Background Despite being variable and poorly characterized, the reported cutaneous manifestations of coronavirus disease 2019 (COVID-19) are of increasing concern. Methodology This
study aimed to determine the prevalence and possible association between COVID-19 and herpes simplex virus (HSV) infection. A nine-item questionnaire was sent to 120 polymerase chain reaction-confirmed COVID-19 patients with a response rate of 66.67%. This cross-sectional observational
study included 80 patients with mild-to-moderate COVID-19 infection who did not require hospitalization or steroid therapy. Results One or more HSV infections were observed in 28 patients (35%) with COVID-19 infection, including 10 (35.7%) males and 18 (64.29%) females. Of the 28 patients, fever was reported in 17 (75%) during COVID-19. Most of the respondents (78%) described a single HSV reactivation, 14.29% had two attacks, and 7.14% experienced three attacks. Compared to previous non-COVID-19-related HSV reactivation, the COVID-19-related attacks were more severe in 12 (42.85%) patients, equally severe in five (17.85%) patients, and less severe in one (3.57%) patient. Interestingly, 10 (35.71%) patients developed an initial symptomatic HSV attack during COVID-19 infection. Conclusions This
study demonstrated a possible association between COVID-19 infection and primary HSV infection or reactivation. COVID-19 direct neuronal effect in addition to COVID-19-related psychological stress, fever, and immunological dysregulation could play a potential role in HSV reactivation or primary infection during COVID-19.