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Last Updated: July 21, 2023

Remdesivir is a nucleotide prodrug of an adenosine analog. It binds to the viral RNA-dependent RNA polymerase and inhibits viral replication by terminating RNA transcription prematurely. Remdesivir has demonstrated in vitro and in vivo activity against SARS-CoV-2. 1

Intravenous remdesivir is approved by the Food and Drug Administration (FDA) for the treatment of COVID-19 in adults and pediatric patients aged ≥28 days and weighing ≥3 kg. In nonhospitalized patients with mild to moderate COVID-19 who are at high risk of progressing to severe disease, remdesivir should be started within 7 days of symptom onset and administered for 3 days. Hospitalized patients should receive remdesivir for 5 days or until hospital discharge, whichever comes first. 2 The FDA prescribing information for remdesivir indicates that if a patient does not clinically improve, clinicians may extend the treatment course for up to 5 additional days (for a total duration of 10 days). See Table 4e for more information.

Remdesivir has been studied in several clinical trials for the treatment of COVID-19. The recommendations from the COVID-19 Treatment Guidelines Panel (the Panel) are based on the results of these studies. See Table 4a for more information.

Recommendations

  • For the Panel’s recommendations and information on the clinical efficacy of using remdesivir to treat high-risk, nonhospitalized patients with mild to moderate COVID-19, see Therapeutic Management of Nonhospitalized Adults With COVID-19 .
  • For the Panel’s recommendations and information on the clinical efficacy of using remdesivir with or without immunomodulators to treat certain hospitalized patients, see Therapeutic Management of Hospitalized Adults With COVID-19 .
  • The data on using combinations of antiviral therapies for the treatment of COVID-19 are limited. 3 Clinical trials are needed to determine the role of combination therapy in treating certain patients.

Monitoring, Adverse Effects, and Drug-Drug Interactions

Remdesivir can cause gastrointestinal symptoms (e.g., nausea), elevated transaminase levels, an increase in prothrombin time without a change in the international normalized ratio, and hypersensitivity reactions.

Before starting patients on remdesivir, the FDA recommends performing liver function and prothrombin time tests as clinically appropriate and repeating these tests during treatment as clinically indicated. Remdesivir may need to be discontinued if a patient’s alanine transaminase (ALT) level increases to >10 times the upper limit of normal, and it should be discontinued if increases in ALT levels and signs or symptoms of liver inflammation are observed. 2

Remdesivir should be administered in a setting where severe hypersensitivity reactions, such as anaphylaxis, can be managed. Patients should be monitored during the infusion and observed for at least 1 hour after the infusion as clinically appropriate.

Currently, no clinical drug-drug interaction studies of remdesivir have been conducted. In vitro, remdesivir is a minor substrate of cytochrome P450 (CYP) 3A4 and a substrate of the drug transporters organic anion transporting polypeptide (OATP) 1B1 and P-glycoprotein. It is also an inhibitor of CYP3A4, OATP1B1, OATP1B3, and multidrug and toxin extrusion protein (MATE) 1. 2 See Table 4e for more information.

Patients Who Are Immunocompromised and Have Prolonged Symptoms and Evidence of Ongoing Viral Replication

Patients who are severely immunocompromised may have a prolonged duration of SARS-CoV-2 replication, which may lead to rapid viral evolution. There is concern that using a single antiviral agent in these patients may result in the emergence of resistant virus. 4 Additional studies are needed to assess this risk. The role of combination antiviral therapy in the treatment of COVID-19 is not yet known.

For patients who are immunocompromised and have prolonged COVID-19 symptoms and evidence of ongoing viral replication (e.g., those with a low cycle threshold value, as measured by a reverse transcription polymerase chain reaction result or with a positive rapid antigen test result) despite receiving a course of antiviral therapy, the optimal management is unknown. Case reports and case series have documented the treatment of these patients with additional antiviral treatments, prolonged courses of antiviral treatments, high-titer COVID-19 convalescent plasma, or combination therapy. 5-9 For a discussion of potential treatment options, see Special Considerations in People Who Are Immunocompromised and Therapeutic Management of Nonhospitalized Adults With COVID-19 .

Considerations in Patients With Renal Insufficiency

Remdesivir is formulated with sulfobutylether-beta-cyclodextrin (SBECD) sodium. 2 SBECD is a vehicle that is primarily eliminated through the kidneys. Accumulation of SBECD in patients with renal impairment may result in liver and renal toxicities.

Basing its decision on safety data primarily from the REDPINE clinical trial and pharmacokinetic data from a Phase 1 trial, the FDA updated the prescribing information for remdesivir to indicate that it can be used without dose adjustment in patients with an estimated glomerular filtration rate (eGFR) of <30 mL/min, including those receiving dialysis. 2

Safety data for the use of remdesivir in patients with severely reduced kidney function are available from 2 randomized controlled trials:

  • The REDPINE study was a manufacturer-sponsored, multinational, double-blind trial of remdesivir versus placebo in hospitalized adults with severe COVID-19 and an eGFR of <30 mL/min. 10 The trial was terminated due to low enrollment. Among 163 remdesivir and 80 placebo recipients with a mean age of 69 years, there were no statistically significant differences in treatment-emergent adverse events or serious treatment-emergent adverse events, including death. Among participants with baseline acute kidney injury or chronic kidney disease, there were no statistically significant differences in the progression of acute kidney injury, the need for renal replacement therapy, or death.
  • The CATCO study was a multicenter, open-label trial that compared the use of remdesivir to standard of care in hospitalized adults with COVID-19. 11 A post hoc analysis was done for 59 patients with a baseline eGFR of <30 mL/min; 15 of these patients were on dialysis. The median age of the cohort was 74 years. Thirty-four patients received remdesivir for a median duration of 10 days, while 25 patients received standard of care. The standard of care patients had a lower median eGFR at baseline (12.4 mL/min) than patients treated with remdesivir (22.7 mL/min). There was no increased risk of renal toxicity at Day 5 among patients treated with remdesivir compared to standard of care, and there were no statistically significant differences in the need for new dialysis, the need for mechanical ventilation, or mortality.

Although both the REDPINE and CATCO trials were underpowered to assess the clinical efficacy of remdesivir in patients with severely reduced kidney function, the available data suggest that remdesivir can be used safely in patients with an eGFR of <30 mL/min. These results are consistent with a systematic review of observational studies 12 and other retrospective studies that have reported that remdesivir was not associated with an increased incidence of adverse effects in patients with COVID-19 who had baseline eGFRs of <30 mL/min. 13-15

Considerations in Pregnancy

See Pregnancy, Lactation, and COVID-19 Therapeutics for the Panel’s guidance regarding the use of remdesivir during pregnancy and lactation.

Considerations in Children

See Special Considerations in Children, Therapeutic Management of Nonhospitalized Children With COVID-19 , and Therapeutic Management of Hospitalized Children With COVID-19 .

  • Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res . 2020;30(3):269-271. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32020029 .
  • Remdesivir (Veklury) [package insert]. Food and Drug Administration. 2023. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/214787s019lbl.pdf .
  • Gliga S, Lübke N, Killer A, et al. Rapid selection of sotrovimab escape variants in severe acute respiratory syndrome coronavirus 2 Omicron-infected immunocompromised patients. Clin Infect Dis . 2023;76(3):408-415. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36189631 .
  • Gandhi S, Klein J, Robertson AJ, et al. De novo emergence of a remdesivir resistance mutation during treatment of persistent SARS-CoV-2 infection in an immunocompromised patient: a case report. Nat Commun . 2022;13(1):1547. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35301314 .
  • Huygens S, Gharbharan A, Serroukh Y, et al. High-titer convalescent plasma plus nirmatrelvir/ritonavir treatment for non-resolving COVID-19 in six immunocompromised patients. J Antimicrob Chemother . 2023;78(7):1644-1648. Available at: https://www.ncbi.nlm.nih.gov/pubmed/37248664 .
  • Brosh-Nissimov T, Ma’aravi N, Leshin-Carmel D, et al. Combination treatment of persistent COVID-19 in immunocompromised patients with remdesivir, nirmaltrevir/ritonavir and tixegavimab/cilgavimab. medRxiv . 2023;Preprint. Available at: https://www.medrxiv.org/content/10.1101/2023.04.07.23288144v1 .
  • Mikulska M, Sepulcri C, Dentone C, et al. Triple combination therapy with two antivirals and monoclonal antibodies for persistent or relapsed SARS-CoV-2 infection in immunocompromised patients. Clin Infect Dis . 2023;Published online ahead of print. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36976301 .
  • Graziani L, Gori L, Manciulli T, et al. Successful use of nirmatrelvir/ritonavir in immunocompromised patients with persistent and/or relapsing COVID-19. J Antimicrob Chemother . 2023;78(2):555-558. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36544352 .
  • Trottier CA, Wong B, Kohli R, et al. Dual antiviral therapy for persistent coronavirus disease 2019 and associated organizing pneumonia in an immunocompromised host. Clin Infect Dis . 2023;76(5):923-925. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36281907 .
  • Santos JR, Goldman JD, Tuttle KR, et al. The REDPINE study: efficacy and safety of remdesivir in people with moderately and severely reduced kidney function hospitalised for COVID-19 pneumonia. Presented at: 33rd European Congress of Clinical Microbiology and Infectious Diseases; April 15–18, 2023; Copenhagen, Denmark. Available at: https://www.askgileadmedical.com/docs/conference/JoseRamon_ECCMID2023_Redpine_P2635@pdf .
  • Cheng M, Fowler R, Murthy S, et al. Remdesivir in patients with severe kidney dysfunction: a secondary analysis of the CATCO randomized trial. JAMA Netw Open . 2022;5(8):e2229236. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36036936 .
  • Davoudi-Monfared E, Ahmadi A, Karimpour-Razkenari E, et al. Remdesivir administration in COVID-19 patients with renal impairment: a systematic review. Am J Ther . 2022;29(5):e520-e533. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35984955 .
  • Sunny S, Samaroo-Campbell J, Abdallah M, Luka A, Quale J. Is remdesivir safe in patients with renal impairment? Experience at a large tertiary urban medical center. Infection . 2023;51(1):247-252. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35616879 .
  • Aiswarya D, Arumugam V, Dineshkumar T, et al. Use of remdesivir in patients with COVID-19 on hemodialysis: a study of safety and tolerance. Kidney Int Rep . 2021;6(3):586-593. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33354635 .
  • Shah MK, Parikh M, Prajapati D, et al. Safety and tolerability of remdesivir in patients with end-stage renal disease on maintenance hemodialysis. Indian J Crit Care Med . 2022;26(5):619-625. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35719430 .

