Compassionate Use of Remdesivir in

Children With Severe COVID-19

David L. Goldman, MD,a Margaret L. Aldrich, MD,a Stefan H.F. Hagmann, MD, MSc,b Alasdair Bamford, MBBS, PhD,c
Andres Camacho-Gonzalez, MD, MSc,d Giuseppe Lapadula, MD, PhD,e Philip Lee, PharmD,a Paolo Bonfanti, MD,e
Christoph C. Carter, MD, PhD,f Yang Zhao, PhD,f Laura Telep, MPH,f Cheryl Pikora, MD, PhD,f Sarjita Naik, PharmD,f
Neal Marshall, MPharm,f Ioannis Katsarolis, MD, PhD,f Moupali Das, MD, MPH,f Adam DeZure, MD,f Polly Desai, MPH,f
Huyen Cao, MD,f Anand P. Chokkalingam, PhD,f Anu Osinusi, MD, MPH,f Diana M. Brainard, MD,f
Ana Méndez-Echevarría, MD, PhDg

Remdesivir shortens time to recovery in adults with severe coronavirus disease

OBJECTIVES: abstract
2019 (COVID-19), but its efficacy and safety in children are unknown. We describe outcomes
in children with severe COVID-19 treated with remdesivir.
METHODS: Seventy-seven hospitalized patients ,18 years old with confirmed severe acute
respiratory syndrome coronavirus 2 infection received remdesivir through a compassionate-
use program between March 21 and April 22, 2020. The intended remdesivir treatment
course was 10 days (200 mg on day 1 and 100 mg daily subsequently for children $40 kg and
5 mg/kg on day 1 and 2.5 mg/kg daily subsequently for children ,40 kg, given
intravenously). Clinical data through 28 days of follow-up were collected.
RESULTS: Median age was 14 years (interquartile range 7–16, range ,2 months to 17 years).
Seventy-nine percent of patients had $1 comorbid condition. At baseline, 90% of children
required supplemental oxygen and 51% required invasive ventilation. By day 28 of follow-up,
88% of patients had a decreased oxygen-support requirement, 83% recovered, and 73% were
discharged. Among children requiring invasive ventilation at baseline, 90% were extubated,
80% recovered, and 67% were discharged. There were 4 deaths, of which 3 were attributed to
COVID-19. Remdesivir was well tolerated, with a low incidence of serious adverse events
(16%). Most adverse events were related to COVID-19 or comorbid conditions. Laboratory
abnormalities, including elevations in transaminase levels, were common; 61% were grades 1
or 2.
Among 77 children treated with remdesivir for severe COVID-19, most recovered
CONCLUSIONS:
and the rate of serious adverse events was low.

a
Children’s Hospital at Montefiore, New York, New York; bSteven and Alexandra Cohen Children’s Medical Center, WHAT’S KNOWN ON THIS SUBJECT: Currently, the only
Northwell Health, New York, New York; cGreat Ormond Street Hospital for Children National Health Service evidence concerning the safety and efficacy of remdesivir in
Foundation Trust, London, United Kingdom; dEmory University and Children’s Healthcare of Atlanta, Atlanta, hospitalized children with coronavirus disease 2019 (COVID-
Georgia; eUniversity of Milan-Bicocca, Monza, Italy; fGilead Sciences Inc, Foster City, California; and gHospital La 19) comes from individual case reports and small series.
Paz, Madrid, Spain
WHAT THIS STUDY ADDS: We report the largest cohort to date
Drs Osinusi, DeZure, Cao, Chokkalingam, and Brainard conceptualized and designed the of children with COVID-19 receiving remdesivir. Although the
compassionate-use program and reviewed and revised the manuscript; Dr Carter coordinated and lack of a control in this compassionate-use program
supervised data collection, drafted the initial manuscript, and reviewed and revised the manuscript; precludes efficacy assessment, these data on remdesivir
Dr Zhao designed the data collection methodology, conducted the initial analyses, and reviewed and safety and outcomes in children with COVID-19 are important.
revised the manuscript; Drs Goldman, Aldrich, Hagmann, Camacho-Gonzalez, Méndez-Echevarría,
Lapadula, Lee, Bonfanti, and Bamford collected data and reviewed and revised the manuscript; To cite: Goldman DL, Aldrich ML, Hagmann SHF, et al.
Ms Telep and Drs Pikora and Das coordinated and supervised data collection and reviewed and Compassionate Use of Remdesivir in Children With Severe
COVID-19. Pediatrics. 2021;147(5):e2020047803

