Herpes Simplex Virus Re-Activation in Patients with SARS-CoV-2 Pneumonia: A Prospective, Observational Study

Abstract

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 units were 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 the 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 doses of steroids while there was no evidence to support an association with the use of tocilizumab Conclusions: our study shows a high incidence of HSV-1 re-activation both virologically and clinically in patients with SARS-CoV-2 severe pneumonia, especially in those treated with steroids.

Reactivation of Herpes Simplex Virus Type 1 (HSV-1) Detected on Bronchoalveolar Lavage Fluid (BALF) Samples in Critically Ill COVID-19 Patients Undergoing Invasive Mechanical Ventilation: Preliminary Results from Two Italian Centers

“…In line with our results, two recent single-center studies reported that in hospitalized patients with severe or critical COVID-19 pneumonia, the frequency of HSV-1 reactivation was 31% on respiratory samples [12], and 30% in the plasma [2]. Differently from our study, an independent association was found between steroid treatment and HSV-1 reactivation [2]. These apparently opposite findings may be explained by the fact that almost all patients in our cohort (39/41) received steroid treatment, thereby drastically reducing our ability to assess their role as a predisposing factor for HSV-1 reactivation in our study.…”

“…In line with our results, two recent single-center studies reported that in hospitalized patients with severe or critical COVID-19 pneumonia, the frequency of HSV-1 reactivation was 31% on respiratory samples [12], and 30% in the plasma [2]. Differently from our study, an independent association was found between steroid treatment and HSV-1 reactivation [2].…”

“…Critically ill patients with coronavirus disease 2019 (COVID-19) pneumonia requiring invasive mechanical ventilation are at risk of developing bacterial, fungal, and viral superinfections [1][2][3][4]. Reactivation of herpes simplex virus type 1 (HSV-1) has been described in intubated critically ill patients with coronavirus disease 2019 (COVID- 19) pneumonia [2,3,[5][6][7][8].…”

“…Both predictors and prognostic implications of HSV-1 reactivation in this peculiar population remain largely elusive, making its management highly heterogenous in terms of prophylactic and therapeutic approaches [2,3,5]. In the present two-center retrospective experience, we aimed to assess the cumulative risk of HSV-1 reactivation detected on bronchoalveolar fluid (BALF) samples in invasively ventilated COVID-19 patients with worsening respiratory function, as well as to exploratorily assess the predictors of HSV-1 reactivation and its possible prognostic impact.…”

Molecular Mechanisms of Possible Action of Phenolic Compounds in COVID-19 Protection and Prevention

“…Here, it is worth mentioning that respiratory diseases are often accompanied by narrowed or obstructed airways, wherein increased consumption of apple and soybean polyphenols has been speculated to improve lung function [161]. Patients with COVID-19 are vulnerable to reactivation of the Herpes simplex 1 virus (HSV) infection causing secondary respiratory infection [162], and polyphenols have been reported to exert anti-HSV activity. Polyphenols are now under consideration as promising therapeutic agents against HSV viremia [163].…”