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INDICATIONS

  • Require hospitalization
  • Have positive results of direct SARS-CoV-2 viral testing, who are not hospitalized, have mild to moderate symptoms, and are at high risk for progression to severe COVID-19, including hospitalization or death
  • Patients with SpO 2 ≤ 94% on room air, OR
  • Requiring supplemental oxygen, OR
  • Requiring mechanical ventilation, OR
  • Requiring extracorporeal membrane oxygenation (ECMO)

NON-FDA APPROVED USES

  • Nonhospitalized patients at high risk for disease progression may be given a 3-day course of remdesivir (200 mg IV on day 1, then 100 mg IV on days 2 and 3).

*Prices represent the specified cost per unit and "Average Wholesale Price" (AWP). ^Dosage is indicated in mg unless otherwise noted.

USUAL ADULT DOSING

Hospitalized Patients (typically 5-day course)

200 mg IV once, followed by 100 mg IV q24h for 4 days (duration can be extended for additional 5 days if no clinical response) or 10 days for patients requiring m echanical ventilation and/or ECMO.

  • In an open-label study, serious adverse events were observed at a higher rate in patients receiving 10-day treatment compared to 5-day treatment. At the same time, there was no significant difference in the clinical outcomes in patients who were not on ECMO or mechanical ventilation.
  • Most patients hospitalized for COVID-19 pneumonia should also receive RDV in conjunction with dexamethasone. See the COVID-19 module for additional details on management.

Mild-Moderate COVID-19 (usually ambulatory patients, 3-day course)

200 mg IV once, followed by 100mg IV q24h for 2 days

Administration instructions: Infuse each dose over 30 to 120 minutes in total volume up to 250 ml of 0.9% normal saline.

Required labs: All patients must have creatinine clearance calculated and liver enzymes obtained before initiation of therapy.

  • Daily LFT monitoring is also required.
  • Remdesivir should not be initiated in patients with ALT ≥ 10 times the upper limit of normal at baseline.

ADULT RENAL DOSING

Dosing in hemodialysis.

Use as normal dosing.

DOSING IN PERITONEAL DIALYSIS

Dosing in renal replacement therapy, other adult renal dosing information.

  • The FDA approval was based on phase 1 and phase 3 REDPINE trials, which showed the pharmacokinetics and safety profile of the drug in patients with severe renal impairment.

PEDIATRIC DOSING

Usual pediatric dosing.

  • Weight ≥3.5 kg - < 40 kg: 5 mg/kg/dose once (max 200 mg/dose), followed by 2.5 mg/kg/dose (max 100 mg/dose) IV Q24h for a total duration of up to 10 days.
  • Weight ≥ 40 kg: 200 mg once, followed by 100 mg IV Q24h, for a total duration of up to 10 days.

Administration instructions: Infuse each dose over 30 to 120 minutes in a total volume of up to 250 ml of sodium chloride 0.9%. Flush line with at least 30 mL sodium chloride 0.9% after remdesivir infusion. Do not administer simultaneously with any other medication or intravenous solutions.

Required labs: Baseline and daily hepatic function tests (ALT, AST, bilirubin, alkaline phosphatase)

  • RDVr should not be initiated in patients with ALT ≥ 10 times the upper limit of normal at baseline.

PEDIATRIC RENAL DOSING

  • No dose changes are needed, and RDV may be used regardless of renal status. See adult renal dosing comments.

ADVERSE DRUG REACTIONS

  • Generally well tolerated.
  • Overall AEs were lower in the RDV arm but not with statistical significance in both ACTT-1 [inpatient] and PINETREE [outpatient].
  • In the ACTT-1 trial, remdesivir had similar rates of AEs compared to placebo.
  • Remdesivir is contraindicated in patients with hypersensitivity to any ingredient of remdesivir.
  • Data below for ACTT-1, inpatient RDV use.
  • Constipation (6-14%)
  • Nausea (5-10%)
  • Vomiting (3%)
  • Diarrhea (3%)
  • Infusion-related reactions: hypotension, nausea, vomiting, diaphoresis, shivering
  • Increased serum glucose (3-11%)
  • Acute respiratory failure (6-11%)
  • Hypoalbuminemia (13%)
  • Hypokalemia (5-12%)
  • Anemia (8-12%)
  • Thrombocytopenia (10%)
  • Increased bilirubin (10%)
  • Or ALT elevation accompanied by signs or symptoms of liver inflammation or increasing conjugated bilirubin, alkaline phosphatase, or INR.
  • If therapy continues, no dose change is necessary.
  • Prothrombin time (PT) elevation without a change in INR
  • Renal: AKI (2-8%), decreased CrCl (3-12%). Rates are higher with a 10-day course compared to 5 days.
  • Pyrexia (5%)
  • Hypoglycemia (4%)
  • Insomnia (5%)
  • Hypersensitivity reactions reported, including angioedema and anaphylaxis

DRUG INTERACTIONS

  • Experts do not expect a significant impact on remdesivir concentrations.
  • Coadministration is not recommended based on tissue culture data displaying potential antagonism, which may lead to a decrease in the antiviral activity of RDV.

Remdesivir showed in vitro activity against SARS-CoV-2 in animal models and in vitro and in vivo activity against MERS-CoV and SARS-CoV-1. EC 50 for SARS-CoV2 was 0.77 μM in one in vitro study.

No clinical data are available on the development of SARS-CoV-2 resistance to remdesivir.

PHARMACOLOGY

Remdesivir is an adenosine nucleotide prodrug that is metabolized to active form nucleoside triphosphate metabolite, which acts as an analog of adenosine triphosphate (ATP) and competes with the natural ATP substrate for incorporation into nascent RNA chains by the SARS-CoV-2 RNA-dependent RNA polymerase, inhibiting viral replication.

PHARMACOKINETIC PARAMETERS

Metabolism and excretion.

  • ~ 74% of remdesivir is recovered in feces and 18% in urine. The majority (49%) of the dose recovered in urine is metabolite GS- 441524, and 10% was recovered as remdesivir.
  • AUC 0-24 = 4.8 μM•h for remdesivir and AUC 0-24 =7.7 μM•h for the nucleoside metabolite after for 200 mg of remdesivir was administered to healthy human subjects.
  • Cmax = 5440 ng/ml for remdesivir and Cmx=152 ng/ml for the metabolite GS- 441524 after 200 mg dose.

Protein Binding

The free fraction in humans was 12.1%.

Cmax, Cmin, and AUC

  • Remdesivir exhibits linear PK profile.
  • Remdesivir: ~1 h
  • Metabolite GS-441524: ~25 h

Distribution

Widely distributed

DOSING FOR DECREASED HEPATIC FUNCTION

  • The PK of remdesivir has not been evaluated in patients with hepatic impairment. It is unknown if a dosage adjustment is needed in patients with hepatic impairment. R emdesivir should not be used in patients with ALT ≥ 10 times the upper limit of normal.

PREGNANCY RISK

  • Remdesivir should be used in pregnancy only if the benefits outweigh the risk to the mother and fetus. In nonclinical reproductive toxicity studies, no adverse effects on embryofetal development were observed when remdesivir was administered to pregnant animals at systemic exposure of the predominating circulating metabolite of remdesivir at 4 times the exposure in humans.
  • In Ebola clinical trial, six out of 98 females who had received remdesivir had a positive pregnancy test. However, obstetric and neonatal outcomes were not reported in the study [15] .

BREASTFEEDING COMPATIBILITY

No data on remdesivir excretion in human breast milk. In animal studies, remdesivir and its metabolites have been detected in nursing mothers.

  • There are two formulations: solution formulation and lyophilized powder formulation.
  • The PINETREE trial supports the use of remdesivir 3-day therapy based on a study of unvaccinated, non-hospitalized patients with less than 7 days of symptoms and at least one risk factor (age ≥ 60 yrs, obesity, hypertension, cardiovascular disease, cerebrovascular disease, diabetes, immune compromise, chronic kidney or liver disease, current cancer or sickle cell disease) for progression to severe disease. Remdesivir achieved an 87% reduction in risk for hospitalization or death within 28d compared to placebo.
  • GFR assessment is no longer required before dosing RDV as now FDA-approved regardless of renal status.
  • There was no significant difference in mortality between remdesivir and placebo (7.1% vs. 11.9%; HR for death, 0.70; 95% CI, 0.47 to 1.04).
  • The median time from symptom onset to randomization was 9 days.
  • The median time to start the study drug from symptom onset was 10 days. Late administration of the drug could be one of the main reasons for the failure of remdesivir to demonstrate improvement in clinical symptoms, as observed in the NIAID ACTT-1 clinical trial as well as the small sample size that did not have the power to detect a difference in clinical outcome. Remdesivir did not show a significant impact on viral load.
  • The duration of remdesivir treatment was evaluated in the randomized, open-label study of patients with COVID-19 pneumonia. This study did not find a significant difference in the clinical status at 14 days after adjusting for baseline differences among the two groups. It is important to note that intubated patients or those on ECMO and those with multiorgan failure were excluded from the study. Patients who received 10-day treatment were more likely to experience serious adverse events (35% vs. 21%) and discontinue treatment due to adverse events (10% vs. 4%) compared to 5-day treatment.
  • A Phase 2/3, open-label, single-arm clinical trial in 53 pediatric patients demonstrated similar results and adverse effects as seen in adults when given remdesivir for up to 10 days. PK data were also similar.
  • In animal studies, when remdesivir was used as prophylaxis, it prevented MERS-CoV clinical disease, reduced MERS-CoV levels, and lung injury [13] [14] .
  • Remdesivir has been tested in humans for treating Ebola virus infection; in a large study of 681 patients, remdesivir (n=175) was inferior to human monoclonal antibodies ( REGN-EB3 and MAb114) [15] .
  • In a mouse model, remdesivir was effective when tested as a treatment for SARS-CoV-1 .

