Impact of Remdesivir on the Treatment of COVID-19 During the First Wave in Spain

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Abstract

Introduction

Spain was one of the most affected countries during the first wave of COVID-19, having the highest mortality rate in Europe. The aim of this retrospective study is to estimate the impact that remdesivir—the first drug for COVID-19 approved in the EU—would have had in the first wave.

Methods

This study simulated the impact that remdesivir could have had on the Spanish National Health System (SNHS) capacity (bed occupancy) and the number of deaths that could have been prevented, based on two scenarios: a real-life scenario (without remdesivir) and an alternative scenario (with remdesivir). It considered the clinical results of the ACTT-1 trial in hospitalized patients with COVID-19 and pneumonia who required supplemental oxygen. The occupancy rates in general wards and ICUs were estimated in both scenarios.

Results

Remdesivir use could have prevented the admission of 2587 patients (43.75%) in the ICUs. It could have also increased the SNHS capacity in 5656 general wards beds and 1700 ICU beds, showing an increase in the number of beds available of 17.53% (95% CI 3.98%–24.42%) and 23.98% (95% CI 21.33%–28.22%), respectively, at the peak of the occupancy rates. Furthermore, remdesivir use could have prevented 7639 deaths due to COVID-19, which implies a 27.51% reduction (95% CI 14.25%–34.07%).

Conclusions

Remdesivir could have relieved the pressure on the SNHS and could have reduced the death toll, providing a better strategy for the management of COVID-19 during the first wave.

Supplementary Information

The online version contains supplementary material available at 10.1007/s12325-021-01804-9.

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Most cited references 13

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Remdesivir for the Treatment of Covid-19 — Final Report

John H. Beigel, Kay Tomashek, Lori Dodd … (2022)

Abstract Background Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. Methods We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. Results A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%). Conclusions Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.)

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Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial Results

Aldo Pietro Maggioni, Jonathan Sterne (2021)

Abstract Background World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs — remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a — in patients hospitalized with coronavirus disease 2019 (Covid-19). Methods We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. Results At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan–Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P=0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P=0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P=0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P=0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. Conclusions These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.)

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Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study

Marina Pollán, Beatriz Pérez-Gómez, Roberto Pastor-Barriuso … (2020)

Summary Background Spain is one of the European countries most affected by the COVID-19 pandemic. Serological surveys are a valuable tool to assess the extent of the epidemic, given the existence of asymptomatic cases and little access to diagnostic tests. This nationwide population-based study aims to estimate the seroprevalence of SARS-CoV-2 infection in Spain at national and regional level. Methods 35 883 households were selected from municipal rolls using two-stage random sampling stratified by province and municipality size, with all residents invited to participate. From April 27 to May 11, 2020, 61 075 participants (75·1% of all contacted individuals within selected households) answered a questionnaire on history of symptoms compatible with COVID-19 and risk factors, received a point-of-care antibody test, and, if agreed, donated a blood sample for additional testing with a chemiluminescent microparticle immunoassay. Prevalences of IgG antibodies were adjusted using sampling weights and post-stratification to allow for differences in non-response rates based on age group, sex, and census-tract income. Using results for both tests, we calculated a seroprevalence range maximising either specificity (positive for both tests) or sensitivity (positive for either test). Findings Seroprevalence was 5·0% (95% CI 4·7–5·4) by the point-of-care test and 4·6% (4·3–5·0) by immunoassay, with a specificity–sensitivity range of 3·7% (3·3–4·0; both tests positive) to 6·2% (5·8–6·6; either test positive), with no differences by sex and lower seroprevalence in children younger than 10 years ( 10%) and lower in coastal areas (<3%). Seroprevalence among 195 participants with positive PCR more than 14 days before the study visit ranged from 87·6% (81·1–92·1; both tests positive) to 91·8% (86·3–95·3; either test positive). In 7273 individuals with anosmia or at least three symptoms, seroprevalence ranged from 15·3% (13·8–16·8) to 19·3% (17·7–21·0). Around a third of seropositive participants were asymptomatic, ranging from 21·9% (19·1–24·9) to 35·8% (33·1–38·5). Only 19·5% (16·3–23·2) of symptomatic participants who were seropositive by both the point-of-care test and immunoassay reported a previous PCR test. Interpretation The majority of the Spanish population is seronegative to SARS-CoV-2 infection, even in hotspot areas. Most PCR-confirmed cases have detectable antibodies, but a substantial proportion of people with symptoms compatible with COVID-19 did not have a PCR test and at least a third of infections determined by serology were asymptomatic. These results emphasise the need for maintaining public health measures to avoid a new epidemic wave. Funding Spanish Ministry of Health, Institute of Health Carlos III, and Spanish National Health System.

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Author and article information

Contributors

Almudena González-Domínguez:

ORCID: http://orcid.org/0000-0002-3509-0961

almudena.gonzalez@weber.org.es

Journal

Journal ID (nlm-ta): Adv Ther

Journal ID (iso-abbrev): Adv Ther

Title: Advances in Therapy

Publisher: Springer Healthcare (Cheshire )

ISSN (Print): 0741-238X

ISSN (Electronic): 1865-8652

Publication date (Electronic): 12 June 2021

Publication date PMC-release: 12 June 2021

Pages: 1-13

Affiliations

[1 ]GRID grid.410458.c, ISNI 0000 0000 9635 9413, Unit of Infectious Diseases, , Hospital Clinic, ; Barcelona, Spain

[2 ]GRID grid.81821.32, ISNI 0000 0000 8970 9163, Unit of Infectious Diseases, Internal Medicine Department, , La Paz University Hospital, ; Madrid, Spain

[3 ]GRID grid.411171.3, ISNI 0000 0004 0425 3881, Unit of Infectious Diseases, Internal Medicine Department, , Principe de Asturias University Hospital, ; Madrid, Spain

[4 ]GRID grid.81821.32, ISNI 0000 0000 8970 9163, Intensive Care Department, , La Paz University Hospital, ; Madrid, Spain

[5 ]GRID grid.411142.3, ISNI 0000 0004 1767 8811, Pharmacy Department, , Hospital del Mar, ; Barcelona, Spain

[6 ]GRID grid.411142.3, ISNI 0000 0004 1767 8811, Infectious Diseases Department, , Hospital del Mar, ; Barcelona, Spain

[7 ]GRID grid.488275.4, ISNI 0000 0004 1793 9401, Gilead Sciences, ; Madrid, Spain

[8 ]GRID grid.510782.9, Pharmacoeconomics and Market Access Department, , Weber, ; Madrid, Spain

[9 ]GRID grid.8048.4, ISNI 0000 0001 2194 2329, Economy and Health Research Seminar, , University of Castilla-La Mancha, ; Toledo, Spain

[10 ]GRID grid.510782.9, Foundation Weber, ; Madrid, Spain

Author information

Almudena González-Domínguez http://orcid.org/0000-0002-3509-0961

Article

Publisher ID: 1804

DOI: 10.1007/s12325-021-01804-9

PMC ID: 8196270

PubMed ID: 34118007

SO-VID: 0cb95c1a-f75f-4fbb-8b4d-68e41cab7fe0

License:

Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

History

Date received : 21 April 2021

Date accepted : 20 May 2021

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100005564, Gilead Sciences;

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Impact of Remdesivir on the Treatment of COVID-19 During the First Wave in Spain

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Abstract

Introduction

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Supplementary Information

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Novel Coronavirus Disease COVID-19

Most cited references 13

Remdesivir for the Treatment of Covid-19 — Final Report

Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial Results

Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study

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