Impact of SARS-CoV-2 infection and viral burden on outcomes in acute decompensated heart failure

Abstract Background/Objectives Patients hospitalized with acute decompensated heart failure (ADHF) represent a clinically vulnerable population. However, the impact of concomitant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the prognostic relevance of viral burden in this setting remain incompletely understood. Methods We conducted a retrospective cohort study including 2,002 adults hospitalized with ADHF at a tertiary academic center between March 2020 and December 2024. SARS-CoV-2 infection was confirmed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) during the index hospitalization. The primary outcome was in-hospital mortality. Secondary clinical outcomes were ICU admission and invasive mechanical ventilation, while hospital and ICU length of stay were assessed as resource-utilization outcomes. Multivariable regression models adjusted for clinically relevant covariates were used to assess associations between infection status and outcomes. Among infected patients, cycle threshold (Ct) values were analyzed as surrogate markers of viral burden. Results Of the 2,002 patients included, 246 (12.3%) had confirmed SARS-CoV-2 infection. Compared with uninfected patients, infected individuals had higher in-hospital mortality (32.5% vs. 20.6%), ICU admission (61.4% vs. 50.7%), and invasive mechanical ventilation (6.5% vs. 2.4%) (all p ≤ 0.002). After multivariable adjustment, SARS-CoV-2 infection remained associated with in-hospital mortality (aOR 2.63, p = 0.0002), ICU admission (aOR 1.79, p = 0.0027), and invasive mechanical ventilation (aOR 2.84, p = 0.0017). Infection was also associated with longer hospital stay (aβ + 9.23 days, p < 0.0001) and longer ICU stay (aβ + 7.85 days, p = 0.0017). Among infected patients, lower median Ct values were associated with higher in-hospital mortality (aOR 0.89 per Ct unit, p = 0.0338), while lower minimum Ct values were associated with longer hospital stay (adjusted β − 0.44 days per Ct unit, p = 0.0359). Conclusions Among patients hospitalized with ADHF, concomitant SARS-CoV-2 infection was associated with substantially worse in-hospital outcomes and greater healthcare resource utilization. The observed associations between lower Ct values and adverse in-hospital outcomes should be considered hypothesis-generating and require prospective validation because Ct values are imperfect surrogate markers of viral burden.