Abstract
BACKGROUND: The survival rate of patients with critical coronavirus disease-19 (COVID-19) over time is inconsistent in different settings. In Japan, a national database was organized to monitor and share the patient generation across the country in an immediate response to the COVID-19 pandemic. This study aimed to evaluate changes in survival over time and the prognostic factors in critical COVID-19 patients receiving mechanical ventilation with/without extracorporeal membrane oxygenation (ECMO) using the largest database in Japan. METHODS: This is a prospective observational cohort study of patients admitted to intensive care units in Japan with fatal COVID-19 pneumonia receiving mechanical ventilation and/or ECMO. We developed a prospective nationwide registry covering > 80% of intensive care units in Japan, and analyzed the association between patients' backgrounds, institutional ECMO experience, and timing of treatment initiation and prognosis between February 2020 and November 2021. Prognostic factors were evaluated by Kaplan-Meier analysis and Cox proportional hazards analysis. RESULTS: A total of 9418 patients were ventilated, of whom 1214 (13%) received ECMO. The overall survival rate for ventilated patients was 79%, 65% for those receiving ECMO. There have been five outbreaks in Japan to date. The survival rate of ventilated patients increased from 76% in the first outbreak to 84% in the fifth outbreak (p < 0.001). The survival rate of ECMO patients remained unchanged at 60-68% from the first to fifth outbreaks (p = 0.084). Age of ≥ 59 (hazard ratio [HR] 2.17; 95% confidence interval [CI] 1.76-2.68), ventilator days of ≥ 3 before starting ECMO (HR 1.91; 95% CI 1.57-2.32), and institutional ECMO experiences of ≥ 11 (HR 0.70; 95% CI 0.58-0.85) were independent prognostic factors for ECMO. CONCLUSIONS: During five COVID-19 outbreaks in Japan, the survival rate of ventilated patients tended to have gradually improved, and that of ECMO patients did not deteriorate. Older age, longer ventilator days before starting ECMO, and fewer institutional ECMO experiences may be independent prognostic factors for critical COVID-19 patients receiving ECMO.