Pregnancy is associated with an increased risk for HSV-2 infection or reactivation

Herpes Simplex viruses consist of two strains known as HSV-1 and HSV-2. Several studies showed higher prevalence of HSV-2 in females and positive effect of progesterone on HSV-2 infection in vitro and in an animal model. In Israel`s Central Virology Laboratory, swab samples are simultaneously examined for HSV-1 and HSV-2 by multiplex real time PCR as part of routine diagnosis. The aim of this study was to explore certain characteristics of HSV 1&2 infection /reactivation, such as differences between gender, site of infection and comorbidity by analyzing lab results versus clinical and demographic anonymous patients` data (approved by Sheba IRB). Between 2011 and 2018 we tested 10,856 swab samples. HSV-2 was rarely found in orofacial swabs in both genders (less than 1%). In all other body areas HSV-2 was statistically more abundant in females than in males (p<0.01). This difference was not identified with respect to HSV -1. Analysis of the medical records of females hospitalized at Sheba Medical Center with proven genital infection with HSV-1 (223 files) or HSV-2 (138 files) showed that malignancies were a prevalent comorbidity in both HSV-1&2 positive females but pregnancies were significantly more common in females who were HSV-2 positive compared to females who were HSV-1 positive (26.09% versus 9.42% respectively p<0.01). Our findings suggest for the first time a link between progesterone, excreted at higher levels during pregnancy or given as treatment to achieve pregnancy, and increased risk for HSV-2 infection/reactivation in humans, previously shown only in tissue cultures and in animal`s model.