Remdesivir for COVID-19: real-time analysis of all 49 studies

Survival analysis based on body mass index in patients with Covid-19 admitted to the intensive care unit of Amir Al-Momenin Hospital in Arak – 2021

Zangeneh et al., Obesity Medicine, doi:10.1016/j.obmed.2022.100420

Retrospective 193 ICU patients in Iran, showing lower mortality with remdesivir treatment, not reaching statistical significance.

risk of death, 32.0% lower, HR 0.68, p = 0.06, Cox proportional hazards.

Zangeneh et al., 5/13/2022, retrospective, Iran, Middle East, peer-reviewed, 3 authors.

Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants

Delandre et al., Pharmaceuticals, doi:10.3390/ph15040445 (In Vitro)

In Vitro study with 30 COVID-19 strains from 14 variants, showing stronger efficacy with ivermectin compared to CQ and remdesivir, and relatively homogeneous efficacy with ivermectin regardless of strain/variant, in contrast to results for CQ and remdesivir.

Remdesivir showed better efficacy for omicron compared to most other variants.

Delandre et al., 4/2/2022, peer-reviewed, 12 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

Acute Kidney Injury and Drugs Prescribed for COVID-19 in Diabetes Patients: A Real-World Disproportionality Analysis

Zhou et al., Frontiers in Pharmacology, doi:10.3389/fphar.2022.833679

FAERS analysis showing significantly increased risk of acute kidney injury with remdesivir.

Zhou et al., 3/17/2022, peer-reviewed, 6 authors.

COVID-19 and Kidney Transplantation: The impact of remdesivir on renal function and outcome - a retrospective cohort study

Elec et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2022.03.015

Retrospective 165 hospitalized COVID-19+ kidney transplant patients, 38 treated with remdesivir, showing no significant difference in mortality, higher ICU admission, and lower ICU mortality. Subject to confounding by time with significant changes to SOC and treatment propensity during the study period.

risk of death, 19.3% lower, RR 0.81, p = 0.66, treatment 7 of 38 (18.4%), control 29 of 127 (22.8%), NNT 23.

risk of mechanical ventilation, 10.9% lower, RR 0.89, p = 0.73, treatment 8 of 38 (21.1%), control 30 of 127 (23.6%), NNT 39.

risk of ICU admission, 71.9% higher, RR 1.72, p = 0.01, treatment 18 of 38 (47.4%), control 35 of 127 (27.6%).

Excluded in after exclusion results of meta analysis: substantial confounding by time possible due to significant changes in SOC and treatment propensity during the study period.

Elec et al., 3/14/2022, retrospective, Romania, Europe, peer-reviewed, 9 authors, study period 1 March, 2020 - 31 May, 2021.

Risk factors of death in mechanically ventilated COVID-19 patients: a retrospective multi-center study

Salehi et al., Research Square, doi:10.21203/rs.3.rs-1362678/v1 (Preprint)

Retrospective 125 mechanically ventilated ICU patients in Iran, showing lower mortality with remdesivir treatment in unadjusted results.

risk of death, 36.6% lower, RR 0.63, p = 0.01, treatment 17 of 40 (42.5%), control 57 of 85 (67.1%), NNT 4.1.

Excluded in after exclusion results of meta analysis: unadjusted results with no group details.

Salehi et al., 3/11/2022, retrospective, Iran, Middle East, preprint, mean age 62.0, 11 authors, study period April 2021 - September 2021.

Efficacy of Various Treatment Modalities on Patient-related Outcome in Hospitalized COVID-19 Patients – A Retrospective Study

Siraj et al., Indian Journal of Clinical Practice, 32:9

Retrospective 1,000 COVID+ hospitalized patients in India, showing lower mortality with famotidine and remdesivir in multivariable logistic regression.

risk of death, 52.9% lower, RR 0.47, p < 0.001, treatment 108 of 413 (26.2%), control 197 of 587 (33.6%), adjusted, OR converted to RR, multivariable.

Siraj et al., 2/28/2022, retrospective, India, South Asia, peer-reviewed, median age 56.0, 13 authors, study period March 2020 - December 2020.

Factors Associated with Death and ICU Referral among COVID-19 Patients Hospitalized in the Secondary Referral Academic Hospital in East Jakarta, Indonesia

Kurniyanto et al., Journal of Clinical Virology Plus, doi:10.1016/j.jcvp.2022.100068

Retrospective 477 hospitalized patients in Indonesia, showing higher mortality with remdesivir in unadjusted results.

risk of death, 460.0% higher, RR 5.60, p < 0.001, treatment 7 of 45 (15.6%), control 12 of 432 (2.8%).

Excluded in after exclusion results of meta analysis: unadjusted results with no group details, substantial unadjusted confounding by indication likely.

Kurniyanto et al., 2/28/2022, retrospective, Indonesia, South Asia, peer-reviewed, 11 authors.

