To the Editor,
We greatly appreciate the thoughtful comments of the Authors [Citation1] on our recent article discussing the potential occurrence of Herpes Zoster and Simplex reactivation following COVID-19 immunization [Citation2].
We agree with the authors of this letter that the reporting rate we found may have been overestimated since several factors, including the health/immunological status prior to vaccination, may have contributed to the occurrence of Herpes reactivations. On the other hand, it is worth mentioning that when estimating the incidence of adverse events (AEs) through spontaneous reporting system databases, the phenomenon of under-reporting should also be taken into account [Citation3]. Therefore, it is reasonable to assume that the real number of AEs occurring in the daily clinical practice is higher than that reported.
Another important issue worth addressing is the fact that Herpes reactivations occur in patients who have already experienced an active Herpes infection in their lifetime; therefore, the real incidence of this AE should be more accurately investigated in cohorts of selected individuals, instead of in the whole vaccinated population. Using selected cohorts of subjects would also allow the investigation of immunological profiles of the cases as a means to confirm for final diagnosis, as suggested by the authors.
Unfortunately, the FAERS database does not provide data on the patients’ immunological state; however, in an attempt to take into account this potential source of biases, we excluded all cases of active Herpes infections at the time of immunization, as well as all cases occurring concomitantly with COVID-19 infections, which is a well-known trigger factor for the occurrence of Herpes reactivation.
Furthermore, for each case, we investigated the presence of concomitant medication at the time of AE onset that exert their pharmacological action or their primary toxicity via immunosuppression, in order to investigate the potential role of other drugs in causing or exacerbating Herpes reactivation.
In conclusion, we would like to point out that although we cannot exclude that COVID-19 vaccines may have triggered Herpes reactivations in our study, most of these suspected AEs were of a non-serious nature and resolved spontaneously, supporting the safety profile of COVID-19 vaccines, which remain strongly recommended.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Acknowledgments
This work was supported by the Regional Centre of Pharmacovigilance of Lombardy (to EC), the Italian Medicines Agency, Agenzia Italiana del Farmaco (AIFA, to EC) and by the Italian Ministry of Health (Ricerca Corrente 2019-2020, to MP; and Progetto Finalizzata RF-2016-02363761 to EC) which are gratefully acknowledged. The funding public institutions had no role in any part of the work. VB is supported by the 37rd cycle Ph.D. programme in “Scienze Farmacologiche Sperimentali e Cliniche,” Università degli Studi di Milano.
Additional information
Funding
References
- Mungmunpuntipantip R, Wiwanitkit V. Correspondence on “Herpes Zoster and Simplex reactivation following COVID-19 vaccination” Expert Rev Vaccines. 2022;21(8):1–1. DOI: 10.1080/14760584.2022.2070155.
- Gringeri M, Battini V, Cammarata G, et al. Herpes zoster and simplex reactivation following COVID-19 vaccination: new insights from a vaccine adverse event reporting system (VAERS) database analysis. Expert Rev Vaccines. 2022 Feb;25:1–10. Online ahead of print.
- Alatawi YM, Hansen RA. Empirical estimation of under-reporting in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). Expert Opin Drug Saf. 2017 Jul;16(7):761–767.