Discussion
This retrospective study of a large cohort of hospitalized patients with
COVID-19 treated with remdesivir in a large healthcare system highlights
several noteworthy observations. First, one in five hospitalized
patients with COVID-19 improved clinically prior to completion of the
5-day course of remdesivir treatment. Second, there was a higher rate of
hospital re-admission or ED visit among those who were dismissed prior
to completion of the standard 5-day course of remdesivir. Third,
mortality at day 28 was associated with older age and having not
completed the 5-day course of remdesivir. As the COVID-19 pandemic
established endemicity worldwide, our clinical observations have
potential applications in its management across the continuum of care
settings.
Our study examined all hospitalized patients with COVID-19 treated with
remdesivir from November 2020 to November 2021, a period that
encompasses the pre-vaccination period to the sequential roll out of
vaccines to eligible patients.11,12 Among our cohort
of >3,000 patients, the mortality rate was 8.7%; this
reflects the high-risk characteristics of our population. Our patients
are predominantly older (56% are older than 65 years old) and had
multiple medical comorbidities (as measured by MASS). Hypertension,
cardiovascular disease and diabetes were the most common underlying
conditions. While medical comorbidities have been associated with severe
outcomes from COVID-19, an older age was the most significant risk
factor for all-cause and COVID-19 related death in this
study.13 The significant association between older age
and severe outcome from COVID-19 is well
described.14-16 Since the conduct of our study, there
has been increasing rates of vaccination among the population, while
treatment options have expanded to reduce the risk of death and severe
disease from COVID-19.
In our cohort, one in five patients who required hospitalization for
COVID-19 improved early prior to completion of the standard 5-day
remdesivir treatment. This is a novel observation that has important
clinical, operational and logistical implications. During the different
waves of the COVID-19 pandemic, especially during the SARS-CoV-2 Delta
wave, healthcare systems were overburdened with high number of patients
requiring medical care in the hospital. This resulted in a shortage of
medical beds and staff to care for the sick hospitalized patients. In
this situation, one wonders if patients who have improved but have not
yet completed the remdesivir course could be safely dismissed from the
hospital. Because of the uncertainty of their outcomes, our program
established hospital-based outpatient infusion centers to allow for
hospital dismissal of stable and improving patients yet provided the
infrastructure to complete the treatment course. This strategy is akin
to well-established outpatient antimicrobial therapy (OPAT) programs,
where intravenous antibiotics are administered in infusion units outside
the hospital settings. As a result of this practice, we estimated a
total of 1077 hospital rooms that were made available to other patients
needing critical services in the hospital.
This study observed that the rate of death by day 28 among patients who
did not complete 5-day course of remdesivir were higher compared to
those who completed the treatment course. In particular, patients who
did not complete remdesivir course in the hospital and did not receive
additional dose of remdesivir as an outpatient had three-time higher
odds of death within 28 days compared to patients who completed the
treatment course. Our findings imply that completion of a planned 5-day
course of remdesivir is crucial to improving outcomes. Physical and
electronic infrastructures to ensure the administration of intravenous
remdesivir in the outpatient setting is therefore important. The
implementation of our strategy was intertwined with the establishment of
the Monoclonal Antibody Treatment (MATRx) Program in November
2020.17 Since the infrastructure of outpatient
remdesivir infusion was operational since November 2020, it was an easy
transition for our program to provide remdesivir as an approved option
for outpatients with mild to moderate COVID-19. Our program have used
the three-day outpatient remdesivir course especially among those with
contraindications to ritonavir-boosted nirmatrelvir and when there is
scarcity of effective anti-spike neutralizing monoclonal
antibodies.10
Despite the benefits of early dismissal (by allowing patients to recover
in the comfort of their home environment), it is important to point out
that there was a higher rate of re-admissions or ED visits among
patients who were dismissed early to complete remdesivir in the
outpatient setting. While it is possible that clinically improving
patients have been prematurely dismissed, the biphasic course of
COVID-19 could have prompted patients to seek further care when their
symptoms rebounded.18 This data further calls into
question the assumptions that patients with COVID-19 selected for
hospital dismissal are well enough that ongoing medical care, including
medication therapy, is unneeded. It is therefore important to remotely
monitor these patients at home, in order to capture early warning signs
that would require further medical intervention.19 It
will also be important to further characterize these patients and define
risk factors for re-admissions in order to mitigate the need for further
medical evaluations.
There are several limitations of this study. First, it is a
retrospective study with inherent deficiencies in capturing all
clinically relevant information for all patients. Second, the cohort was
stratified patients into four groups, with varying demographic and
clinical characteristics. We attempted to adjust for them in the
multivariable analysis. Third, the findings may only apply to healthcare
systems with the infrastructure that allows for the safe administration
of remdesivir in the outpatient setting. While our program adapted this
novel strategy in conjunction with the implementation of anti-spike
monoclonal antibody infusion, the logistics of scheduling once daily
doses of remdesivir for patients was challenging (but not impossible) to
implement. It will be important to assess the economic impact of this
practice as well as patient perception and satisfaction of this strategy
of care.
This study of over 3000 patients hospitalized for COVID-19 highlights
the importance of completing a 5-day course of remdesivir treatment.
Older age was significantly associated with a higher risk of death,
while completion of the full course of remdesivir was associated with
lower risk of death. Among patients who have improved clinically to
allow for early hospital dismissal, it is important to ensure that they
complete their treatment course in the outpatient setting. This novel
strategy of transitioning remdesivir treatment among hospitalized
patients from inpatient to the outpatient setting appears to be
associated with clinical benefits, in addition to decongesting an
overburdened hospital system. This strategy could be implemented
selectively among stable patients, especially when hospitals are
overburdened with a census exceeding their capacity for care.