Herpes Simplex re-activation in patients with SARS-CoV2 pneumonia: a prospective observational study.

Background: Herpes simplex 1 co-infections in patients with COVID-19 are considered relatively uncommon; some reports on re-activations in patients in intensive-care unit have been published. The aim of the study was to analyze herpetic re-activations and their clinical manifestations in hospitalized COVID-19 patients, performing HSV-1 PCR on plasma twice a week. Methods: We conducted a prospective, observational, single-center study involving 70 consecutive patients with severe/critical SARS-CoV-2 pneumonia tested for HSV-1 hospitalized at Azienda Ospedaliero-Universitaria of Modena. Results: Of these 70 patients, 21 (30.0%) showed detectable viremia and 13 (62%) had clinically relevant manifestations of HSV-1 infection corresponding to 15 events (4 pneumonia, 5 herpes labialis, 3 gingivostomatitis, one encephalitis and two hepatitis). HSV-1 positive patients were more frequently treated with steroids than HSV-1 negative patients (76.2% vs 49.0%, p 0.036) and more often underwent mechanical ventilation (IMV) (57.1% vs 22.4%, p 0.005). In the unadjusted logistic regression analysis, steroid treatment, IMV, and higher LDH were significantly associated with an increased risk of HSV1 re-activation (odds ratio 3.33, 4.61, and 16.9, respectively). The association with use of steroids was even stronger after controlling for previous use of both tocilizumab and IMV (OR=5.13, 95% CI:1.36-19.32, p=0.016). The effect size was larger when restricting to participants who were treated with high dose of steroids while there was no evidence to support an association with use of tocilizumab. Conclusions: Our study shows a high incidence of HSV-1 reactivation both virologically and clinically in patients with SARS-CoV-51 2 severe pneumonia, especially in those treated with steroids.