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PEDIATRICS Volume 147, number 5, May 2021:e2020047803 ARTICLE
Coronavirus disease 2019 (COVID-
19) is a respiratory illness caused by
severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) with
clinical manifestations ranging from
asymptomatic disease to hypoxemic
respiratory failure and death. As of
March 11, 2021, .3 million cases of
COVID-19 in children 0 to 17 years of
age have been reported in the United
States, representing ∼13% of all
cases.1 According to the American
Academy of Pediatrics and the
Children’s Hospital Association, up to
3.0% of all COVID-19 cases in
children resulted in hospitalization,
but COVID-19-related mortality
among children is low (,0.2%).1
Centers for Disease Control and
Prevention surveillance data through
July 25, 2020, indicate that the
pediatric hospitalization rate for
COVID-19 was 8 per 100 000
population compared with 164.5 per
100 000 in adults; however, 1 in 3
hospitalized children required ICU
care, a proportion similar to that
observed in adults. Children
hospitalized for COVID-19 were more
likely to be Black or Hispanic and had
a high prevalence of underlying
medical conditions, including obesity,
chronic lung disease, and
prematurity.2 In addition to
pulmonary disease, SARS-CoV-2
infection in children has been
associated with multisystem
inflammatory syndrome in children
and cardiac dysfunction.3–5
Remdesivir is a nucleotide analogue
that selectively inhibits the RNA-
dependent RNA polymerase of
several viruses, including SARS-CoV-
2.6,7 Part 1 of the Adaptive COVID-19
Treatment Trial demonstrated that
a 10-day course of remdesivir was
superior to placebo in reducing time
to recovery in hospitalized adults
with severe COVID-19.8 The SIMPLE
Severe trial showed that outcomes
with 5 days of remdesivir treatment
of severe COVID-19 were similar to
10 days of treatment.9 The SIMPLE
Moderate trial revealed clinical
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2 GOLDMAN et al
benefit of 5 days of remdesivir for
moderate COVID-19 relative to
standard of care.10 These studies did
not demonstrate a mortality benefit
of remdesivir. In contrast, the World
Health Organization SOLIDARITY trial
did not show an effect on duration of
hospitalization of remdesivir,
hydroxychloroquine, lopinavir, or
interferon.11
Optimal therapy for children with
severe COVID-19 is unknown;
although supportive care is likely to
be adequate for most cases, initial
expert guidance suggests that
antiviral therapy with remdesivir
should be considered in some cases.12
Here, we report clinical outcomes in
77 hospitalized children who received
remdesivir as part of the
compassionate-use program.
Although this study cannot evaluate
the efficacy of remdesivir, it provides
valuable data on safety and the
clinical features of severe COVID-19
in children.
METHODS
Compassionate-Use Program
Description and Population
Gilead Sciences began accepting
requests from clinicians for
compassionate use of remdesivir in
children with COVID-19 on March 21,
2020. Instructions for the use of
remdesivir were outlined in a single
patient protocol (SPP) (see
Supplemental Information), including
guidance on dosing, administration,
clinical procedures, laboratory tests,
and concomitant medication
administration. Access was limited to
hospitalized patients with polymerase
chain reaction–confirmed SARS-CoV-
2 infections and severe
manifestations of COVID-19. Patients
were generally required to have
oxygen saturation of #94% while
breathing ambient air or a need for
oxygen support, although decisions
were based on an individualized risk/
benefit assessment, and, in some
cases, patients were accepted because
of concern for extrapulmonary
manifestations of SARS-CoV-2
infection, serious comorbidities, or
radiographic findings.13,14 Remdesivir
was not provided for patients with
creatinine clearance (by an age-
appropriate estimated glomerular
filtration rate formula) of ,30 mL per
minute, serum levels of alanine
aminotransferase (ALT) .5 times the
upper limit of normal, or evidence of
multiorgan failure. Concomitant
administration of other
investigational agents for COVID-19
was not permitted in the SPP;
however, treating physicians did
administer these in some cases.
Children weighing $40 kg received
a loading dose of 200 mg
intravenously on day 1, plus 100 mg
intravenously on subsequent days.
Children weighing ,40 kg received
a loading dose of 5 mg/kg
intravenously on day 1, plus 2.5
mg/kg intravenously on subsequent
days. A 10-day course of therapy was
recommended, but shorter courses
were sometimes given at the
clinician’s discretion. Supportive
therapy and study drug
discontinuation were also at
clinicians’ discretion. Patients were
followed through 28 days
postinitiation or until discharge or
death, if either occurred before 28
days had passed. Some patients
included in this analysis have been
reported previously in case reports.
Program Oversight
For each patient, we obtained
regulatory and institutional review
board or independent ethics
committee approval, with consent
secured for all patients on the basis of
local regulations. The sponsor (Gilead
Sciences) designed and conducted the
program according to the SPP,
collected the data, monitored
program conduct, and performed all
statistical analyses. All authors were
