Reactivations of the Herpesviridae or herpes simplex virus (HSV) and cytomegalovirus (CMV) in the lungs of COVID-19 patients have been recorded. It is still being determined if these viral reactivations are more common than they are in other patients. Study of 145 patients with severe COVID-19 pneumonia requiring invasive mechanical ventilation who underwent HSV and CMV testing in bronchoalveolar lavage during fiberoptic bronchoscopy for suspicion of ventilator-associated pneumonia. Researchers analyzed a historical cohort of 89 patients with severe influenza pneumonia needing invasive mechanical ventilation and compared their rates of HSV and CMV lung reactivations and HSV bronchopneumonitis. The HSV and CMV lung reactivations rates were 50% and 42% among the 145 COVID-19 patients and 63% and 28% among the 89 influenza patients, respectively. The percentage of HSV bronchopneumonitis was similar in both groups (31% and 25%, respectively), although the cumulative incidence of HSV lung reactivation was higher in influenza than in COVID-19 patients (P=0.03). The cumulative incidence of CMV lung reactivation was comparable between COVID-19 and influenza patients (P=0.07), even after accounting for extubation and death as competing events. In COVID-19 patients, influenza patients, and when all patients were put together, the outcomes of those with HSV or CMV lung reactivations were comparable to those without. Reactivations of herpes simplex virus (HSV) and cytomegalovirus (CMV) in the lungs frequently occur in COVID-19 patients but not more frequently than in patients with influenza-associated severe pneumonia, despite the latter group having a more severe illness at ICU admission and the former group having a longer duration of mechanical ventilation. Patients with reactivations of HSV or CMV in the lungs may benefit from antiviral treatment, but the exact nature of Herpesviridae is still unknown.