Age and Comorbidity Predict COVID-19 Death More Accurately Than Innate Immune Response

Despite the rapid advances made in COVID-19 prevention and treatment, its pathophysiology is not well understood. One study sought to explore how age, comorbidities, and immune profile lead to mortality.

The study was presented virtually this morning by lead author Aditya Mohan during the 51st annual Critical Care Congress. The study authors noted that immune function dysregulation is one of the key facets of COVID-19 disease, and COVID-19-induced hyperinflammation increases the risk of mortality. However, they hypothesized age and comorbidities would be more predictive of COVID-19 outcome than innate immune response severity.

The prospective cohort study followed 67 severely ill COVID-19 patients who required intensive care unit treatment at Duke. The investigators collected whole blood and serum samples of from the participants, beginning at approximately 8 days after their COVID-19 diagnosis and continuing until discharge or death. They performed multiplexed inflammatory chemokine measurement of sera and flow cytometry of fresh blood samples.

Using the Charlson Comorbidity Index (CCI), the investigators calculated how comorbid conditions affected COVID-19 mortality. Cox proportional hazard analysis and repeated measures ANOVA determined the association between patient factors and disease outcomes.

Of the 67 patients severe COVID-19 included in the study, 46 were male and the average age was 59 years. The patients that died of COVID-19 disease tended to be older (survivors 54±14 years versus deceased 66±12 years) and had a higher comorbidity burden (CCI of survivors1.3±1.5 versus deceased 2.3±2.3). Common comorbidities among the deceased included liver disease, CKD, solid tumors, HIV/AIDS, and higher Body Mass Index and sodium levels. Age and comorbidities were significantly associated with mortality.

After assessing peripheral immune cells and chemokines, mortality and age over 65 years were linked to elevated levels of inflammatory chemokines CCL2, CCL4, CCL11, and CCL20. Neutrophilia, lower CD8-T counts, and elevated levels of CXCL8, CXCL9, and CXCL10 were associated with mortality, but not age. Regardless of mortality, however, older patients had lower CD4-T counts.

The investigators concluded that advanced age and comorbidity burden independently raise the risk of COVID-19 mortality. They noted the difference in the longitudinal assessment of immune cells and chemokines, indicating age-associated immune changes are not the cause of all inflammatory changes associated with COVID-19 mortality.

The study, “Age and Comorbidities Predict COVID-19 Outcome Regardless of Severity of Innate Immune Response,” was presented on April 18, 2022, during the 51st Critical Care Congress.