Remdesivir Administration for Sars Cov 2 Pneumonia in Icu and Non- Icu Patients: Outcome and Post-treatment Differences

Remdesivir Administration for Sars Cov 2 Pneumonia in Icu and Non- Icu Patients: Outcome and Post-treatment Differences | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Remdesivir Administration for Sars Cov 2 Pneumonia in Icu and Non- Icu Patients: Outcome and Post-treatment Differences Antonio Sabba, Giancarlo Pontoni, Maria Santangelo, Nadir Rachedi, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2324373/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose This prospective observation and monocentric study aims to verify the outcome (Healing/Death) of Remdesivir, a nucleotide analogue prodrug of adenosine, for two hospital patients groups: patients in standard oxygen therapy and patients undergoing mechanical ventilation. Methods 449 patients affected by Covid-19 were hospitalized at the Rome Military Hospital between March 2020 and July 2022. Depending on the severity of the disease they were assigned either to the Functional Health Emergency Unit (UFES) - if suffering from interstitial pneumonia with a clinical manifestation of dyspnoea associated with peripheral oxygen saturation < 92%, and oxygen atmospheric pressure therapy - or to the Intensive Care Unit (ICU) - if the blood gas-lytic index P/F (ratio between partial pressure of arterial O2 and inspired fraction of O2) was below 150. The two patient categories were further separated into a study group undergoing Remdesivir therapy and a control group treated alternatively with Lopinavir/Ritonavir either Hydroxychlorochina or Tocilizumab. Results The results highlight the importance of the adoption of Remdesivir in the initial stages of infection to prevent the systemic spread and viral multiplication and, in the subsequent phase, a cytokine storm resulting in acute respiratory failure and multi organ failure. The use of the drug in the most advanced stages of the disease is not associated with a real impact on patient outcomes. Therefore, there is a statistically significant correspondence between the early use of remdesevir in the treatment of Sars Cov 2 disease - in addition to guidelines therapies - and a favorable clinical outcome. Covid 19 Remdesivir Intensive Care Figures Figure 1 Figure 2 Introduction On 11 March 2020 the Health World Organization (WHO) characterized the international outbreak of new virus (SARS COV 2) and related the infection as a pandemic[ 1 ]. Airborne transmission from an active case is the most common spread mechanism. Transmission between asymptomatic patients is possible, but less common[ 2 ]. The incubation period can last up to 2 weeks. In the early phase of infection patients usually present mild and common flu-like symptoms[ 3 ]. The radiological findings are similar to other viral pneumonia[ 4 ]. The early stage of SARS COV 2 infection present flu-like symptoms in 90% of cases and it is characterized by fever (> 90% of pts and could reach 39°C or more), cough (dry cough in 45–80% of pts, productive cough in 28%), sickness (44–80% of pts), dispnea (20–50% of pts, half of them developed dispnea within 8 days), throat-ache (5% of pts), headache (3–20% of pts), myalgia (11–23% of pts)[ 5 ]. During COVID 19 progression 15–30% of patients developed acute respiratory distress syndrome (ARDS, median 9 days) and needed intensive care unit (ICU) admission and respiratory support treatments[ 6 ]. Illness progression was more common in patients with baseline associated disease, especially in patients who presented arterial hypertension and diabetes mellitus[ 7 ]. ARDS is serious medical condition and need to be treated with life support technique as non-invasive and invasive mechanical ventilation and positive pressure ventilation in order to improve pulmonary gas exchange. In extreme conditions and in selective patients Extra-Corporeal Membrane Oxygenation (ECMO) should be considered[ 8 ]. Remdesivir is an oral prodrug, nucleotide analogue of adenosine. It is metabolized into the host cells to the active triphosphate form, which is the active form of the parent compound. The active form acts as adenosine triphosphate (ATP) competitive substrate. When Remdesivir replaces ATP into the new RNA (made by SARS COV 2 RNA-polymerase RNA-dependent) it causes subsequent chain termination during viral RNA replication[ 9 ]. Remdesivir has efficacy against SARS COV 2 infection in vitro on primary human respiratory epithelial cells[ 10 ]. The aim of the present study is to assess the Remdesivir efficacy in reducing mortality when administered in patients undergoing O2 standard and mechanical ventilated treatments. Methods All consecutive patients admitted to “Celio” Military Policlinic in Rome during the study period with positive SARS COV 2 swab were evaluated for enrollment. The study was authorized by local Ethical Committee. All recruitable patients were informed about nature of the study and any aspects including Remdesivir administration, data collection and follow up. A Written informed consent was obtained from all subjects. The inclusion criteria included: age > 18 yo, positive swab for SARS COV 2, SpO2 < 92% in room air. The exclusion criteria included: allergy to the active substance or to any other ingredient of Remdesivir, patients with stage 4 and 5 of renal failure (definied as estimated glomerular filtration rate < 30ml/min), patients with markedly increase in transaminases (ASAT and ALAT 5 times above the lab limit), pregnancy. Stable patients - defined as patients presenting pneumonia, SpO2 < 92% in room air and clinical improvement after O2 standard therapy - were admitted to UFES. Unstable patients - defined as patients who presented PaO2/FiO2 < 150 - were admitted to ICU. All patients received best available treatments including low molecular weight heparin 100UI/kg/die, dexamethasone 6mg/die for 10 days or methylprednisolone 40mg/die for 10 days, acetaminophen 1g when body temperature raised over 38°C. Remdesivir was available from 12-05-2020. All consecutive patients enrolled in this study after 12-05-2020 received Remdesivir on top of the best available