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

Abstract

Reactivation of herpes simplex virus type 1 (HSV-1) has been described in critically ill patients with coronavirus disease 2019 (COVID-19) pneumonia. In the present two-center retrospective experience, we primarily 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. The secondary objectives were the identification of predictors for HSV-1 reactivation and the assessment of its possible prognostic impact. Overall, 41 patients met the study inclusion criteria, and 12/41 patients developed HSV-1 reactivation (29%). No independent predictors of HSV-1 reactivation were identified in the present study. No association was found between HSV-1 reactivation and mortality. Eleven out of 12 patients with HSV-1 reactivation received antiviral therapy with intravenous acyclovir. In conclusion, HSV-1 reactivation is frequently detected in intubated patients with COVID-19. An antiviral treatment in COVID-19 patients with HSV-1 reactivation and worsening respiratory function might be considered.

Herpes Simplex Virus 1 (HSV-1) Reactivation in Critically Ill COVID-19 Patients: A Brief Narrative Review

“…HSV-1 is a double-stranded DNA alpha herpesvirus that instigates a lifelong infection within their hosts, establishing a latent infection and reactivating when the host immune system is weakened. We previously observed that as many as 25% of mechanically ventilated COVID-19 patients may reactivate HSV-1 in their low respiratory tract after 30 days of intensive care [ 15 ]. In a similar way, Franceschini observed that up to 30% of patients with severe/critical SARS-CoV-2 pneumonia experienced HSV-1 DNAemia, with 62% of them showing clinically relevant manifestations of HSV-1 infection [ 14 ].…”

“…In a retrospective study, we also assessed the cumulative risk of HSV-1 reactivation detected on BALF samples in critically ill patients with COVID-19, by means of PCR [ 15 ]. HSV-1 reactivation was defined in the presence of HSV-1 DNA ≥ 10 4 copies/ml on BALF samples in the presence of worsening respiratory function.…”

“…With the limit of the small sample size (and consequently of low power), no independent association was observed between HSV-1 reactivation and mortality in an adjusted Cox regression model including HSV-1 reactivation as a time-dependent covariate (HR 1.07, with 95% CI from 0.24 to 4.86, p = 0.928). No association was observed between treatment with steroids and HSV-1 reactivation [ 15 ].…”

“…Regarding antiviral treatment, the proportion of critically ill patients with HSV-1 reactivation detected by PCR who received antiviral treatment with acyclovir ranged from 70 to 92% across the different studies [ 15 , 16 , 58 ]. In the study by Franceschini et al, patients with COVID-19 pneumonia admitted to the ICU or receiving non-invasive ventilation received acyclovir prophylaxis [ 14 ].…”

“…HSV-1 reactivation in the presence of severe manifestations such as systemic skin manifestations, hepatitis, or encephalitis (all of them have been reported to possibly occur [ 14 , 44 , 60 , 61 ]), as well as in presence of worsening of respiratory function and pulmonary lesions [ 15 , 58 ], may be considered as clinically significant. However, reactivations without a manifest clinical picture are more controversial.…”