Basis for recommendation

Comment: The PINETREE study compared 3 days of outpatient RDV infusion (200 mg day 1 and 100 mg on days 2 and 3) to placebo among ambulatory patients ≥12 years old who had ≥1 risk factor for severe COVID-19 and ≤7 days of symptoms. Characteristics among the 279 RDV and 283 placebo patients were balanced with a mean age of 50, 50% women, and 61% with diabetes mellitus as the primary risk for severe COVID-19. The primary outcome was COVID-19-related hospitalization or death 28 days after enrollment. In the RDV arm, 2 (0.7%) participants had a COVID-19-related hospitalization compared to 15 (5.3%) in the placebo arm (p=0.008), for a relative risk reduction of 87%. There were no deaths in either arm. Adverse events were similar in both arms.

Comment: In this final report, a double-blind, randomized, placebo-controlled trial, IV remdesivir, was compared to placebo for treating hospitalized adults with severe Covid-19 lower respiratory tract infection. Remdesivir was given for 10 days (200 mg on day 1, followed by 100 mg daily for up to 9 days). In the analysis of 1059 patients (538 in remdesivir and 521 in placebo), the median time to recovery was significantly shorter remdesivir group compared to placebo, 10 days vs. 15 days respectively, the rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P< 0.001, by a log-rank test). Most patients had one or two pre-existing conditions, most commonly hypertension (49.6%), obesity (37.0%), and type 2 diabetes mellitus (29.7%). The median number from symptom onset to randomization was 9 days. The Kaplan–Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and 163 of the 516 patients who received a placebo (31.6%).

Comment: In this randomized, open-label, phase III trial, remdesivir 5 days (n=200) vs. 10 days (n=197) course was compared in hospitalized patients (≥12 y/o) SARS-CoV-2 pneumonia with oxygen saturation of ≤ 94% while they were breathing ambient air or were receiving supplemental oxygen. Intubated patients or those on ECMO, as well as those with multiorgan failure, were excluded. More patients at baseline had a higher disease severity in the 10-day group (p=0.02). There was no difference in the clinical status at day 14 between the two groups after adjustment for bassline clinical status (p=0.14). The median time to clinical improvement was 10 days in both groups. Discharge rates were higher in patients with symptoms < 10 days before receiving remdesivir (62% vs. 49%). There was no difference in mortality or length of hospital stay between the two groups. The most common adverse events were nausea (9%), worsening respiratory failure (8%), and elevated ALT (7%).

Comment: The current placement of RDV, including revised recommendations regarding use in reduced GFR states per FDA prescribing information.

Comment: The current placement of RDV, including revised recommendations regarding the use in reduced GFR states per FDA prescribing information.

Comment: Analysis of 8 RCTs suggested a 23% mortality reduction in those receiving RDV vs placebo for those who did not require supplement oxygen but not benefit for those who had it started while on iMV or ECMO.

Comment: A retrospective study using a large data set and careful matching within the cohort found that those receiving RDV were more likely to gain clinical improvement by d28 if on no or low-flow oxygen. Although the study had no overall mortality benefit, it did find it to be so in the no or low-flow oxygen groups, suggesting earlier administration is necessary for this antiviral.

Comment: The final SOLIDARITY analysis that concludes no mortality benefit in this early, non-placebo-controlled trial is presented here. The authors also include a meta-analysis of RDV showing benefits among SOLIDARITY, ACTT-1 and Wuhan trials. This also showed no mortality benefit statistically ort effect on patients with COVID-19 who are already being ventilated. Among other hospitalized patients, it has a negligible effect on death or progression to ventilation (or both).

Comment: This European trial did not show benefit if RDV was received > 7d after the onset of symptoms with either d15 or d28 as endpoints for clinical status assessment. The difference with ACTT-1 was likely based on DisCoVeRy having a larger proportion of patients on steroids and requiring oxygen (so more advanced in disease course). Missing from the abstract was that RDV in DisCoVeRy In DisCoVeRy in the subset of participants without mechanical ventilation or ECMO significantly delayed the need for new mechanical ventilation or ECMO, or death--which was in keeping with ACTT-1

Comment: The WHO-sponsored large trial did not show a mortality benefit, although this four-arm trial lacked a placebo. It is unclear if subgroups may benefit. Patients could be moved to another group at the clinician’s discretion, and there was no placebo arm. Also, RDV did not appear to have a great effect on the need for ventilation or hospital LOS.

Comment: Report of compassionate use of remdesivir in 53 patients with severe COVID-19; 75% received the full 10-day course of remdesivir. At baseline, 57% of patients were receiving mechanical ventilation and 8% were on ECMO. During the follow-up period (median of 18 days), 68% of patients showed improvement in oxygen support (57% of ventilated patients were extubated), 47% were discharged and 13% died. Adverse events were reported in 60% of patients, with 23% experiencing serious adverse events.

Comment: In this randomized, double-blind, placebo-controlled trial (n=237) in China, a remdesivir 10-day course was compared to a placebo for the treatment of severe COVID-19 pneumonia (O2 saturation ≤ 94% or PaO2/FiO2 ratio of ≤300 mm Hg). The median time to start the study drug from symptom onset was 10 days. 28% of patients in the remdesivir arm also received lopinavir/ritonavir. Remdesivir use did not result in a significant clinical improvement 28 days after randomization compared to placebo. Patients who received remdesivir within 10 days of symptom onset in the ITT population had a numerically faster time to clinical improvement than those receiving a placebo. However, this was not statistically significant (18 vs. 23 days). Viral load decreases over time were similar in both groups. Adverse events were reported in 66% of patients receiving remdesivir and 64% receiving placebo.

Comment: In the rhesus macaque (non-human primate model), remdesivir given 24h before inoculation with MERS-CoV as a prophylactic agent was effective in preventing MERS-CoV−induced clinical disease (including the formation of lesions formed in the lungs) and inhibiting MERS-CoV replication in respiratory tissues. Remdesivir was also given as treatment 12 h post-inoculation in the same primate model and was effective in reducing clinical signs, including the severity of the lung lesions and viral replication.

Comment: This study demonstrates that remdesivir, combined with interferon beta, had superior activity against MERS-CoV to lopinavir/ritonavir in vitro. Furthermore, when remdesivir was given to mice to prevent and treat MERS-CoV, it demonstrated clinical improvement and reduced viral loads. On the other hand combination of lopinavir/ritonavir with interferon beta was not as effective as remdesivir and reduced viral loads but had no impact on improving the clinical status of mice.

Comment: A total of 681 patients with Ebola virus were randomly assigned in a 1:1:1:1 ratio to 1) triple monoclonal antibody ZMapp, 2) remdesivir, or 3) a single monoclonal antibody MAb114, or 4) the triple monoclonal antibody REGN-EB3. At the interim analysis, data showed the superiority of MAb114 and REGN-EB3 to ZMapp and remdesivir concerning mortality. At that point, patients were re-assigned only to the MAb114 and REGN-EB3 and the remdesivir arm was terminated. Mortality at 28 days in the remdesivir arm was 53.1% vs. 49.7% in ZMapp vs. 35.1% in Mab114 vs. 33.5% in REGN-EB3.A total of 9 adverse events occurred in the remdesivir arm that were unrelated to the underlying Ebola virus disease. Rating: Important

Comment: A phase 2/3, single-arm, open-label trial enrolling 53 pediatric patients who received remdesivir for up to 10 days. Outcomes were similar to those seen in the adult population, with no differences in the incidence of adverse effects or pharmacokinetic parameters. This data led to the FDA lowering the age/weight criteria for remdesivir approval.

Comment: As an FDA-approved drug, PI information, is for both outpatient and inpatient use.

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FDA’s approval of Veklury (remdesivir) for the treatment of COVID-19—the science of safety and effectiveness

[10/22/2020] FDA recognizes that patients affected by coronavirus 2019 (COVID-19) are in great need of medicines to treat this disease. To help meet this need, the agency is helping to speed the development of promising therapies through its Coronavirus Treatment Acceleration Program (CTAP). Today, FDA approved Veklury (remdesivir), the first drug approved to treat COVID-19, for use in adults and pediatric patients 12 years of age and older and weighing at least 40 kg (about 88 pounds) requiring hospitalization.

This approval does not include the entire population that had been authorized to use Veklury under a mechanism called emergency use authorization (EUA), which is not the same as approval. FDA also revised the EUA for Veklury, originally issued on May 1, 2020, to permit the drug’s use for treatment of suspected or laboratory confirmed COVID-19 in hospitalized pediatric patients weighing 3.5 kg to less than 40 kg or  hospitalized pediatric patients less than 12 years of age weighing at least 3.5 kg.

As a public health agency, FDA uses the best scientific information available to make decisions through a deliberative process.  Drugs must undergo a rigorous evaluation of safety, quality, and effectiveness before they can be approved for use in the United States.

FDA approval of a drug regulated by the Center for Drug Evaluation and Research (CDER) means that CDER has reviewed data on the drug’s effects, and the agency has determined the drug’s benefits outweigh its risks for the approved population when used according to the drug’s approved labeling. The drug approval process takes place within a structured framework that includes:

  • Analysis of the target condition and available treatments
  • Assessment of benefits and risks from clinical data
  • Strategies for managing risks

CDER carefully considered these factors throughout the regulatory process for evaluating Veklury.