Inhaled remdesivir reduces viral burden in a nonhuman primate model of SARS-CoV-2 infection

Vermillion et al., Science Translational Medicine, doi:10.1126/scitranslmed.abl8282

African green monkey study of inhaled versus IV remdesivir, showing similar efficacy with inhalation. Comparable concentrations of the active triphosphate in the lower respiratory tract were found with ~20x lower dose using inhalation, and there was lower systemic exposure to remdesivir and metabolites.

Vermillion et al., 12/30/2021, peer-reviewed, 26 authors.

Pattern of medication utilization in hospitalized patients with COVID-19 in three District Headquarters Hospitals in the Punjab province of Pakistan

Mustafa et al., Exploratory Research in Clinical and Social Pharmacy, doi:10.1016/j.rcsop.2021.100101

Retrospective 444 hospitalized patients in Pakistan, showing lower mortality with remdesivir treatment in unadjusted results, not reaching statistical significance.

risk of death, 32.7% lower, RR 0.67, p = 0.21, treatment 16 of 200 (8.0%), control 29 of 244 (11.9%), NNT 26.

Excluded in after exclusion results of meta analysis: unadjusted results with no group details.

Mustafa et al., 12/29/2021, retrospective, Pakistan, South Asia, peer-reviewed, 7 authors.

Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients

Gottlieb et al., New England Journal of Medicine, doi:10.1056/NEJMoa2116846

RCT high-risk outpatients, 279 treated with remdesivir and 283 control patients, median 5 days from symptoms, showing significantly lower hospitalization with treatment. NCT04501952.

risk of death/hospitalization, 87.0% lower, RR 0.13, p = 0.008, treatment 2 of 279 (0.7%), control 15 of 283 (5.3%), NNT 22, adjusted, COVID-19 related hospitalization or death from any cause @day 28, primary outcome.

risk of no recovery, 29.1% lower, RR 0.71, p = 0.31, treatment 43 of 66 (65.2%), control 45 of 60 (75.0%), adjusted, alleviation of symptoms @day 14.

risk of no recovery, 47.9% lower, RR 0.52, p = 0.003, treatment 108 of 169 (63.9%), control 132 of 165 (80.0%), NNT 6.2, adjusted, post-hoc alleviation of symptoms @day 14.

Gottlieb et al., 12/22/2021, Double Blind Randomized Controlled Trial, multiple countries, multiple regions, peer-reviewed, 30 authors, study period 18 September, 2020 - 8 April, 2021, average treatment delay 5.0 days, trial NCT04501952.

Determinants of Outcome Among Critically Ill Police Personnel With COVID-19: A Retrospective Observational Study From Andhra Pradesh, India

Jamir et al., Cureus, doi:10.7759/cureus.20394

Retrospective 266 COVID-19 ICU patients in India, showing significantly lower mortality with PVP-I oral gargling and topical nasal use, and non-statistically significant higher mortality with ivermectin and lower mortality with remdesivir.

risk of death, 8.0% lower, RR 0.92, p = 0.77, treatment 60 of 181 (33.1%), control 41 of 85 (48.2%), NNT 6.6, adjusted, multivariable Cox regression.

Jamir et al., 12/13/2021, retrospective, India, South Asia, peer-reviewed, 6 authors, study period June 2020 - October 2020.

Association Between Androgen Deprivation Therapy and Mortality Among Patients With Prostate Cancer and COVID-19

Schmidt et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2021.34330

Retrospective 1,106 prostate cancer patients, showing higher mortality with remdesivir treatment.

risk of severe case, 509.0% higher, OR 6.09, p < 0.001, treatment 43, control 434, adjusted, propensity score matching, multivariable, RR approximated with OR, excluded in exclusion analyses: confounding by indication is likely and adjustments do not consider COVID-19 severity at baseline.

Schmidt et al., 11/12/2021, retrospective, USA, North America, peer-reviewed, 42 authors, study period 17 March, 2020 - 11 February, 2021.

Remdesivir treatment in hospitalized patients with COVID-19: a comparative analysis of in-hospital all-cause mortality in a large multi-center observational cohort

Mozaffari et al., Clinical Infectious Diseases, doi:10.1093/cid/ciab875

Retrospective 28,855 remdesivir patients with PSM matched controls, showing lower mortality with treatment.

risk of death, 12.0% lower, HR 0.88, p = 0.003, treatment 4,441 of 28,855 (15.4%), control 5,499 of 28,855 (19.1%), NNT 27, adjusted, 28 days, PSM, Cox proportional hazards.

risk of death, 24.0% lower, HR 0.76, p < 0.001, treatment 3,057 of 28,855 (10.6%), control 4,437 of 28,855 (15.4%), NNT 21, adjusted, 14 days, PSM, Cox proportional hazards.

Mozaffari et al., 10/1/2021, retrospective, USA, North America, peer-reviewed, 12 authors.

Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial

Ader et al., Lancet Infectious Diseases, doi:10.1016/S1473-3099(21)00485-0

RCT 857 hospitalized patients, showing no significant differences with remdesivir treatment. DISCOVERY trial. EudraCT2020-000936-23, NCT04315948.

risk of death, 6.4% lower, RR 0.94, p = 0.77, treatment 34 of 414 (8.2%), control 37 of 418 (8.9%), NNT 156, adjusted, OR converted to RR, 28 days.

risk of 7-point scale, 9.9% lower, OR 0.90, p = 0.39, treatment 414, control 418, 28 days, RR approximated with OR.

risk of 7-point scale, 2.0% higher, OR 1.02, p = 0.85, treatment 414, control 418, 15 days, RR approximated with OR.

Ader et al., 9/14/2021, Randomized Controlled Trial, multiple countries, multiple regions, peer-reviewed, 17 authors, average treatment delay 9.0 days, trial NCT04315948.

Remdesivir and Mortality in Patients with COVID-19

Diaz et al., Clinical Infectious Diseases, doi:10.1093/cid/ciab698

Retrospective 1138 hospitalized patients in the USA, 286 treated with remdesivir, showing lower mortality with treatment.

risk of death, 34.7% lower, RR 0.65, p = 0.01, treatment 33 of 286 (11.5%), control 173 of 852 (20.3%), NNT 11, adjusted, OR converted to RR, multivariable Cox proportional-hazards.

Diaz et al., 8/19/2021, retrospective, USA, North America, peer-reviewed, 45 authors.

Comparative study between the therapeutic effect of remdesivir versus hydroxychloroquine in COVID-19 hospitalized patients

Eldeen et al., Microbes and Infectious Diseases, doi:10.21608/mid.2021.85877.1177

Small study comparing 25 HCQ and 25 remdesivir hospitalized patients, reporting faster viral clearance with remdesivir. The article proof is missing the results for the HCQ group. Confounding by time is likely - remdesivir patients were after HCQ patients in time, and treatment protocols improved over the period of the study.

Eldeen et al., 8/16/2021, peer-reviewed, 5 authors.

Another step toward final call on Remdesivir efficacy as a treatment for hospitalized COVID-19 patients: a multicenter open-label trial

Hosseini et al., medRxiv, doi:10.1101/2021.08.13.21261992 (Preprint)

Single arm remdesivir trial with 145 hospitalized patients showing no statistically significant difference between "early" and "late" administration, however the treatment delays may be better described as late and very late. The text of the paper defines early and late as less than or more than 7 days from symptom onset, however the CONSORT diagram says during or after 7 days post admission.

Hosseini et al., 8/13/2021, preprint, 15 authors.

The association of remdesivir and in-hospital outcomes for COVID-19 patients treated with steroids

Kuno et al., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkab256

PSM retrospective 3,372 hospitalized patients in the USA treated with steroids, showing no significant difference in mortality with remdesivir, but a lower risk of acute kidney injury.

risk of death, 0.9% lower, RR 0.99, p = 0.96, treatment 214 of 999 (21.4%), control 216 of 999 (21.6%), NNT 499, PSM.

risk of mechanical ventilation, no change, RR 1.00, p = 1.00, treatment 140 of 999 (14.0%), control 140 of 999 (14.0%), PSM.

risk of ICU admission, 17.1% higher, RR 1.17, p = 0.05, treatment 260 of 999 (26.0%), control 222 of 999 (22.2%), PSM.

Kuno et al., 8/9/2021, retrospective, propensity score matching, USA, North America, peer-reviewed, 6 authors.

Remdesivir for the treatment of COVID‐19

Anseems et al., Cochrane Database of Systematic Reviews, doi:10.1002/14651858.CD014962 (Preprint) (meta analysis)

Review of 5 RCTs prior to April 17, 2021 showing mortality RR 0.93 [0.81-1.06] for hospitalized patients.

Anseems et al., 8/5/2021, preprint, 10 authors.

Remdesivir for the treatment of COVID-19 disease: A retrospective comparative study of patients treated with and without Remdesivir

Madan et al., medRxiv, doi:10.1101/2021.07.15.21260600 (Preprint)

Retrospective 1,262 hospitalized patients, 398 treated with remdesivir, showing unadjusted lower mortality with treatment, and a treatment delay-response relationship.

risk of death, 44.4% lower, RR 0.56, p = 0.03, treatment 23 of 398 (5.8%), control 27 of 260 (10.4%), NNT 22, unadjusted.

risk of death, 65.6% lower, RR 0.34, p = 0.04, treatment 4 of 112 (3.6%), control 27 of 260 (10.4%), NNT 15, unadjusted, <5 days from onset.

risk of death, 61.7% lower, RR 0.38, p = 0.009, treatment 9 of 226 (4.0%), control 27 of 260 (10.4%), NNT 16, unadjusted, 5-10 days from onset.

risk of death, 60.5% higher, RR 1.60, p = 0.18, treatment 10 of 60 (16.7%), control 27 of 260 (10.4%), unadjusted, >10 days from onset.

Excluded in after exclusion results of meta analysis: excessive unadjusted differences between groups.

