Reactivation of Human herpesviruses (HHVs) following SARS-CoV-2 infection and vaccination: a systematic review of clinical studies

Aims Human herpesviruses (HHVs) can establish latency and reactivate during critical illness and in the context of SARS-CoV-2 infection or vaccination. This systematic review aimed to evaluate available evidence on HHV reactivation in the setting of SARS-CoV-2 infection and vaccination.Materials and methods A systematic literature search was conducted across multiple databases including Web of Science, PubMed, Embase, and Scopus published from 2019 to 2025. Moreover, the quality and risk-of-bias assessments for all included studies were conducted using the Newcastle – Ottawa Scale (NOS) and the Joanna Briggs Institute (JBI) tools.Results HHV reactivation was frequently observed in critically ill COVID-19 patients, particularly involving Epstein – Barr virus (EBV), Herpes simplex virus type 1 (HSV-1), Cytomegalovirus (CMV), and Human herpesvirus 6 (HHV-6). Reactivation rates among reported cohorts varied, with EBV reactivation documented in approximately 65% of cases with herpesvirus reactivation and HSV-1 detectable in around 30%. Reactivation has also been documented post-vaccination, with herpes zoster and herpes simplex reactivations observed.Conclusions The study revealed an association between SARS-CoV-2 infection/vaccination and HHV reactivation, especially in severe COVID-19 cases. These findings demonstrated the need for further research to clarify the clinical significance and underlying mechanisms of HHV reactivation in this context.