Regardless of what laboratory, clinical, or other evidence may exist about a drug, CDER particularly focuses on the results of randomized, controlled clinical trials, which we consider to be the gold standard. CDER’s detailed review of Veklury clinical trials that supported FDA approval this week reflects our independent clinical evaluation of the safety and effectiveness of this drug in certain patients requiring hospitalization for COVID-19.

Additional Information

Among other trials supporting FDA’s approval of Veklury, the ACTT-1 clinical trial sponsored by the National Institute of Allergy and Infectious Diseases showed a significantly faster time to recovery in patients taking Veklury (about 10 days) compared to the placebo group (about 15 days).

The clinical trial also showed Veklury to be safe for the patient population for which it is approved. Veklury should only be administered in a hospital or in a healthcare setting capable of providing acute care comparable to inpatient hospital care.  

FDA oversight of Veklury does not end with approval, and continued safety monitoring  after approval is an important FDA duty for all the products that the agency regulates.

Important information about using Veklury to treat COVID-19 for its approved use is available in the prescribing information which includes dosing instructions, potential side effects and drug interactions. Possible side effects include: increased levels of liver enzymes, which may be a sign of liver injury; and allergic reactions, which may include changes in blood pressure and heart rate, low blood oxygen level, fever, shortness of breath, wheezing, swelling (e.g., lips, around eyes, under the skin), rash, nausea, sweating or shivering. Similar safety information about using Veklury to treat COVID-19 in certain hospitalized pediatric patients under the EUA is available in the fact sheets fortohealth care providers and patients/caregivers.

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Why remdesivir, a highly effective COVID treatment, is a last resort for providers

Pien Huang

Drugmaker Gilead says remdesivir has proved effective at treating patients early in the course of the disease. Dirk Waem/Belga/AFP via Getty Images hide caption

Drugmaker Gilead says remdesivir has proved effective at treating patients early in the course of the disease.

In late December, as the omicron variant surged, the roster of early COVID-19 treatments was looking slim. Newly authorized pills for COVID-19 were in short supply. Several monoclonal antibody drugs didn't seem to work .

Then an older drug, remdesivir, emerged as an effective option.

Over the past year and a half, the drug — sold in the U.S. under the brand Veklury — had been used in hospitals to treat very sick patients with COVID-19. But new data from the drugmaker Gilead showed that remdesivir could also help high-risk patients avoid the hospital. In other words, it could help patients with medical conditions like immune suppression and diabetes ward off severe COVID-19 disease.

The FDA limits the use of some monoclonal antibodies treatments

Medical Treatments

The fda limits the use of some monoclonal antibodies treatments.

While the drug had shown mixed results in studies as a treatment for hospitalized patients, it has proved surprisingly effective, according to Gilead's data, at treating patients early in the course of the disease. Public health experts say it could be enormously useful at a time when other early COVID-19 treatments — such as monoclonal antibodies and COVID pills — are unavailable or in short supply. But the drug hasn't gotten much traction among health care providers because it takes significant time, staff and resources to give out.

The appeal of remdesivir

The results of Gilead's study on using remdesivir early in the course of illness , published in The New England Journal of Medicine , were "truly dramatic," says Dr. Jane Kelly, assistant state epidemiologist for South Carolina, who is not affiliated with the study. "It resulted in an 87% lower risk of hospitalization or death than placebo."

Those results put it on par with monoclonal antibodies and Paxlovid, a COVID-19 pill, which are the best available COVID treatments out there. Remdesivir's side effects — mainly, nausea — are tame for most people.

Other traits add to remdesivir's appeal. It's the only early treatment available to children under 12 . Plus it works against omicron – while some other early treatment options do not. And, while other early treatments are in short supply, there's plenty of remdesivir to go around.

Federal agencies now recommend remdesivir as one of four options for treating early COVID-19. These medicines, when started within five to 10 days of the onset of symptoms, could help patients who might get very sick from COVID-19 — such as some patients with cancer or chronic lung disease — rid their systems of the virus.

Expensive and hard to give to patients

But remdesivir has drawbacks. It takes more resources to administer than the antiviral pills and comes with substantial upfront costs, which stand in the way of widespread use.

For starters, remdesivir is a drug infusion that must be given intravenously, in a clinical setting. Compared with other outpatient options, the drug takes more space and staff to infuse, says Dr. Cameron Wolfe , an infectious disease specialist and professor of medicine at Duke University.

Duke's infusion clinic, like many others, was set up to treat COVID-19 patients with monoclonal antibodies – a treatment which takes a single infusion session lasting 1 to 2 hours, Wolfe explains. But treating patients with remdesivir takes three such infusion sessions over consecutive days. That means a clinic could treat one patient with remdesivir — or three patients with monoclonal antibodies — in the same amount of time.

To accommodate the remdesivir treatments, the Duke clinic had to expand their hours from five days a week to seven. "You don't want someone to get Dose 1 on a Friday, and wait 72 hours [to get the next dose]," says Wolfe.

Treating patients with monoclonal antibodies is preferred because it's more efficient, says Wolfe. But because the supply of monoclonals is limited, he estimates the clinic infused around 130 people with remdesivir in January.

Then there's the issue of initial costs. Remdesivir is the only early treatment that has a supply that is not currently controlled by the U.S. government . That also means it doesn't get sent to health care providers for free. It's available on the commercial market — so clinics pay around $520 per vial, or $2,080 per course, for the drug up front (a person getting outpatient remdesivir treatment receives two vials on the first day; and one vial each on the next two). Putting it into someone's arm adds to that cost.

For providers to get reimbursed, they "have to bill Medicare or a patient's insurance. That might be a consideration to somebody who might be slapped with a co-pay," says Dr. Peter Chin-Hong , an infectious disease specialist at University of California, San Francisco.

These cost issues add to the hurdles providers face in using COVID-19 medicines to keep patients out of the hospital.

"It's hard enough already with these COVID treatments. You're trying to make sure that patients qualify — that they've got their positive test and they're within that symptom window," says Erin Fox , a senior pharmacy director at University of Utah Health. "But then with remdesivir, you have that added challenge of trying to assure payment."

Remdesivir on the back burner

For these reasons, health care providers consider remdesivir to be low on the list of treatment options — available if necessary, but hard to implement.

Fox says her health system in Utah has treated only about 15 early COVID-19 patients with remdesivir so far. A larger-than-expected shipment of monoclonal antibody treatments received last month, provided free by the U.S. government, puts remdesivir on the back burner for now. "We have it, we want to use it, but we're kind of turning it on and off depending on how much sotrovimab we're getting," Fox says.

Baylor St. Luke's Medical Center in Houston also recently received an influx of other COVID-19 medications, and has ample supplies of monoclonal antibodies and COVID-19 pills, says Dr. Mayar Al Mohajer , chief of infectious diseases there. "We have access to three out of the four therapeutics. So, we didn't feel that providing outpatient remdesivir would provide an extra benefit for us," he says.

Remdesivir's role as a top COVID-19 treatment may be short-lived. "I think 'stopgap' is probably a good description," says Michael Ganio of the American Society of Health System Pharmacists . In other words, its use may be limited to times when monoclonals and pills are in short supply.

Over the next few months, the supply crunch on other highly effective COVID-19 treatments – that can be taken at home as pills or given in a single infusion – is expected to ease. "Those therapies are just easier to administer, and they're going to end up being preferred," Ganio says.

Still, experts say, remdesivir has been a crucial option in this omicron surge, when virus mutations knocked out a few other treatment options . As the virus evolves, the option to use remdesivir could be key again.

Remdesivir shouldn't be used on hospitalized Covid-19 patients, WHO advises

The antiviral remdesivir should not be used as treatment for hospitalized Covid-19 patients, the World Health Organization said Thursday, only a month after the Food and Drug Administration approved the drug to treat patients over age 12 who are hospitalized with Covid-19 .

Remdesivir, also known as Veklury, and the steroid dexamethasone are the only drugs authorized to treat Covid-19 patients. But a recent massive global study of remdesivir's effectiveness , run by the WHO, showed that remdesivir had little or no impact on hospitalized patients, contradicting previous trials.

"Remdesivir has no meaningful effect on mortality or on other important outcomes for patients, such as the need for mechanical ventilation or time to clinical improvement," experts from the WHO Guideline Development Group wrote in a statement. The review was published in The BMJ, a medical journal.

In light of the interim data from the WHO's "Solidarity" trial — which included data from more than 11,200 people in 30 countries — "remdesivir is now classified as a drug you should not use routinely in Covid-19 patients," the president of the European Society of Intensive Care Medicine, Jozef Kesecioglu, said in an interview with Reuters.

Gilead Sciences, which makes remdesivir, has questioned the WHO's findings. In in an emailed statement, the drugmaker said: "We are confident that doctors on the front lines recognize the clinical benefit of Veklury based on robust evidence from multiple randomized, controlled studies."

While doctors and hospitals are not obliged to follow the WHO's advice, the recommendation could curb the use of remdesivir.

The drug, however, remains widely used in hospitals, including in the U.S. It is authorized or approved for use in more than 50 countries, and it was one of the medicines administered to President Donald Trump when he tested positive for the coronavirus in October.

An earlier study conducted by the National Institutes of Health found that remdesivir reduced the length of hospital stays among patients with moderate illness by about four days, from 15 to 11.

Because remdesivir is thought to work by stopping the virus from replicating, it is likely to have more impact earlier in the course of the illness, Dr. Hugh Cassiere, a pulmonologist at Northwell Health in New York, told NBC News.

Download the NBC News app for full coverage of the coronavirus outbreak

"If you were to start remdesivir really early on, you'd expect to have more bang for the buck," Cassiere said.

Dr. Ken Lyn-Kew of National Jewish Health in Denver agreed that it is important to continue to study remdesivir, but he is not as enthusiastic about using the drug for patients in advanced stages of the illness. "The data show it really doesn't work very well in hospitalized patients," Lyn-Kew said.

Kesecioglu said there was not enough data about when remdesivir might be effective or for which patients, leading to the decision to discourage its routine use in intensive care.