treatments. The control group is represented by patients that fit inclusion criteria, and was admitted to the hospital before Remdesivir approval. In control arm patients received best available treatments plus Lopinavir/Ritonavir (400/100mg twice a day for 7 days), Hydroxychloroquine (200mg twice a day) when necessary or Tocilizumab same doses above). In treatment group patients received best available treatments plus Remdesivir for 5 days (200mg loading dose the day of enrollment and 100mg/die for next 4 days). Four cases - characterized by serious clinical condition and rapidly worsening - were treated with Remdesivir (same doses above) and Tocilizumab (400mg one shot). Statisticasl Analysis Qualitative variables were expressed as number and percentages. Quantitative variables were reported as mean, median, standard deviation (DS) and range. Frequencies and contingency tables were used to describe categorical variables. Baseline data included age, sex, comorbidities, admission ward and other clinical parameters (transfer to ICU, necessity of tracheal intubation etc…). Unadjusted univariate analyses was based on Person Chi square test for categorical variables. Continuous variables was analysed by means t-test, in accordance with normality of the distribution. A logistic regression model was used to evaluate study primary endpoint. At first, all non-binary covariates (age and number of comorbidities) were dichotomized according to their median and univariate logistic regressions were performed. Variable response was patients’ outcome (survive or death). Therefore, two multivariate logistic models were built, one for each group including the covariates that had reached the statistical significance at the univariate analysis. Odds ratios (OR) were used as a measure of effect size. A p value of 0.05 or lower was considered as statistically significant. Statistical analysis were performed using the software STATA version 14.2 (StataCorp LLC, College Station, TX). Results We enrolled 449 patients affected by COVID 19 admitted to “Celio” Military Polyclinic in Rome between March 2020 and July 2022. Stable patients, admitted to UFES, were 334 (74%), while unstable patients admitted to ICU were 115 (26%). (Table 1) The average age was 62.0 yo (range 24–29; DS 14.7) and males represented most patients admitted (n = 339, 75.5%). 230 patients (51%) presented 1 or less comorbidity, while 49% presented two or more comorbidities. 23 stable patients (7% of UFES pts) admitted to UFES required the ICU admission after worsening clinical conditions. Endotracheal intubation was necessary in 67 patients (58% of ICU pts) admitted to ICU. 104 patients (23%) did not receive any antiviral therapy. In our hospital, Remdesivir was the most used antiviral drug (n = 266, 59% of patients). Only 4 patients (less than 1% of total pts) received Remdesivir plus Tocilizumab. 354 patients (79%) survived COVID 19 pneumonia. The UFES and ICU groups showed heterogeneity for age, sex and number of comorbidities. Mean difference of 8.2 years was found between the UFES and ICU groups, with statistical significance (p < 0.001). After the age dichotomy based on the median value of 60 years, 38% (n = 89) of patients over 60 years of age versus 13% (n = 26) of children under 60 were admitted to treatment in -tensive and this difference reached a level of p < 0.01 statistical significance. Male patients were admitted to intensive care in 64% (n = 74) of cases, while female patients in 36% (n = 41) of cases and the difference was statistically significant (p = 0.001) Patients with none or at least one comorbidity condition were admitted to intensive care in 19% (n = 44), while patients with two or more comorbidities were admitted to intensive care in 32% (n = 71) of cases with a statistically significant difference (p = 0.001). Remdesivir was administered in 61% (n = 203) of UFES patients and 55% (n = 64) of ICU patients, but this difference was not statistically significant (p = 0.26). Remdesivir was more prescribed in patients less than 60 years old (65%, n = 145) than in those over 60 (53%, n = 121) and in patients with none or at least one comorbidity (67%, n = 155) versus two or more comorbidities (51%, n = 112). These differences reach a statistical significance level of 0.01 and < 0.001, respectively. In intensive care, remdesivir was administered in 43% (n = 29) of patients undergone IOT and in 71% (n = 34) of patients in NIV, with a statistically significant p = 0.003. There is no significant difference (p = 0.25) when comparing remdesivir prescriptions in male (61%, n = 206) and female (55%, n = 61) patients (Figures. 1 and 2). 90% of UFES patients survived (n = 300) and 53% of ICU patients (n = 61) survived. Males survived in the 83% (n = 283) of cases, while female patients in the 65% (n = 71). The 98% of patients less than 60 years old survived (n = 217), while patients older than 60 years of age in the 60% (n = 137) of cases. 88% of patients treated with remdesivir survived (n = 233), while the remaining in 66% (n = 121) of cases. 91% of patients with none or at least one comorbidity condition survived (n = 210), while patients with two or more comorbidities survived in 66% (n = 144) of cases. Each of the last five differences reached a level of statistical significance (p < 0.001). Univariate logistic regression analysis was performed for each group. Univariate analysis of the UFES group showed a negative association between remdesivir treatment and death (OR 0.09, p 60 (OR 58, p < 0.001), female sex (OR 3, p = 0.03), two or more comorbidities (OR 53, p 60 and death (OR 12, p < 0.001). Multivariate logistic regression analysis of the UFES group showed a negative association with remdesivir and death (OR 0.1, p 60 (OR 20, p = 0.005), two or plus comorbidities (OR 12, p = 0.01) and death. Multivariate analysis of the ICU group showed a loss of significance of all co-varied, except for > 60 years of age. Older age remains the only independent predictor of death (OR 11.6, p < 0.01) in this group. Discussions The results of this study highlight the importance of Remdesivir in the early stages of infection, to prevent systemic viral