given access to the reported data and
took responsibility for their integrity
and completeness. A professional
writer employed by the sponsor
assisted in the writing of this article.
Procedures
This program had no prespecified end
points. An electronic case report form
was used by clinicians to report
patient medical history, changes in
clinical status, remdesivir
administration, adverse events, and
laboratory results on each day of
treatment, day 15, and day 28.
Medical history and adverse events
were coded by using the Medical
Dictionary for Regulatory Activities
version 22.1. Clinicians ascertained
and documented in the electronic
case report form the date of COVID-
19 symptom onset. The timing of
onset for medical history was not
collected, and, therefore, the
chronological relationship to COVID-
19 diagnosis cannot be ascertained.
Clinicians were asked to perform
daily laboratory tests during
remdesivir therapy (see SPP in the
Supplemental Information). No
further follow-up under the
compassionate-use program protocol
was required after hospital discharge
or day 28, whichever came first.
Outcomes
We assessed clinical outcomes,
including safety, respiratory support
status, hospital discharge, and
recovery. Baseline was defined as the
day of first remdesivir dose. Duration
of symptoms was defined as the time
elapsed between date of COVID-19
symptom onset and baseline.
Recovery was defined as hospital
discharge for children on room air at
baseline (N = 8) and improvement to
room air or discharge for all others.
For patients who were on invasive
mechanical ventilation at baseline, we
report extubation and time to
extubation. Changes in clinical status
are reported by using the modified
ordinal scale (Fig 1).9,15,16
Statistical Methods
The analysis population included all
children who initiated compassionate
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PEDIATRICS Volume 147, number 5, May 2021
use of remdesivir on or before April
22, 2020, and for whom clinical data
for baseline and at least 1 subsequent
day were available as of May 9, 2020.
The population was stratified by age
category (#12 and .12 years) and
requirement for invasive mechanical
ventilation at baseline. No sample size
calculation was performed.
Time to recovery and time to
discharge were analyzed with
stratification by baseline respiratory
support status (invasive versus
noninvasive). The proportions of
patients achieving the outcomes of
recovery or discharge were assessed
through day 28 by using the
cumulative incidence function
method, with death as the competing
risk. P values for these analyses
were from a Cox regression
model.
Multivariate analysis was performed
by using a Cox regression model.
Variables in the final model were
selected by using a stepwise
procedure (entry variables included
baseline invasive status [yes or no],
sex [male or female], age group [#12
or .12 years], and duration of
symptoms [,8 or $8 days]). Hazard
ratios and P values were calculated
with death as a competing risk.
The Division of AIDS Table for
Grading the Severity of Adult and
Pediatric Adverse Event, Version 2.1
(July 2017) was used for assigning
toxicity grades (0–4) to laboratory
results.17 Treatment-emergent
laboratory abnormalities were
defined as results that increase at
least 1 toxicity grade from baseline at
any postbaseline time point.
RESULTS
Baseline Demographics and Clinical
Characteristics
The analysis population included 77
children: 58 (75%) in the United
States, 7 (9%) in Spain, 6 (8%) in the
United Kingdom, 4 (5%) in Italy, and
1 each (1%) in France and Germany
(Table 1). The median age of patients
was 14 years (interquartile range
[IQR] 7–16; range ,2 months to 17
years), and 46 (60%) of patients were
male. At baseline, 39 patients (51%)
were on invasive respiratory support
(38 on invasive mechanical
ventilation and 1 on venovenous
extracorporeal membrane
oxygenation [ECMO]). Of the
remaining 38 patients, 6 were
receiving noninvasive positive
pressure ventilation, 14 were
receiving high-flow oxygen, 10 were
receiving low-flow oxygen, and 8
were breathing room air. The median
duration of COVID-19 symptoms
before baseline was shorter in the
group receiving invasive
respiratory support at baseline (7
days, IQR 5–8) than in the
noninvasive group (9 days, IQR 7–12)
(P = .005).
Of the 77 children treated, 61 (79%)
had at least 1 comorbid medical
condition (Supplemental Table 4).
Twenty-two (29%) had preexisting
pulmonary or thoracic conditions
(including 7 [9%] with asthma), 17
(22%) had metabolism and nutrition
disorders (including 10 [13%] with
obesity), 22 (29%) had congenital
disorders, 4 [5%] had cerebral palsy,
13 (17%) had other neurologic
disorders (including 7 [9%] with
seizure disorders), and 5 (6%) had
history of premature birth. Among
those with history of premature birth,
2 were .1 year old at baseline. The
remaining 3 were an ex–33-week
infant 5 weeks old at baseline, an
ex–33-week infant 9 weeks old at
baseline, and an ex–32-week infant 5
weeks old at baseline (Supplemental
Table 4).
Remdesivir Exposure, Disposition,
and Concomitant Medications
Forty-eight patients (62%) received
all 10 doses of remdesivir, 23 (30%)
received 5 to 9 doses, and 6 (8%)
received fewer than 5 doses. Almost
all patients (75 of 77 [97%]) had the
full 28 days of follow-up or had died
3