Madan et al., 7/19/2021, retrospective, India, South Asia, preprint, 22 authors.

Association of Remdesivir Treatment With Survival and Length of Hospital Stay Among US Veterans Hospitalized With COVID-19

Ohl et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2021.14741

Retrospective 5,898 hospitalized patients in the USA, 2,374 receiving remdesivir treatment, showing no significant difference in mortality, and a longer time to hospital discharge with treatment.

risk of death, 6.0% higher, HR 1.06, p = 0.66, treatment 143 of 1,172 (12.2%), control 124 of 1,172 (10.6%), adjusted, PSM, Cox proportional hazards regression.

hospitalization time, 100% higher, relative time 2.00, p < 0.001, treatment 1,172, control 1,172, PSM, Cox proportional hazards regression.

Ohl et al., 7/15/2021, retrospective, propensity score matching, USA, North America, peer-reviewed, 9 authors.

Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19

Barrat-Due et al., Annals of Internal Medicine, doi:10.7326/M21-0653

Small RCT in Norway with 52 HCQ and 42 remdesivir patients, showing no significant differences with treatment. Add-on trial to WHO Solidarity. NCT04321616.

risk of death, no change, RR 1.00, p = 1.00, treatment 3 of 37 (8.1%), control 4 of 53 (7.5%), adjusted.

Barrat-Due et al., 7/13/2021, Double Blind Randomized Controlled Trial, Norway, Europe, peer-reviewed, 41 authors, average treatment delay 8.0 days, trial NCT04321616.

Evaluation of the effectiveness of remdesivir in treating severe COVID-19 using data from the ISARIC WHO Clinical Characterisation Protocol UK: a prospective, national cohort study

Arch et al., medRxiv, doi:10.1101/2021.06.18.21259072 (Preprint)

Prospective PSM analysis of remdesivir use in the UK showing statistically significantly lower mortality at 28 days. For unspecified reasons, the study prioritized short-term outcomes. Mortality at 14 days was also lower but not statistically significant. Confounding by indication is likely and may only be partially addressed by the variables included in the PSM.

risk of death, 19.9% lower, RR 0.80, p = 0.03, treatment 203 of 1,491 (13.6%), control 777 of 4,676 (16.6%), NNT 33, OR converted to RR, 28 days, PSM.

risk of death, 18.0% lower, RR 0.82, p = 0.12, treatment 140 of 1,502 (9.3%), control 565 of 4,728 (12.0%), NNT 38, OR converted to RR, 28 days, PSM.

risk of mechanical ventilation, 68.0% higher, RR 1.68, p = 0.003, treatment 106 of 1,498 (7.1%), control 153 of 4,602 (3.3%), OR converted to RR, 28 days, PSM.

Arch et al., 6/21/2021, prospective, propensity score matching, United Kingdom, Europe, preprint, 10 authors, average treatment delay 6.0 days.

Case Characteristics, Clinical Data, And Outcomes of Hospitalized COVID-19 Patients In Qom Province, Iran: A Prospective Cohort Study

Pourhoseingholi et al., Research Square, doi:10.21203/rs.3.rs-365321/v2 (Preprint)

Prospective study of 2,468 hospitalized COVID-19 patients in Iran, showing no significant difference with remdesivir treatment. IR.MUQ.REC.1399.013.

risk of death, 2.0% higher, HR 1.02, p = 0.92, treatment 42 of 123 (34.1%), control 297 of 2,345 (12.7%), adjusted, multivariable, Cox proportional hazards.

Pourhoseingholi et al., 5/26/2021, prospective, Iran, Middle East, preprint, mean age 57.9, 11 authors, study period 2 February, 2020 - 20 July, 2020, average treatment delay 7.4 days.

Assessing Efficacy of Antiviral Therapy for COVID-19 Patients: A Case Study on Remdesivir with Bayesian Synthesis Design and Multistate Analysis

Liao et al., Journal of the Formosan Medical Association, doi:10.1016/j.jfma.2021.04.026 (meta analysis)

Bayesian synthesis design and multistate analysis of remdesivir results showing 31% [18-44%] lower risk of death and 10% [1-18%] higher recovery.

Liao et al., 5/4/2021, peer-reviewed, 7 authors.

Epidemiology, outcomes, and utilization of intensive care unit resources for critically ill COVID-19 patients in Libya: A prospective multi-center cohort study

Elhadi et al., PLOS ONE, doi:10.1371/journal.pone.0251085

Prospective study of 465 COVID-19 ICU patients in Libya showing no significant differences with treatment.

risk of death, 10.9% higher, RR 1.11, p = 0.65, treatment 14 of 21 (66.7%), control 267 of 444 (60.1%).

Excluded in after exclusion results of meta analysis: unadjusted results with no group details.

Elhadi et al., 4/30/2021, prospective, Libya, Africa, peer-reviewed, 21 authors, study period 29 May, 2020 - 30 December, 2020.

