Background Preapproval trials showed that messenger RNA (mRNA)–based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a good safety profile, yet these tria...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2110475

Safety of the BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting.

Myocarditis has been recognized as a rare complication of coronavirus disease 2019 (COVID-19) mRNA vaccinations, especially in young adult and adolescent males. According to the US Centers for Disease Control and Prevention, myocarditis/pericarditis rates are ≈12.6 cases per million doses of second-dose mRNA vaccine among individuals 12 to 39 years of age. In reported cases, patients with myocarditis invariably presented with chest pain, usually 2 to 3 days after a second dose of mRNA vaccination, and had elevated cardiac troponin levels. ECG was abnormal with ST elevations in most, and cardiac MRI was suggestive of myocarditis in all tested patients. There was no evidence of acute COVID-19 or other viral infections. In 1 case, a cardiomyopathy gene panel was negative, but autoantibody levels against certain self-antigens and frequency of natural killer cells were increased. Although the mechanisms for development of myocarditis are not clear, molecular mimicry between the spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and self-antigens, trigger of preexisting dysregulated immune pathways in certain individuals, immune response to mRNA, and activation of immunologic pathways, and dysregulated cytokine expression have been proposed. The reasons for male predominance in myocarditis cases are unknown, but possible explanations relate to sex hormone differences in immune response and myocarditis, and also underdiagnosis of cardiac disease in women. Almost all patients had resolution of symptoms and signs and improvement in diagnostic markers and imaging with or without treatment. Despite rare cases of myocarditis, the benefit-risk assessment for COVID-19 vaccination shows a favorable balance for all age and sex groups; therefore, COVID-19 vaccination is recommended for everyone ≥12 years of age.

https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.056135

Myocarditis With COVID-19 mRNA Vaccines.

Importance
Vaccination against COVID-19 provides clear public health benefits, but vaccination also carries potential risks. The risks and outcomes of myocarditis after COVID-19 vaccination are unclear.


Objective
To describe reports of myocarditis and the reporting rates after mRNA-based COVID-19 vaccination in the US.


Design, Setting, and Participants
Descriptive study of reports of myocarditis to the Vaccine Adverse Event Reporting System (VAERS) that occurred after mRNA-based COVID-19 vaccine administration between December 2020 and August 2021 in 192 405 448 individuals older than 12 years of age in the US; data were processed by VAERS as of September 30, 2021.


Exposures
Vaccination with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna).


Main Outcomes and Measures
Reports of myocarditis to VAERS were adjudicated and summarized for all age groups. Crude reporting rates were calculated across age and sex strata. Expected rates of myocarditis by age and sex were calculated using 2017-2019 claims data. For persons younger than 30 years of age, medical record reviews and clinician interviews were conducted to describe clinical presentation, diagnostic test results, treatment, and early outcomes.


Results
Among 192 405 448 persons receiving a total of 354 100 845 mRNA-based COVID-19 vaccines during the study period, there were 1991 reports of myocarditis to VAERS and 1626 of these reports met the case definition of myocarditis. Of those with myocarditis, the median age was 21 years (IQR, 16-31 years) and the median time to symptom onset was 2 days (IQR, 1-3 days). Males comprised 82% of the myocarditis cases for whom sex was reported. The crude reporting rates for cases of myocarditis within 7 days after COVID-19 vaccination exceeded the expected rates of myocarditis across multiple age and sex strata. The rates of myocarditis were highest after the second vaccination dose in adolescent males aged 12 to 15 years (70.7 per million doses of the BNT162b2 vaccine), in adolescent males aged 16 to 17 years (105.9 per million doses of the BNT162b2 vaccine), and in young men aged 18 to 24 years (52.4 and 56.3 per million doses of the BNT162b2 vaccine and the mRNA-1273 vaccine, respectively). There were 826 cases of myocarditis among those younger than 30 years of age who had detailed clinical information available; of these cases, 792 of 809 (98%) had elevated troponin levels, 569 of 794 (72%) had abnormal electrocardiogram results, and 223 of 312 (72%) had abnormal cardiac magnetic resonance imaging results. Approximately 96% of persons (784/813) were hospitalized and 87% (577/661) of these had resolution of presenting symptoms by hospital discharge. The most common treatment was nonsteroidal anti-inflammatory drugs (589/676; 87%).