FIGURE 1
Modified ordinal scale. IMV, invasive mechanical ventilation (by endotracheal tube or tracheostomy);
NIPPV noninvasive positive pressure ventilation.
or been discharged by day 28. The 2
patients who did not complete 28
days of follow-up both completed 10
days of remdesivir and were on room
air at the last available follow-up.
Concomitant medications with
potential effects on COVID-19
included hydroxychloroquine (in 31%
of patients in the invasive group and
21% in the noninvasive group),
methylprednisolone (in 23% and
16%, respectively), anakinra (in 8%
and 5%, respectively), tocilizumab (in
8% and 3%, respectively),
hydrocortisone (in 5% of patients in
the invasive group), and
dexamethasone (in 5% of patients in
the invasive group).
TABLE 1 Baseline Demographic and Clinical Characteristics
Invasive Oxygen, Noninvasive Oxygen,
Median age (range), y
Age, n (%)
,2 mo
2 mo to ,1 y
1–,5 y
5–12 y
.12 y
Sex, n (%)
Male
Female
Median duration of symptoms (quartile 1,
quartile 3), d
Median duration of hospitalization (quartile
1, quartile 3), d
Median duration of invasive oxygen support
(quartile 1, quartile 3), d
ALT level #50 U/L, n (%)
Median ALT level (quartile 1, quartile 3), U/L
Data are n (%) or median (IQR), except age, which is median (range).
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4 GOLDMAN et al
longer than the median of 7 days (IQR
5–15) to recovery for those not
receiving invasive respiratory
support at baseline (P = .005) (Fig
2A).
Discharge
Overall, the rate of hospital discharge
by day 28 was 73% (56 of 77). As
with recovery, the rate of discharge
was lower among patients on invasive
respiratory support at baseline than
among those not on invasive
ventilation (67% [26 of 39] vs 79%
Clinical Outcomes [30 of 38]). Similar to recovery, the
median time to discharge for patients
Recovery
receiving invasive respiratory
By day 28 after the initiation of support at baseline was significantly
remdesivir dosing, 83% of patients longer at 20 days (IQR 17 to not
(64 of 77) had recovered: 79% (31 of available) than the median of 13 days
39) of those on invasive respiratory (IQR 7–22) for those not receiving
support at baseline were extubated, invasive respiratory support at
and 87% (33 of 38) of those not on baseline (P = .005) (Fig 2B).
invasive respiratory support had
improved to room air or were Shift in Distribution of Status on Ordinal
discharged. A smaller proportion of Scale
patients aged #12 years recovered by At day 28, the majority of patients
day 28 than those aged .12 years experienced an improvement in the
(75% vs 90%, P = .019). The median distribution of clinical support status
time to recovery for patients from baseline. Sixty-eight (88%)
receiving invasive respiratory improved by at least 1 category in
support at baseline was 16 days (IQR clinical support, 5 (6%) did not
11–28), which was significantly change status, and 4 (5%) had
worsened status (Fig 3). One patient
who was on ECMO at baseline
required invasive mechanical
ventilation (but not ECMO) at day 28.
Total, Three additional patients started
n = 39 n = 38 N = 77
ECMO after baseline; of these, 2 were
11 (0–17) 15 (0–17) 14 (0–17) discharged and 1 required low-flow
4 (10) 0 4 (5)
oxygen at day 28. Improvement was
5 (13) 3 (8) 8 (10) less consistent among younger
3 (8) 1 (3) 4 (5) patients: of the 36 patients who were
11 (28) 9 (24) 20 (26) aged #12 years, 4 (11%) had
16 (41) 25 (66) 41 (53) worsened clinical status, 3 (8%) did
23 (59) 23 (61) 46 (60)
not change, and 29 (81%) had
16 (41) 15 (39) 31 (40) improved clinical status. Of the 41
7 (5, 8) 9 (7, 12) 8 (6, 10) patients who were aged .12 years,
none had worsened clinical status, 2
4 (3, 5) 4 (2, 7) 4 (3, 5) (5%) did not change, and 39 (95%)
2 (2, 3) 0 2 (2, 3)
had improved clinical status. The
proportion of younger children with
25 (66) 31 (84) 56 (75) invasive respiratory support at
33 (21, 69) 31 (20, 44) 32 (20, 51) baseline was higher than that in older
patients (59% of patients aged #12

