Factors associated with death outcome in patients with severe coronavirus disease-19 (COVID-19): a case-control study

Abstract

Rationale: Up to date, the exploration of clinical features in severe COVID-19 patients were mostly from the same center in Wuhan, China. The clinical data in other centers is limited. This study aims to explore the feasible parameters which could be used in clinical practice to predict the prognosis in hospitalized patients with severe coronavirus disease-19 (COVID-19). Methods: In this case-control study, patients with severe COVID-19 in this newly established isolation center on admission between 27 January 2020 to 19 March 2020 were divided to discharge group and death event group. Clinical information was collected and analyzed for the following objectives: 1. Comparisons of basic characteristics between two groups; 2. Risk factors for death on admission using logistic regression; 3. Dynamic changes of radiographic and laboratory parameters between two groups in the course. Results: 124 patients with severe COVID-19 on admission were included and divided into discharge group (n=35) and death event group (n=89). Sex, SpO2, breath rate, diastolic pressure, neutrophil, lymphocyte, C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), and D-dimer were significantly correlated with death events identified using bivariate logistic regression. Further multivariate logistic regression demonstrated a significant model fitting with C-index of 0.845 (p<0.001), in which SpO2≤89%, lymphocyte≤0.64×10⁹/L, CRP>77.35mg/L, PCT>0.20μg/L, and LDH>481U/L were the independent risk factors with the ORs of 2.959, 4.015, 2.852, 3.554, and 3.185, respectively (p<0.04). In the course, persistently lower lymphocyte with higher levels of CRP, PCT, IL-6, neutrophil, LDH, D-dimer, cardiac troponin I (cTnI), brain natriuretic peptide (BNP), and increased CD4+/CD8+ T-lymphocyte ratio and were observed in death events group, while these parameters stayed stable or improved in discharge group. Conclusions: On admission, the levels of SpO2, lymphocyte, CRP, PCT, and LDH could predict the prognosis of severe COVID-19 patients. Systematic inflammation with induced cardiac dysfunction was likely a primary reason for death events in severe COVID-19 except for acute respiratory distress syndrome.

Keywords: COVID-19; Critical care; Prognosis; Radiography; Risk factors.

Figure 1

Flowchart of inclusion of the patients.

Figure 2

ROC curve of multivariate logistic regression. Note: C-index of the predicted probability was 0.845 (p<0.001).

Figure 3

Typical radiographic aggravation manifestations. Note: A-C from a patient in discharge group with fever and cough for six days. After admission, chest DR showed a large area of air-space opacity in the bilateral lungs (DR score: 17 points) (A). Day 6, worsening respiratory failure (hypoxemia and tachypnea) necessitated intubation and ventilation (Critical aggravation). Chest DR demonstrated progressive diffuse opacity of bilateral lungs (DR score: 17 points) (B). Day 11, the intubation was removed and face-mask oxygen treatment was performed. Day 22, chest DR demonstrated partial absorption of the lesions with the reduced density in bilateral lungs (DR score: 14 points) (C). The patient eventually recovered and discharged on Day 38. D-F from a patient in death event group with fever for one week. After admission, chest DR showed a large area of air-space opacity in the left mid-zone and bilaterally lower zones (DR score: 10 points) (D). Day 4, worsening respiratory failure (hypoxemia and tachypnea) necessitated intubation and ventilation (Critical aggravation). Chest DR demonstrated progressive diffuse opacity of bilateral lungs, with bilateral air bronchograms (DR score: 15 points) (E). Day 9, chest DR demonstrated complete opacity of bilateral lungs, with bilateral air bronchograms and a right pleural effusion (DR score: 24 points) (F). The patient eventually died on Day 12 due to refractory respiratory failure.

Figure 4

Dynamic changes in DR scores and laboratory parameters between two groups. Note: Imaginary lines indicated the normal reference boundary; Man-Whitney U test (*p<0.05; **p<0.01; ***p<0.001).

Figure 5

Dynamic changes in cytokine profile between two groups. Note: Imaginary lines indicated the normal reference boundary; Man-Whitney U test (*p<0.05; **p<0.01; ***p<0.001).

Figure 6

Dynamic changes in Lymphocyte subsets between two groups. Note: Imaginary lines indicated the normal reference boundary; Man-Whitney U test (*p<0.05; **p<0.01; ***p<0.001).