Veklury® (remdesivir)

Long COVID Symptoms

This document is in response to your request for information regarding assessment of long COVID symptoms following the use of Veklury® (remdesivir [RDV]).

Some data may be outside of the US FDA-approved prescribing information. In providing this data, Gilead Sciences, Inc. is not making any representation as to its clinical relevance or to the use of any Gilead product(s). For information about the approved conditions of use of any Gilead drug product, please consult the FDA-approved prescribing information.

The full indication, important safety information, and boxed warnings are available at:
www.gilead.com/-/media/files/pdfs/medicines/covid-19/veklury/veklury_pi.

Summary

Available Data on Long COVID Symptoms Following the Use of RDV

A randomized, open-label, multicenter study evaluated the effects of RDV on participant recovery, LCS symptoms, and QoL outcomes 1 year after hospitalization in 181 adult participants who were hospitalized with COVID-19.1

• At 1-year posthospitalization, 85% of participants in the RDV group and 86% of participants in the SoC group reported that they were fully or largely recovered. The occurrence of LCS symptoms was not statistically different between the RDV and SoC groups (P>0.05), and the QoL outcome scores were similar between the two groups.1

A prospective cohort study evaluated the prevalence of and risk factors for LCS in 449 participants hospitalized with COVID-19 who had ≥6 months of follow-up after discharge.2

• The prevalence of LCS was 71.7% at 1 month after discharge and 45.9% at 6 months after discharge. A multivariate analysis showed that treatment with RDV reduced the rate of LCS (OR, 0.641; 95% CI: 0.413–0.782; P<0.001) and reduced LCS severity (P<0.001) compared with treatment without RDV.2

A retrospective cohort study evaluated the effect of RDV on the incidence of LCS-related symptoms and diagnoses in 52,006 patients in the US who were hospitalized with COVID‑19.3

• Results from an age-stratified analysis showed that treatment with RDV reduced the rate of LCS-related symptoms and diagnoses in patients aged <65 years (HR, 0.9; 95% CI: 0.86–0.93) as well as those aged ≥65 years (HR, 0.9; 95% CI: 0.86–0.95) compared with treatment without RDV.3

Available Data on Long COVID Symptoms Following the Use of RDV

SOLIDARITY Finland Trial: Long-Term Effects on QoL1

Study design and demographics

A randomized, open-label, multicenter study conducted in Finland (NCT04978259) evaluated the effects of RDV on participant recovery (primary endpoint), LCS symptoms, and QoL outcomes 1 year after hospitalization in adult participants who were hospitalized with COVID-19 between July 23, 2020, and January 27, 2021. Participants were randomly assigned 1:1 to receive RDV plus local SoC treatment (RDV group; n=114) or local SoC treatment without RDV (SoC group, n=94). Study outcomes were evaluated based on results from questionnaires completed by the participants 1 year posthospitalization.

In the RDV and SoC groups, respectively, the mean age of participants was 57.2 and 59.7 years, most (64.9% and 63.8%) were male, 17.5% and 17% had diabetes, 74% and 79% required oxygen at the time of hospital admission, 69.3% and 76.6% received dexamethasone, and the median (IQR) duration of hospital stay was 8 (6–11) and 8.5 (6–‍15) days.

Results

Of the 208 participants enrolled in the study, 181 participants completed the 1‑year survey. Five participants (2.4%) died during hospitalization (due to COVID-19), 5 (2.4%) died during the 1‑year follow-up, 5 (2.4%) declined participation in the long-term evaluation, and 12 (5.8%) were unable to be reached. Of the 10 participants who died, 5 (4.4%) were in the RDV group, and 5 (5.3%) were in the SoC group (RR, 0.82; 95% CI: 0.25–2.76; absolute difference, ‑0.9%; 95% CI: -7.9 to 5.3%). For participants who received RDV, the median (IQR) duration of treatment was 5 (4–8) days.

At Year 1 posthospitalization, 85% of participants in the RDV group and 86% of participants in the SoC group reported they were fully or largely recovered (RR, 0.94; 95% CI: 0.47–1.9; absolute difference, -0.9%; 95% CI: -11 to 10%), and stratification by the need for oxygen at hospital admission did not change the recovery estimate. The occurrence of LCS symptoms (eg, anxiety, change in sense of smell/taste, chest pressure or discomfort) was not statistically different between the RDV and SoC groups (P>0.05), and the QoL outcome scores were similar between the two groups (Table 1). The median (IQR) EQ‑visual analog scale score (self-report of overall health state ranging from 0 [worst imaginable health state] to 100 [best imaginable health state]) was 75.5 (67.8–85) and 80 (67.5–86.5) for the RDV and SoC groups, respectively (ordered logistic regression OR, 0.83; 95% CI: 0.49–1.4).

Table 1. SOLIDARITY Finland: 1-Year QoL Outcomes1

Abbreviation: mMRC=modified Medical Research Council.

aAbsolute difference: -3.3% (95% CI:-12 to 4.4%).

Fatigue (26%), joint pain (22%), persistent respiratory mucus (21%), and problems with memory (19%) or attention/concentration (18%) were the LCS symptoms most often reported as moderately or severely bothersome.

Prospective Cohort Study2

Study design and demographics

A prospective cohort study evaluated the prevalence of and risk factors for LCS in participants hospitalized with COVID-19 from March 10, 2020, to January 15, 2021, at a hospital in Italy. Participants who required low-flow oxygen at admission/baseline and had ≥6 months of follow-up were included. The primary endpoint was the prevalence and severity of LCS at the 1-month (Visit 1) and 6-month (Visit 2) postdischarge follow-up visits. The PCFS scale (Grade 0–4) was used to assess the level of severity of LCS. Grades of 3 to 4 indicated significant functional limitations in daily life.

