Discussion
The primary findings of this study relate to the survival rate and complications associated with patients with ARDS due to COVID-19 who are treated with VV-ECMO. Patients with ARDS due to COVID-19, compared to patients with ARDS due to influenza, had a significantly higher ECMO mortality, with less patients surviving to ECMO decannulation. At the same time, patients with COVID-19 had an increased risk for developing new infections, with significantly higher rates of pneumonia and sepsis among COVID-19 patients.
The treatment of ARDS with ECMO remains disputed, despite its increased use in treating ARDS in the past decade.13,14 While the exact mortality rate of treating ARDS with ECMO varies by research study, it is typically accepted to range between 34-39%.13,15,16 This mortality rate is still better on ECMO than was reported by the ARDS definition task force, which highlights the importance of patient selection.3 Thus, it is generally recognized that ECMO should be primarily used for refractory cases of ARDS, in which a patient remains severely hypoxic despite aggressive treatment.15
A 2020 study by Acosta and Singer suggests that the pathogenesis and clinical course of ARDS due to influenza resembles ARDS due to COVID-19.32 However, differences in patient outcomes illustrates that there must be an difference between the two. The paper speculated that these severe cases may be due to SARS-CoV-2’s ability to dampen the inflammatory response to severe infection and impede normal pulmonary recovery to damage, which would exacerbate ARDS and lead to the observed increased mortality rate among patients with COVID-19. This again brings to question the treatment protocols that utilize potent and high dose immunosuppressants.21,22
Acosta and Singer emphasize that while mild to moderate cases of influenza and COVID-19 may present similarly, their prognoses diverge in severe cases. This idea is supported by a body of evidence which indicate that severe cases of COVID-19 have a higher mortality rate than severe cases of influenza. For example, one study found that patients who are admitted to the ICU for COVID-19 have a 3.7 times higher risk of death than patients treated in the ICU for influenza.6Similarly, another study detailed that hospitalized patients in the Veteran’s Health Administration had a 5 times higher risk for death than hospitalized patients with influenza.33 These studies are consistent with the trends at our institution.
In our study, we also discovered that while COVID-19 patients had lower rates of certain pre-existing conditions, they still had a higher mortality rate. Influenza patients had significantly higher rates of pre-ECMO acute kidney injury and coronary artery disease, as well as a higher body surface area. However, this is likely due to our restricted inclusion criteria for ECMO placement in COVID-19 patients and should not be used to make any definite conclusions on the impact of pre-existing conditions on mortality rate between influenza and COVID-19 patients.
An important finding of our study was the significantly higher rates of secondary bacterial infection in COVID-19 patients. Of the 28 COVID-19 patients, 14 (50%) developed a new infection during ECMO placement, with 10 (36%) developing bacterial pneumonia and 9 (32%) developing blood culture-positive sepsis. It is important to note that bacterial infection is a common complication for any patient who undergoes ECMO placement, and infections can lead to pneumonia and sepsis, both of which significantly increase these patients’ mortality rate.11 However, our research indicates that comparatively, patients with ARDS due to COVID-19 develop new infections more commonly when on ECMO than patients with ARDS due to influenza. This finding is backed by recent research on cases of COVID-19. COVID-19 has been statistically linked with cases of bacterial superinfection, especially in critically ill patients, which has been documented to lead to bacterial pneumonia and sepsis.34–36 Secondary bacterial infection in COVID-19 patients has also been significantly associated with poor outcomes and an increased mortality rate, even when patients are treated with aggressive antimicrobial therapies.37
The increased risk of infection may be a result of immunomodulation therapy in treating COVID-19. While immunomodulation therapy has been shown to decrease the mortality rate of COVID-19,38,39it has also been associated with an increased infection rate. In our study, 93% of COVID-19 patients were on some form of immunotherapy – either steroids, interleukin inhibitors, or both – while only 12% of influenza patients were immunosuppressed prior to ECMO initiation (p<0.001). Ultimately, it is possible – and even likely – that the decreased ECMO survival rate among our COVID-19 patients is partially caused by the increased incidence of bacterial superinfections.
Our study is limited by its small sample size and being based in one hospital center that provided ECMO support for a twelve hospital health system. It is also possible that there was selection bias in this study, even though ECMO placement was determined by a multidisciplinary team of physicians. Moreover, influenza patients dated back to 2010, while all COVID-19 patients were treated in 2020; it is possible that changes in ECMO protocol due to COVID-19 and associated treatment protocols with ECMO could impact patient outcomes and complication rates.
Despite its limitations, this study provides significant data on 28 patients with COVID-19 and effectively compares patients with ARDS due to COVID-19 to patients with ARDS due to influenza. This paper is one of a growing number of studies on COVID-19, and we hope that our findings contribute to a better understanding of how to effectively treat COVID-19.