A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination.

Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined.The study's primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization.New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV).New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group.Passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a finding that requires further study to include long-term outcomes surveillance. Active safety surveillance is needed to identify adverse events that are not well understood or previously recognized

Prospective Cases of New Onset Myocarditis/Pericarditis or cTnT Elevation Following Immunization with Either Smallpox or Trivalent Influenza Vaccine.

<p>*<b>Healthy 2002</b>: DoD Defense Medical Surveillance System pre-SPX MP incidence data.³</p><p>^‡<b>Prospective clinical myocarditis/pericarditis</b> cases included 4 Caucasian male cases of probable myocarditis (new onset cardiac symptoms (chest pain, dyspnea on exertion and/or at rest, palpitations) and cTnT elevations ≥0.02 ng/ml with the pre-vaccine level <0.01 ng/ml). The 5^th case (female) was acute suspect pericarditis presenting with characteristic chest pain and no cTnT elevations or ECG changes. There were no cases in the TIV prospective study cohort.</p><p>^§<b>Comparison of Prospective Smallpox Vaccine Cohort with published historic retrospective epidemiologic estimate of myocarditis/pericarditis disease incidence in comparable population pre-SPX vaccine</b>: P<0.001.</p><p>^ǁSubclinical myocarditis is defined by increases in cTnT (above pre-immunization levels) without classic new onset cardiac symptoms. The comparison cohort does not reflect a dynamic change but a single level in time in healthy population subsequently followed for mortality relative risk. <b>Possible subclinical pericarditis</b>: There were no cases of possible subclinical pericarditis identified through the blinded ECG series review process.</p><p>Prospective Cases of New Onset Myocarditis/Pericarditis or cTnT Elevation Following Immunization with Either Smallpox or Trivalent Influenza Vaccine.</p

Subject enrollment, exclusions and outcomes for two prospective cohorts, post-smallpox and annual trivalent influenza vaccine.

<p>Subject enrollment, exclusions and outcomes for two prospective cohorts, post-smallpox and annual trivalent influenza vaccine.</p

Pericarditis case definition for surveillance of adverse events after smallpox vaccination in the United States, 2003¹³.

<p>*<b>ECG findings</b>: Electrocardiogram findings not previously documented.</p><p>Pericarditis case definition for surveillance of adverse events after smallpox vaccination in the United States, 2003¹³.</p

Risk of COVID-19 after natural infection or vaccinationResearch in context

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health