Decreased In-Hospital Mortality Associated with Aspirin Administration in Hospitalized Patients Due to Severe COVID-19

Aghajani et al., Journal of Medical Virology, doi:10.1002/jmv.27053

Retrospective 991 hospitalized patients in Iran focusing on aspirin use but also showing results for HCQ, remdesivir, and favipiravir.

risk of death, 18.6% lower, HR 0.81, p = 0.49, treatment 46, control 945, univariate Cox proportional regression.

Aghajani et al., 4/29/2021, retrospective, Iran, Middle East, peer-reviewed, 7 authors.

3219 hospitalised patients with COVID-19 in Southeast Michigan: a retrospective case cohort study

Mulhem et al., BMJ Open, doi:10.1136/bmjopen-2020-042042

Retrospective database analysis of 3,219 hospitalized patients in the USA. Very different results in the time period analysis (Table S2), and results significantly different to other studies for the same medications (e.g., heparin OR 3.06 [2.44-3.83]) suggest significant confounding by indication and confounding by time.

risk of death, 85.7% higher, RR 1.86, p = 0.54, treatment 1 of 8 (12.5%), control 515 of 3,211 (16.0%), adjusted, OR converted to RR, logistic regression.

Excluded in after exclusion results of meta analysis: substantial unadjusted confounding by indication likely, substantial confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically.

Mulhem et al., 4/7/2021, retrospective, database analysis, USA, North America, peer-reviewed, 3 authors.

Clinical outcomes of using remdesivir in patients with moderate to severe COVID-19: A prospective randomised study

Mahajan et al., Indian Journal of Anasthesia, doi:10.4103/ija.IJA_149_21

Small RCT with 34 remdesivir patients and 36 controls finding no significant difference in clinical outcomes.

risk of death, 76.5% higher, RR 1.76, p = 0.47, treatment 5 of 34 (14.7%), control 3 of 36 (8.3%).

risk of mechanical ventilation, 111.8% higher, RR 2.12, p = 0.42, treatment 4 of 34 (11.8%), control 2 of 36 (5.6%).

Mahajan et al., 3/20/2021, Randomized Controlled Trial, India, South Asia, peer-reviewed, 3 authors, average treatment delay 6.84 days.

Efficacy of remdesivir in hospitalized nonsevere COVID-19 patients in Japan: A large observational study using the COVID-19 Registry Japan

Tsuzuki et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2022.02.039 (preprint 3/10/2021)

Retrospective database analysis of 12,487 hospitalized patients in Japan, showing lower risk of oxygen requirement, but no significant difference in mortality or ventilation/ECMO.

risk of death, 4.0% higher, HR 1.04, p = 0.21, treatment 69 of 824 (8.4%), control 285 of 11,663 (2.4%), adjusted, day 30.

risk of mechanical ventilation or ECMO, 1.7% lower, HR 0.98, p = 0.68, treatment 48 of 824 (5.8%), control 98 of 11,663 (0.8%), adjusted.

risk of progression, 15.0% lower, HR 0.85, p = 0.68, treatment 559 of 824 (67.8%), control 1,784 of 11,663 (15.3%), adjusted.

Tsuzuki et al., 3/10/2021, retrospective, Japan, Asia, peer-reviewed, 21 authors, average treatment delay 6.0 days.

A real-life setting evaluation of the effect of remdesivir on viral load in COVID-19 patients admitted to a large tertiary center in Israel

Goldberg et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2021.02.029

Retrospective 29 remdesivir patients and 113 controls, not finding a significant difference in nasopharyngeal viral load or hospitalization time. Hospitalization time was lower with treatment, with a larger reduction for non-intubated patients, although not statistically significant in both cases.

hospitalization time, 9.2% lower, relative time 0.91, p = 0.77, treatment 29, control 113.

hospitalization time, 21.8% lower, relative time 0.78, p = 0.30, non-intubated patients only.

risk of no viral clearance, 0.1% lower, RR 1.00, p = 0.98, treatment 29, control 113, relative change in Ct values.

Goldberg et al., 3/9/2021, retrospective, Israel, Middle East, peer-reviewed, 7 authors.

A single-center retrospective cohort study of Covid-19 medications: Remdesivir, Favipiravir, Methylprednisolone, Dexamethasone, and Interferon β1a and their combinations

Fateh et al., medRxiv, doi:10.1101/2021.03.05.21251351 (Preprint)

Retrospective 324 hospitalized patients in Iran reporting on the use remdesivir, favipiravir, methylprednisolone, dexamethasone, and interferon β1a and their combinations. There is no control group in this study, however authors suggest that interferon β1a, corticosteroids, and remdesivir may not have a significant effect on mortality of hospitalization time.

Fateh et al., 3/8/2021, retrospective, Iran, Middle East, preprint, 7 authors.

