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2.
Am J Cardiovasc Drugs ; 22(6): 705-710, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2000144

ABSTRACT

BACKGROUND: COVID-19, is primarily a respiratory illness but is known to cause extrapulmonary manifestations, especially on the cardiovascular system. Bradycardia is commonly reported in COVID-19 patients despite no prior history of occurrence, and many studies have shown an association with increased mortality. Multiple case reports have been published showcasing remdesivir potentially causing bradycardia. Our aim was to investigate the incidence of bradycardia in patients receiving remdesivir and examine the association with disease severity and survival outcomes. METHODS: A retrospective study was performed including 160 COVID-19 patients receiving remdesivir for 5 days. Patients' demographics, comorbidities, medication, vital signs, laboratory tests and outcome were recorded. Bradycardia was defined as a heart rate < 60 beats/min and severe bradycardia < 50 beats/min. RESULTS: One hundred eighteen (73.8%) patients experienced at least one episode of bradycardia during hospitalisation. Bradycardia was present in 12 (7.5%) patients before treatment with remdesivir. The rate of bradycardia increased up to the 6th day of hospitalisation (40.6%) and subsequently diminished and normalised within 5 days after the last remdesivir dose (5% at Day 10). Severe bradycardia was observed in 13 (7.5%) patients. No difference was observed in ICU admission between groups (bradycardia vs no bradycardia). When we stratified patients according to the outcome of hospitalisation, no significant difference was observed in the occurrence of bradycardia between groups (alive vs dead) [p = 0.853]. CONCLUSIONS: Treatment with remdesivir may be associated with new-onset bradycardia in hospitalised patients with COVID-19. However, bradycardia is transient and is not associated with ICU admission and mortality.


Subject(s)
COVID-19 , Humans , COVID-19/drug therapy , Retrospective Studies , SARS-CoV-2 , Treatment Outcome , Adenosine Monophosphate/adverse effects
7.
Pharm Pat Anal ; 11(2): 57-73, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1875949

ABSTRACT

By December 2021, the COVID-19 caused approximately 6.1 million deaths around the world. Several vaccines have been approved, but there is still a need for non-prophylactic treatments for COVID-19. Remdesivir is an antiviral drug approved for emergency use against COVID-19 in several countries, but one of the first clinical trials was inconclusive about the mortality reduction, although the drug showed a reduction in the recovery time of hospitalized patients. Thus, the present investigation revisits the clinical evidence of using remdesivir for COVID-19 treatment, patent status, pharmacology and chemistry. We found 184 families of patents in the Cortellis database, and concerning the clinical evidence, we retrieved 14 systematic reviews with meta-analysis involving remdesivir as a treatment for COVID-19, discussing the reduction of adverse events, hospitalization days, mortality rate and the mechanical ventilation period.


Subject(s)
COVID-19 , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/adverse effects , COVID-19/drug therapy , Humans , SARS-CoV-2
9.
BMJ Open ; 12(3): e048502, 2022 03 02.
Article in English | MEDLINE | ID: covidwho-1822067

ABSTRACT

BACKGROUND: To summarise specific adverse effects of remdesivir, hydroxychloroquine and lopinavir/ritonavir in patients with COVID-19. METHODS: We searched 32 databases through 27 October 2020. We included randomised trials comparing any of the drugs of interest to placebo or standard care, or against each other. We conducted fixed-effects pairwise meta-analysis and assessed the certainty of evidence using the grading of recommendations assessment, development and evaluation approach. RESULTS: We included 16 randomised trials which enrolled 8152 patients. For most interventions and outcomes the certainty of the evidence was very low to low except for gastrointestinal adverse effects from hydroxychloroquine, which was moderate certainty. Compared with standard care or placebo, low certainty evidence suggests that remdesivir may not have an important effect on acute kidney injury (risk difference (RD) 8 fewer per 1000, 95% CI 27 fewer to 21 more) or cognitive dysfunction/delirium (RD 3 more per 1000, 95% CI 12 fewer to 19 more). Low certainty evidence suggests that hydroxychloroquine may increase the risk of cardiac toxicity (RD 10 more per 1000, 95% CI 0 more to 30 more) and cognitive dysfunction/delirium (RD 33 more per 1000, 95% CI 18 fewer to 84 more), whereas moderate certainty evidence suggests hydroxychloroquine probably increases the risk of diarrhoea (RD 106 more per 1000, 95% CI 48 more to 175 more) and nausea and/or vomiting (RD 62 more per 1000, 95% CI 23 more to 110 more) compared with standard care or placebo. Low certainty evidence suggests lopinavir/ritonavir may increase the risk of diarrhoea (RD 168 more per 1000, 95% CI 58 more to 330 more) and nausea and/or vomiting (RD 160 more per 1000, 95% CI 100 more to 210 more) compared with standard care or placebo. DISCUSSION: Hydroxychloroquine probably increases the risk of diarrhoea and nausea and/or vomiting and may increase the risk of cardiac toxicity and cognitive dysfunction/delirium. Lopinavir/ritonavir may increase the risk of diarrhoea and nausea and/or vomiting. Remdesivir may have no important effect on risk of acute kidney injury or cognitive dysfunction/delirium. These findings provide important information to support the development of evidence-based management strategies for patients with COVID-19.