That means doctors should use remdesivir only occasionally, not as a standard treatment for Covid-19 patients.

Ten months into the pandemic, a debate continues to rage in the medical industry about which drugs are best to treat hospitalized Covid-19 patients.

Remdesivir has potential side-effects on the kidneys, according to data Gilead shared with the European Medicines Agency, which is assessing its possible toxicity.

Separately, the FDA issued emergency use authorization Thursday for remdesivir in combination with Eli Lilly's baricitinib, a pill used to treat rheumatoid arthritis.

In a clinical trial of hospitalized Covid-19 patients, the combined treatment was shown to reduce time to recovery within 29 days after beginning the medications, compared to patients who received a placebo with remdesivir, the FDA said in a statement. The agency said ongoing research will be needed to confirm the benefit.

Full coverage of the coronavirus outbreak

i was given remdesivir

Erika Edwards is a health and medical news writer and reporter for NBC News and "TODAY."

Generic name: remdesivir [  rem-DES-i-veer  ] Brand name: Veklury Dosage forms: intravenous powder for injection (100 mg), intravenous solution (5 mg/mL) Drug class: Purine nucleosides

Medically reviewed by Drugs.com on May 12, 2022. Written by Cerner Multum .

What is remdesivir?

Remdesivir is used to treat adults and children at least 28 days and older who weigh at least 7 pounds (3 kilograms) with positive results for COVID-19 who are:

in a hospital; or

not in a hospital and have mild-to-moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death.

Remdesivir may also be used for purposes not listed in this medication guide.

Remdesivir side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Some side effects may occur during or after the injection. Tell your caregiver right away if you have:

severe headache , pounding in your neck or ears;

fast, slow, or pounding heartbeats;

wheezing , trouble breathing;

swelling in your face;

fever , chills, or shivering;

itching , sweating ; or

a light-headed feeling, like you might pass out;

Common side effects of remdesivir may include:

abnormal liver function tests.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Remdesivir is for use only in people with COVID-19. You must remain under the care of a doctor while receiving remdesivir.

Before taking this medicine

You should not be treated with remdesivir if you are allergic to it.

Tell your doctor if you have ever had:

liver disease ; or

kidney disease.

Tell your doctor if you are pregnant or plan to become pregnant, or if you are breastfeeding.

If you are pregnant, your name may be listed on a pregnancy registry to track the effects of remdesivir on the baby.

How is remdesivir given?

Your doctor will perform blood tests to make sure you do not have conditions that would prevent you from safely using remdesivir.

Remdesivir is given as an infusion into a vein. A healthcare provider will give you this injection.

remdesivir must be given slowly, and the infusion can take 30 to 120 minutes to complete.

If you are hospitalized: remdesivir is usually given once per day for up to 10 days.

If you are not hospitalized: remdesivir is usually given once per day for 3 days.

You will need frequent blood tests to check your liver function.

You must remain under the care of a doctor while you are being treated with remdesivir for COVID-19.

Remdesivir dosing information

Usual Adult Dose for COVID-19:

Loading dose (Day 1): 200 mg IV as a single dose Maintenance dose (from Day 2): 100 mg IV once a day Duration of Therapy: -Hospitalized patients requiring invasive mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO): 10 days total -Hospitalized patients not requiring invasive mechanical ventilation and/or ECMO: 5 days; may extend up to 5 additional days (for a total of up to 10 days) if no clinical improvement shown -Nonhospitalized patients: 3 days total Use: For the treatment of coronavirus disease 2019 (COVID-19) in patients who are: -Hospitalized, or -Not hospitalized, have mild to moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death

Usual Pediatric Dose for COVID-19:

28 Days of Age and Older: Weight 3 to less than 40 kg: -Loading dose (Day 1): 5 mg/kg IV as a single dose -Maintenance dose (from Day 2): 2.5 mg/kg IV once a day Weight at least 40 kg: -Loading dose (Day 1): 200 mg IV as a single dose -Maintenance dose (from Day 2): 100 mg IV once a day Duration of Therapy: -Hospitalized patients requiring invasive mechanical ventilation and/or ECMO: 10 days total -Hospitalized patients not requiring invasive mechanical ventilation and/or ECMO: 5 days; may extend up to 5 additional days (for a total of up to 10 days) if no clinical improvement shown -Nonhospitalized patients: 3 days total Comments: -The lyophilized powder formulation is the only approved dosage form for pediatric patients weighing 3 to less than 40 kg. Use: For the treatment of COVID-19 in patients who are: -Hospitalized, or -Not hospitalized, have mild to moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death

What happens if I miss a dose?

Because you will receive remdesivir in a clinical setting, you are not likely to miss a dose.

What happens if I overdose?

Since remdesivir is given by a healthcare professional in a medical setting, you will be treated quickly if an overdose occurs.

What should I avoid while receiving remdesivir?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

What other drugs will affect remdesivir?

Tell your doctor if you also take chloroquine or hydroxychloroquine . Either of these other medicines could make remdesivir less effective.

Other drugs may affect remdesivir, including prescription and over-the-counter medicines, vitamins , and herbal products . Tell your doctor about all your current medicines and any medicine you start or stop using.

Frequently asked questions

  • Can Remdesivir be used to treat COVID-19 (coronavirus)?

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The journey of remdesivir: from Ebola to COVID-19

1 Pharmacy Service, North Florida/South Georgia Veterans Health System, Gainesville, FL, USA

Ashutosh M Shukla

2 Department of Medicine, North Florida/South Georgia Veterans Health System, Gainesville, FL, USA

3 Department of Medicine, University of Florida, Gainesville, FL, USA

Gajapathiraju Chamarthi

Asmita gupte.

Countries around the world are currently fighting the coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a betacoronavirus, belonging to the same genus as severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV. Currently, there are no proven antiviral therapies for COVID-19. Numerous clinical trials have been initiated to identify an effective treatment. One leading candidate is remdesivir (GS-5734), a broad-spectrum antiviral that was initially developed for the treatment of Ebola virus (EBOV). Although remdesivir performed well in preclinical studies, it did not meet efficacy endpoints in a randomized trial conducted during an Ebola outbreak. Remdesivir holds promise for treating COVID-19 based on in vitro activity against SARS-CoV-2, uncontrolled clinical reports, and limited data from randomized trials. Overall, current data are insufficient to judge the efficacy of remdesivir for COVID-19, and the results of additional randomized studies are eagerly anticipated. In this narrative review, we provide an overview of Ebola and coronavirus outbreaks. We then summarize preclinical and clinical studies of remdesivir for Ebola and COVID-19.

For over two decades, global health leaders have been cautioning the world about another pandemic comparable in severity and scope to the 1918 influenza epidemic. 1 Two major outbreaks afflicted the world in the 20th century, that is, the 1918 influenza epidemic and the ongoing human immunodeficiency virus (HIV) pandemic. 2 The 21st century has already seen a significant number of outbreaks: severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002, the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, and the Ebola virus (EBOV) in 2014. Currently, we are in the midst of an unprecedented pandemic due to SARS-CoV-2, coronavirus disease 2019 (COVID-19). These outbreaks have posed many challenges: an important one being the public health aspect, but also the lack of effective therapies and vaccines. Prevention of complications and supportive treatment are the standard of care for most of these recent viral disease outbreaks. 3 No treatment has been proven effective for the current COVID-19 pandemic. The medical community is under immense pressure, and many clinicians are embarking on using experimental treatments based on poorly conducted clinical trials and observational data. 4 Randomized controlled trials conducted efficiently and promptly are the only way to find effective therapies.

Remdesivir (GS-5734) is an investigational broad-spectrum antiviral drug that has demonstrated activity against ribonucleic acid (RNA) viruses of several families, including Coronaviridae (such as SARS-CoV, MERS-CoV, and strains of bat coronaviruses), Paramyxoviridae (such as Nipah virus, respiratory syncytial virus, and Hendra virus), and Filoviridae (such as EBOV). 5 – 9 In this narrative review, we will summarize the studies available to date for remdesivir in the context of viral outbreaks, especially its development as an antiviral agent for Ebola and coronaviruses. We searched PubMed for published clinical and preclinical reports assessing remdesivir for Ebola virus disease (EVD), SARS, MERS, and COVID-19. The search terms used were (‘Ebola virus’, ‘severe acute respiratory syndrome’, ‘SARS-CoV’, ‘Middle East respiratory syndrome’, ‘MERS-CoV’, ‘COVID-19’, ‘2019-nCoV’, ‘SARS-CoV-2’) and (‘remdesivir’ or ‘GS-5734’). The references of the selected papers were reviewed to identify additional pertinent reports.

Overview of human coronavirus outbreaks

Coronaviruses are large, enveloped, positive-strand RNA viruses that can be divided into four genera: alphacoronavirus, betacoronavirus, deltacoronavirus and gammacoronavirus. 10 Alpha and beta CoV are known to cause human disease. Until recently, human coronavirus (HCoV) received relatively less attention as they were considered low-virulence organisms and believed to cause only mild, self-limiting upper respiratory infection in humans. 11 , 12

The first coronavirus outbreak, SARS, caused by SARS-CoV, occurred in the Guangdong Province of China in 2002–2003. The mortality rate during this outbreak was 9%, with a higher mortality rate (50%) in the elderly population. This outbreak was largely contained because of relatively inefficient transmission, which mainly occurred through direct contact with infected individuals. Hence, strict quarantine of infected patients restricted the spread of the disease, and the outbreak ceased after affecting 8098 people and causing death in 774 patients. 13

The next coronavirus outbreak occurred in the Middle East (Saudi Arabia) in 2012 and was named the MERS-CoV. This virus caused severe lower respiratory infection with a mortality rate of about 35%. Per the World Health Organization’s (WHO) report, the total number of reported cases globally was 2519, out of which 866 patients died. 13 Both MERS-CoV and SARS-CoV originated from bats. However, serologic studies for antibody testing in dromedary camels suggested that camels were the intermediate host for MERS-CoV. 14

MERS-CoV shared many clinical features with SARS-CoV, such as severe atypical pneumonia. However, there were some differences, with MERS causing prominent gastrointestinal (GI) symptoms and acute kidney injury. The investigators attributed the differences in clinical manifestations to the involvement of different receptors used by these two viruses. While MERS binds to the human dipeptidyl peptidase receptor (present in the lower airway, GI tract, and kidney), SARS binds to the angiotensin-converting enzyme (ACE)-2 receptor. 12 , 13 The treatments for these coronavirus outbreaks largely relied on supportive care.

