Lyra Olson, NA
MD PhD Student
Duke University School of Medicine, United States
Disclosure information not submitted.
Sarah Morrison, NA
Physician Assistant
Duke Medical Center, United States
Disclosure information not submitted.
Bryan Kraft, NA
Assistant Professor of Medicine
Duke Medical Center, United States
Disclosure information not submitted.
Lingye Chen, NA
Medical Instructor
Duke Medical Center, United States
Disclosure information not submitted.
Smita Nair, NA
Professor of Surgery
Duke Medical Center, United States
Disclosure information not submitted.
Bruce Sullenger, NA
Professor of Surgery
Duke Medical Center, United States
Disclosure information not submitted.
George Kasotakis, MD, MPH, FACS, FCCM
Assistant Professor of Surgery
Duke University Medical Center, United States
Disclosure information not submitted.
Title: Age and Comorbidities Predict COVID-19 Outcome Regardless of Severity of Innate Immune Response
Introduction: Although, SARS-CoV-2-induced hyperinflammation is one of the mechanisms underlying this severe mortality, the association between age and innate immune response in COVID-19 mortality remains unclear. We hypothesized that age and comorbidities would predict outcome in COVID-19 patients regardless of severity of innate immune response.
Methods: A prospective cohort study of severely ill COVID-19 patients requiring ICU level care was performed to assess the contributions of age, comorbidities, and innate immune response on mortality. Flow cytometry of fresh blood and multiplexed inflammatory chemokine measurement of sera was performed on samples collected longitudinally from COVID-19 patients beginning on average 8 days after diagnosis. The aggregate impact of comorbid conditions was calculated with the Charlson Comorbidity Index (CCI) and association between patient factors and outcomes was calculated via Cox proportional hazard analysis and repeated measures ANOVA.
Results: In total, 67 patients (46 male, aged 59±14 years) were included in the study. Compared to survivors, the patients that died were older (survivors 54±14 versus deceased 66±12) and had a higher burden of comorbid conditions (age excluded CCI: survivors 1.3±1.5 versus deceased 2.3±2.3). In a Cox Proportional Hazards analysis, age and comorbidities had a statistically significant association with mortality (age: RR, 1.09, 95% CI, 1.07 to 1.11 and age-excluded CCI: RR, 1.24, 95% CI, 1.14 to 1.35). After longitudinal assessment of peripheral immune cells and chemokines, mortality and older age ( >65) were each associated with elevated levels of inflammatory chemokines CCL2, CCL4, CCL11, and CCL20. Neutrophilia, lower CD8-T counts, and elevated levels CXCL8, CXCL9, and CXCL10 were associated with mortality, but not age, while lower CD4-T counts were found in older patients regardless of mortality.
Conclusions: Increasing age and comorbidities independently raise mortality risk in COVID-19. Notably, longitudinal assessment of immune cells and chemokines shows an imperfect overlap between age, mortality, and immune response, suggesting that age-associated immune changes influence but do not account for all inflammatory changes associated with COVID-19 mortality.