BackgroundThe value of the soluble
receptor for advanced glycation end-products (sRAGE) as a
biomarker in
COVID-19 is not well understood. We tested the association between plasma sRAGE and illness severity, viral burden, and clinical outcomes in hospitalized patients with
COVID-19 who were not mechanically ventilated.MethodsBaseline sRAGE was measured among participants enrolled in the ACTIV-3/TICO trial of
bamlanivimab for hospitalized patients with
COVID-19. Spearman's rank correlation was used to assess the relationship between sRAGE and other plasma
biomarkers, including viral nucleocapsid
antigen. Fine-Gray models adjusted for baseline supplemental
oxygen requirement,
antigen level, positive endogenous anti-nucleocapsid antibody response, sex, age, BMI,
diabetes mellitus, renal impairment,
corticosteroid treatment, and log2-transformed
IL-6 level were used to assess the association between baseline sRAGE and time to sustained recovery. Cox regression adjusted for the same factors was used to assess the association between sRAGE and mortality.ResultsAmong 277 participants, baseline sRAGE was strongly correlated with viral plasma
antigen concentration (ρ = 0.57). There was a weaker correlation between sRAGE and
biomarkers of systemic
inflammation, such as
IL-6 (ρ = 0.36) and CRP (ρ = 0.20). Participants with plasma sRAGE in the highest quartile had a significantly lower rate of sustained recovery (adjusted recovery rate ratio, 0.64 [95% CI, 0.43-0.90]) and a higher unadjusted risk of death (HR, 4.70 [95% CI, 2.01-10.99]) compared with participants in the lower quartiles.ConclusionElevated plasma sRAGE in hospitalized, nonventilated patients with
COVID-19 was an
indicator of both clinical illness severity and plasma viral load. Plasma sRAGE in the highest quartile was associated with a lower likelihood of sustained recovery and higher unadjusted risk of death. These findings, which we believe to be novel, indicate that plasma sRAGE may be a promising
biomarker for
COVID-19 prognostication and clinical trial enrichment.Trial RegistrationClinicalTrials.gov NCT04501978.FundingNIH (5T32GM008440-24, 18X107CF6, HHSN261201500003I, R35HL140026, and OT2HL156812).