On December 31, 2019, China reported a cluster of atypical pneumonia cases with an unknown etiology. 15 Early cases were associated with the Huanan Seafood Wholesale Market in Wuhan, Hubei Province. Soon after that, the causative pathogen was identified as a novel betacoronavirus (SARS-CoV-2), and the disease was ultimately named COVID-19. SARS-CoV-2 has high sequence homology with bat coronaviruses (~87% identical sequences with bat-SL-CoVZC45 and bat-SL-CoVZXC21), which supports the hypothesis of bat origin. When compared with SARS-CoV and MERS-CoV, SARS-CoV-2 has a genetic similarity of 79 and 50%, respectively. 13 The clinical presentation of COVID-19 ranges from asymptomatic carriage to severe viral pneumonia causing acute respiratory distress syndrome. Fever and GI symptoms are common. At the time of this report, COVID-19 has spread across the globe with 2,397,216 confirmed cases and 162,956 deaths according to the WHO situation report. 16

Overview of Ebola virus outbreaks

Ebola viruses belong to the family Filoviridae, a taxonomic group of enveloped, non-segmented, negative-strand RNA viruses. There are five different species of EBOV that can infect humans, but they differ in their virulence and disease progression, with a case fatality rate ranging from 40% for Bundibugyo EBOV to 70–90% for Zaire EBOV. Humans infected with EBOV initially have non-specific symptoms, such as nausea, vomiting, and diarrhea, with the hemorrhagic phase occurring in half of the cases. 17 Outbreaks of EVD have mainly been limited to Africa; however, in recent times, a small number for patients have been transferred to hospitals with modern technology in the USA and Germany. The mortality rate in Africa is often very high compared to patients who have received supportive care in developed countries. There are no approved drugs for the treatment of EVD. During the 2014–2016 West African outbreak and subsequent outbreak in the Democratic Republic of Congo (DRC), several investigational treatments, such as antibody therapy and remdesivir, were evaluated in clinical trials. 18

In summary, it has been challenging to evaluate investigational drugs in randomized controlled trials during outbreak situations. The initial response to the COVID-19 outbreak was to use treatments that were not shown to be effective in properly conducted trials. Most studies thus far have lacked adequate controls, are observational, and have a very small number of patients that precludes any meaningful statistics regarding efficacy. Here, we review the available studies for the antiviral remdesivir (Gilead Sciences, Inc.) in an attempt to present an impartial review of data available for this drug, with a specific focus on outbreaks of EBOV and now SARS-CoV-2.

Chemistry and pharmacology of remdesivir

Remdesivir (previously GS-5734; chemical formula C 27 H 35 N 6 O 8 P) is a monophosphoramidate prodrug of a C-adenosine nucleoside analogue ( Figure 1 ). 19 – 21 Remdesivir terminates viral RNA synthesis by inhibiting viral RNA-dependent RNA polymerase (RdRp). The active form, remdesivir triphosphate, competes with native adenosine triphosphate for chain inclusion, resulting in delayed chain termination. 22 Remdesivir displays linear pharmacokinetics and a prolonged intracellular half-life (>35 hours for the active parent triphosphate). Remdesivir triphosphate was found to accumulate in peripheral blood mononuclear cells, suggesting a loading dose that could accelerate the achievement of a steady state. 23 These characteristics support the dosing regimen used in clinical studies to date: 200 mg intravenously on the first day, followed by 100 mg intravenously once daily (5–10 days total). Detailed information regarding remdesivir metabolism and elimination is unavailable. 23

An external file that holds a picture, illustration, etc.
Object name is dic-2020-4-14-g001.jpg

Chemical structure of remdesivir. 21

Source: US National Library of Medicine.

Antiviral activity

Remdesivir exhibits broad in vitro antiviral action against zoonotic and human pathogens from multiple virus families ( Table 1 ). Remdesivir’s activity has been consistent when tested against members of the Filoviridae, Paramyxoviridae, Pneumoviridae, and Coronaviridae . 6 Among HCoV, remdesivir inhibits three of the endemic strains associated with respiratory illness (HCoV-OC43, 229E, and NL63) as well as the less common MERS-CoV, SARS-CoV, and novel SARS-CoV-2. 7 – 9 , 24 In addition, remdesivir possesses activity against SARS-like and MERS-like bat coronaviruses (HKU3, WIV1, SHC014, and HKU5). 7 Although most preclinical research has been in vitro , remdesivir was also effective in non-human primate (NHP) models of MERS, Nipah virus infection, and EVD. 5 , 25 , 26

Broad in vitro activity of remdesivir against human viral pathogens.

EC50: Half maximal effective concentration, HCoV, human coronavirus; MERS-CoV, Middle East respiratory syndrome coronavirus; SARS-CoV, severe acute respiratory syndrome coronavirus.

Remdesivir is less potent against the Flaviviridae, with moderate activity against Hepatitis C, Dengue, and Yellow Fever viruses. 6 Remdesivir has poor-to-negligible activity against tick-borne flaviviruses (Alkhurma hemorrhagic fever, Kyasanur forest disease, Omsk hemorrhagic fever, tick-borne encephalitis) and West Nile, Lassa, vesicular stomatitis, Rift Valley fever, and Crimean–Congo hemorrhagic fever viruses. 6

Remdesivir for Ebola

Preclinical data.

Remdesivir was first identified during a broad screening for compounds with activity against emerging viruses. 19 The original screening program was primarily geared toward identifying candidates that could inhibit RNA viruses, namely Coronaviridae and Flaviviridae. Subsequent to the 2013–2016 EVD outbreak in West Africa, some previously screened compounds were further investigated against EBOV. Remdesivir was observed to have high potency against EBOV across multiple cell lines, with an anti-EBOV half maximal effective concentration (EC50) of 0.086 μM in human macrophages. Remdesivir was chosen for continued clinical development based upon its potency and a chemical structure amenable to rapid scale-up. 19 The first in vivo efficacy evaluation was completed in an non-human primate (NHP) model of EVD. 5 In the NHP EVD model, previously healthy rhesus monkeys received an intramuscular inoculation of EBOV, which results in death after a clinical course mimicking human EVD. NHP was challenged with EBOV followed by receipt of various remdesivir dosing regimens. The time from inoculation to remdesivir initiation varied between study groups (as soon as 30 minutes after viral challenge and up to 3 days after viral challenge). Lower doses (3 mg/kg daily) demonstrated a measurable antiviral effect with survival rates between 33 and 66%. However, higher doses were most promising, with 6/6 NHP surviving after receiving remdesivir 10 mg/kg daily starting on day 3. This was the first report of a molecule providing post-exposure protection from EVD and supported the further evaluation of remdesivir in human EVD.

Clinical efficacy

A limited number of case reports described the use of remdesivir for EVD through emergency compassionate use protocols prior to the completion of formal clinical trials. 27 , 28 The first case described the use of remdesivir for EBOV meningoencephalitis in a 39-year-old woman who had fully recovered from an episode of EVD 9 months earlier. The second case involved an infant diagnosed with EVD on her first day of life following birth from an EBOV-positive mother. 28 Although both patients in these reports survived, it is difficult to make conclusions regarding the role remdesivir played in their recovery as multiple therapies were administered.

A randomized multi-intervention trial was later conducted during the EVD outbreak in the DRC. 18 Patients of any age, including pregnant women, were eligible for enrollment if they tested positive for EBOV. Patients received standard supportive care along with an assignment to one of four treatment arms in a 1:1:1:1 ratio. Study treatments included ZMapp (a triple monoclonal antibody), MAb114 (a single human monoclonal antibody derived from an Ebola survivor), REGN-EB3 (a mixture of three human immunoglobulin G1 [IgG1] monoclonal antibodies), and intravenous remdesivir. Remdesivir was administered at a dose of 200 mg on day 1, followed by 100 mg daily for 9–13 days. Weight-based doses were used for pediatric patients. The primary outcome was mortality at day 28. Nearly 700 patients had been randomized when an interim analysis led to early cessation of the trial. The data and safety monitoring board found higher mortality in the ZMapp and remdesivir groups compared to the MAb114 and REGN-EB3 groups. Further, the REGN-EB3 group had met a prespecified threshold for efficacy. A total of 673 patients were included in the final analysis. The mean age of enrolled patients was 29 years and 56% of patients were women (6% of whom were pregnant). At day 28, mortality rates were: remdesivir (53.1%), ZMapp (49.7%), MAb114 (35.1%), and REGN-EB3 (33.5%). For remdesivir, 85 and 29% of patients with high- and low-viral loads at baseline died, respectively.

In summary, despite potent in vitro activity against EBOV and unprecedented success in animal models of EVD, the journey of remdesivir for human EVD culminated in disappointing results.

Remdesivir for COVID-19

Remdesivir was known to inhibit the replication of coronaviruses prior to the emergence of SARS-CoV-2. Wang and colleagues published the first report affirming that remdesivir, among other existing antivirals, could effectively inhibit SARS-CoV-2 replication. 29 The investigators evaluated the activity of seven drugs against SARS-CoV-2 in the non-human Vero E6 cells: ribavirin, penciclovir, nitazoxanide, nafamostat, chloroquine, favipiravir, and remdesivir. The EC50 was lowest for remdesivir (0.77 μM), followed by chloroquine (1.13 μM). A simulated molecular docking experiment also predicted remdesivir would bind to SARS-CoV-2 RdRp with high affinity. 30 A number of factors have led to the public and medical interest in remdesivir for the treatment of SARS-CoV-2 in recent times. First, in vitro activity against SARS-CoV-2 has been confirmed. Second, remdesivir has an established dosing and safety profile. Finally, effective treatments for COVID-19 are desperately needed.

