Capillary Leak Syndrome and COVID-19 Vaccines: An Analysis of the European Spontaneous Reporting System EudraVigilance

ABSTRACT

Introduction: Recently, capillary leak syndrome (CLS) emerged as new suspected adverse event after immunization (AEFI) associated to COVID-19 vaccination. This condition is rare, but serious and potentially fatal [1]. Objective(s) Our pharmacovigilance study aims to evaluate the onset of CLS as AEFI with COVID-19 mRNA vaccines (Spikevax and Comirnaty) compared to viral vector vaccines (Janssen and Vaxzevria). Method(s) We carried out descriptive and disproportionality analyses of all Individual Case Safety Reports (ICSRs) reporting a vaccine COVID-19 as suspected drug and the CLS as AEFI, which were collected in the pharmacovigilance database EudraVigilance from January 1st, 2021, to January 14th, 2022. For the disproportionality analysis we applied the Reporting Odds Ratio (ROR) 95% CI. Result(s) During study period, CLS was described as AEFI in 84 out of 1,357,962 ICRs reporting a vaccine COVID-19 as suspected drug and collected in the EV database. Overall, the ICSR reported by CLS were mainly related to the viral vector COVID-19, Vaxzevria-, (N = 36) and Janssen-, (N = 9), while the ICSR reported to vaccines COVID-19 mRNA were 39 (Comirnaty-, N = 33;Spikevax-, N = 6). Majority of ICSRs were reported by healthcare professionals (N = 60;71.4%). The nonhealthcare professional represented the primary source in the 41.7% of Vaxzevria related ICSRs. Majority of the patients were adult (N = 49;58.3%). The female gender accounted in more than 65% of ICSRs referred both to mRNA and viral vector vaccines. The CLS outcome was more frequently favorable in mRNA ICSRs (N = 13;33,3%). On the other hand, among the ICSRs reporting CLS with unfavorable outcome (N = 25;29.8%) we found 9 ICSRs describing fatal CLS (Comirnaty N = 1;Vaxzevria N = 4;Janssen N = 4). From disproportionality analysis emerged a lower CLS reporting probability after COVID-19 vaccination with mRNA vaccines compared to viral vector-based ones. Conclusion(s) According to our results, few ICSRs describing CLS have been collected in EV in front of billion administered doses. This could underline the rarity of this AEFI or the limit of underreporting of spontaneous reporting and therefore also our study. Since the significant clinical relevance of CLS, this AEFI requires a careful monitoring. Healthcare professionals as well as patients should be aware of the signs and symptoms of CLS. Patients with a history of CLS require particular attention because of a possible risk of flare-up of disease. Since a precise mechanism is still not identified, further studies are necessary to confirm the causal relationship between CLS and COVID-19 vaccination.