spread and multiplication from triggering a cytokine storm, that can lead to a fatal acute respiratory and multiorgan failure. It is clear that the early administration of Remdesivir in patients in the early stages of infection (within 10 days from the first positive) can generate various clinical benefits, reducting the hositalization as well as the consumption of health resources because it reduces the access to intensive care units. The statistical analysis of the available data confirmed the efficacy of Remdesivir in the early stages of Covid-19. However it demonstrates that the use of the drug in the most advanced stages of the disease is not associated with a real improvement on patients’ outcome. The study design shows that some subgroups of patients – particularly the group under 60 - had clear clinical benefits if Remdesivir was aministrated on the onset phase. The Remdesivir active principle is in fact recognized in a highly water-soluble molecule that shows poor pulmonary diffusion which is why the therapeutic window of efficacy appears to be closely related to tissue distribution famacokinetics during the phase that immediately preceds the parenchymal damage. This work shows therapeutic efficacy in the first 5 days of intravenous administration of Remdesivir, following the loading dose. It is also necessary to underline the different behavior of the drug when administered late in patients undergoing mechanical ventilation, compared to those who only needed low-flow oxygen therapy, whose share of recovery - decidedly relevant - reaches statistical significance. The study shows that the timely use of Remdesevir in addition to the other standard therapies -considering the results conducted in a single center- leads to favorable clinical outcomes guaranteeing a statistically significant cure and avoids the unfortunate evolution of the disease, particularly in patients not undergoing mechanical ventilation and under the age of 60. However, a certain clinical efficacy - though not significant - should be remarked even in patients under mechanical ventilation. Conclusions are similar to literature constitutes and this is a further confirmation of the clinical efficacy of Remmdesevir in the treatment of Sars Cov 2 disease. Table 1 Main demographic, hospitalization and clinical features at the time of hospitalization Demographic and hospitalization features a n (number) % (percentage) Clinical features a n (number) % (percentage) Age Class (years) Number of comorbidities 24–60 222 49.4 0 143 31.8 61–93 227 51.6 1 87 19.4 2 56 12.5 Sex 3 or more 163 36.3 Male 339 75.5 Female 110 24.5 Pharmacotherapy None 104 23.2 Ward at admission Remdesivir 262 58.4 UFES 334 74.4 Tocilizumab 6 1.3 ICU 115 25.6 Tocilizumab + Remdesivir 4 0.9 Tocilizumab + Kal 3 0.7 ICU transfer Kal + ClK 42 9.4 Yes 23 6.9 Kal 15 3.3 No 311 93.1 ClK 13 2.9 IOT (ICU patients) Outcome Yes 67 58.3 Survive 354 78.8 No 48 41.7 Death 95 21.2 a Numbers may not add up to 449 because of missing data. Percentages may not add up to 100 because of rounding. Table 2 Multivariate logistic regression analysis of factors associated to death in UFES patients Death OR (95% CI) p Treatment with remdesivir 0.10 (0.04–0.30) 60 years) 20.4 (2.53–164.41) < 0.005* * Statistical significance (p < 0.05) Take home Message The early administration of Remdesivir in patients in the early stages of infection (within 10 days from the first positive) can generate various clinical benefits. Tweet The early use of remdesevir in the treatment of Sars Cov 2 disease - in addition to guidelines therapies- generates a favorable clinical outcome. Declarations Statements and Declarations We confirm that this manuscript has not been published elsewhere and is not under consideration by another journal. All authors have approved the manuscript and agree with its submission to SCIENCE. All Authors declare that no one received any found All Authors do not have any interest’s conflict. The contribution of all co-authors was equal. References Silva Francisco R, Benittes F, Lamarca AP, et al. Pervasive transmission of E484K and emergence of VUI-NP13L with evidence of SARS-CoV-2 co- infection events by two different lineages in Rio Grande do Sul, Brazil. medRxiv 2021, posted 26 January. Full-text: https://doi.org/10.1101/2021.01.21.21249764 Callaway E 20210121. Fast - spreading COVID variant can elude immune responses . Nature News 21 January 2021. Full-text: https://www.nature.com/articles/d41586-021-00121-z Starr TN, Greaney AJ, Hilton SK, et al. Deep Mutational Scanning of SARS- CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding. Cell. 2020 Sep 3;182(5):1295–1310. e20.PubMed:https://pubmed.gov/32841599.Full-text https://doi.org/10.1016/j Tillett RL, Sevinsky JR, Hartley PD, et al. Genomic evidence for reinfection with SARS-CoV-2: a case study. Lancet Infect Dis. 2021 Jan;21(1):52–58. PubMed: https://pubmed.gov/33058797 . Full-text: https://doi.org/10.1016/S1473- 3099(20)30764-7 Davies NG, Barnard RC, Jarvis CI et al. Estimated transmissibility and severity of novel SARSCoV - 2 Variant of Concern 202012 / 01 in England . medRxiv 2020, published 26 December. Full-text: https://doi.org/10.1101/2020.12.24.20248822 Wölfel, R. Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with COVID-2019 . Nature 2020;581:465–9. Buss LF, Prete Jr A, Abrahim CMM, et al. Three-quarters attack rate of SARS- CoV-2 in the Brazilian Amazon during a largely unmitigated epidemic. Science 2020b, published 8 December. Full-text: https://doi.org/10.1126/science.abe9728 Cui S, Chen S, Li X, Liu S, Wang F.Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost 2020 Apr 9. doi: 10.1111/jth.14830 . Remdesivir nella terapia dei pazienti adulti con COVID-19 (aggiornamento al 24/11/2020) Agenzia Italiana del Farmaco: Farmaci utilizzabili per il trattamento del Covid-19 Egor P. Tchesnokov 1,2, Joy Y. Feng 3, Danielle P. Porter 3 and Matthias Götte Mechanism of Inhibition of Ebola Virus RNA-Dependent RNA Polymerase by Remdesivir CDC. 2014–2016 Ebola Outbreak inWest Africa. Available online: https://www.cdc.gov/vhf/ebola/history/ 2014-2016-outbreak/index.html Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2324373","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":156211986,"identity":"77228326-dbbf-49f5-b6cc-e6145f333199","order_by":0,"name":"Antonio 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Differences\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eOn 11 March 2020 the Health World Organization (WHO) characterized the international outbreak of new virus (SARS COV 2) and related the infection as a pandemic[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAirborne transmission from an active case is the most common spread mechanism. Transmission between asymptomatic patients is possible, but less common[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe incubation period can last up to 2 weeks. In the early phase of infection patients usually present mild and common flu-like symptoms[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The radiological findings are similar to other viral pneumonia[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe early stage of SARS COV 2 infection present flu-like symptoms in 90% of cases and it is characterized by fever (\u0026gt;\u0026thinsp;90% of pts and could reach 39\u0026deg;C or more), cough (dry cough in 45\u0026ndash;80% of pts, productive cough in 28%), sickness (44\u0026ndash;80% of pts), dispnea (20\u0026ndash;50% of pts, half of them developed dispnea within 8 days), throat-ache (5% of pts), headache (3\u0026ndash;20% of pts), myalgia (11\u0026ndash;23% of pts)[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDuring COVID 19 progression 15\u0026ndash;30% of patients developed acute respiratory distress syndrome (ARDS, median 9 days) and needed intensive care unit (ICU) admission and respiratory support treatments[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIllness progression was more common in patients with baseline associated disease, especially in patients who presented arterial hypertension and diabetes mellitus[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eARDS is serious medical condition and need to be treated with life support technique as non-invasive and invasive mechanical ventilation and positive pressure ventilation in order to improve pulmonary gas exchange. In extreme conditions and in selective patients Extra-Corporeal Membrane Oxygenation (ECMO) should be considered[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRemdesivir is an oral prodrug, nucleotide analogue of adenosine. It is metabolized into the host cells to the active triphosphate form, which is the active form of the parent compound. The active form acts as adenosine triphosphate (ATP) competitive substrate. When Remdesivir replaces ATP into the new RNA (made by SARS COV 2 RNA-polymerase RNA-dependent) it causes subsequent chain termination during viral RNA replication[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRemdesivir has efficacy against SARS COV 2 infection in vitro on primary human respiratory epithelial cells[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe aim of the present study is to assess the Remdesivir efficacy in reducing mortality when administered in patients undergoing O2 standard and mechanical ventilated treatments.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eAll consecutive patients admitted to \u0026ldquo;Celio\u0026rdquo; Military Policlinic in Rome during the study period with positive SARS COV 2 swab were evaluated for enrollment.\u003c/p\u003e \u003cp\u003e The study was authorized by local Ethical Committee. All recruitable patients were informed about nature of the study and any aspects including Remdesivir administration, data collection and follow up. A Written informed consent was obtained from all subjects.\u003c/p\u003e \u003cp\u003eThe inclusion criteria included: age\u0026thinsp;\u0026gt;\u0026thinsp;18 yo, positive swab for SARS COV 2, SpO2\u0026thinsp;\u0026lt;\u0026thinsp;92% in room air.\u003c/p\u003e \u003cp\u003eThe exclusion criteria included: allergy to the active substance or to any other ingredient of Remdesivir, patients with stage 4 and 5 of renal failure (definied as estimated glomerular filtration rate\u0026thinsp;\u0026lt;\u0026thinsp;30ml/min), patients with markedly increase in transaminases (ASAT and ALAT 5 times above the lab limit), pregnancy.\u003c/p\u003e \u003cp\u003eStable patients - defined as patients presenting pneumonia, SpO2\u0026thinsp;\u0026lt;\u0026thinsp;92% in room air and clinical improvement after O2 standard therapy - were admitted to UFES. Unstable patients - defined as patients who presented PaO2/FiO2\u0026thinsp;\u0026lt;\u0026thinsp;150 - were admitted to ICU.\u003c/p\u003e \u003cp\u003eAll patients received best available treatments including low molecular weight heparin 100UI/kg/die, dexamethasone 6mg/die for 10 days or methylprednisolone 40mg/die for 10 days, acetaminophen 1g when body temperature raised over 38\u0026deg;C.\u003c/p\u003e \u003cp\u003eRemdesivir was available from 12-05-2020. All consecutive patients enrolled in this study after 12-05-2020 received Remdesivir on top of the best available treatments.\u003c/p\u003e \u003cp\u003eThe control group is represented by patients that fit inclusion criteria, and was admitted to the hospital before Remdesivir approval.\u003c/p\u003e \u003cp\u003eIn control arm patients received best available treatments plus Lopinavir/Ritonavir (400/100mg twice a day for 7 days), Hydroxychloroquine (200mg twice a day) when necessary or Tocilizumab same doses above).\u003c/p\u003e \u003cp\u003eIn treatment group patients received best available treatments plus Remdesivir for 5 days (200mg loading dose the day of enrollment and 100mg/die for next 4 days). Four cases - characterized by serious clinical condition and rapidly worsening - were treated with Remdesivir (same doses above) and Tocilizumab (400mg one shot).\u003c/p\u003e\n\u003ch3\u003eStatisticasl Analysis\u003c/h3\u003e\n\u003cp\u003eQualitative variables were expressed as number and percentages. Quantitative variables were reported as mean, median, standard deviation (DS) and range.\u003c/p\u003e \u003cp\u003eFrequencies and contingency tables were used to describe categorical variables.