As the COVID-19 pandemic spread, Gilead Sciences, Inc. facilitated emergency access to remdesivir through a compassionate use program for patients with severe disease and no access to a clinical trial. Individual requests for compassionate use have since been halted in favor of a newly expanded access program (exception: compassionate use requests for pregnant women and children <18 years old are still accepted). 31 The initial clinical efficacy data for remdesivir in COVID-19 have centered on the case reports wherein patients received remdesivir through the compassionate use process. All cases described received remdesivir 200 mg intravenously on day 1, followed by 100 mg for up to 9 more days.

The first patient diagnosed with COVID-19 in the United States was treated with remdesivir. 32 The patient was a 35-year-old man with a limited past medical history and recent travel to Wuhan, China. He was admitted to a hospital for airborne isolation and monitoring. Remdesivir was initiated on hospital day 7 due to increasing oxygen requirements and ongoing pyrexia. The patient improved the following day, and was mostly asymptomatic at the time the report was published. A more recent report describes the use of remdesivir in a 40-year-old man who was hospitalized with severe COVID-19 requiring mechanical ventilation. 33 Remdesivir was not started until day 13 of illness. The patient was extubated 72 hours later, and a full recovery was expected at the time of publication. The authors hypothesize that remdesivir may retain a therapeutic effect even when started late in a disease course. A non-peer reviewed manuscript is available that describes the outcomes of the first 12 patients in the United States with COVID-19. 34 Three patients received remdesivir and all 12 patients clinically recovered. Retrospective cohort studies have been published detailing COVID-19 outcomes in patients requiring extracorporeal membrane oxygenation (ECMO) and those with a history of solid organ transplant. 35 , 36 In the ECMO cohort, 3/5 survivors received remdesivir and 1/10 non-survivors received remdesivir. In the transplant cohort, only 2/90 patients received remdesivir and their specific outcomes were not reported.

Grein and colleagues recently reported their experience with the compassionate use of remdesivir for COVID-19 in a multicenter open label cohort that enrolled 61 patients (of note, this analysis included previously reported cases). 37 Compassionate use approvals were reserved for hospitalized patients with an oxygen saturation of ≤94% on room air or the need for oxygen support. Patients were required to have a creatinine clearance (CrCl) greater than 30 mL/min and hepatic transaminases less than five times the upper limit of normal. There were no predefined endpoints or enrollment goals. A total of 53 patients were included in the final analysis (8 patients were excluded due to missing or erroneous data). The median age was 64 years and 64% of patients were receiving invasive ventilation at baseline (including 7% receiving ECMO). The median time from symptom onset to remdesivir initiation was 12 days. After starting remdesivir, 36 of 53 patients (68%) showed improvement based on their level of oxygen support. Of those receiving invasive mechanical ventilation, 17/30 (57%) were extubated. Three out of four patients (75%) receiving ECMO were able to stop ECMO. Seven (13%) patients died. The risk of death was increased in patients who were ≥70 years of age, those with higher serum creatinine, and those requiring invasive ventilation. The authors suggest the 13% mortality rate is noteworthy given previously reported mortality rates of 17–78% in severe COVID-19. Unfortunately, conclusions regarding the clinical effect of remdesivir are hampered by the lack of a control group and delay in initiation of therapy. Additionally, the direct antiviral effect of remdesivir was not assessed with viral load measurements. The sample size was small, and a substantial proportion of patients given remdesivir were eventually excluded from analysis (8/61, 13%).

Finally, 4 months into the disease, the data from randomized trials are beginning to emerge. One of the first randomized, placebo-controlled, double-blind study in severe COVID-19 was released at the time of manuscript preparation, ( {"type":"clinical-trial","attrs":{"text":"NCT04257656","term_id":"NCT04257656"}} NCT04257656 , Table 2 ). 38 Wang and colleagues randomized hospitalized patients with severe COVID-19 in a 2:1 allocation to remdesivir (n=158) to matching placebo (n=78). 38 Remdesivir was given in the dose of 200 mg on day 1 followed by 100 mg daily on days 2–10. The primary endpoint was time to clinical improvement, defined as a two-point reduction in disease severity on a six-point ordinal scale. The baseline characteristics though largely balanced had higher proportion of patients with medical comorbidities and presenting later than 10 days with higher respiratory rate. At baseline, most patients required supplemental oxygen, but not mechanical ventilation. In the efficacy analysis, time to clinical improvement was similar between groups (median 21 days in the remdesivir group versus 23 days with placebo; hazard ratio [HR]: 1.23 [95% confidence interval (CI): 0.87–1.75]). Mortality at 28 days was also similar between groups (22 [14%] died in the remdesivir group versus 10 [13%] with placebo). SARS-CoV-2 RNA loads were not reduced with remdesivir compared to placebo. The trial was halted before target enrollment was reached as the COVID-19 outbreak subsided in the study region. As such, the statistical power was reduced from a planned 80 to 58%, and the study remained inconclusive.

Ongoing randomized trials for remdesivir registered on ClinicalTrials.gov .

COVID-19, coronavirus disease 2019; CrCl, creatinine clearance; eGFR, estimated glomerular filtration rate.

While the results of the study from China are inconclusive, the preliminary results of the first randomized controlled study from the USA conducted under the auspices of the National Institute of Allergy and Infectious Disease, Adaptive COVID-19 Treatment Trial have also been released ( {"type":"clinical-trial","attrs":{"text":"NCT04280705","term_id":"NCT04280705"}} NCT04280705 , Table 2 ) on the same day through a press release. 39 Although full data release is awaited, the preliminary analysis of over 1063 enrollments showed that the median time to recovery was shorter in those who treated with remdesivir compared to those treated with placebo (11 days versus 15 days, p <0.001). The results also showed a trend toward survival benefit with remdesivir (mortality of 8% in remdesivir arm versus 11.6% in placebo, p =0.059). In absence of details, it is also uncertain as to what proportion of the population received treatment with additional therapeutic agents for COVID-19. Finally, in another press release, Gilead Sciences Inc. summarized results of an open-label study comparing the treatment regimen of 5 versus 10 days of remdesivir for severe COVID-19 ( {"type":"clinical-trial","attrs":{"text":"NCT04292899","term_id":"NCT04292899"}} NCT04292899 , Table 2 ). 40 Clinical improvement was similar with either regimen; however, lack of placebo arm and limitation of the study details prohibit meaningful conclusions.

Together, these reports suggest a promising role for remdesivir for COVID-19, though its effects on hard outcomes, including mortality, are still pending. Release of the full reports of these recently reported randomized studies and of the ongoing studies referenced in Table 2 will be needed to judge the true efficacy and safety of remdesivir for COVID-19.

Safety profile

Remdesivir has a low affinity for human RNA Polymerase II and human mitochondrial RNA polymerase, which is expected to contribute to a favorable safety profile in humans. 22 Safety was initially evaluated in phase one of the dose-ranging studies. 23 Single doses from 3 to 225 mg were well tolerated with no observed toxicities. Multiple administrations of remdesivir 150 mg for 7 or 14 days led to reversible grade 1 and 2 alanine aminotransferase (ALT) and aspartate transaminase (AST) elevations. Remdesivir is not considered to have reproductive or developmental toxicity. Remdesivir injection is formulated with sulfobutylether-β-cyclodextrin (SBECD). 41 Other drug products formulated with SBEDC, such as intravenous voriconazole, carry warnings for SBECD accumulation in patients with renal dysfunction. 41 However, the clinical significance of vehicle accumulation is unclear. 42 Patients with CrCl < 30 mL/min have been excluded from remdesivir compassionate use and expanded access protocols thus far. 31 Some ongoing clinical trials ( Table 2 ) are excluding patients with CrCl ≤ 50 mL/min.

In the open-label COVID-19 compassionate use cohort, 37 32/53 (60%) patients reported adverse events, while 4/53 (8%) experienced adverse events leading to discontinuation. The most common adverse events were increased hepatic enzymes, diarrhea, rash, and renal impairment. This constellation of events is difficult to interpret as there is a significant overlap with clinical attributes of severe COVID-19. No new safety concerns were noted in the published COVID-19 randomized trial. Adverse events leading to drug discontinuation occurred in 18 (12%) remdesivir patients and 4 (5%) placebo patients. 38 Reported adverse events were uncommon in the landmark EVD trial. The full toxicity profile will be further elucidated as results emerge from additional placebo-controlled trials in COVID-19.

Looking forward

There are currently seven randomized trials involving remdesivir registered on ClinicalTrials.gov ( Table 2 ). Two of these trials, both conducted in China ( {"type":"clinical-trial","attrs":{"text":"NCT04257656","term_id":"NCT04257656"}} NCT04257656 and {"type":"clinical-trial","attrs":{"text":"NCT04252664","term_id":"NCT04252664"}} NCT04252664 ), were recently terminated or suspended. The information posted to ClinicalTrials.gov indicates difficulty enrolling subjects as the COVID-19 pandemic has come under control in the region. Of the two halted studies, results have only been released for {"type":"clinical-trial","attrs":{"text":"NCT04257656","term_id":"NCT04257656"}} NCT04257656 , as described earlier. 38 The remaining active trials include comparisons with placebo, active comparators (e.g., hydroxychloroquine and lopinavir/ritonavir), short (5 days) versus long (10 days) remdesivir regimens, and patients with moderate-to-severe COVID-19.