FIGURE 2
Time to recovery and discharge in children who received remdesivir. A and B, Time to recovery (A)
and time to discharge (B) stratified by baseline respiratory support status. P values were derived
from a Cox regression model.
years versus 41% of patients aged
.12 years).
Multivariate Analysis
In a multivariate regression analysis
conducted to determine which
baseline factors may have been
associated with time to recovery,
patients on invasive ventilation at
baseline had significantly longer time
to recovery than those not on invasive
ventilation at baseline (hazard ratio
of 0.47 [95% confidence interval
0.28–0.78; P = .0035]) and patients
aged #12 years had significantly
longer time to recovery than those
.12 years (hazard ratio of 0.54 [95%
confidence interval 0.33–0.89; P =
.016]).
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PEDIATRICS Volume 147, number 5, May 2021
Safety
Overall, 25 patients (32%)
experienced at least 1 adverse event,
with a higher proportion among
patients on invasive respiratory
support at baseline than among those
not on invasive respiratory support
(38% [15 of 39] vs 26% [10 of 38])
(Table 2, Supplemental Table 5).
Twenty-six serious adverse events
were reported in 12 patients, with
a rate of 21% (8 of 39) in the invasive
respiratory support group and 11%
(4 of 38) in those not on invasive
respiratory support (Supplemental
Table 6).
The only adverse events that
occurred in .1 patient were elevated
ALT levels (2 patients [5%] in the
invasive group and 3 [8%] in the
noninvasive group), elevated
aspartate aminotransferase (AST)
levels (3 patients [8%] in the invasive
group and 1 [3%] in the noninvasive
group), and anemia (2 patients [5%]
in the invasive group). Likewise, the
only serious adverse events that
occurred in .1 patient were
elevations of transaminase levels:
both groups had 1 grade 3 and 1
grade 4 elevation of ALT and AST
levels (Supplemental Table 6). There
were 3 renal adverse events reported
in 1 invasive group patient each:
hematuria, toxic nephropathy, and
renal impairment. None of the renal
adverse events were attributed to
remdesivir by the clinician or led to
discontinuation. Laboratory safety
findings included 5 cases of grade 3
or 4 elevations of ALT levels in each
group, which resolved or improved in
all cases in which postelevation
follow-up was available (Table 2,
Supplemental Fig 4). There were 8
cases of grade 3 to 4 elevations of
creatinine levels in the invasive group
and 6 in the noninvasive group (Table
2).
Five patients discontinued remdesivir
because of adverse events: 2 patients
in the group receiving invasive
respiratory support (both for
elevated liver enzyme levels) and 3
patients not receiving invasive
respiratory support (1 because of
rash, 1 because of a relapse of acute
lymphoid leukemia, and 1 because of
elevated liver enzyme levels).
Overall, 4 of the 77 patients (5%)
died, 2 in each oxygen-support group.
In the group receiving invasive
respiratory support, a 14-year-old
boy with history of autism, seizure
disorder, and gastrostomy tube
dependency died 3 weeks after
treatment from COVID-19 with
suspected cytokine storm
contributing, and an 11-year-old girl
with history of dermatomyositis and
interstitial lung disease died of
multiorgan failure due to Gram-
negative bacteremia and
5
FIGURE 3
Clinical outcomes in children treated with remdesivir at day 28. For each oxygen-support category, percentages were calculated with the number of
patients at baseline as the denominator. Improvement (blue cells), no change (beige), and worsening (pink) in oxygen-support status are shown. Invasive
ventilation includes invasive mechanical ventilation (IMV), ECMO, or both. Noninvasive ventilation includes nasal high-flow oxygen therapy, noninvasive
positive pressure ventilation (NIPPV), or both. a A fourth death (reported in Table 1) occurred after day 28. BL, baseline.

