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.
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: 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). Methods: 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. Results: 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 non-healthcare 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: 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.
ABSTRACT
Introduction: Although the International and National Regulatory Authorities encourage COVID-19 vaccination in pregnant women [1-2], the scientific evidence supporting maternal exposure to COVID-19 vaccines during pregnancy is still limited and further studies are needed to monitor their safety profile in order to evaluate the potential consequences in both mother and child. Objective: We aimed to investigate Adverse Events Following Immunization (AEFI) with COVID-19 vaccines that occurred after maternal exposure during pregnancy. Methods: We retrieved Individual Case Safety Reports (ICSRs) following maternal exposure to COVID-19 vaccines during pregnancy from the EudraVigilance database of the European Medicines Agency during the year 2021. We investigated outcomes related to the mother and child age groups (defined as fetus, infant, and neonate). The Reporting Odds Ratio (ROR) was computed to compare the reporting probability of spontaneous abortion between each COVID-19 vaccine and all other COVID-19 vaccines. Results: During the study period (1 January 2021-31 December 2021), among 1,315,315 ICSRs related to COVID-19 vaccines, we retrieved 3,252 (0.25%) reports of AEFI that occurred after maternal exposure during pregnancy. More than half (58.24%) of ICSRs were submitted by non-healthcare professionals. The majority (87.82%) of ICSRs concerned serious AEFI. More cases of AEFI occurred in pregnant women (n = 2,764;85.0%) than in child age groups (n = 258;7.9%). Moreover, 55.16% ICSRs related to pregnant women exposed to COVID-19 vaccines involved non pregnancy-specific adverse events, mostly headache, pyrexia, fatigue, myalgia, and pain in extremities. The 17.92% were pregnancy-, neonatal-, or fetal-specific adverse events. Moderna and Oxford-AstraZeneca vaccines had a higher reporting probability of spontaneous abortion (ROR 1.2, 95% CI 1.05-1.38, P = 0.009;and ROR 1.26, 95% CI 1.08-1.47, respectively), while a lower reporting probability was found for Pfizer-BioNTech vaccine compared with all other Covid-19 vaccines (ROR 0.73, 95% CI 0.64-0.84). We also observed that 5.8% (n = 188) of cases reported a fatal outcome, 17 of them were clearly associated with the mother, while 171 with the child. Conclusion: We did not observe any strong insight into any unknown adverse events associated with COVID-19 vaccination. However, we analyzed data related to only one year of the vaccination program. Therefore, our experience also highlights the need for continuing to monitor the safety profile of COVID-19 vaccines and to identify long-term adverse events following immunization. In conclusion, in the European context, the analysis of real-world evidence suggests that the benefits of COVID-19 vaccines during pregnancy outweigh the possible risks for pregnant women and children.