Risk Factors for Severe Disease and Efficacy of Treatment in Patients Infected With COVID-19: A Systematic Review, Meta-Analysis, and Meta-Regression Analysis

Abstract

The coronavirus disease 2019 (COVID-19) pandemic spread globally in the beginning of 2020. At present, predictors of severe disease and the efficacy of different treatments are not well understood. We conducted a systematic review and meta-analysis of all published studies up to 15 March 2020, which reported COVID-19 clinical features and/or treatment outcomes. Forty-five studies reporting 4203 patients were included. Pooled rates of intensive care unit (ICU) admission, mortality, and acute respiratory distress syndrome (ARDS) were 10.9%, 4.3%, and 18.4%, respectively. On meta-regression, ICU admission was predicted by increased leukocyte count (P < .0001), alanine aminotransferase (P = .024), and aspartate transaminase (P = .0040); elevated lactate dehydrogenase (LDH) (P < .0001); and increased procalcitonin (P < .0001). ARDS was predicted by elevated LDH (P < .0001), while mortality was predicted by increased leukocyte count (P = .0005) and elevated LDH (P < .0001). Treatment with lopinavir-ritonavir showed no significant benefit in mortality and ARDS rates. Corticosteroids were associated with a higher rate of ARDS (P = .0003).

Keywords: COVID-19; coronavirus; risk factor; severe; treatment.

Figure 1.

Bubble plot for meta-regression of transformed ICU admission rate against percentages of patients with leukocytosis (A), increased ALT (B), increased AST (C), elevated LDH (D), and increased procalcitonin (E) in each study. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ICU, intensive care unit; LDH, lactate dehydrogenase.

Figure 2.

Bubble plot for meta-regression of transformed proportion of ARDS against percentage of patients with elevated LDH in each study. Abbreviations: ARDS, acute respiratory distress syndrome; LDH, lactate dehydrogenase.

Figure 3.

Bubble plot for meta-regression of transformed mortality rate against percentages of patients with leukocytosis (A) and elevated LDH (B) in each study. Abbreviation: LDH, lactate dehydrogenase.

Figure 4.

Forest plot for subgroup analysis of ARDS by type of antiviral used. The event rate is the incidence of ARDS in lopinavir and ritonavir recipients (top of figure) versus recipients of other/nonspecified antivirals (bottom of figure). Abbreviations: CI, confidence interval; ARDS, acute respiratory distress syndrome.

Figure 5.

Bubble plot for meta-regression of transformed ARDS rate against percentage of patients on corticosteroids in each study. Abbreviation: ARDS, acute respiratory distress syndrome.