hemophagocytic lymphohistiocytosis completing a 10-day course of evidence of meningoencephalitis and

the day after stopping treatment on treatment. A 5-year-old patient in the subsequently died because of brain
day 9. In the noninvasive group, a 4- noninvasive group died 6 days after herniation; the cause of the
month-old with history of atrial septal completing a 10-day course of meningoencephalitis is unknown.
defect and pulmonary hypertension remdesivir. This patient presented
died of COVID-19 9 days after with clinical and radiographic
DISCUSSION
TABLE 2 Overall Safety Summary Although most children who become
Invasive Oxygen Noninvasive Oxygen Total
infected with SARS-CoV-2 experience
(n = 39), n (%) (n = 38), n (%) (N = 77), n (%) mild or no symptoms and recover
Any AE 15 (38) 10 (26) 25 (32)
fully without medical care, a subset of
Any serious AE 8 (21) 4 (11) 12 (16) pediatric patients develop life-
Death 2 (5) 2 (5) 4 (5) threatening symptoms and require
AE occurring in .1 patient hospitalization. For those children
ALT level increased 2 (5) 3 (8) 5 (6) requiring admission to the ICU,
AST level increased 3 (8) 1 (3) 4 (5)
Anemia 2 (5) 0 2 (3)
mortality is considerably lower than
Laboratory abnormality, any grade 30 (77) 31 (82) 61 (79) that reported in adults and many
ALT level increased 14 (36) 23 (61) 37 (48) recover fully with only supportive
AST level increased 23 (64) 18 (47) 41 (55) care.18 A number of case reports and
Creatinine level increased 15 (38) 15 (39) 30 (39) small case series have been published
Laboratory abnormality, grade 3–4 15 (38) 11 (29) 26 (34)
ALT level increased (.5 3 ULN) 5 (13) 5 (13) 10 (13)
regarding the use of remdesivir in
AST level increased (.5 3 ULN) 11 (28) 4 (11) 15 (19) these patients,18–23 but the present
Creatinine level increased (.1.8 3 ULN) 8 (21) 6 (16) 14 (18) report, describing outcomes in 77
AE, adverse event; ULN, upper limit of normal. pediatric patients with severe COVID-
19 who received remdesivir on