Conclusions and Relevance
Based on passive surveillance reporting in the US, the risk of myocarditis after receiving mRNA-based COVID-19 vaccines was increased across multiple age and sex strata and was highest after the second vaccination dose in adolescent males and young men. This risk should be considered in the context of the benefits of COVID-19 vaccination.

Myocarditis Cases Reported After mRNA-Based COVID-19 Vaccination in the US From December 2020 to August 2021.

Importance Safety surveillance of vaccines against COVID-19 is critical to ensure safety, maintain trust, and inform policy. Objectives To monitor 23 serious outcomes weekly, using comprehensive health records on a diverse population. Design, Setting, and Participants This study represents an interim analysis of safety surveillance data from Vaccine Safety Datalink. The 10 162 227 vaccine-eligible members of 8 participating US health plans were monitored with administrative data updated weekly and supplemented with medical record review for selected outcomes from December 14, 2020, through June 26, 2021. Exposures Receipt of BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) COVID-19 vaccination, with a risk interval of 21 days for individuals after vaccine dose 1 or 2 compared with an interval of 22 to 42 days for similar individuals after vaccine dose 1 or 2. Main Outcomes and Measures Incidence of serious outcomes, including acute myocardial infarction, Bell palsy, cerebral venous sinus thrombosis, Guillain-Barre syndrome, myocarditis/pericarditis, pulmonary embolism, stroke, and thrombosis with thrombocytopenia syndrome. Incidence of events that occurred among vaccine recipients 1 to 21 days after either dose 1 or 2 of a messenger RNA (mRNA) vaccine was compared with that of vaccinated concurrent comparators who, on the same calendar day, had received their most recent dose 22 to 42 days earlier. Rate ratios (RRs) were estimated by Poisson regression, adjusted for age, sex, race and ethnicity, health plan, and calendar day. For a signal, a 1-sidedP  Results A total of 11 845 128 doses of mRNA vaccines (57% BNT162b2; 6 175 813 first doses and 5 669 315 second doses) were administered to 6.2 million individuals (mean age, 49 years; 54% female individuals). The incidence of events per 1 000 000 person-years during the risk vs comparison intervals for ischemic stroke was 1612 vs 1781 (RR, 0.97; 95% CI, 0.87-1.08); for appendicitis, 1179 vs 1345 (RR, 0.82; 95% CI, 0.73-0.93); and for acute myocardial infarction, 935 vs 1030 (RR, 1.02; 95% CI, 0.89-1.18). No vaccine-outcome association met the prespecified requirement for a signal. Incidence of confirmed anaphylaxis was 4.8 (95% CI, 3.2-6.9) per million doses of BNT162b2 and 5.1 (95% CI, 3.3-7.6) per million doses of mRNA-1273. Conclusions and Relevance In interim analyses of surveillance of mRNA COVID-19 vaccines, incidence of selected serious outcomes was not significantly higher 1 to 21 days postvaccination compared with 22 to 42 days postvaccination. While CIs were wide for many outcomes, surveillance is ongoing.

/pdf/surveillance-for-adverse-events-after-covid-19-mrna-54kfqtjivn.pdf

Surveillance for Adverse Events After COVID-19 mRNA Vaccination.

Background At interim analysis in a phase 3, observer-blinded, placebo-controlled clinical trial, the mRNA-1273 vaccine showed 94.1% efficacy in preventing coronavirus disease 2019 (Covid-...

/pdf/efficacy-of-the-mrna-1273-sars-cov-2-vaccine-at-completion-55ft5w18nl.pdf

Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at Completion of Blinded Phase.