Infectious disease outbreaks have shaped the course of human history, and with every new outbreak come new challenges. Today, scientists and clinicians around the globe are fighting to halt the COVID-19 pandemic. A chief concern remains: there are no antiviral treatments proven to be effective in fully published, peer-reviewed, randomized placebo-controlled trials. Remdesivir has emerged as a promising candidate based on its in vitro activity against SARS-CoV-2, uncontrolled clinical reports, and limited data from randomized trials. However, expectations should be tempered based on lessons from the past. Remdesivir has potent in vitro activity against EBOV, and was highly efficacious in an animal model of EVD. Unfortunately, early hopes for a new paradigm in EVD management were deflated with the completion of the first randomized trial. Remdesivir holds promise for COVID-19, but the first published randomized trial was underpowered and inconclusive. High-quality data are still lacking at this time. Thus, clinicians across the world now eagerly await complete results from additional randomized trials in COVID-19. Will remdesivir deliver?

Acknowledgements

The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government.

Contributions: All authors contributed equally to the preparation of this review. Joe Pardo and Asmita Gupte were involved in the organization, review and critique of the manuscript. Ashutosh Shukla was involved in the conception, execution, review and critique of the manuscript. Gajapathiraju Chamarthi was involved in the review and critique of the manuscript. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Disclosure and potential conflicts of interest: The authors declare that they have no conflicts of interest. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2020/05/dic.2020-4-14-COI.pdf

Funding declaration: Ashutosh M Shukla reports ongoing grant support from the Department of Veterans Affairs, Clinical Science Research and Development and Health Services Research and Developments.

Correct attribution: Copyright © 2020 Pardo J, Shukla AM, Chamarthi G, Gupte A. https://doi.org/10.7573/dic.2020-4-14 . Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0.

Article URL: https://www.drugsincontext.com/the-journey-of-remdesivir:-from-ebola-to-covid-19

Provenance: submitted; externally peer reviewed.

Peer review comments to author: 30 April 2020

Drugs in Context is published by BioExcel Publishing Ltd. Registered office: Plaza Building, Lee High Road, London, England, SE13 5PT.

BioExcel Publishing Limited is registered in England Number 10038393. VAT GB 252 7720 07.

For all manuscript and submissions enquiries, contact the Editor-in-Chief [email protected]

For all permissions, rights and reprints, contact David Hughes [email protected]

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Viral, host factors or both as coronavirus disease 2019 (covid-19) biomarkers.

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Marius Trøseid, Viral, Host Factors or Both as Coronavirus Disease 2019 (COVID-19) Biomarkers, Clinical Infectious Diseases , 2024;, ciad779, https://doi.org/10.1093/cid/ciad779

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To the   Editor — From early in the coronavirus disease 2019 (COVID-19) pandemic, it became evident that the natural disease course undergoes different stages, from an initial mild viral phase to a more severe inflammatory phase and ultimately to a critical thromboinflammatory phase, often corresponding to acute respiratory distress syndrome in hospitalized patients. Most treatment guidelines have kept these disease stages in their algorithms, generally recommending early antiviral treatment for the mild to moderate disease, and immunomodulatory treatment for severe to critical disease [ 1]. However, as the virus has changed from pre-omicron to omicron variants, and the target population from immunologically naive to mostly vaccinated or recovered, these phases are less distinct [ 2].

Hence, the choice of antiviral or immunomodulatory treatment, or even the combination is often performed on clinical judgement and unfortunately without the support of validated biomarkers. As most treatment trials of hospitalized patients on antivirals such as remdesivir [ 3], or immunomodulators such as dexamethasone [ 4] or tocilizumab [ 5] have required sample sizes of several thousand to show efficacy, the number needed to treat are generally high, meaning that the risk/benefit-ratio for a particular drug for a particular patient is hard to predict. More tailored treatment algorithms based not only on clinical status but also on host and viral factors are therefore needed.

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Posted by Richard Willett - Memes and headline comments by David Icke Posted on 21 February 2024

Remdesivir was used to mass murder people and put ‘covid’ on their death certificate..

i was given remdesivir

Remdesivir- please never allow it into your body pic.twitter.com/yG40d0Kqx3 — John Olooney (@OlooneyJohn) February 20, 2024

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COMMENTS

  1. Remdesivir

    Drug Info Clinical Data Last Updated: July 21, 2023 Remdesivir is a nucleotide prodrug of an adenosine analog. It binds to the viral RNA-dependent RNA polymerase and inhibits viral replication by terminating RNA transcription prematurely. Remdesivir has demonstrated in vitro and in vivo activity against SARS-CoV-2. 1

  2. PDF Fact Sheet for Patients And Parent/Caregivers remdesivir

    Emergency Use Authorization (EUA ) Of Remdesivir For Coronavirus Disease 2019 (COVID-19) You are being given a medicine called remdesivir for the treatment of coronavirus disease 2019 (COVID-19). This ... time remdesivir was given. Signs and symptoms of infusion-related reactions may include: low blood pressure, nausea, vomiting, sweating, and ...

  3. PDF Remdesivir Fact Sheet for Patients and Caregivers

    You are being given a medicine called remdesivir for the treatment of coronavirus disease 2019 (COVID-19). This fact sheet contains information to help you understand the risks and benefits of taking remdesivir, which you have received or may receive. There is no U.S. Food and Drug Administration (FDA) approved product available to treat COVID-19.

  4. Remdesivir

    Remdesivir is approved for the treatment of coronavirus disease 2019 ( COVID-19) in adult and pediatric patients (28 days of age and older and who weigh at least 3 kg) who: Require hospitalization

  5. Remdesivir

    Infusion-related reactions have been seen during a remdesivir infusion or around the time remdesivir was given. [29] Signs and symptoms of infusion-related reactions may include: low blood pressure, nausea, vomiting, sweating, and shivering. [29] Increases in levels of liver enzymes, seen in abnormal liver blood tests. [29]

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    Today, the U.S. Food and Drug Administration issued an emergency use authorization for the investigational antiviral drug remdesivir for the treatment of suspected or laboratory-confirmed...

  10. COVID-19 drugs: Are there any that work?

    The FDA has approved an antiviral drug called remdesivir (Veklury) to treat COVID-19 in adults and children who are age 12 and older. Remdesivir may be prescribed for people who are hospitalized with COVID-19 and need supplemental oxygen or have a higher risk of serious illness. It's given through a needle in the skin (intravenously).

  11. FDA's approval of Veklury (remdesivir) for the treatment of COVID-19

    Today, FDA approved Veklury (remdesivir), the first drug approved to treat COVID-19, for use in adults and pediatric patients 12 years of age and older and weighing at least 40 kg (about 88...

  12. Why remdesivir, a highly effective COVID treatment, is a last ...

    For starters, remdesivir is a drug infusion that must be given intravenously, in a clinical setting. Compared with other outpatient options, the drug takes more space and staff to infuse, says...

  13. Remdesivir for 5 or 10 Days in Patients with Severe Covid-19

    Remdesivir is an RNA polymerase inhibitor with potent antiviral activity in vitro and efficacy in animal models of coronavirus disease 2019 (Covid-19). Methods

  14. Remdesivir shouldn't be used on hospitalized Covid-19 ...

    The antiviral remdesivir should not be used as treatment for hospitalized Covid-19 patients, the World Health Organization said Thursday, only a month after the Food and Drug Administration...

  15. What We Know About Remdesivir So Far

    Remdesivir has been in the headlines a lot recently. ... Early study results suggest that hospitalized patients who were given remdesivir may experience a faster recovery time compared to those ...

  16. Remdesivir Uses, Side Effects & Warnings

    Remdesivir is used to treat adults and children at least 28 days and older who weigh at least 7 pounds (3 kilograms) with positive results for COVID-19 who are: in a hospital; or not in a hospital and have mild-to-moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death.

  17. The journey of remdesivir: from Ebola to COVID-19

    Remdesivir (GS-5734) is an investigational broad-spectrum antiviral drug that has demonstrated activity against ribonucleic acid (RNA) viruses of several families, including Coronaviridae (such as SARS-CoV, MERS-CoV, and strains of bat coronaviruses), Paramyxoviridae (such as Nipah virus, respiratory syncytial virus, and Hendra virus), and Filov...

  18. Remdesivir (Intravenous Route) Proper Use

    Remdesivir (Intravenous Route) A nurse or other trained health professional will give you this medicine in a medical facility. It is given through a needle placed into one of your veins. It must be given slowly, so the needle will have to stay in place for at least 30 to 120 minutes. This medicine comes with a patient information leaflet.

  19. To treat Covid-19, President Trump is taking remdesivir ...

    President Trump is being given a five-day course of the antiviral drug remdesivir, one of the doctors treating him said during a briefing on Saturday. The treatment is intended to shorten...

  20. Viral, Host Factors or Both as Coronavirus Disease 2019 (COVID-19

    In different trials, viral loads have been given with different outputs, including quantitative viral loads (copies/mL), normalized viral loads (copies/cells) or cycle threshold (CT) values, and performed on different sequencing platforms. ... Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO ...

  21. A case report of QTc prolongation: Drug induced or myocarditis in

    The US Food and Drug Administration (FDA) approved the Remdesivir for the treatment of COVID-19 in hospitalized patients in October 2020. 3 It is a nucleotide prodrug of an adenosine analog. It binds to the viral RNA-dependent RNA polymerase and inhibits viral replication by terminating RNA transcription prematurely.

  22. UCSF lands $3M 'long Covid' tissue bank to find answers to virus

    Gilead Sciences Inc. (NASDAQ: GILD), the Foster City-based drug developer that developed remdesivir as the first therapy for hospitalized SARS-CoV-2 patients, continues to work in the Covid space ...

  23. Insights on Remdesivir Injection: Essential Information

    Despite the promising aspects of Remdesivir, there are considerations and challenges associated with its use. One notable consideration is the timing of administration. The drug appears to be most effective when given early in the course of the illness, emphasizing the importance of prompt diagnosis and treatment.

  24. Remdesivir was used to mass murder people and put 'Covid' on their

    Remdesivir causes multiple organ failure - especially the kidneys and so the patient fills up with fluid and this makes it impossible to breathe. 'Oh, another Covid respiratory death.' The drug was widely given after people tested positive with a test NOT testing for the fake 'virus' and mass-killer Anthony Fauci is in this up to his neck and beyond.