Critically ill COVID-19 patients frequently reactivate HSV-1 but not HSV-2. HSV-1 reactivation in critically ill COVID-19 patients was associated with an increased risk of day-60 mortality and hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) occurrence.

The association between HSV-1 reactivation and mortality may be useful for the clinician to identify patients with the worst prognosis.

Further studies are necessary to determine the causality relationship.

Of the 153 COVID-19 patients admitted for ≥ 48 h from Feb-2020 to Feb-2021, 40/153 (26.1%) patients had confirmed HSV-1 reactivation 19/61 (31.1%) with HSV-positive respiratory samples, and 36/146 (24.7%) with HSV-positive blood samples.

Day-60 mortality was higher in patients with HSV-1 reactivation (57.5%) versus without (33.6%, p = 0.001).

After adjustment for mortality risk factors, HSV-1 reactivation was associated with an increased mortality risk.

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