Cardiac Complications Higher After COVID-19 Than Vaccination

Cardiac complications are rare following both SARS-CoV-2 infection and mRNA COVID-19 vaccination, but that risk is significantly higher following the infection itself across all age groups, for both males and females. That’s the takeaway from more than a year’s worth of data culled from the National Patient-Centered Clinical Research Network (PCORnet).

“Our overall topline conclusions of this were that the overall risk of these cardiac complications is low. It’s low after COVID and it’s low after vaccination, no matter how you slice vaccination,” lead author Jason Block, MD (Harvard Pilgrim Health Care Institute, Boston, MA), told TCTMD. “The overall risk is low, but even in the population of patients that have the highest risk of cardiac complications after a vaccination, and that’s males 12 to 17 after the second dose: even in that group we found that the risk of cardiac complications after testing positive for SARS-CoV-2 was higher than it was after vaccination.”

The study is the latest to try and disentangle the cardiovascular risks of infection as compared with the risks of vaccination. Earlier this week, investigators writing in Circulation concluded that the risk of myocarditis in patients hospitalized with COVID-19 was greater than that linked to a COVID-19 vaccine.

The idea of comparing cardiac complications directly—and myocarditis risk in particular—was spurred by the reports of cases following vaccination, Block confirmed. “The whole idea was to put risks in context, not to downplay either, because I think the post-COVID and the postvaccine complications are both really important to understand and to know about, but we did feel like it was important to have them side by side to provide that context. To help people understand the overall benefit-risk calculation of vaccination, you need to know if you could have a consequence of vaccination. Well, what’s the consequence of not being vaccinated and potentially having a COVID-related sequelae?”

The comparative analysis was published April 8, 2022, in Morbidity and Mortality Weekly Report.

Apples to Apples

For the current analysis, Block and colleagues reviewed electronic health records (EHRs) from 40 US health systems from January 1, 2021, to January 31, 2022, collating cases of myocarditis, pericarditis, or multisystem inflammatory syndrome in children (MIS-C) due to COVID-19 in three different combinations according to ICD-10-CM codes. Case counts were analyzed according to whether they occurred in the context of a positive COVID-19 test, a first, second, unspecified, or any vaccination, and all were stratified by age and sex.

As Block et al summarize, the total population analyzed (age 5 and up) was more than 15 million and included 814,525 subjects in the “infection cohort,” 2.55 million who’d had a first vaccine dose, 2.48 million who’d had a second dose, 1.68 million in the “unspecified” vaccine cohort, and 6.71 million in the “any dose” group.

Among males aged 5 to 11, the incidence of myocarditis and myocarditis/pericarditis were highest following infection (12.6-17.6 cases per 100,000 patients) but amounted to just 0-4 cases per 100,000 after the first vaccine dose and zero after the second dose.

In this same age group, incidences of myocarditis, pericarditis, or MIS-C were 93.0-133.2 per 100,000 patients after infection but not seen following inoculation. Because there were no or few cases of myocarditis or pericarditis after vaccination, relative risks for a comparison with COVID-19 myocarditis/pericarditis cases could not be calculated. 

In males 12-17, the incidence of myocarditis or pericarditis were 50.1-64.9 cases per 100,000 after COVID-19 infection, 2.2-3.3 after the first vaccine dose, and 22.0-35.9 after the second dose. When MIS-C cases were considered as well, incidence jumped to 150.5-180.0 after infection. This yielded an overall relative risk of an adverse cardiac outcome following infection as compared with a first vaccine dose of 4.9-6.0, and of 1.8-5.6 after a second dose, both statistically significant findings.

A similar pattern was seen among males aged 18-29. Here the incidence of myocarditis and myocarditis/pericarditis after COVID-19 infection was 55.3-100.6 per 100,000 after infection, but just 0.9-8.1 after a first vaccine dose and 6.5-15.0 after a second dose. Again, the incidence of EHR codes for myocarditis/pericarditis/MIS-C were 97.2-140.8 after infection (investigators did not look for MIS-C codes following vaccination, because the syndrome was defined as a post-COVID phenomenon). That amounted to an overall RR of adverse cardiac outcomes following infection versus one- or two-dose vaccination of 7.2-61.8 and 6.7-8.5, respectively.

As Block noted for TCTMD, the myocarditis signal following vaccination has been strongest in males aged 12 to 17 following a second dose. This analysis, however, should be reassuring. “Even in that group, we found that the risk of cardiac complications after testing positive for SARS-CoV-2 was higher than it was after vaccination,” he said. “The risk ratios in that group were the smallest risk ratios that we found over all the population age-stratified and sex-stratified comparisons that we did, but even in that group the risk was higher after COVID.”

For males aged 30 and up, cardiovascular complications remained higher following infection than after vaccinations, yielding RRs that were again statistically significant in favor of vaccination.

Similar Patterns in Female Patients

In females aged 5 to 11, the search turned up no cases of myocarditis/pericarditis after vaccination but 5.4-10.8 cases per 100,000 after infection, and in those aged 12 and older, the incidence of cardiac outcomes did not vary by age but remained higher after infection (11.9-61.7 cases per 100,000) than after a first (0.5-6.2) or second (0.5-5.4) vaccine dose. Incidences of myocarditis, pericarditis, or MIS-C by ICD-10-CM code were 27.1–93.3 after infection. As a whole, cardiac outcomes were significantly more common following a confirmed COVID-19 case than they were after first or second injections.

“I think this is just one additional piece of information for people to consider,” Block said, noting that the paper does not take into account the other known complications of COVID-19. “This cardiac complication issue seems to be the most important risk that has emerged after mRNA vaccination, but there are lots of risks after COVID infection and those should be accounted for, too. What we wanted to do in this paper was just squarely focus on this single category of risk and compare that.”

Block and colleagues point out that these findings, while subject to the limitations of observational data, are in line with similar analyses from the UK and Israel.

Correction: an earlier version of this study misattributed the findings for males aged 12-17.