key: cord-0902817-l5e2utrk authors: van Dam, C.S.; Lede, I.; Schaar, J.; Al-Dulaimy, M.; Rösken, R.; Smits, M. title: Herpes Zoster after COVID-vaccination date: 2021-08-21 journal: Int J Infect Dis DOI: 10.1016/j.ijid.2021.08.048 sha: 87fb9e503d1dde5aa168cdc30f55428e0ed04d22 doc_id: 902817 cord_uid: l5e2utrk COVID-19 presents in various ways, but mainly as a pulmonary disease (Marzano 2020). Skin manifestations have been reported, including reactivation of the varicella zoster virus (Marzano 2020). In this case report, we describe two adults developing herpes zoster after vaccination with tozinameran (the Pfizer-BioNTech COVID-19 mRNA vaccine). A possible cause for this reaction is a transient lymphocytopenia that occurs after the vaccination – similar to that in COVID-19 disease (Mulligan 2020, Wang 2020, Qin 2020, Brabilla 2020, Wang 2020, Wei 2017). With the perspective of vaccinating older and/or immunocompromised adults, our observations can be the starting point of further evaluation of the possible relation between COVID-19, COVID-vaccines and Herpes Zoster. We are in the midst of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or COVID-19 pandemic. Although COVID-19 presents mainly as a disease affecting the pulmonary system, several skin manifestations have been reported in COVID-19 patients (Marzano 2020) . One remarkable finding is reactivation of the varicella zoster virus (VZV), causing herpes zoster (HZ) (Marzano 2020, Wang 2020, Qin 2020, Ferreira 2020, Tartari 2020, Elsaie 2020, Recalcati 2020 , Bhardwaj 2021 . In some patients, HZ was the presenting symptom of COVID-19 infection (Elsaie 2020 Case 1 is a 29-year-old female health care professional with no noteworthy medical history, except for chicken pox three times as a child, and once during adolescence. Despite this, she never had HZ. On January 8 th 2021, she received the first dose of tozinameran, with no adverse reactions until January 23 rd , when she noticed painful grouped vesicles on the left lateral of the ox coccyges (dermatoma S3), clinically diagnosed as being HZ. ( figure 1A) . On January 29 th , she received the second dose of the vaccine. At that time, there was still some ulceration left, but there was no relapse of HZ after the second dose. After two weeks, the lesions had resolved without medical intervention. 4 Case 2 is a 34-year-old male health care professional with a medical history of ulcerative colitis, for which he has been using infliximab and mesalazine for 4 years without infectious complications. He had chicken pox as a child, but never HZ. He received his first dose of tozinameran on January 12 th 2021, with no adverse reactions the following days. On January 25 th , he noticed painful and swollen inguinal lymph nodes, after which he saw a rash on his right leg. He visited the ER, where a papulovesicular rash was seen in dermatoma S2 ( figure 1B ). Blood analysis was normal. A PCR test performed on vesical fluid was positive for VZV. He was prescribed valacyclovir 1 gram thrice daily for 10 days, and recovered completely. On in lymphocytes the first days following injection (Mulligan 2020 ). In the dosage now used worldwide, which is 30 micrograms, 45.5% of the recipients had lymphocytes below 1x10 9 , 6 with one subject (9.1%) having grade 3 lymphopenia (0.2 -0.5 x10 9 ). These decreases were transient, and lymphocyte levels returned to normal 6 -8 days after vaccination. Also, the phase-I/II trial with ChAdOx1 nCoV-19 showed transient lymphocytopenia in 46% of the participants (Folegatti 2020) . It is conceivable that this short period of lymphocytopenia, both after COVID-19 infection and after vaccination can trigger a VZV reactivation. Although a full discussion regarding the role of T-regulatory cells is beyond the scope of this report, the authors of the nature-study speculate that the lymphopenia might be caused by an increase in type 1 interferons. (Sahin 2020) This would cause rolling and adhesion of lymphocytes to the endothelium, and consequently less T-cells to be measured in blood samples (Kamphuis 2006 ). However, functionality would not be decreased, and normally type 1 interferons inhibit varicella zoster replications (Kamphuis 2006 , Ku 2016 ).] It would be interesting to see whether patients developing VZV after vaccination have altered interferon responses. In conclusion, we report of 2 cases who developed herpes zoster after vaccination with tozinameran. While frequently a harmless condition, disseminated zoster could have fatal consequences. With the perspective of vaccinating older and/or immunocompromised adults, our observations require further evaluation of the possible relation between COVID- 19 and Herpes Zoster. All of the above listed authors have no conflicts of interest to report. There was no funding or other financial support of any organization. Written informed consent was obtained from the participants in this case report. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Legend: A: female patient with grouped vesicles in dermatoma S3; B: male patient with grouped vesicles in dermatoma S2 Herpes zoster after inactivated COVID-19 vaccine: a cutaneous adverse effect of the vaccine Immunopathogenesis and Potential Therapies Herpes zoster following inactivated COVID-19 vaccine: A coexistence or coincidence? 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Accessed on Decreased absolute numbers of CD3+ T cells and CD8+ T cells during aging in herpes zoster patients Transmission of varicella-zoster-virus (VZV) in family: Calls for attention during COVID-19 outbreak