Cytomegalovirus DNAemia in Hospitalized Adults With SARS-CoV-2 Infection Requiring Supplemental Oxygen: Virologic and Clinical Characteristics and Association With Outcomes

Clinical Snapshot

Key Findings

• P Value: Not explicitly stated but CI excludes 1.0

• Effect Size: Adjusted hazard ratio 0.3 for CMV DNAemia vs no DNAemia

• Primary Outcome: Probability of clinical improvement by day 29

• Nnt Or Sensitivity: Cumulative incidence of CMV DNAemia: 11% overall (6.3% OS5, 16.4% OS6, 24.7% OS7)

• Confidence Interval: 95% CI: 0.17-0.56

Clinical Application

CMV PCR testing readily available in Australian tertiary hospitals; could be incorporated into routine monitoring protocols Relevant for Australian ICUs and respiratory wards managing severe COVID-19; CMV PCR covered under MBS for immunocompromised patients, may require expanded indications Hospitalized adults with moderate-to-severe COVID-19 requiring supplemental oxygen, particularly those with risk factors (older age, male sex, lymphopenia, corticosteroid use)

Abstract

BACKGROUND: Cytomegalovirus (CMV) reactivation occurs in the context of coronavirus disease 2019 (COVID-19); however, the viral kinetics, risk factors, and clinical outcomes are poorly defined. METHODS: We examined the association of CMV DNAemia with clinical outcomes among participants of a randomized trial of remdesivir with or without baricitinib (National Institute of Allergy and Infectious Diseases [NIAID], Adaptive COVID-19 Treatment Trial 2 [ACTT-2]). Plasma CMV DNAemia from CMV-seropositive participants with COVID-19 (NIAID ordinal scale [OS] 5, 6, or 7 at entry) were assessed longitudinally by quantitative polymerase chain reaction. Factors associated with CMV DNAemia, and clinical outcomes were analyzed by Cox regression and proportional odds models. RESULTS: Of 772 trial participants with available samples, 643 (83%) were CMV seropositive. Baseline CMV serostatus was not associated with COVID-19 outcomes. The cumulative incidence of CMV DNAemia among seropositive persons by day 28 was overall 11% (baseline OS 5, 6.3%; OS 6, 16.4%; OS 7, 24.7%), and was associated with older age, baseline OS, male sex, lymphopenia, and systemic corticosteroid use, while remdesivir and baricitinib did not affect risk. CMV DNAemia was associated with a lower probability of improvement by day 29 (adjusted hazard ratio, 0.3 [95% confidence interval, .17-.56]), with a more pronounced delay of recovery with higher CMV viral load. CMV DNAemia was also associated with higher severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and death. CONCLUSIONS: In hospitalized adults with COVID-19 requiring oxygen, CMV viremia occurs within well-defined clinical risks and is independently associated with delayed recovery from illness, higher SARS-CoV-2 viral load, and increased mortality.

References

1. 1.Boeckh, M., Xie, H., Stevens-Ayers, T., Sircy, L., Zamora, D., Goldman, J. D., Woods, C. W., Stapleton, R. D., Rubenfeld, G., Kalil, A., Jerome, K. R., Dasgupta, S., & Limaye, A. P. (2026). Cytomegalovirus DNAemia in hospitalized adults with SARS-CoV-2 infection requiring supplemental oxygen: Virologic and clinical characteristics and association with outcomes. *The Journal of Infectious Diseases*. https://doi.org/10.1093/infdis/jiaf649