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6 GOLDMAN et al
a compassionate-use basis, is by far
the largest set of data on the use of
remdesivir to treat pediatric COVID-
19 to date. Despite the inherent
limitations of data collected in
a program of this type, we believe
these results represent an important
contribution to understanding
COVID-19 in pediatric patients
and the safety and possible benefit
of remdesivir in this population.
In this cohort of children, the majority
recovered regardless of the need for
invasive mechanical ventilation at
baseline. Without a control arm, we
cannot know whether remdesivir
contributed to recovery. Children who
required invasive respiratory support
at baseline were less likely to recover
and recovered more slowly, but
nevertheless, nearly 80% had
recovered by day 28, demonstrating
that good clinical outcomes can be
achieved even in those with severe
presentations.
At least 79% of the children in this
compassionate-use program had
comorbid conditions. The most
common comorbidities reported
included asthma, obesity, neurologic
disorders (including seizure
disorders), prematurity, and
hematologic conditions (both
malignant and nonmalignant). These
findings are remarkably similar to
those reported in Centers for Disease
Control and Prevention surveillance
data of children hospitalized with
COVID-19, highlighting the potential
role of these conditions in
predisposing patients to severe
illness.2
revised the manuscript; Ms Naik, Mr Marshall, Dr Katsarolis, and Ms Desai coordinated data collection and critically reviewed the manuscript for important
intellectual content; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
DOI: https://doi.org/10.1542/peds.2020-047803
Accepted for publication Feb 10, 2021
Address correspondence to Christoph C. Carter, MD, PhD, Gilead Sciences, 333 Lakeside Dr, Foster City, CA 94404. E-mail: christoph.carter7@gilead.com
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2021 by the American Academy of Pediatrics
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PEDIATRICS Volume 147, number 5, May 2021
Overall, remdesivir was well
tolerated. Only anemia and
transaminase elevations were
reported in .1 patient. The observed
transaminase elevation may be
attributable to COVID-19 illness,
remdesivir, or a combination of the
two. COVID-19 has a well-established
association with liver injury,24–28 and
remdesivir has been implicated in
transient mild-to-moderate
transaminitis in healthy volunteers
and in patients infected with Ebola
virus.29 Most of the treatment-
emergent transaminase elevations we
observed were mild, and the more
severe (grade 3–4) elevations were
reversible.
Interpretation of the results of this
descriptive analysis is necessarily
limited by the nature of the data. This
was not a clinical study designed for
the collection of data, but
a compassionate-use program
undertaken to provide remdesivir to
patients who were seriously ill.
Without comparative data from
a randomly assigned control group, it
is not possible to say if the high level
of recovery observed in these patients
was due to the effects of remdesivir,
the natural course of the disease, or
other therapeutic interventions.
Another limitation is the relatively
short duration of follow-up (28 days),
at which point 4 patients remained on
invasive respiratory support.
CONCLUSIONS
Children receiving remdesivir for
severe COVID-19 in this
compassionate-use program had
a high rate of clinical recovery with
a favorable tolerability profile;
however, in the absence of a control
arm, no conclusions can be made
about the efficacy of remdesivir in
children. The safety, tolerability,
pharmacokinetics, and efficacy of
remdesivir in children are currently
being assessed in a phase 2 and 3
study (NCT04431453).
ACKNOWLEDGMENTS
We thank the children who
participated in this program and their
partners and families and the
principal investigators and their
colleagues and staff, as well as the
Gilead remdesivir compassionate-use
eligibility review team (Supplemental
Information). We express our
solidarity with those who are or have
been ill with COVID-19, their families,
and the health care workers on the
front lines of this pandemic. We also
thank Sarah Tse, Gretchen Schmelz,
and Deborah Ajayi (BioScience
Communications) for preparing
graphics and David McNeel (Gilead)
for providing editorial assistance.
ABBREVIATIONS
ALT: alanine aminotransferase
AST: aspartate aminotransferase
COVID-19: coronavirus disease
2019
ECMO: extracorporeal membrane
oxygenation
IQR: interquartile range
SARS-CoV-2: severe acute respira-
tory syndrome coro-
navirus 2
SPP: single patient protocol
7
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
FUNDING: Funded by Gilead Sciences. The program was designed and conducted by the sponsor (Gilead Sciences). Gilead collected the data, monitored conduct of
the program, and performed the statistical analyses.
POTENTIAL CONFLICT OF INTEREST: Dr Bamford serves as a paid consultant to Gilead in relation to treatment of coronavirus disease 2019 in children. Dr Camacho-
Gonzalez receives research support from Janssen and Merck and serves as a consultant for Theratechnologies. Drs Carter and Zhao, Ms Telep, Dr Pikora, Dr Naik,
Mr Marshall, Drs Katsarolis, Das, and DeZure, Ms Desai, and Drs Cao, Chokkalingam, Osinusi, and Brainard are employees of and own stock in Gilead Sciences. Dr
Méndez-Echevarría is the principal investigator in La Paz Hospital of the clinical trial GS-US-540-5823 (funded by Gilead) and has participated in an advisory board
on coronavirus disease 2019 for Gilead; the other authors have indicated they have no potential conflicts of interest to disclose.
COMPANION PAPER: A companion to this article can be found online at www.pediatrics.org/cgi/doi/10.1542/peds.2021-050212.