\u003c/p\u003e \u003cp\u003eBaseline data included age, sex, comorbidities, admission ward and other clinical parameters (transfer to ICU, necessity of tracheal intubation etc\u0026hellip;).\u003c/p\u003e \u003cp\u003eUnadjusted univariate analyses was based on Person Chi square test for categorical variables. Continuous variables was analysed by means t-test, in accordance with normality of the distribution.\u003c/p\u003e \u003cp\u003eA logistic regression model was used to evaluate study primary endpoint.\u003c/p\u003e \u003cp\u003eAt first, all non-binary covariates (age and number of comorbidities) were dichotomized according to their median and univariate logistic regressions were performed. Variable response was patients\u0026rsquo; outcome (survive or death). Therefore, two multivariate logistic models were built, one for each group including the covariates that had reached the statistical significance at the univariate analysis.\u003c/p\u003e \u003cp\u003eOdds ratios (OR) were used as a measure of effect size. A p value of 0.05 or lower was considered as statistically significant.\u003c/p\u003e \u003cp\u003eStatistical analysis were performed using the software STATA version 14.2 (StataCorp LLC, College Station, TX).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eWe enrolled 449 patients affected by COVID 19 admitted to \u0026ldquo;Celio\u0026rdquo; Military Polyclinic in Rome between March 2020 and July 2022.\u003c/p\u003e \u003cp\u003eStable patients, admitted to UFES, were 334 (74%), while unstable patients admitted to ICU were 115 (26%). (Table\u0026nbsp;1)\u003c/p\u003e \u003cp\u003eThe average age was 62.0 yo (range 24\u0026ndash;29; DS 14.7) and males represented most patients admitted (n\u0026thinsp;=\u0026thinsp;339, 75.5%). 230 patients (51%) presented 1 or less comorbidity, while 49% presented two or more comorbidities. 23 stable patients (7% of UFES pts) admitted to UFES required the ICU admission after worsening clinical conditions. Endotracheal intubation was necessary in 67 patients (58% of ICU pts) admitted to ICU.\u003c/p\u003e \u003cp\u003e104 patients (23%) did not receive any antiviral therapy. In our hospital, Remdesivir was the most used antiviral drug (n\u0026thinsp;=\u0026thinsp;266, 59% of patients). Only 4 patients (less than 1% of total pts) received Remdesivir plus Tocilizumab. 354 patients (79%) survived COVID 19 pneumonia.\u003c/p\u003e \u003cp\u003eThe UFES and ICU groups showed heterogeneity for age, sex and number of comorbidities. Mean difference of 8.2 years was found between the UFES and ICU groups, with statistical significance (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). After the age dichotomy based on the median value of 60 years, 38% (n\u0026thinsp;=\u0026thinsp;89) of patients over 60 years of age versus 13% (n\u0026thinsp;=\u0026thinsp;26) of children under 60 were admitted to treatment in -tensive and this difference reached a level of p\u0026thinsp;\u0026lt;\u0026thinsp;0.01 statistical significance.\u003c/p\u003e \u003cp\u003eMale patients were admitted to intensive care in 64% (n\u0026thinsp;=\u0026thinsp;74) of cases, while female patients in 36% (n\u0026thinsp;=\u0026thinsp;41) of cases and the difference was statistically significant (p\u0026thinsp;=\u0026thinsp;0.001)\u003c/p\u003e \u003cp\u003ePatients with none or at least one comorbidity condition were admitted to intensive care in 19% (n\u0026thinsp;=\u0026thinsp;44), while patients with two or more comorbidities were admitted to intensive care in 32% (n\u0026thinsp;=\u0026thinsp;71) of cases with a statistically significant difference (p\u0026thinsp;=\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eRemdesivir was administered in 61% (n\u0026thinsp;=\u0026thinsp;203) of UFES patients and 55% (n\u0026thinsp;=\u0026thinsp;64) of ICU patients, but this difference was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.26). Remdesivir was more prescribed in patients less than 60 years old (65%, n\u0026thinsp;=\u0026thinsp;145) than in those over 60 (53%, n\u0026thinsp;=\u0026thinsp;121) and in patients with none or at least one comorbidity (67%, n\u0026thinsp;=\u0026thinsp;155) versus two or more comorbidities (51%, n\u0026thinsp;=\u0026thinsp;112). These differences reach a statistical significance level of 0.01 and \u0026lt;\u0026thinsp;0.001, respectively. In intensive care, remdesivir was administered in 43% (n\u0026thinsp;=\u0026thinsp;29) of patients undergone IOT and in 71% (n\u0026thinsp;=\u0026thinsp;34) of patients in NIV, with a statistically significant p\u0026thinsp;=\u0026thinsp;0.003.\u003c/p\u003e \u003cp\u003eThere is no significant difference (p\u0026thinsp;=\u0026thinsp;0.25) when comparing remdesivir prescriptions in male (61%, n\u0026thinsp;=\u0026thinsp;206) and female (55%, n\u0026thinsp;=\u0026thinsp;61) patients (Figures. 1 and 2).\u003c/p\u003e \u003cp\u003e90% of UFES patients survived (n\u0026thinsp;=\u0026thinsp;300) and 53% of ICU patients (n\u0026thinsp;=\u0026thinsp;61) survived. Males survived in the 83% (n\u0026thinsp;=\u0026thinsp;283) of cases, while female patients in the 65% (n\u0026thinsp;=\u0026thinsp;71). The 98% of patients less than 60 years old survived (n\u0026thinsp;=\u0026thinsp;217), while patients older than 60 years of age in the 60% (n\u0026thinsp;=\u0026thinsp;137) of cases. 88% of patients treated with remdesivir survived (n\u0026thinsp;=\u0026thinsp;233), while the remaining in 66% (n\u0026thinsp;=\u0026thinsp;121) of cases. 