Carforio et al, in a December 2021 review entitled, “Clinically Suspected and Biopsy-Proven Myocarditis Temporally Associated with SARS-CoV-2 Infection,” noted the severe limitations of published case series and uncontrolled retrospective studies describing a putative covid-19 myocarditis.
“In these retrospective studies, particularly taking into consideration the patients’ demography (elderly with multiple comorbidities) and the fact that other noninflammatory causes for troponin, ECG [electrocardiogram], and echocardiographic abnormalities (e.g., type 1 or type 2 myocardial infarction, changes secondary to severe hypoxia, cardiogenic shock, respiratory tract obstruction, pulmonary embolism) were not excluded, a diagnosis of even ‘clinically suspected myocarditis’ seems highly unlikely”
Moreover, the authors, referring to their own considerable experience at a tertiary referral center for heart failure, myocarditis, and heart transplantation, reported,
“…we did not observe a higher frequency of myocarditis temporally associated with SARS-CoV-2. Although SARS-CoV-2 infection occurred in about 10% of our prospective cohort of 800 myocarditis patients on active follow-up, the clinical course of all infected cases was mild/asymptomatic and did not translate into a worsening of their cardiac status in terms of symptoms, arrhythmia, ECG, echocardiography, or CMR (cardiac magnetic resonance imaging) features.”
I will return to the focus of Carforio et al’s review, i.e., analyzing pooled data on endomyocardial biopsy/autopsy tissue characterizations among suspected “covid-19 myocarditis cases.” But we now have the first large-scale, controlled, population-based epidemiological data—albeit subject to the same lack of biopsy/autopsy findings limitations alluded to by Carforio et al—of the potential association between SARS-CoV-2 infection/covid-19 disease, and myocarditis/pericarditis. Suffice to say, the results are resoundingly negative.
Tuvali et al, employing a retrospective cohort design within the Israeli Clalit Health Services Organization (a Health Maintenance Organization), studied 196,992 adults after SARS-CoV-2 infection occurring between March 2020, and January, 2021. Diagnoses of inpatient, hospitalized myocarditis, and pericarditis from 10-days after positive PCR (polymerase chain reaction) testing were retrieved. The minimum observation period was 18-days, and follow-up ended on February 28, 2021. The control group consisted of 590,976 age- and sex-matched (3:1) persons who were PCR negative for SARS-CoV-2, and had no past positive PCR test. None of those studied in either group were covid-19 vaccinated.
Nine patients who were SARS-CoV-2 positive developed myocarditis (0.0046%), and eleven developed pericarditis (0.0056%). Twenty-seven patients in the SARS-CoV-2 negative control cohort (0.0046%) were diagnosed with myocarditis, while 52 developed pericarditis (0.0088%). SARS-CoV-2/covid-19 infection was not associated with either myocarditis (hazard ratio 1.08, 95% confidence interval 0.45-2.56), or pericarditis (hazard ratio 0.53, 95% confidence interval 0.25-1.13), upon multivariable proportional hazards modeling adjusted for age, sex. Body mass index, diabetes, hyperlipidemia, obesity, chronic kidney injury, smoking, peripheral vascular disease, acute coronary syndrome, and essential hypertension. The authors concluded, appositely, that the incidence of myocarditis and pericarditis in covid-19 infected patients was not increased relative to uninfected, matched controls.
Key tables and figures from the Tuvali et al study are presented below.
Returning to the Carforio et al review, those authors tabulated and synthesized the limited data on endomyocardial biopsy (EMB)/autopsy findings in n=226 putative covid-19 myocarditis cases, concluding:
“Overall, so far human data seem to indicate that histologically proven myocarditis temporally related to SARS-CoV-2 is uncommon. The presence of SARS-CoV-2 within the myocardium is still elusive. The frequency of myocarditis temporally related to SARS-CoV-2 may be actually overestimated, since current data come from highly selected patients undergoing autopsy, whereas the majority of infected patients survive and do not develop cardiac complications. Strong evidence for a SARS-CoV-2 role in direct infection of cardiac myocytes leading to virus induced myocarditis in patients is missing… [T]here is not yet definitive EMB/autopsy proof that SARS-CoV-2 causes direct cardiomyocyte damage in association with histological myocarditis.”
Carforio et al’s tabulations are reproduced below.