Famotidine Use Is Not Associated With 30-day Mortality: A Coarsened Exact Match Study in 7158 Hospitalized Patients With Coronavirus Disease 2019 From a Large Healthcare System

Yeramaneni et al., Gastroenterology, doi:10.1053/j.gastro.2020.10.011

Retrospective 7,158 hospitalized COVID-19 patients in the USA, showing no significant difference in mortality with remdesivir treatment.

risk of death, 24.0% higher, OR 1.24, p = 0.87, treatment 32, control 7,126, adjusted, multivariable, RR approximated with OR.

Yeramaneni et al., 2/28/2021, retrospective, USA, North America, peer-reviewed, 6 authors, study period 11 February, 2020 - 8 May, 2020.

Serious bradycardia and remdesivir for coronavirus 2019 (COVID-19): a new safety concerns

Touafchia et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2021.02.013

Comparison of bradycardia in COVID-19 patients treated with remdesivir compared to those treated with HCQ, lopinavir/ritonavir, tocilizumab or glucocorticoids, finding increased risk of bradycardia with remdesivir.

Touafchia et al., 2/27/2021, peer-reviewed, 6 authors.

Remdesivir potently inhibits carboxylesterase‐2 through covalent modifications: signifying strong drug‐drug interactions

Shen et al., Fundamentals of Clinical Pharmacology, doi:10.1111/fcp.12643

Analysis finding that remdesivir at nanomolar concentrations inhibits carboxylesterase‐2 (CES2) through covalent modifications. CES2 is a major drug‐metabolizing enzyme. Authors conclude that caution must be exercised when remdesivir is used along with drugs hydrolyzed by CES2.

Shen et al., 12/28/2020, peer-reviewed, 3 authors.

Remdesivir-ivermectin combination displays synergistic interaction with improved in vitro activity against SARS-CoV-2

Jeffreys et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2022.106542 (preprint 12/24/2020) (In Vitro)

In Vitro study showing enhanced antiviral activity of ivermectin and remdesivir in combination.

Jeffreys et al., 12/24/2020, peer-reviewed, 17 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

Remdesivir and Acute Renal Failure: A Potential Safety Signal From Disproportionality Analysis of the WHO Safety Database

Gérard et al., Clinical Pharmacology & Therapeutics, doi:10.1002/cpt.2145

VigiBase retrospective showing a 20x increase in the risk of acute renal failure with remdesivir.

Gérard et al., 12/19/2020, peer-reviewed, 8 authors.

Efficacy of Remdesivir in Covid-19 Patients; Multicenter Study in Lahore

Ullah et al., International Journal of Sciences, doi:10.18483/ijSci.2417

Small late stage (hospitalized, <12 days symptoms) remdesivir study showing non-statistically significant higher mortality with treatment.

No adjustments were made for differences in the groups. Remdesivir mean age was 49 vs. control 57. Baseline oxygen requirement was 13.4 liters treatment vs. 10.8 control. Potential confounding by indication.

risk of death, 100% higher, RR 2.00, p = 0.33, treatment 8 of 30 (26.7%), control 4 of 30 (13.3%).

risk of mechanical ventilation, 250.0% higher, RR 3.50, p = 0.15, treatment 7 of 30 (23.3%), control 2 of 30 (6.7%).

Ullah et al., 11/29/2020, retrospective, Pakistan, South Asia, peer-reviewed, 8 authors.

Effectiveness of remdesivir with and without dexamethasone in hospitalized patients with COVID-19

Garibaldi et al., medRxiv, doi:10.1101/2020.11.19.20234153 (Preprint)

Retrospective 303 remdesivir patients and 303 matched controls showing significantly faster clinical improvement, and lower (but not statistically significant) mortality.

risk of death, 20.0% lower, HR 0.80, p = 0.44, treatment 23 of 303 (7.6%), control 45 of 303 (14.9%), adjusted.

risk of no improvement at day 28, 35.0% better, RR 0.65, p < 0.001, treatment 52 of 303 (17.2%), control 80 of 303 (26.4%), NNT 11, adjusted.

Garibaldi et al., 11/20/2020, retrospective, USA, North America, preprint, 10 authors.

Remdesivir-based therapy improved recovery of patients with COVID-19 in the SARSTer multicentre, real-world study

Flisiak et al., medRxiv, doi:10.1101/2020.10.30.20215301 (Preprint)

Retrospective study comparing 122 remdesivir patients and 211 lopinavir/ritonavir patients, showing higher rates of clinical improvement with remdesivir and lower mortality (not statistically significant).

all patients, 48.9% lower, RR 0.51, p = 0.18, treatment 5 of 122 (4.1%), control 17 of 211 (8.1%), NNT 25, OR converted to RR.

SpO₂<95%, 58.0% lower, RR 0.42, p = 0.13, treatment 4 of 82 (4.9%), control 14 of 119 (11.8%), NNT 15, OR converted to RR.

no clinical improvement, 56.5% lower, RR 0.44, p = 0.01, treatment 9 of 122 (7.4%), control 36 of 211 (17.1%), NNT 10, OR converted to RR.