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 Compassionate Use of Remdesivir in Children With Severe COVID-19
David L. Goldman, Margaret L. Aldrich, Stefan H.F. Hagmann, Alasdair Bamford,
Andres Camacho-Gonzalez, Giuseppe Lapadula, Philip Lee, Paolo Bonfanti,
Christoph C. Carter, Yang Zhao, Laura Telep, Cheryl Pikora, Sarjita Naik, Neal
Marshall, Ioannis Katsarolis, Moupali Das, Adam DeZure, Polly Desai, Huyen Cao,
Anand P. Chokkalingam, Anu Osinusi, Diana M. Brainard and Ana
Méndez-Echevarría
Pediatrics 2021;147;
DOI: 10.1542/peds.2020-047803 originally published online April 21, 2021;

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 Compassionate Use of Remdesivir in Children With Severe COVID-19
David L. Goldman, Margaret L. Aldrich, Stefan H.F. Hagmann, Alasdair Bamford,
Andres Camacho-Gonzalez, Giuseppe Lapadula, Philip Lee, Paolo Bonfanti,
Christoph C. Carter, Yang Zhao, Laura Telep, Cheryl Pikora, Sarjita Naik, Neal
Marshall, Ioannis Katsarolis, Moupali Das, Adam DeZure, Polly Desai, Huyen Cao,
Anand P. Chokkalingam, Anu Osinusi, Diana M. Brainard and Ana
Méndez-Echevarría
Pediatrics 2021;147;
DOI: 10.1542/peds.2020-047803 originally published online April 21, 2021;

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pediatrics.aappublications.org/content/147/5/e2020047803

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