusionsCOVID-19 vaccination reduced the risk of post COVID-19 complications, including cardiac and thromboembolic outcomes. These effects were more pronounced for acute (1-month) post COVID-19 outcomes, consistent with known reductions in disease severity following breakthrough vs unvaccinated SARS-CoV-2 infection. RelevanceThese findings highlight the importance of COVID-19 vaccination to prevent cardiovascular outcomes after COVID-19, beyond respiratory disease. Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the impact of COVID-19 vaccination to prevent cardiac complications and thromboembolic events following a SARS-CoV-2 infection? FindingsResults from this multinational cohort study showed that COVID-19 vaccination reduced risk for acute and subacute COVID-19 heart failure, as well as venous and arterial thromboembolic events following SARS-CoV-2 infection. MeaningThese findings highlight yet another benefit of vaccination against COVID-19, and support the recommendations for COVID-19 vaccination even in people at high cardiovascular risk.

Bivalent mRNA COVID-19 Vaccine-Related Pericarditis on 18 F-FDG PET/CT.

ABSTRACT: A 13-year-old boy was suspected with pericarditis after a second booster dose of bivalent mRNA COVID-19 vaccine. After specific preparation for cardiac inflammation with carbohydrate-free, high-fat diet, the 18 F-FDG PET/CT successfully demonstrated simultaneous presentation of vaccination-related axillary lymphadenopathy and pericarditis without the interference of physiological myocardial uptake.

Real-world Effectiveness of BNT162b2 in Children and Adolescents in Preventing Infection and Severe Diseases with SARS-CoV-2 During the Delta and Omicron Periods: Findings from Trial Emulation Using an EHR-based Cohort (preprint)

BACKGROUND The current understanding of the long-term effectiveness of the BNT162b2 vaccine for a range of outcomes across diverse U.S. pediatric populations is limited. In this study, we assessed the effectiveness of BNT162b2 against various strains of the SARS-CoV-2 virus using data from a national collaboration of pediatric health systems (PEDSnet). METHODS We emulated three target trials to assess the real-world effectiveness of BNT162b2: adolescents aged 12 to 20 years during the Delta variant period (Target trial 1), children aged 5 to 11 years (Target trial 2) and adolescents aged 12 to 20 years during the Omicron variant period (Target trial 3). The outcomes included documented infection, COVID-19 illness severity, admission to an intensive care unit (ICU), and two cardiac-related outcomes, myocarditis and pericarditis. In the U.S., immunization records are often captured and stored across multiple disconnected sources, resulting in incomplete vaccination records in patients' electronic health records (EHR). We implemented a novel trial emulation pipeline accounting for possible misclassification bias in vaccine documentation in EHRs. The effectiveness of the BNT162b2 vaccine was estimated from the Poisson regression model with confounders balanced via propensity score stratification. RESULTS During the Delta period, the BNT162b2 vaccine demonstrated an overall effectiveness 98.4% (95% CI, 98.1 to 98.7) against documented infection among adolescents, with no significant waning after receipt of the first dose. During the Omicron period, the overall effectiveness was estimated to be 74.3% (95% CI, 72.2 to 76.2) in preventing documented infection among children, which was higher against moderate or severe COVID-19 (75.5%; 95% CI, 69.0 to 81.0) and ICU admission with COVID-19 (84.9%; 95% CI, 64.8 to 93.5). In the adolescent population, the overall effectiveness against documented Omicron infection was 85.5% (95% CI, 83.8 to 87.1), with effectiveness of 84.8% (95% CI, 77.3 to 89.9) against moderate or severe COVID-19, and 91.5% (95% CI, 69.5 to 97.6) against ICU admission with COVID-19. The effectiveness of the BNT162b2 vaccine against the Omicron variant declined after 4 months following the first dose and then stabilized with higher levels of uncertainty. Across all three cohorts, the risk of cardiac outcomes was approximately 65% to 85% lower in the vaccinated group than that of the unvaccinated group accounting for possible misclassification bias. CONCLUSIONS This study suggests BNT162b2 was effective among children and adolescents in Delta and Omicron periods for a range of COVID-19-related outcomes and is associated with a lower risk for cardiac complications. Waning effectiveness over time suggests that revaccination may be needed in the future.

