High serum lactate dehydrogenase and dyspnea: Positive predictors of adverse outcome in critical COVID-19 patients in Yichang

Abstract

Background: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in China, constitutes a Public Health Emergency of International Concern. It is well known that COVID-19 patients may have increased serum lactate dehydrogenase (LDH) levels in the early stage. The clinical changes in LDH may have predictive value in disease evolution and prognosis in critically ill COVID-19 patients.

Aim: To examine serum LDH and clinical characteristics in patients with COVID-19 and their predictive value for prognosis.

Methods: This retrospective study analyzed the clinical data of forty-seven critical COVID-19 patients in the intensive care unit of the Third People's Hospital of Yichang City from January 27 to March 25, 2020 and divided them into survivors and non-survivors. The patients were diagnosed according to the World Health Organization interim guidance and critical cases met any one of the following criteria: Respiratory failure and required mechanical ventilation, the occurrence of shock, and the combined failure of other organs that required intensive care unit monitoring and treatments, according to the diagnostic criteria of critical COVID-19. Clinical data including symptoms, detection of SARS-CoV-2, chest computed tomography (CT) images, changes in serum LDH in different clinical phases, and prognosis were collected. Statistical analysis of the data was performed. Continuous variables were expressed as median (interquartile range) and compared with the Mann-Whitney U test. Categorical variables were compared with the Chi-square test. Survival data were analyzed using Kaplan-Meier survival curves and log-rank tests.

Results: According to chest CT images, we observed the alveolitis and fibrosis stages in all critical patients in this study. Most non-survivors died in the fibrosis stage. Non-survivors had fewer days of hospitalization, shorter disease duration, shorter duration of alveolitis and fibrosis, and had dyspnea symptoms at disease onset (P = 0.05). Both first and lowest LDH values in the alveolitis stage were more pronounced in non-survivors than in survivors (449.0 U/L vs 288.0 U/L, P = 0.0243; 445.0 U/L vs 288.0 U/L, P = 0.0199, respectively), while the first, lowest and highest values of serum LDH in non-survivors were all significantly increased compared to survivors in the fibrosis phase (449.0 U/L vs 225.5 U/L, P = 0.0028; 432.0 U/L vs 191.0 U/L, P = 0.0007; 1303.0 U/L vs 263.5 U/L, P = 0.0001, respectively). The cut-off points of first LDH values in the alveolitis and fibrosis phase for distinction of non-survivors from survivors were 397.0 U/L and 263.0 U/L, respectively. In the fibrosis stage, non-survivors had more days with high LDH than survivors (7.0 d vs 0.0 d, P = 0.0002). Importantly, patients with high LDH had a significantly shorter median survival time than patients with low LDH in the alveolitis phase (22.0 d vs 36.5 d, P = 0.0002), while patients with high LDH also had a significantly shorter median survival time than patients with low LDH in the fibrosis phase (27.5 d vs 40.0 d, P = 0.0008). The proportion of non-survivors with detectable SARS-CoV-2 until death in the alveolitis stage was significantly increased compared with that in the fibrosis stage (100% vs 35.7%, P = 0.0220).

Conclusion: High LDH and dyspnea symptoms were positive predictors of an adverse outcome in critical COVID-19. The rapid progressive fibrosis stage was more perilous than the alveolitis stage, even if SARS-CoV-2 is undetectable.

Keywords: COVID-19; Dyspnea; Lactate dehydrogenase; Overall survival; Pulmonary fibrosis; SARS-CoV-2.

Figure 1

Chest computed tomography of critical coronavirus disease 2019 patients with different severity. A: Chest computed tomography (CT) of a 71-year-old man (non-survivor, case 1) showed multifocal and bilateral ground-glass opacities (GGO) in the alveolitis stage (Day 7 of illness); B: Chest CT of a 73-year-old male patient (survivor, case 2) exhibited slight GGO in the alveolitis stage (Day 7 of illness); C: Classified into the fibrosis stage (Day 20 of illness) and Chest CT (case 1) showed bilateral massive shadows of high density and GGO, accompanied by the air bronchogram sign and reticular pattern in the fibrosis stage; and D: Chest CT (case 2) showed that bilateral and multifocal lesions were observed with a combination of mixed GGO, reticular pattern, bronchiectasis and few consolidation (Day 20 of illness).

Figure 2

The relationship between serum lactate dehydrogenase levels and the prognosis of patients with critical coronavirus disease 2019. The first, lowest and highest values of serum lactate dehydrogenase (LDH), together with the days with high LDH (≥ 397.0 U/L in the alveolitis phase and ≥ 263.0 U/L in the fibrosis phase according to the receiver operating characteristic curve analysis, respectively) and the ratio of the days with high LDH to disease duration were analyzed by the Mann-Whitney U test between non-survivors and survivors in the alveolitis phase and fibrosis phase. P < 0.05 was considered statistically significant. LDH: Lactate dehydrogenase.

Figure 3

Association between the first value of serum lactate dehydrogenase and survival time of patients with critical coronavirus disease 2019. Kaplan-Meier analysis and the log-rank test were performed to analyze the association between the first values of serum lactate dehydrogenase (LDH) and the survival time of patients with critical coronavirus disease 2019. A: Patients with high LDH (≥ 397.0 U/L) had a significantly shorter survival time compared to those with low LDH (< 397.0 U/L) in the alveolitis phase; B: Patients with high LDH (≥ 263.0 U/L) also had a significantly shorter survival time compared to those with low LDH (< 263.0 U/L) in the fibrosis phase. LDH: Lactate dehydrogenase.

Figure 4

Proportion of non-survivors with detectable severe acute respiratory syndrome coronavirus 2 until death in the alveolitis and fibrosis phase. All non-survivors (100.0%) who died in the alveolitis stage had a persistent positive test for severe acute respiratory syndrome coronavirus 2 until death. Only 5 patients (35.7%) who died in the pulmonary fibrosis stage had positive virus nucleic acid test results. SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2.