A total of 449 participants were included in the analysis, and of those, 163 received RDV for COVID‑19 treatment. The median age of all participants was 65 years, 78% were male, 86.8% received corticosteroids, 15.8% had diabetes, and 14.2% had cardiovascular disease. The median (IQR) duration of hospitalization was 10.5 (7–14.5) days, 42% of participants required continuous positive airway pressure/noninvasive ventilation, 13.8% required ICU admission, 69.5% were discharged to home, 30.5% were discharged to a long‑term care facility, 38% required oxygen at home, 27.2% required rehabilitation after discharge, and 0.9% required rehospitalization.

Results

In the overall study population, the prevalence of LCS was 71.7% (n=322) at Visit 1 and 45.9% (n=206) at Visit 2. At Visits 1 and 2, 147 and 133 participants, respectively, had a score of 2 to 3 on the PCFS, and 175 and 73 participants, respectively, had a score of >3.

In the multivariate analysis of risk factors for LCS, participants treated with RDV showed a 35.9% reduction in the rate of LCS (OR, 0.641; 95% CI: 0.413–0.782; P<0.001), whereas ICU admission (OR, 2.551; 95% CI: 1.998–6.819; P=0.019) and duration of hospitalization (OR, 2.255; 95% CI: 1.018–6.992; P=0.016) were positive predictors of LCS.

In a comparison of PCFS scale scores between patients treated with RDV and those without RDV treatment at Visit 1, 123 participants who were treated with RDV were not affected by LCS (Grade 0–1), compared with 81 who did not receive RDV. The group that received RDV treatment had a reduced rate of more severe PCFS scores (2–3 and >3) than the group that did not receive RDV treatment (P<0.001 for all comparisons; Table 2).

Table 2. PCFS Severity According to RDV Treatment (Boglione et al)2

A survival analysis found that participants treated with RDV were less likely to develop LCS than those who did not receive RDV (P<0.001; χ2=14.614).

Retrospective Cohort Study3

Study design and demographics

A retrospective cohort study evaluated the effect of RDV during the first 2 days of hospitalization on the incidence of symptoms and diagnoses associated with LCS in patients in the US who were hospitalized with COVID-19 between May 1, 2020, and September 30, 2021. Patients aged ≥12 years who were hospitalized with COVID-19 for ≥2 days were identified from the HealthVerity database, and results were stratified according to age (<65 vs ≥65 years) at the time of hospitalization. The maximum duration of follow-up was 268 days.

A total of 52,006 patients were included in the analysis, including 33,578 patients aged <65 years (12,145 of whom received RDV) and 18,428 aged ≥65 years (5019 of whom received RDV). The RDV and no-RDV groups in both age cohorts were generally similar; approximately 50% of patients required ICU admission and 44% to 52% of patients were male. Fewer patients in the RDV group than in the no-RDV group required no oxygen support on Days 1 and 2 of hospitalization (<65 years, 63% vs 74%; ≥65 years, 63% vs 72%). More patients in the RDV group than in the no-RDV group received treatment with corticosteroids (<65 years, 95% vs 52%; ≥65 years, 94% vs 48%), immunomodulators (<65 years, 9% vs 2%; ≥65 years, 6% vs 1%), convalescent plasma (<65 years, 11% vs 2%; ≥65 years, 14% vs 2%), and/or anticoagulants (<65 years, 16% vs 26%; ≥65 years, 26% vs 38%).

Results

Treatment with RDV was associated with reduced risk of experiencing any LCS-related symptom or diagnosis in both patients aged <65 years (HR, 0.9; 95% CI: 0.86–0.93) and those aged ≥65 years (HR, 0.9; 95% CI: 0.86–0.95). Of the 16 individual LCS-related symptoms and diagnoses included in the analysis, RDV treatment was associated with reduced risk of eight symptoms in patients aged <65 years and six symptoms in patients aged ≥65 years (Table 3).

Table 3. Effect of RDV on Risk of LCS-Related Symptoms and Diagnoses (Berry et al)3

Note: Shaded cells indicate outcomes with lower relative hazards (upper bound of 95% CI was <1).

References

1. Nevalainen OPO, Horstia S, Laakkonen S, et al. Effect of remdesivir post hospitalization for COVID-19 infection from the randomized SOLIDARITY Finland trial. Nature communications. 2022;13(1):6152. https://www.ncbi.nlm.nih.gov/pubmed/36257950
2. Boglione L, Meli G, Poletti F, et al. Risk factors and incidence of long-COVID syndrome in hospitalized patients: does remdesivir have a protective effect? QJM. 2021:1-7.
3. Berry M, Kong AM, Paredes R, et al. Effect of Remdesivir on Post-COVID Conditions Among Individuals Hospitalized With COVID-19 by Age [Poster 657]. Paper presented at: 31st Conference on Retroviruses and Opportunistic Infections (CROI); March 3-6, 2024; Denver, CO.

Abbreviations

HR=hazard ratio
ICU=intensive care unit
LCS=long COVID syndrome
OR=odds ratio
PCFS=Post–COVID-19 Functional Status Scale
QoL=quality-of-life
RDV=remdesivir
RR=risk ratio
SoC=standard of care

Product Label

For the full indication, important safety information, and boxed warning(s), please refer to the Veklury US Prescribing Information available at:
www.gilead.com/-/media/files/pdfs/medicines/covid-19/veklury/veklury_pi.

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