SARS-CoV-2 infection, viral burden, and variant-specific outcomes in hospitalized patients with heart failure.

Abstract

Patients with heart failure (HF) are particularly vulnerable to systemic infection; however, the combined impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, viral burden, and emerging viral variants on outcomes in established HF remains incompletely defined. We investigated the independent association between SARS-CoV-2 infection and adverse in-hospital outcomes and evaluated the prognostic relevance of viral load and variant-specific patterns. 2826 consecutive patients hospitalized with documented HF between March 2020 and October 2024 were analyzed. SARS-CoV-2 infection was confirmed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) from nasopharyngeal swabs. Primary outcomes were cardiac decompensation, intensive care unit (ICU) admission, invasive mechanical ventilation, and in-hospital mortality. Secondary outcomes included total and ICU length of stay. Univariable and multivariable regression models were applied to assess associations with clinical outcomes. Viral burden was approximated using median and lowest cycle threshold (Ct) values. SARS-CoV-2 infection (n = 324, 11.5%) was independently associated with cardiac decompensation (adjusted OR 1.66), ICU admission (adjusted OR 1.95), invasive ventilation (adjusted OR 2.76), and in-hospital mortality (adjusted OR 2.60; all p < 0.01). Infection was further associated with prolonged hospitalization (+9.4 days) and ICU stay (+9.1 days; both p < 0.001). Among infected patients, lower median Ct values were independently associated with mortality (adjusted OR per unit increase 0.90; p = 0.0388). Earlier variants demonstrated substantially higher mortality and ICU utilization compared with Omicron sublineages. In hospitalized HF patients, SARS-CoV-2 infection independently increased mortality and healthcare resource utilization. Persistent viral burden and variant-specific heterogeneity further refined risk stratification, underscoring the sustained vulnerability of this high-risk population.