Flisiak et al., 11/3/2020, retrospective, Poland, Europe, preprint, 23 authors.

Clinical course and outcome of COVID-19 acute respiratory distress syndrome: data from a national repository

Solh et al., medRxiv, doi:10.1101/2020.10.16.20214130 (Preprint)

Retrospective database analysis of 7,816 Veterans Affairs hospitalized patients showing 47% reduction in progression from ARDS to mortality.

risk of death, 47.0% lower, HR 0.53, p < 0.001, treatment 63 of 219 (28.8%), control 202 of 424 (47.6%), NNT 5.3, adjusted.

Excluded in after exclusion results of meta analysis: very late stage, >50% on oxygen/ventilation at baseline, substantial unadjusted confounding by indication likely.

Solh et al., 10/20/2020, retrospective, database analysis, USA, North America, preprint, 5 authors.

Repurposed antiviral drugs for COVID-19; interim WHO SOLIDARITY trial results

SOLIDARITY Trial Consortium, NEJM, doi:10.1056/NEJMoa2023184 (preprint 10/15)

WHO SOLIDARITY open-label RCT with 2,750 very late stage (76% on oxygen/ventilation) remdesivir patients, mortality relative risk RR 0.95 [0.81-1.11], p=0.50. Non-ventilated patients show a greater benefit, RR 0.86 [0.72-1.04], p = 0.13.

risk of death, 5.0% lower, RR 0.95, p = 0.53, treatment 301 of 2,743 (11.0%), control 303 of 2,708 (11.2%), NNT 464.

non-ventilated patients, 14.0% lower, RR 0.86, p = 0.13.

SOLIDARITY et al., 10/15/2020, Randomized Controlled Trial, multiple countries, multiple regions, peer-reviewed, 15 authors.

Remdesivir for the Treatment of Covid-19 — Final Report

Beigel et al., NEJM, doi:10.1056/NEJMoa2007764

RCT 1,062 hospitalized patients showing faster recovery time with treatment, median 10 days vs. 15 days for placebo, rate ratio for recovery 1.29, p<0.001. Day 29 mortality was 11.4% with remdesivir and 15.2% with placebo, hazard ratio HR 0.73 [0.52-1.03].

risk of death, 27.0% lower, HR 0.73, p = 0.07, treatment 541, control 521.

risk of no recovery, 22.5% lower, RR 0.78, p < 0.001, treatment 541, control 521.

Beigel et al., 10/8/2020, Randomized Controlled Trial, USA, North America, peer-reviewed, 12 authors, average treatment delay 9.0 days.

Patient Characteristics and Outcomes of 11,721 Patients with COVID19 Hospitalized Across the United States

Fried et al., Clinical Infectious Disease, doi:10.1093/cid/ciaa1268

Database analysis of 11,721 hospitalized patients, 48 treated with remdesivir.

Data inconsistencies have been found in this study, for example 99.4% of patients treated with HCQ were treated in urban hospitals, compared to 65% of untreated patients (Supplemental Table 3), while patients are distributed in a more balanced manner between teaching or not-teaching hospitals, as well as in the most urbanized (Northeast) and less urbanized (Midwest) regions of the United States [academic.oup.com].

1. academic.oup.com, https://academic.oup.com/cid/advan..e/doi/10.1093/cid/ciaa1618/5934822.

risk of death, 61.2% lower, RR 0.39, p = 0.02, treatment 4 of 48 (8.3%), control 2,510 of 11,673 (21.5%), NNT 7.6, remdesivir vs. non-remdesivir.

risk of mechanical ventilation, 36.8% higher, RR 1.37, p = 0.25, treatment 11 of 48 (22.9%), control 1,956 of 11,673 (16.8%), remdesivir vs. non-remdesivir.

Excluded in after exclusion results of meta analysis: excessive unadjusted differences between groups, substantial unadjusted confounding by indication likely.

Fried et al., 8/28/2020, retrospective, database analysis, USA, North America, peer-reviewed, 11 authors.

Effectiveness of remdesivir in patients with COVID-19 under mechanical ventilation in an Italian ICU

Pasquini et al., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkaa321

Retrospective 51 ICU patients under mechanical ventilation, 25 treated with remdesivir, showing lower mortality with treatment.

risk of death, 16.2% lower, RR 0.84, p = 0.03, treatment 14 of 25 (56.0%), control 24 of 26 (92.3%), NNT 2.8, adjusted, OR converted to RR, multivariate.

Pasquini et al., 8/23/2020, retrospective, Italy, Europe, peer-reviewed, 9 authors.

Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19A Randomized Clinical Trial

Spinner et al., JAMA, doi:10.1001/jama.2020.16349

Late stage (median 8 days from symptom onset) RCT 584 patients with moderate COVID-19 showing (non-statistically significant) lower mortality.

5-day remdesivir had significantly higher odds of a better clinical status distribution on the 7-point ordinal scale, odds ratio OR 1.65, p = 0.02. The difference for 10-day remdesivir was not statistically significant, p=0.18.

