RAGE has potential pathogenetic and prognostic value in non-intubated hospitalized patients with COVID-19

The 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 non-mechanically ventilated hospitalized COVID-19 patients. Baseline sRAGE was measured among participants enrolled in the ACTIV-3/TICO trial of bamlanivimab for hospitalized COVID-19. Spearman 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 antibody response, gender, age, body mass index, diabetes mellitus, renal impairment, 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. Among 277 participants, baseline sRAGE was strongly correlated with viral plasma antigen concentration (? = 0.57). There was a weaker correlation between sRAGE and biomarkers of systemic inflammation such as IL-6 (? = 0.36) and CRP (? = 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. Elevated plasma sRAGE in hospitalized, non-ventilated patients with COVID-19 was an indicator of both clinical illness severity and plasma viral load and was associated with a lower likelihood of sustained recovery. These novel results indicate that plasma sRAGE may be a promising biomarker for COVID-19 prognostication and clinical trial enrichment.

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