ArticlePloS one2026
Herpesvirus reactivation is associated with mortality in critically ill ICU patients with COVID-19: Insights from a retrospective single-center analysis of 455 cases.
Article in PloS one, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundCritically ill patients with COVID-19 frequently develop viral reactivation, yet the clinical significance of herpes simplex virus type 1 (HSV-1) and cytomegalovirus (CMV) remains a matter of debate.
methodsWe conducted a retrospective single-center study of 455 consecutive intensive care unit (ICU) patients with confirmed SARS-CoV-2 infection between March 2020 and December 2021. Patients underwent screening for HSV-1 and CMV in whole blood and respiratory samples. A multivariable model was used to independently investigate risk factors associated with mortality.
resultsThe mean age was 57 years (range: 13-94 years), and 316 (69%) were male. During a median ICU stay of 14 (0-90) days, viral reactivation (either HSV-1 or CMV or both) occurred in 164 (36%) patients. HSV-1 and CMV co-reactivation was detected in 57 (13%) patients, isolated HSV-1 reactivation was observed in 54 (12%) patients and isolated CMV reactivation in 53 (12%) patients. Median time from ICU admission to viral detection was 4 days, with a stepwise increase with longer ICU stay. Detection of HSV-1 was associated with decreased ICU survival (32% versus 67%; p < 0.001) which remained significant after multivariable adjustment. Detection of HSV-1 but not CMV was associated with an increased need for invasive mechanical ventilation, veno-venous extracorporeal membrane oxygenation therapy, and the need for renal replacement therapy. Higher neutrophil-lymphocyte ratios were independently associated with an increased risk of ICU mortality and correlated with detection of HSV-1 and CMV.
conclusionHerpesvirus reactivation was common in critically ill patients with COVID-19. HSV-1 reactivation was associated with a more severe course of disease and increased ICU mortality.
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