91% of patients with none or at least one comorbidity condition survived (n\u0026thinsp;=\u0026thinsp;210), while patients with two or more comorbidities survived in 66% (n\u0026thinsp;=\u0026thinsp;144) of cases. Each of the last five differences reached a level of statistical significance (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Univariate logistic regression analysis was performed for each group. Univariate analysis of the UFES group showed a negative association between remdesivir treatment and death (OR 0.09, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and a positive association of age\u0026thinsp;\u0026gt;\u0026thinsp;60 (OR 58, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), female sex (OR 3, p\u0026thinsp;=\u0026thinsp;0.03), two or more comorbidities (OR 53, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and death (Table\u0026nbsp;2). Univariate analysis of the ICU group showed a negative association between remdesivir treatment and death (OR 0.5, p\u0026thinsp;=\u0026thinsp;0.04) and a positive association between age\u0026thinsp;\u0026gt;\u0026thinsp;60 and death (OR 12, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Multivariate logistic regression analysis of the UFES group showed a negative association with remdesivir and death (OR 0.1, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and a positive association of age\u0026thinsp;\u0026gt;\u0026thinsp;60 (OR 20, p\u0026thinsp;=\u0026thinsp;0.005), two or plus comorbidities (OR 12, p\u0026thinsp;=\u0026thinsp;0.01) and death. Multivariate analysis of the ICU group showed a loss of significance of all co-varied, except for \u0026gt;\u0026thinsp;60 years of age. Older age remains the only independent predictor of death (OR 11.6, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) in this group.\u003c/p\u003e"},{"header":"Discussions","content":"\u003cp\u003eThe results of this study highlight the importance of Remdesivir in the early stages of infection, to prevent systemic viral spread and multiplication from triggering a cytokine storm, that can lead to a fatal acute respiratory and multiorgan failure. It is clear that the early administration of Remdesivir in patients in the early stages of infection (within 10 days from the first positive) can generate various clinical benefits, reducting the hositalization as well as the consumption of health resources because it reduces the access to intensive care units. The statistical analysis of the available data confirmed the efficacy of Remdesivir in the early stages of Covid-19. However it demonstrates that the use of the drug in the most advanced stages of the disease is not associated with a real improvement on patients\u0026rsquo; outcome. The study design shows that some subgroups of patients \u0026ndash; particularly the group under 60 - had clear clinical benefits if Remdesivir was aministrated on the onset phase. The Remdesivir active principle is in fact recognized in a highly water-soluble molecule that shows poor pulmonary diffusion which is why the therapeutic window of efficacy appears to be closely related to tissue distribution famacokinetics during the phase that immediately preceds the parenchymal damage. This work shows therapeutic efficacy in the first 5 days of intravenous administration of Remdesivir, following the loading dose. It is also necessary to underline the different behavior of the drug when administered late in patients undergoing mechanical ventilation, compared to those who only needed low-flow oxygen therapy, whose share of recovery - decidedly relevant - reaches statistical significance.\u003c/p\u003e \u003cp\u003eThe study shows that the timely use of Remdesevir in addition to the other standard therapies -considering the results conducted in a single center- leads to favorable clinical outcomes guaranteeing a statistically significant cure and avoids the unfortunate evolution of the disease, particularly in patients not undergoing mechanical ventilation and under the age of 60. However, a certain clinical efficacy - though not significant - should be remarked even in patients under mechanical ventilation. Conclusions are similar to literature constitutes and this is a further confirmation of the clinical efficacy of Remmdesevir in the treatment of Sars Cov 2 disease.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"12\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTable\u0026nbsp;1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"9\" nameend=\"c10\" namest=\"c2\"\u003e \u003cp\u003eMain demographic, hospitalization and clinical features at the time of hospitalization\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"1\" nameend=\"c12\" namest=\"c12\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDemographic and hospitalization features \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e\u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(number)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e\u003cb\u003e% (percentage)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003e\u003cb\u003eClinical features\u003c/b\u003e \u003csup\u003e\u003cb\u003ea\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(number)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003e% (percentage)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c12\" namest=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eAge Class (years)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c10\" namest=\"c7\"\u003e \u003cp\u003e\u003cem\u003eNumber of comorbidities\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e24\u0026ndash;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e222\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e49.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e143\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e31.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c12\" namest=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e61\u0026ndash;93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e227\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e51.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e19.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c12\" namest=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e12.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c12\" namest=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eSex\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003e3 or more\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e163\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e36.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c12\" namest=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e339\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e75.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c12\" namest=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e24.