Sex‐specific differences in myocardial injury incidence after COVID‐19 mRNA‐1273 booster vaccination

Natacha Buergin, Pedro Lopez‐Ayala, Julia R. Hirsiger, Philip Mueller, Daniela Median, Noemi Glarner, Klara Rumora, Timon Herrmann, Luca Koechlin, Philip Haaf, Katharina Rentsch, Manuel Battegay, Florian Banderet, Christoph T. Berger, Christian Mueller

To explore the incidence and potential mechanisms of oligosymptomatic myocardial injury following COVID-19 mRNA booster vaccination. Hospital employees scheduled to undergo mRNA-1273 booster vaccination were assessed for mRNA-1273 vaccination-associated myocardial injury, defined as acute dynamic increase in high-sensitivity cardiac troponin T (hs-cTnT) concentration above the sex-specific upper-limit of normal on day 3 (48-96 h) after vaccination without evidence of an alternative cause. To explore possible mechanisms, antibodies against IL-1RA, the SARS-CoV2-Nucleoprotein(NP) and -Spike(S1) proteins and an array of 14 inflammatory cytokines were quantified. Among 777 participants, median age 37 years, 69.5% women, 40 participants (5.1% [95%CI, 3.7%-7.0%]) had elevated hs-cTnT concentration on day 3 and mRNA-1273 vaccine-associated myocardial injury was adjudicated in 22 participants (2.8% [95%CI, 1.7%-4.3%]). Twenty cases occurred in women (3.7% [95%CI, 2.3%-5.7%]), two in men (0.8% [95%CI, 0.1%-3.0%]). Hs-cTnT-elevations were mild and only temporary. No patient had ECG-changes, and none developed major adverse cardiac events within 30 days (0% [95%CI, 0%-0.4%]). In the overall booster cohort, hs-cTnT concentrations (day 3; median 5 [IQR, 4-6] ng/L) were significantly higher compared to matched controls (n = 777, median 3 [IQR, 3-5] ng/L, p < 0.001). Cases had comparable systemic reactogenicity, concentrations of anti-IL-1RA, anti-NP, anti-S1, and markers quantifying systemic inflammation, but lower concentrations of IFN-λ1(IL-29) and GM-CSF versus persons without vaccine-associated myocardial injury. mRNA-1273 vaccine-associated myocardial injury was more common than previously thought, being mild and transient, and more frequent in women versus men. The possible protective role of IFN-λ1(IL-29) and GM-CSF warrant further studies. This article is protected by copyright. All rights reserved.