LAUSR

Tocilizumab is known to improve outcomes in patients with severe coronavirus disease 2019 (COVID-19) pneumonia. However, little is known about its utility in patients with COVID-19 who require respiratory support with venovenous extracorporeal membrane oxygenation (V-V ECMO). We performed an observational cohort study of adult patients with COVID-19 admitted between March 1 and April 24, 2020 who required support with V-V ECMO due to acute respiratory failure. Patients who received tocilizumab 400 mg intravenous given once in addition to standard of care were compared to those who received standard of care alone. The primary outcome was time to hospital discharge. Twenty-nine patients with severe COVID-19 supported with V-V ECMO were evaluated, 22 of whom received tocilizumab and 7 who did not. Pneumothorax (18% vs. 86%, p = 0.007) and need for a thoracostomy tube (23% vs. 71%, p = 0.03), were significantly lower in the tocilizumab group. There was no difference in secondary bacterial infections between groups (73% vs. 100%, p = 0.25). The median length of ECMO support (16 vs. 64 days, p = 0.04), mechanical ventilation (36 vs. 127 days, p = 0.02), and hospital length of stay (40 vs. 138 days, p = 0.008) were all significantly reduced in patients who received tocilizumab (Table 3). Survival to hospital discharge did not differ between groups (95% vs. 86%, p = 0.43). Tocilizumab therapy was associated with significantly decreased hospital length of stay in patients on V-V ECMO. More data on COVID-19 targeted therapies in patients on V-V ECMO are needed. Acute respiratory distress syndrome (ARDS) developed in approximately 30–40% of patients with coronavirus disease 2019 (COVID-19) during the first wave of the pandemic, leading to significant morbidity and mortality.1,2 Several institutions reported successful outcomes with the use of venovenous extracorporeal membrane oxygenation (V-V ECMO) to support the most critically ill of these patients.3,4 However, little is known about the effects of concomitant antiviral or immunotherapies in this cohort because they were often excluded from clinical trials. Moreover, while there is a trend toward increased use of ECMO for patients with severe COVID-19, in-hospital mortality in these patients remains substantially high and appears to be rising, revealing an unmet need in their management.5 Tocilizumab, a monoclonal antibody inhibitor of the interleukin 6 (IL-6) receptor, was a commonly employed off-label immunotherapy from the outset of the pandemic based on the association of elevated IL-6 levels with more severe disease and increased mortality.6–9 The preponderance of observational data of tocilizumab in patients with COVID-19 suggested decreased duration of mechanical ventilation and improved survival but was subject to potential selection bias.10–12 Subsequently, randomized clinical trials confirmed the beneficial effect of tocilizumab on survival in large cohorts of patients with COVID-19.13,14 A meta-analysis of observational and randomized studies found greater reduction in in-hospital mortality in patients who received tocilizumab within 10 days of symptom onset or were admitted to the ICU, supporting potential benefit in the most critically ill patients if given early.15 However, data on tocilizumab specifically in patients on ECMO is limited to case reports.16–18 Although their respiratory function is supported, patients on ECMO still stand to potentially benefit from tocilizumab by reducing inflammation in the lungs and reversing immune cell exhaustion, which may expedite time to lung recovery.19,20 In addition, because tocilizumab is a systemic therapy, there may be additional benefit to the patient outside of its effects on the lung. Here, we report on our observations on the use of tocilizumab in COVID-19 patients on V-V ECMO.