Our results suggest the RESP score does not accurately predict in-hospital survival for patients with COVID-19 ARDS managed with VV-ECMO. In our COVID-19 ARDS cohort, the RESP score had a poor discriminative ability to predict survival and was not significantly associated with survival.

The reasons for the poor performance of the RESP score in our COVID-19 patients are unclear. Differences in the pathophysiology between COVID-19 ARDS and non-COVID-19 ARDS may reduce the clinical benefit of ECMO support for patients with COVID-19 ARDS. Alternatively, clinical variables not contained in the RESP score may better predict outcomes for patients with COVID-19 ARDS supported with ECMO. It is also possible that because the two study cohorts were treated exclusively in separate, consecutive time periods that differences in outcomes are related to changes in patient care (e.g. staffing shortages, increased patient volumes, different management practices) and not true differences between the cohorts.

Our study has several limitations. Its retrospective design makes it difficult to control for unmeasured confounding. Additionally, as our primary hypothesis was testing the discriminative ability of the previously published RESP score using a ROC curve, we did not adjust for other potential causes of poor outcomes in our models. As all patients were treated at a single center, its external validity may be limited.

In conclusion, the RESP score did not predict survival in patients with COVID-19 ARDS at our high volume ECMO center. Further studies are needed to confirm these findings in larger cohorts of patients with COVID-19 ARDS, especially those patients treated outside the height of the pandemic when shortages in medical staff and resources may have contributed to poor outcomes. Novel clinical decision support tools may be needed to identify patients with COVID-19 ARDS likely to benefit from VV-ECMO support in the future.