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c10\" namest=\"c7\"\u003e \u003cp\u003e\u003cem\u003ePharmacotherapy\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e104\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e23.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c12\" namest=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eWard at admission\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003eRemdesivir\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e262\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e58.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c12\" namest=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eUFES\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e334\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e74.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003eTocilizumab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c12\" namest=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eICU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e25.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003eTocilizumab\u0026thinsp;+\u0026thinsp;Remdesivir\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c12\" namest=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003eTocilizumab\u0026thinsp;+\u0026thinsp;Kal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c12\" namest=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eICU transfer\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003eKal\u0026thinsp;+\u0026thinsp;ClK\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e9.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c12\" namest=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e6.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003eKal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c12\" namest=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e311\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e93.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003eClK\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c12\" namest=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eIOT (ICU patients)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003e\u003cem\u003eOutcome\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c12\" namest=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e58.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003eSurvive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e354\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e78.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c12\" namest=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e41.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003eDeath\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e21.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c12\" namest=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003csup\u003ea\u003c/sup\u003e Numbers may not add up to 449 because of missing data. Percentages may not add up to 100 because of rounding.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabb\" border=\"1\"\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTable\u0026nbsp;2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eMultivariate logistic regression analysis of factors associated to death in UFES patients\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDeath\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eOR (95% CI)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003ep\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTreatment with remdesivir\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.10 (0.04\u0026ndash;0.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eComorbidities (2 or more)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.58 (1.68\u0026ndash;109.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.014*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSex (male)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.89 (0.73\u0026ndash;4.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.190\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAge (\u0026gt;\u0026thinsp;60 years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20.4 (2.53\u0026ndash;164.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.005*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e* Statistical significance (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eTake home Message\u003c/h2\u003e \u003cp\u003eThe early administration of Remdesivir in patients in the early stages of infection (within 10 days from the first positive) can generate various clinical benefits.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eTweet\u003c/h2\u003e \u003cp\u003e The early use of remdesevir in the treatment of Sars Cov 2 disease - in addition to guidelines therapies- generates a favorable clinical outcome.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eStatements and Declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe confirm that this manuscript has not been published elsewhere and is not\u003c/p\u003e\n\u003cp\u003eunder consideration by another journal.\u003c/p\u003e\n\u003cp\u003eAll authors have approved the manuscript and agree with its submission to SCIENCE.\u003c/p\u003e\n\u003cp\u003eAll Authors declare that no one received any found\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll Authors do not have any interest\u0026rsquo;s conflict.\u003c/p\u003e\n\u003cp\u003eThe contribution of all co-authors was equal.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSilva Francisco R, Benittes F, Lamarca AP, et al. Pervasive transmission of E484K and emergence of VUI-NP13L with evidence of SARS-CoV-2 co- infection events by two different lineages in Rio Grande do Sul, Brazil. medRxiv 2021, posted 26 January. Full-text:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1101/2021.01.21.21249764\u003c/span\u003e\u003cspan address=\"10.1101/2021.01.21.21249764\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCallaway E 20210121. \u003cb\u003eFast\u003c/b\u003e-\u003cb\u003espreading COVID variant can elude immune responses\u003c/b\u003e. Nature News 21 January 2021. Full-text: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.nature.com/articles/d41586-021-00121-z\u003c/span\u003e\u003cspan address=\"https://www.nature.com/articles/d41586-021-00121-z\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStarr TN, Greaney AJ, Hilton SK, et al. Deep Mutational Scanning of SARS- CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding. Cell. 2020 Sep 3;182(5):1295\u0026ndash;1310.