To the Editor: I read with interest the study by Beyls et al.1 which compared the different clinical characteristics and outcomes of patients with COVID-19–related respiratory distress syndrome (CARDS) requiring veno-venous extracorporeal membrane oxygenation (VV-ECMO) during the three epidemic waves of COVID-19 in France. Despite the increasing knowledge on the particularities of severe COVID-19 and the growing experience in the management of severe CARDS, that study revealed a massive increase in the 90 day mortality of patients undergoing VV-ECMO during the second epidemic wave. One plausible explanation for that important observation could be the fact that over the course of the pandemic, new variants of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have continuously emerged. Because the different waves of infection were mainly associated with one or more SARS-CoV-2 “variants of concern” (VOC) with different pathogenicity, it appears obvious that the pathogenicity of the dominant VOC in an infection wave can have important impacts on the outcomes of patients with severe COVID-19. Indeed, the Delta/B.1.617.2 variant, which was dominant during the second wave, is known to be associated with higher risk of death than both the previously dominant VOCs (i.e., Alpha/B.1.1.7, Beta/B.1.351 and Gamma/P.1) and the Omicron/B1.1.529 variant which became the dominant VOC during third wave.2,3 The excessively high mortality rate (i.e., 85.7%1) of patients supported by ECMO during the second wave deserves particular attention because a renewed appearance of more pathogenic VOCs cannot be ruled out. The high incidence of extensive pulmonary thrombotic microangiopathy associated with severe ventilation-perfusion mismatch, increased resistance in the pulmonary circulation and frequent afterload-induced right ventricular (RV) failure, which were identified as distinct features of severe CARDS (especially in infections caused by the Delta/B.1.617.2 variant) were often the leading cause of death attributed to COVID-19.4,5 Early detection of patients with increasing RV hemodynamic overloading can facilitate the selection of the most appropriate management (including the requirement of ECMO or a combined respiratory and circulatory support), which can be decisive for the patients’ survival.4 In severe RV afterload mismatch, the RV output decreases substantially, and RV dilation-related tricuspid regurgitation can rapidly increase. In such situations, attempting to treat the underlying etiology of impaired gas exchange using VV-ECMO alone may become insufficient.4 Considering the high incidence and the deleterious prognostic impact of right heart involvement in severe COVID-19 it seems likely that this was also the major cause of the high mortality rate documented by Beyls et al.1 for their ECMO-supported patients (92% with VV-ECMO) during the second wave. Thus, close monitoring of the right heart in patients with CARDS associated with hemodynamic instability, already before overt RV failure develops, could substantially improve therapeutic decision-making. It is therefore difficult to understand the still limited use of routine echocardiography for the surveillance of hospitalized patients with COVID-19. Echocardiography can improve the identification of patients with CARDS requiring ECMO therapy, the selection of the most appropriate support strategy (VV-ECMO, veno-arterial-ECMO, or VV-ECMO plus RV or left ventricle temporary percutaneous mechanical support) and also the weaning decision-making after cardiopulmonary amelioration during the support.