5 or 10 day remdesivir vs. control 28 day mortality, 34.9% lower, RR 0.65, p = 0.50, treatment 5 of 384 (1.3%), control 4 of 200 (2.0%), NNT 143.

Spinner et al., 8/21/2020, Randomized Controlled Trial, multiple countries, multiple regions, peer-reviewed, 30 authors, average treatment delay 8.0 days.

Remdesivir for Severe Coronavirus Disease 2019 (COVID-19) Versus a Cohort Receiving Standard of Care

Olender et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa1041

Comparative analysis between remdesivir trial GS-US-540–5773 and a retrospective SOC cohort with similar inclusion criteria, showing lower mortality and higher recovery at day 14 with remdesivir.

risk of death, 58.8% lower, RR 0.41, p = 0.001, treatment 24 of 312 (7.7%), control 102 of 818 (12.5%), OR converted to RR, day 14, weighted multivariable logistic regression.

Olender et al., 7/24/2020, retrospective, USA, North America, peer-reviewed, 33 authors.

Case report study of the first five COVID-19 patients treated with remdesivir in France

Dubert et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.06.093

Early report on 5 ICU patients treated with remdesivir highlighting issues with usage in critically ill patients.

Dubert et al., 6/30/2020, peer-reviewed, 15 authors.

Efficacy and Safety of Remdesivir for COVID-19 Treatment: An Analysis of Randomized, Double-Blind, Placebo-Controlled Trials

Zhu et al., medRxiv, doi:10.1101/2020.06.22.20136531 (Preprint) (meta analysis)

Meta analysis of Beigel and Wang RCTs showing remdesivir significantly decreased mortality (8.18% vs. 12.70%, RR 0.64 [0.44-0.92], p = 0.175).

risk of death, 36.0% lower, RR 0.64, p = 0.02.

Zhu et al., 6/29/2020, preprint, 11 authors.

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

Goldman et al., NEJM, doi:10.1056/NEJMoa2015301

RCT of remdesivir for 5 or 10 days with no placebo control group, showing no significant differences between 5 and 10 day treatment. NCT04292899.

Goldman et al., 5/27/2020, peer-reviewed, 26 authors, trial NCT04292899.

Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial

Wang et al., Lancet, doi:10.1016/S0140-6736(20)31022-9

Small RCT with 237 hospitalized patients in China with severe COVID-19, not showing statistically significant benefits. 158 treatment patients and 79 control patients.

While too small for significance, the subgroup treated within 10 days showed reduced mortality RR 0.76, p = 0.58, and reduced median time to clinical improvement of 18 days vs. 23 days, hazard ratio 1.52 [0.95-2.43].

all patients, 8.6% higher, RR 1.09, p = 1.00, treatment 22 of 158 (13.9%), control 10 of 78 (12.8%).

<10 days from symptoms, 24.3% lower, RR 0.76, p = 0.58, treatment 8 of 71 (11.3%), control 7 of 47 (14.9%), NNT 28.

>10 days from symptoms, 47.6% higher, RR 1.48, p = 0.76, treatment 12 of 84 (14.3%), control 3 of 31 (9.7%).

Wang et al., 4/29/2020, Randomized Controlled Trial, China, Asia, peer-reviewed, 46 authors, average treatment delay 11.0 days.

Compassionate Use of Remdesivir for Patients with Severe Covid-19

Grein et al., NEJM, doi:10.1056/NEJMoa2007016

Report on compassionate use of remdesivir with 61 severe COVID-19 patients, showing clinical improvement in 36 of 53 patients.

Grein et al., 4/10/2020, peer-reviewed, 59 authors.

Antiandrogens	(meta)	Lactoferrin	(meta)
Aspirin	(meta)	Melatonin	(meta)
Bamlaniv../e..	(meta)	Metformin	(meta)
Bebtelovimab	(meta)	Molnupiravir	(meta)
Bromhexine	(meta)	N-acetylcys..	(meta)
Budesonide	(meta)	Nigella Sativa	(meta)
Cannabidiol	(meta)	Nitazoxanide	(meta)
Casirivimab/i..	(meta)	Paxlovid	(meta)
Colchicine	(meta)	Peg.. Lambda	(meta)
Conv. Plasma	(meta)	Povidone-Iod..	(meta)
Curcumin	(meta)	Probiotics	(meta)
Diet	(meta)	Proxalutamide	(meta)
Ensitrelvir	(meta)	Quercetin	(meta)
Ensovibep	(meta)	Remdesivir	(meta)
Exercise	(meta)	Sleep	(meta)
Famotidine	(meta)	Sotrovimab	(meta)
Favipiravir	(meta)	Tixagev../c..	(meta)
Fluvoxamine	(meta)	Vitamin A	(meta)
Hydroxychlor..	(meta)	Vitamin C	(meta)
Iota-carragee..	(meta)	Vitamin D	(meta)
Ivermectin	(meta)	Zinc	(meta)

Other Treatments		Global Adoption