Methods
Study design and patient population
This is a retrospective multi-site cohort study of adult patients during
a one-year period from 11/6/2020 to 11/5/2021. All patients were
admitted to one of the Mayo Clinic hospitals with COVID-19 diagnosis and
received at least one dose of intravenous remdesivir. Per our standard
practice, all patients hospitalized for COVID-19 were assessed for
eligibility for a 5-day remdesivir course in the inpatient setting.
For this study, the patients were categorized into those who: 1)
completed the 5-day remdesivir course entirely inpatient, 2) completed
remdesivir course after transitioning to the outpatient setting, 3) did
not complete remdesivir course but remained inpatient, and 4) did not
complete remdesivir after discharge from the hospital. Determination of
inpatient or outpatient status was based on patient classes, department,
and manual review when unable to determine by other methods. Remdesivir
treatment course was categorized as incomplete if <5 doses or
<600 mg total was documented in the medication administration
record.
Patients were eligible for this study if they were ≥18 years of age and
received a first course of remdesivir. If there were >2
calendar days between doses of remdesivir, these were considered
separate courses and the subsequent course(s) were excluded. Other
exclusion criteria included receipt of an anti-spike neutralizing
monoclonal antibody or convalescent plasma, use of remdesivir under
another study protocol, and patients transitioning from an outside
facility during remdesivir treatment. Minnesota residents who declined
research authorization were excluded. The Mayo Clinic Institutional
Review Board deemed this study to be exempt.
Clinical variables and outcomes
All-cause mortality was defined as death within 28 days of the first
dose of remdesivir. Death related to COVID-19 was determined by chart
review by study team physician or clinical pharmacist. Second review was
performed by study physician if cause of death was unable to be
determined by clinical pharmacist.
Liver function tests (LFT, alanine and aspartate aminotransferases) were
reviewed for 10 days from the start of remdesivir treatment. Body mass
index (BMI), World Health Organization (WHO) ordinal scale, Monoclonal
Antibody Screening Score (MASS), and use of steroids, baricitinib, or
tocilizumab were collected. MASS is a clinical risk prioritization score
for the allocation of anti-spike monoclonal antibodies, and includes
age, body mass index, chronic heart, kidney and lung diseases, diabetes
mellitus, hypertension, pregnancy and an immunosuppressed condition or
treatment.10 Primary diagnosis code was used to
identify hospital and emergency care encounters related to COVID-19
within 30 days of the last administered dose of remdesivir and long
COVID related encounters within 180 days.
Statistical analysis
Data are summarized using medians and interquartile ranges (IQR) for
continuous data and frequencies and percentages for categorical data.
Patient characteristics were compared between groups using
Kruskal-Wallis tests for continuous data and either Chi-square or
Fisher’s exact tests for categorical data. Multivariable logistic
regression was used to assess associations between treatment group and
the outcomes of having an abnormal LFT, all-cause mortality within 28
days, and death related to COVID-19 within 28 days of remdesivir
treatment initiation after adjusting for age, sex, and MASS score. Rates
of subsequent ED visit or hospitalization within 30 days and subsequent
long COVID encounters within 180 of remdesivir initiation were estimated
using the Aalen-Johansen method, where death was considered a competing
risk. Cox proportional hazards regression was used to assess the
associations between these outcomes and treatment groups. Pairwise
comparisons between groups were adjusted for multiple comparisons using
the false discovery rate method. All analyses were performed using SAS
version 9.4 software (SAS Institute, Inc; Cary, NC).