Acute myopericarditis and left shoulder capsulitis following second dose of mRNA SARS-CoV-2 Moderna vaccination.

Vaccination against mRNA SARS-CoV-2 has been administered on a very large scale and various side effects have been described. The increased risk of myopericarditis is known, and only a few cases of shoulder capsulitis have been reported after vaccination. These two pathologies have never been reported in the same patient after vaccination. Our article presents the history of a man in his 40s who presented with myopericarditis a few days after vaccination against SARS-CoV-2 with mRNA(Messenger RNA) Moderna® vaccine and who at the same time developed shoulder capsulitis. His cardiovascular symptoms resolved rapidly, and his shoulder symptoms improved/resolved within 1 year. This case should make physicians aware of the possibility of several concomitant side effects following vaccination against SARS-CoV-2.

Pericarditis related to post-acute COVID infection: A case report and review of the literature.

Cardiovascular involvement has been described in acute and recovered COVID-19 patients. Here, we present a case of symptomatic pericarditis with persistent symptoms for at least six months after the acute infection and report 66 published cases of pericarditis in discharged COVID patients. Patient mean age ± SD was 49.7 ± 13.3 years, ranging from 15 to 75 years and 57.6% were female. A proportion of 89.4% patients reported at least one comorbidity, with autoimmune and allergic disorders, hypertension and dyslipidaemia, as the most frequent. Only 8.3% of patients experienced severe symptoms of acute COVID-19. The time between acute COVID and pericarditis symptoms varied from 14 to 255 days. Chest pain (90.9%), tachycardia (60.0%) and dyspnoea (38.2%) were the most frequent symptoms in post-acute pericarditis. A proportion of 45.5% and 87% of patients had an abnormal electrocardiogram and abnormal transthoracic ultrasound, respectively. Colchicine combined with non-steroidal anti-inflammatory drug (NSAID) or acetylsalicylic acid (aspirin) were prescribed to 39/54 (72%) patients. Of them, 12 were switched to corticosteroid therapy due to non-response to the first-line treatment. Only 6 patients had persisting symptoms and were considered as non-respondent to therapy.Our report highlights that pericarditis should be suspected in COVID-19 patients with persistent chest pain and dyspnoea when pulmonary function is normal. Treatment with non-steroidal anti-inflammatory and colchicine is usually effective but corticosteroids are sometimes required.

Arrhythmias after COVID-19 Vaccination: Have We Left All Stones Unturned? (preprint)

-529391451442Citation: To be added by editorial staff during production. Academic Editor: Firstname Lastname Received: date Revised: date Accepted: date Published: date Copyright: © 2023 by the authors. Submitted for possible open access publication under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).0Citation: To be added by editorial staff during production. Academic Editor: Firstname Lastname Received: date Revised: date Accepted: date Published: date Copyright: © 2023 by the authors. Submitted for possible open access publication under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Abstract: SARS-CoV-2 vaccination offered the opportunity to get out of the pandemic and thereby worldwide health, social, and economic disasters. However, in addition to efficacy, safety is an important issue for any vaccine. The mRNA-based vaccine platform is considered to be safe but side effects are being reported more frequently as more and more people around the world become treated. Myo-pericarditis is the major, but not the only cardiovascular complication of this vaccine, hence it is important not to underestimate other side effects. We report a case series of patients affected by cardiac arrhythmias post mRNA vaccine from our clinical practice and the literature. Reviewing the official vigilance database emerged that heart rhythm disorders after Covid vaccination are not uncommon and deserve more clinical and scientific attention. Since Covid vaccine is the only vaccination to have been related to this side effect questions arose about whether these vaccines could affect heart conduction. Although the risk-benefit is clearly in favor of vaccination heart rhythm disorders are not a negligible issue and there are red flags in the literature about the risk of post-vaccination malignant arrhythmias in some predisposed patients. In light of these findings, we investigated the potential mechanism for the Covid vaccine to impact on cardiac electrophysiology and cause heart rhythm disorders.

