Role of MR-proADM and Monocyte CD169 in Predicting In-Hospital and 60-Day Mortality in COVID-19 Patients

Abstract

Objectives: Mid-regional pro-adrenomedullin (MR-proADM) and monocyte CD169 (CD169) are valuable prognostic indicators of severe COVID-19.

Methods: We assessed the predictive ability of a single measurement of MR-proADM and CD169 at emergency department (ED) admission to forecast in-hospital and 60-day mortality in adult COVID-19 patients. We analyzed clinical and laboratory data, with in-hospital mortality as the primary endpoint and 60-day mortality as the secondary endpoint. We examined associations with clinical and laboratory variables through univariate and multivariate analyses.

Results: Data from 382 patients over 14 months were analyzed. Significant predictors of in-hospital mortality included age ⩾ 70 years (hazard ratio [HR] 8.1; 95% confidence interval [CI] 2.2-29.5), CD169 ratio ⩾ 20 (HR: 2.4; 95%CI: 1.6-5.6), MR-proADM ⩾ 1.1 mmol/L (HR: 5.1; 95%CI: 1.7-15.6), the need for invasive mechanical ventilation (HR: 6.8; 95%CI: 2.4-19.1), and active cancer (HR: 5.2; 95%CI: 1.8-15.2). For 60-day mortality, only elevated MR-proADM levels showed predictive value (HR: 6.7; 95%CI: 1.7-25.0), while high serologic titer was protective (HR: 0.4; 95%CI: 0.1-0.9).

Conclusion: A single MR-proADM and CD169 measurement upon ED admission has prognostic value for in-hospital mortality, with MR-proADM also predicting 60-day mortality.

Keywords: CD169; COVID-19; MR-proADM; Prognostic biomarkers; SARS-CoV-2; flow cytometry.

Figure 1.

Recruitment flowchart. The initial population consisted of 393 unselected adult patients with COVID-19. Three hundred and eighty-two patients were included in the study after the exclusion of 11 patients due to missing data or lack of consent. Of these patients, 50 (13%) died during hospitalization. A further 48 patients (12%) died during the 60-day follow-up period.

Figure 2.

Cox regression multivariable analysis of predictive in-hospital mortality variables. Agecat = age (Young: <70 years; Old: ⩾70 years); cd169cat = CD169 (Low: <20 ratio; High: ⩾20 ratio); proADMcat = MR-proADM (Low: <1.0 nmol/L; High: ⩾1 nmol/L); IOT = orotracheal intubation and need for invasive mechanical ventilation (0: no; 1: yes); pHcat = pH (Acid: <7.30; alkalosis: >7.45); and tumore = active cancer (0: no; 1: yes). AIC 250.6; P-value = 4.88 × 10⁻⁹; concordance index = 0.84.

Figure 3.

Kaplan–Meier curve for pH (P-value = .0004) for in-hospital mortality. In yellow, patients with pH > 7.45; in red, patients with pH in the normal range (7.35-7.45); in blue, patients with pH < 7.35. Survival rate (%) on the y-axis, time (days) on the x-axis.

Figure 4.

Aailen test (Chi² 20.87; P-value = .004). AgecatElderly: ⩾70 years; cd169cathigh: ⩾20 ratio; IOT1: orotracheal intubation and need for invasive mechanical ventilation; pHcatAlkalosis: pH < 7.45; pHcatNormal: pH 7.35 to 7.45; MR-proADMcathigh: ⩾1.1 mol/L; tumore 1: active cancer. Age andMR-proADM level showed an exponential increase in mortality over amount.

Figure 5.

Cox regression multivariable analysis of predictive 60-day mortality variables. AIC 139.5, concordance index 0.72; P-value = .007. MR-proADMcat = MR-proADM (Low: <1.1 nmol/L; High: ⩾1.1 nmol/L); pHcat = pH (Acid: <7.35; alkalosis: >7.45); and serology = anti-SarsCoV2 antibody titer (low_titre: <5 U/mL; high_titre: ⩾5 U/mL).

Figure 6.

Kaplan–Meier curves for in-hospital mortality according to the MR-proADM level (A) and further subdivided by SARS-CoV-2 vaccination status (B). (A) In-hospital mortality according to MR-proADM values, P < .0001. (B) In-hospital mortality according to MR-proADM values and SARS-CoV-2 vaccination status, P < .0001: in red, vaccinated patients with low MR-proADM levels; in blue, unvaccinated patients with low MR-proADM levels; in green, unvaccinated patients with high MR-proADM levels; in purple, vaccinated patients with high MR-proADM levels. Survival rate (%) is shown on the y-axis, and time (days) is shown on the x-axis.

Figure 7.

Kaplan-Meier curves for 60-day mortality according to the MR-proADM level (A) and further subdivided by SARS-CoV-2 vaccination status (B). (A) 60-day mortality according to MR-proADM values, p value = 0.01. (B) 60-day mortality according to MR-proADM values and SARS-CoV-2 vaccination status, p value = 0.062: in red, vaccinated patients with low MR-proADM levels; in blue, unvaccinated patients with low MR-proADM levels; in green, unvaccinated patients with high MR-proADM levels; in purple, vaccinated patients with high MR-proADM levels. Survival rate (%) is shown on the y-axis, and time (days) is shown on the x-axis.