Plasma sCD14-ST, but Not sCD14, Is Inversely Associated with Risk for SARS-CoV2 Positivity and Positively Associated with COVID-19-Related Respiratory Failure in Critically Ill Patients Admitted Under Suspicion for COVID-19

Abstract

Intro: Early innate immune responses are hypothesized to impact inflammation and therefore severity of disease and organ injury in COVID-19. Prior work in sepsis has identified CD14 as a marker of innate immune responses to bacterial infection and emerging evidence has implicated CD14 in COVID-19. CD14 exists in membrane bound and soluble (sCD14) form. A soluble N-terminal fragment of sCD14, sCD14 subtype (sCD14-ST, “Presepsin”) has been shown to have utility in diagnosis of sepsis and prognosis of associated organ failure and death. Goal: To determine the relationship between plasma sCD14 and sCD14-ST levels, COVID-19 status, and COVID-19 related outcomes in a cohort of prospectively enrolled critically ill patients admitted under suspicion for COVID-19. Methods: Critically ill patients under investigation for COVID-19 were prospectively enrolled between April 2020 and November 2020 at three hospitals affiliated with University of Washington. We ascertained COVID-19 status by SARS-CoV-2 RT-PCR upon admission. We measured plasma sCD14 and sCD14-ST levels in samples collected within 24 hours of admission. We tested for associations between biomarker levels and COVID-19 status using logistic regression adjusting for age, sex and APACHE III. In patients with COVID-19, we tested for associations between biomarker levels and disease severity and clinical outcomes using regression analyses adjusting for age, sex and APACHE III. Results: The cohort (n=222) mean age was 55 years, it was predominantly male (66%), in hospital mortality was 26%, and 50% of patients were positive by SARS-CoV-2 RT-PCR. Patients with COVID-19 had lower APACHE III scores (p: 0.013) than non-COVID-19. SCD14-ST levels were inversely associated with risk of SARS-CoV-2 positivity in multivariate regression (OR: 0.70, 95% CI: 0.57-0.84). Among patients with COVID-19, sCD14-ST levels were associated with higher APACHE III scores (beta: 7.3, 95% CI: 4.1-11), lower ventilatorfree days (beta:-1.6, 95% CI:-3.2 to-0.05) and higher risk for AKI (OR: 1.6, 95% CI: 1.0 to 2.7). SCD14-ST levels were not associated with these clinical outcomes in non-COVID-19 controls. In contrast to sCD14-ST levels, sCD14 levels did not differ between COVID-19 and non-COVID-19 patients and were not associated with COVID-19 clinical outcomes. Conclusions: In critically ill patients, sCD14-ST levels are inversely associated with risk of COVID-19 and positively associated with severity of disease and clinical outcomes among patients with COVID-19 while sCD14 levels were not associated with COVID-19 status or related outcomes. Early measurements of sCD14-ST levels could have prognostic utility in COVID-19.