Systemic inflammation is associated with worse outcomes from SARS-CoV-2 infection but not neutralizing antibody.

Abstract

Systemic inflammation is associated with COVID-19 mortality rates, but the impact of inflammation on neutralizing antibodies to severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and on outcomes is poorly understood. This study aimed to determine the association between neutralizing antibody responses, inflammation, and clinical outcomes in hospitalized patients with COVID-19. Two hundred and eight patients presenting to the ED with symptomatic SARS-CoV-2 were included. Neutralization was assessed using the architect angiotensin-converting enzyme-2 (ACE2) binding inhibition assay, and inflammation was assessed using C reactive protein (CRP) and interleukin 6 (IL-6). Medical records were examined for 30-day mortality and 10-day intubation. Correlation between biomarkers was assessed and Kaplan-Meier curves and Cox proportional hazards models were constructed for outcomes. Thirty-seven (18%) patients died and 59 (28%) required intubation. There was a correlation between IL-6 and CRP (r = 0.34) but not ACE-2 (r < 0.06). Patients that died had higher CRP (14 mg/dl, 8-21) than those that survived (5 mg/dl, 2-11) and IL-6 (died = 344 pg/ml, 138-870 vs. survived = 65 pg/ml, 28-140). ACE-2 inhibition trended higher in those who survived (18%, 0%-65%) than those who died (3%, 0%-48%). Patients with elevated IL-6, elevated CRP, or low ACE2 inhibition had higher mortality. Only IL-6 (hazard ratio: 1.28, 95% CI 1.08-1.52) and age (1.04, 1.01-1.08) were associated with mortality in multivariate models. Elevated IL-6 was associated with 30-day mortality from SARS-CoV-2 infection. Lower ACE-2 inhibition was not independently associated with mortality or correlated with inflammatory markers, implying the importance of other aspects of the immune response for reducing SARS-CoV-2 mortality risk.IMPORTANCEWhile systemic inflammation associated with worse outcomes from SARS-CoV-2 infection, it is not associated with neutralizing antibody concentrations, implying the importance of other aspects of the immune response for reducing SARS-CoV-2 mortality risk.