Trials of coronavirus disease 2019 (COVID-19) vaccination included limited numbers of children, so they may not have detected rare but important adverse events in this population. We report 7 cases of acute myocarditis or myopericarditis in healthy male adolescents who presented with chest pain all within 4 days after the second dose of Pfizer-BioNTech COVID-19 vaccination. Five patients had fever around the time of presentation. Acute COVID-19 was ruled out in all 7 cases on the basis of negative severe acute respiratory syndrome coronavirus 2 real-time reverse transcription polymerase chain reaction test results of specimens obtained by using nasopharyngeal swabs. None of the patients met criteria for multisystem inflammatory syndrome in children. Six of the 7 patients had negative severe acute respiratory syndrome coronavirus 2 nucleocapsid antibody assay results, suggesting no previous infection. All patients had an elevated troponin. Cardiac MRI revealed late gadolinium enhancement characteristic of myocarditis. All 7 patients resolved their symptoms rapidly. Three patients were treated with nonsteroidal antiinflammatory drugs only, and 4 received intravenous immunoglobulin and corticosteroids. In this report, we provide a summary of each adolescent's clinical course and evaluation. No causal relationship between vaccine administration and myocarditis has been established. Continued monitoring and reporting to the US Food and Drug Administration Vaccine Adverse Event Reporting System is strongly recommended.

Symptomatic Acute Myocarditis in 7 Adolescents After Pfizer-BioNTech COVID-19 Vaccination.

Antimicrobial stewardship (AMS), the evidence-based use of antimicrobials, is an effective strategy in controlling antimicrobial resistance (AMR) in humans by reducing the irrational use of antimicrobials. Stewardship in children is less studied. This study assessed the knowledge, attitude, and practice of physicians prescribing antibiotics to children in Bayelsa State, Nigeria to identify gaps in AMS and possible solutions. Following ethical approval, a semi structured questionnaire was distributed among 40 paediatricians and gynaecologists at the two public tertiary healthcare facilities in Bayelsa State (the Niger Delta University Teaching Hospital and the Federal Medical Centre) for self-completion. Responses were expressed as percentages and analyzed using Bloom9s cutoffs. The Capability, Opportunity, Motivation, and Behaviour (COM-B) model was employed to identify gaps for intervention in prescribing behavior with gaps in each component identified by aggregate scores 90% rated the most acceptable. Questionnaires were administered from August to September 2021. The response rate was 68% (27/40). Participants were paediatricians (81%, 22/27) and gynaecologists (19%, 5/27). Antimicrobial Susceptibility Testing (AST) was not performed before antibiotic selection nine times out of 10 (89%, 24/27). In a third (37%, 10/27) of cases, 2-3 antibiotics were prescribed. The top three antibiotics, in rank order, were: cefuroxime or amoxicillin 41% (11/27); ciprofloxacin or amoxicillin 30% (8/27), and azithromycin (33%, 9/27). Aggregate COM-B scores were: capability, 74%; opportunity, 78%; and motivation, 87%. The most acceptable (100%, 27/27) options to improving antibiotic prescribing were: availability of resistance data, availability of guidelines, readily accessible microbiological data, and easy access to infectious disease physicians. There are gaps in knowledge of AMR and opportunity for rational prescribing. There is need for antimicrobial resistance data to promote pediatric AMS at the surveyed healthcare facilities.

https://www.medrxiv.org/content/medrxiv/early/2021/12/02/2021.11.30.21267070.full.pdf

Antimicrobial stewardship among Nigerian children: A pilot study of the knowledge, attitude, and practice of prescribers at two tertiary healthcare facilities in Bayelsa State.

Leonard Emuren

Papers

Symptomatic Acute Myocarditis in 7 Adolescents After Pfizer-BioNTech COVID-19 Vaccination.

Antimicrobial stewardship among Nigerian children: A pilot study of the knowledge, attitude, and practice of prescribers at two tertiary healthcare facilities in Bayelsa State.