Early risk markers for severe clinical course and fatal outcome in German patients with COVID-19

Abstract

Background: Some patients with Corona Virus Disease 2019 (COVID-19) develop a severe clinical course with acute respiratory distress syndrome (ARDS) and fatal outcome. Clinical manifestations and biomarkers in early stages of disease with relevant predictive impact for outcomes remain largely unexplored. We aimed to identify parameters which are significantly different between subgroups.

Design: 125 patients with COVID-19 were analysed. Patients with ARDS (N = 59) or non-ARDS (N = 66) were compared, as well as fatal outcome versus survival in the two groups.

Key results: ARDS and non-ARDS patients did not differ with respect to comorbidities or medication on developing a fatal outcome versus survival. Body mass index was higher in patients with ARDS versus non-ARDS (p = 0.01), but not different within the groups in survivors versus non-survivors. Interleukin-6 levels on admission were higher in patients with ARDS compared to non-ARDS as well as in patients with fatal outcome versus survivors, whereas lymphocyte levels were lower in the different subgroups (all p<0.05). There was a highly significant 3.5-fold difference in fever load in non-survivors compared to survivors (p<0.0001). Extrapulmonary viral spread was detected more often in patients with fatal outcome compared to survivors (P = 0.01). Further the detection of SARS-CoV-2 in serum showed a significantly more severe course and an increased risk of death (both p<0.05).

Conclusions: We have identified early risk markers for a severe clinical course, like ARDS or fatal outcome. This data might help develop a strategy to address new therapeutic options early in patients with COVID-19 and at high risk for fatal outcome.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Inflammatory burden compared in the different subgroups.

(A) CRP (C reactive protein) in mg/l for each individual with Median [IQR25; IQR75] of ARDS patients vs. Non-ARDS patients (orange, 205.3 [101.7; 309.0], N = 46 vs. green, 65.9 [25.0; 113.0], N = 63), Non-Survivors vs. Survivors (black, 132.6 [38.0; 293.5], N = 33 vs. red, 88.4 [28.3; 168.9], N = 76). (B) PCT (Procalcitonin) in ng/ml for each individual with Median [IQR25; IQR75] of ARDS patients vs. Non-ARDS patients (orange, 0.66 [0.3; 2.6], N = 52 vs. green, 0.1 [0.07; 0.18], N = 57), Non-Survivors vs Survivors (black, 0.45 [0.11; 2.1], N = 34 vs. red, 0.14 [0.09; 0.47], N = 75). (C) Interleukin-6 in pg/ml for each individual with Median [IQR25; IQR75] of ARDS patients vs. Non-ARDS patients (orange, 275.8 [103.4; 364.5], N = 39 vs. green, 61.9 [28.5; 123.0], N = 19), Non-Survivors vs. Survivors (black, 306.8 [102.1; 594.6], N = 21 vs. red, 116.6 [43.9; 188.1], N = 37). (D) Lymphocytes in % for each individual with Median [IQR25; IQR75] of ARDS patients vs. Non-ARDS patients (orange, 7.0 [4.2; 10.9], N = 48 vs. green, 11.5 [7.0; 20.5], N = 40), Non-Survivors vs. Survivors (black, 6.0 [3.0; 9.6], N = 29 vs. red, 10.0 [7.0; 16.1], N = 59). (E) Mean temperature by hospital days of Non-Survivors (black, Mean ± SEM, N = 3–34) and Survivors (red, Mean ± SEM, N = 33–81). (F) Area under the temperature curve (see 1E) in relative arbitrary units with Mean ± SEM for Non-Survivors vs. Survivors (black, 9.7 ± 3.1, N = 3–34 vs. red, 2.7 ± 3.2, N = 33–81).

Fig 2. The potential effect of risk factors on patient outcome.

Plot of logistic regression with adjusted Odds Ratio (point estimate and 95% CI) of different risk factors (logistic regression by means of base R Generalized Linear Model(glm)). COPD: chronic obstructive lung disease, OSAS: obstructive sleep apnea syndrome, HTN: hypertension, DM2: type 2 diabetes mellitus, CKD: chronic kidney disease, PAD: peripheral artery disease.

Fig 3. The potential impact on viremia on patient outcome via thrombocyte course.

(A) Thrombocytes in 1/nl by hospital days for Non-Survivors (N = 4–28) and Survivors (N = 9–57). (B) Thrombocytes in 1/nl by hospital days dichotomized by viremia (sero-positive on the left-hand side vs. sero-negative on the right-hand side) for Non-Survivors (sero-positive: N = 4–7, sero-negative: N = 4–5) and Survivors (sero-positive N = 4–7, sero-negative N = 4–23). Patient numbers vary between different time points in the figures, but the time point refers to the initial admission for each patient.

Fig 4. The probability of survival and intubation for patient outcome.

(A) Cumulative incidence (Dead: N = 38; Discharged: N = 87; no censored patients). (B) Probability of intubation of all ARDS patients, discharged vs. dead, with Kaplan-Meier method (dead: N = 24, 2 censored patients; discharged: N = 18).