\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ee20.PubMed:https://pubmed.gov/32841599.Full-text\u003c/span\u003e\u003cspan address=\"http://e20.PubMed:https://pubmed.gov/32841599.Full-text\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e \u003cdiv class=\"ExternalRefDOI\"\u003ehttps://doi.org/10.1016/j\u003c/div\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTillett RL, Sevinsky JR, Hartley PD, et al. Genomic evidence for reinfection with SARS-CoV-2: a case study. Lancet Infect Dis. 2021 Jan;21(1):52\u0026ndash;58. PubMed: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.gov/33058797\u003c/span\u003e\u003cspan address=\"https://pubmed.gov/33058797\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Full-text: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/S1473- 3099(20)30764-7\u003c/span\u003e\u003cspan address=\"10.1016/S1473- 3099(20)30764-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDavies NG, Barnard RC, Jarvis CI et al. \u003cb\u003eEstimated transmissibility and severity of novel SARSCoV\u003c/b\u003e- \u003cb\u003e2 Variant of Concern 202012\u003c/b\u003e/\u003cb\u003e01 in England\u003c/b\u003e. medRxiv 2020, published 26 December. Full-text: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1101/2020.12.24.20248822\u003c/span\u003e\u003cspan address=\"10.1101/2020.12.24.20248822\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eW\u0026ouml;lfel, R. Corman VM, Guggemos W, et al. \u003cb\u003eVirological assessment of hospitalized patients with COVID-2019\u003c/b\u003e. Nature 2020;581:465\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBuss LF, Prete Jr A, Abrahim CMM, et al. Three-quarters attack rate of SARS- CoV-2 in the Brazilian Amazon during a largely unmitigated epidemic. Science 2020b, published 8 December. Full-text: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1126/science.abe9728\u003c/span\u003e\u003cspan address=\"10.1126/science.abe9728\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCui S, Chen S, Li X, Liu S, Wang F.Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost 2020 Apr 9. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/jth.14830\u003c/span\u003e\u003cspan address=\"10.1111/jth.14830\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRemdesivir nella terapia dei pazienti adulti con COVID-19 (aggiornamento al 24/11/2020) Agenzia Italiana del Farmaco: Farmaci utilizzabili per il trattamento del Covid-19\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEgor P. Tchesnokov 1,2, Joy Y. Feng 3, Danielle P. Porter 3 and Matthias G\u0026ouml;tte Mechanism of Inhibition of Ebola Virus RNA-Dependent RNA Polymerase by Remdesivir CDC. 2014\u0026ndash;2016 Ebola Outbreak inWest Africa. Available online: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.cdc.gov/vhf/ebola/history/ 2014-2016-outbreak/index.html\u003c/span\u003e\u003cspan address=\"https://www.cdc.gov/vhf/ebola/history/ 2014-2016-outbreak/index.html\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Covid 19, Remdesivir, Intensive Care","lastPublishedDoi":"10.21203/rs.3.rs-2324373/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2324373/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eThis prospective observation and monocentric study aims to verify the outcome (Healing/Death) of Remdesivir, a nucleotide analogue prodrug of adenosine, for two hospital patients groups: patients in standard oxygen therapy and patients undergoing mechanical ventilation.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e449 patients affected by Covid-19 were hospitalized at the Rome Military Hospital between March 2020 and July 2022. Depending on the severity of the disease they were assigned either to the Functional Health Emergency Unit (UFES) - if suffering from interstitial pneumonia with a clinical manifestation of dyspnoea associated with peripheral oxygen saturation\u0026thinsp;\u0026lt;\u0026thinsp;92%, and oxygen atmospheric pressure therapy - or to the Intensive Care Unit (ICU) - if the blood gas-lytic index P/F (ratio between partial pressure of arterial O2 and inspired fraction of O2) was below 150. The two patient categories were further separated into a study group undergoing Remdesivir therapy and a control group treated alternatively with Lopinavir/Ritonavir either Hydroxychlorochina or Tocilizumab.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe results highlight the importance of the adoption of Remdesivir in the initial stages of infection to prevent the systemic spread and viral multiplication and, in the subsequent phase, a cytokine storm resulting in acute respiratory failure and multi organ failure. The use of the drug in the most advanced stages of the disease is not associated with a real impact on patient outcomes. Therefore, there is a statistically significant correspondence between the early use of remdesevir in the treatment of Sars Cov 2 disease - in addition to guidelines therapies - and a favorable clinical outcome.\u003c/p\u003e","manuscriptTitle":"Remdesivir Administration for Sars Cov 2 Pneumonia in Icu and Non- Icu Patients: Outcome and Post-treatment Differences","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-12-05 20:21:54","doi":"10.21203/rs.3.rs-2324373/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3a463419-cf32-4e4d-9cd4-4fdbcbc669b0","owner":[],"postedDate":"December 5th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-12-05T20:21:56+00:00","versionOfRecord":[],"versionCreatedAt":"2022-12-05 20:21:54","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2324373","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2324373","identity":"rs-2324373","version":["v1"]},"buildId":"rHA-KDH7Qsr4HCuvH75dn","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}