Chitinase-3-like protein-1 at hospital admission predicts COVID-19 outcome: a prospective cohort study

Abstract

Infectious and inflammatory stimuli elicit the generation of chitinase-3-like protein-1 (CHI3L1), involved in tissue damage, repair and remodeling. We evaluated whether plasma CHI3L1 at disease onset predicts clinical outcome of patients with Coronavirus 2019 (COVID-19) disease. Blood from 191 prospectively followed COVID-19 patients were collected at hospital admission between March 18th and May 5th, 2020. Plasma from 80 survivors was collected one month post-discharge. Forty age- and sex-matched healthy volunteers served as controls. Primary outcome was transfer to intensive care unit (ICU) or death. CHI3L1 was higher in COVID-19 patients than controls (p < 0.0001). Patients with unfavorable outcome (41 patients admitted to ICU, 47 died) had significantly higher CHI3L1 levels than non-ICU survivors (p < 0.0001). CHI3L1 levels abated in survivors one month post-discharge, regardless of initial disease severity (p < 0.0001), although remaining higher than controls (p < 0.05). Cox regression analysis revealed that CHI3L1 levels predict primary outcome independently of age, sex, comorbidities, degree of respiratory insufficiency and systemic inflammation or time from symptom onset to sampling (p < 0.0001). Kaplan-Meier curve analysis confirmed that patients with CHI3L1 levels above the median (361 ng/mL) had a poorer prognosis (log rank test, p < 0.0001). Plasma CHI3L1 is increased in COVID-19 patients and predicts adverse outcome.

Figure 1

CHI3L1 plasma levels in COVID-19 patients and healthy controls. CHI3L1 plasma levels in: (A) age- and sex-matched healthy controls (HC) and COVID-19 patients at hospital admission (COVID-19 patients T0); (B) COVID-19 patients transferred to ICU or who died (Death/ICU) and patients with favorable outcome (No death/ICU); (C) eighty survivors at hospital admission (T0) and one month after discharge (T1). *** < 0.0001.

Figure 2

Correlations of CHI3L1 plasma levels with PaO₂/FiO2, CRP, NLR and LDH levels. Spearman’s test was used to correlate CHI3L1 levels with PaO₂/FiO2 (A), CRP (B), NLR (C) and LDH (D) values at the hospital admission.

Figure 3

Kaplan–Meier curves depicting rates of adverse autcome (transfer to ICU or death) in patients with CHI3L1 levels below (low) or above (high) the median value of 361 ng/mL. Log rank test, p < 0.0001.