SARS-CoV-2, vaccination or autoimmunity as causes of cardiac inflammation. Which form prevails?

The causes of cardiac inflammation during the COVID-19 pandemic are manifold and complex, and may have changed with different virus variants and vaccinations. The underlying viral etiology is self-evident, but its role in the pathogenic process is diverse. The view of many pathologists that myocyte necrosis and cellular infiltrates are indispensable for myocarditis does not suffice and contradicts the clinical criteria of myocarditis, i.e., a combination of serological evidence of necrosis based on troponins or MRI features of necrosis, edema, and inflammation based on prolonged T1 and T2 times and late gadolinium enhancement. The definition of myocarditis is still debated by pathologists and clinicians. We have learned that myocarditis and pericarditis can be induced by the virus via different pathways of action such as direct viral damage to the myocardium through the ACE2 receptor. Indirect damage occurs via immunological effector organs such as the innate immune system by macrophages and cytokines, and then later the acquired immune system via T cells, overactive proinflammatory cytokines, and cardiac autoantibodies. Cardiovascular diseases lead to more severe courses of SARS-CoV­2 disease. Thus, heart failure patients have a double risk for complicated courses and lethal outcome. So do patients with diabetes, hypertension, and renal insufficiency. Independent of the definition, myocarditis patients benefitted from intensive hospital care, ventilation, if needed, and cortisone treatment. Postvaccination myocarditis and pericarditis affect primarily young male patients after the second RNA vaccine. Both are rare events but severe enough to deserve our full attention, because treatment according to current guidelines is available and necessary.

Safety of the BNT162b2 COVID-19 Vaccine in Children Aged 5 to 17 Years.

Importance: Active monitoring of health outcomes after COVID-19 vaccination offers early detection of rare outcomes that may not be identified in prelicensure trials. Objective: To conduct near-real-time monitoring of health outcomes following BNT162b2 COVID-19 vaccination in the US pediatric population aged 5 to 17 years. Design, Setting, and Participants: This population-based study was conducted under a public health surveillance mandate from the US Food and Drug Administration. Participants aged 5 to 17 years were included if they received BNT162b2 COVID-19 vaccination through mid 2022 and had continuous enrollment in a medical health insurance plan from the start of an outcome-specific clean window until the COVID-19 vaccination. Surveillance of 20 prespecified health outcomes was conducted in near real time within a cohort of vaccinated individuals from the earliest Emergency Use Authorization date for the BNT162b2 vaccination (December 11, 2020) and was expanded as more pediatric age groups received authorization through May and June 2022. All 20 health outcomes were monitored descriptively, 13 of which additionally underwent sequential testing. For these 13 health outcomes, the increased risk of each outcome after vaccination was compared with a historical baseline with adjustments for repeated looks at the data as well as a claims processing delay. A sequential testing approach was used, which declared a safety signal when the log likelihood ratio comparing the observed rate ratio against the null hypothesis exceeded a critical value. Exposure: Exposure was defined as receipt of a BNT162b2 COVID-19 vaccine dose. The primary analysis assessed primary series doses together (dose 1 + dose 2), and dose-specific secondary analyses were conducted. Follow-up time was censored for death, disenrollment, end of the outcome-specific risk window, end of the study period, or a receipt of a subsequent vaccine dose. Main Outcomes: Twenty prespecified health outcomes: 13 were assessed using sequential testing and 7 were monitored descriptively because of a lack of historical comparator data. Results: This study included 3 017 352 enrollees aged 5 to 17 years. Of the enrollees across all 3 databases, 1 510 817 (50.1%) were males, 1 506 499 (49.9%) were females, and 2 867 436 (95.0%) lived in an urban area. In the primary sequential analyses, a safety signal was observed only for myocarditis or pericarditis after primary series vaccination with BNT162b2 in the age group 12 to 17 years across all 3 databases. No safety signals were observed for the 12 other outcomes assessed using sequential testing. Conclusions and Relevance: Among 20 health outcomes that were monitored in near real time, a safety signal was identified for only myocarditis or pericarditis. Consistent with other published reports, these results provide additional evidence that COVID-19 vaccines are safe in children.