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.