In-hospital cardiovascular outcomes of COVID-19-associated cytokine storm: a population-level study

Background In severe COVID-19, hyperinflammatory “Cytokine Storm” (CS) can escalate disease severity, yet large-scale data on its cardiovascular impacts remain limited. Objective To assess the influence of CS severity on in-hospital cardiovascular outcomes and mortality in COVID-19 patients. Methods A retrospective analysis of the 2021 National Inpatient Sample (NIS) was performed, including adults (≥18 years) hospitalized with a principal COVID-19 diagnosis (ICD-10: U07.1), while excluding other hyperinflammatory conditions. CS was identified and categorized into four severity grades (ICD-10: D89.83). Multivariable logistic regression was utilized to assess associations between CS severity and in-hospital outcomes. Results In a weighted cohort of 1,428,892 hospitalized adults with COVID-19, 15,290 (1.1%) had CS. Mortality rose from 8.3% in non-CS patients to 26.9% in grade 4 (adjusted odds ratio [aOR] 3.334; 95% CI [2.810–3.956]), accompanied by increases in cardiac arrest (1.7%–4.4%; aOR 1.742; [1.234–2.459]) and venous thromboembolism (4.8%–9.4%; aOR 1.739; [1.369–2.210]) ( p all < 0.05). Myocardial Infarction (non-CS: 3.3% vs. Grade 4: 3.1%) and Cardiac Arrhythmias (non-CS: 14.4% vs. grade 4: 14.4%) remained similar across groups but showed decreased adjusted odds in grade 2 (aOR 0.328 [0.221–0.488]; aOR 0.738 [0.641–0.850]) ( p all < 0.05). Heart failure incidence declined with advancing CS grade (non-CS: 13.5% vs. grade 4: 12.5%), with grades 1 and 2 showing reduced odds (aOR 0.651; [0.475–0.892]), (aOR 0.702; [0.584–0.845]) ( p all < 0.05). Cardiogenic shock, Ischemic CVA, and Transient Ischemic attack were infrequent and excluded from graded analyses. Compared with non-CS patients, those with grade 4 had a longer median length of stay (5 days vs. 11 days) and higher median total cost (US $44,363 vs. US $142,280) ( p all < 0.05). Conclusion Within this cohort, advanced CS demonstrated an association with increased mortality and select cardiovascular complications in hospitalized COVID-19 patients; Moreover, certain events, such as arrhythmias and heart failure, showed nuanced patterns, underscoring the complex interplay between hyperinflammation and cardiac pathophysiology.