Subject(s)
Adenosine Monophosphate/adverse effects , Alanine/adverse effects , COVID-19 , Hydroxychloroquine , Lopinavir/adverse effects , Ritonavir/adverse effects , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , COVID-19/drug therapy , Drug Combinations , Humans , Hydroxychloroquine/adverse effects , Randomized Controlled Trials as Topic , SARS-CoV-2
10.
J Med Virol ; 94(8): 3783-3790, 2022 08.
Article in English | MEDLINE | ID: covidwho-1819371

ABSTRACT

We aimed to assess longitudinal changes in clinical indexes of corona disease 2019 (Covid-19) patients with mild pulmonary infection during 5 days of remdesivir therapy and determine the effect of age and gender on remdesivir adverse effects (AE). Patients' clinical data including inflammatory markers, liver and renal function tests, and heart rate (HR) were extracted from medical records. Linear mixed model (LMM) was used to analyze longitudinal changes in patients' clinical indexes. Gender and age were inserted in LMM as covariates to find their correlation with AE and clinical indexes. Of 84 patients, 35 patients met our criteria for the study. There were significant increases in mean levels of white blood cell (WBC; p = 0.005), alanine aminotransferase (ALT; p = 0.001), aspartate aminotransferase (p = 0.001), blood urea nitrogen (BUN; p = 0.001), and creatinine (p = 0.006), whereas mean levels of erythrocyte sedimentation rate (p = 0.005), C-reactive protein (p = 0.001), alkaline phosphatase (p = 0.001), and potassium (p = 0.003) decreased significantly. Estimated glomerular filtration rate (p = 0.001) and HR (p = 0.001) showed a notable decline over the course of treatment. LMM analysis showed that mean changes in WBC (ß = 0.94, p = 0.029), creatinine (ß = 0.12, p = 0.020), and HR (ß = 6.47, p = 0.008) were greater in males than in females. Also, age of patients had a significant effect on the mean changes of WBC (ß = -0.02, p = 0.023), sodium (ß = -0.06, p = 0.010), BUN (ß = 0.23, p = 0.001), and HR (ß = -0.29, p = 0.001). Despite no renal and liver dysfunction, Covid-19 patients with mild pulmonary infection may develop some remdesivir AE and attributed side effects might be affected by gender and age of patients.


Subject(s)
COVID-19 , Drug-Related Side Effects and Adverse Reactions , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/analogs & derivatives , Alanine/adverse effects , Alanine/analogs & derivatives , COVID-19/drug therapy , Creatinine , Female , Humans , Male
12.
Ann Intern Med ; 175(2): 234-243, 2022 02.
Article in English | MEDLINE | ID: covidwho-1753917

ABSTRACT

BACKGROUND: In a randomized, placebo-controlled, clinical trial, bamlanivimab, a SARS-CoV-2-neutralizing monoclonal antibody, given in combination with remdesivir, did not improve outcomes among hospitalized patients with COVID-19 based on an early futility assessment. OBJECTIVE: To evaluate the a priori hypothesis that bamlanivimab has greater benefit in patients without detectable levels of endogenous neutralizing antibody (nAb) at study entry than in those with antibodies, especially if viral levels are high. DESIGN: Randomized, placebo-controlled trial. (ClinicalTrials.gov: NCT04501978). SETTING: Multicenter trial. PATIENTS: Hospitalized patients with COVID-19 without end-organ failure. INTERVENTION: Bamlanivimab (7000 mg) or placebo. MEASUREMENTS: Antibody, antigen, and viral RNA levels were centrally measured on stored specimens collected at baseline. Patients were followed for 90 days for sustained recovery (defined as discharge to home and remaining home for 14 consecutive days) and a composite safety outcome (death, serious adverse events, organ failure, or serious infections). RESULTS: Among 314 participants (163 receiving bamlanivimab and 151 placebo), the median time to sustained recovery was 19 days and did not differ between the bamlanivimab and placebo groups (subhazard ratio [sHR], 0.99 [95% CI, 0.79 to 1.22]; sHR > 1 favors bamlanivimab). At entry, 50% evidenced production of anti-spike nAbs; 50% had SARS-CoV-2 nucleocapsid plasma antigen levels of at least 1000 ng/L. Among those without and with nAbs at study entry, the sHRs were 1.24 (CI, 0.90 to 1.70) and 0.74 (CI, 0.54 to 1.00), respectively (nominal P for interaction = 0.018). The sHR (bamlanivimab vs. placebo) was also more than 1 for those with plasma antigen or nasal viral RNA levels above median level at entry and was greatest for those without antibodies and with elevated levels of antigen (sHR, 1.48 [CI, 0.99 to 2.23]) or viral RNA (sHR, 1.89 [CI, 1.23 to 2.91]). Hazard ratios for the composite safety outcome (<1 favors bamlanivimab) also differed by serostatus at entry: 0.67 (CI, 0.37 to 1.20) for those without and 1.79 (CI, 0.92 to 3.48) for those with nAbs. LIMITATION: Subgroup analysis of a trial prematurely stopped because of futility; small sample size; multiple subgroups analyzed. CONCLUSION: Efficacy and safety of bamlanivimab may differ depending on whether an endogenous nAb response has been mounted. The limited sample size of the study does not allow firm conclusions based on these findings, and further independent trials are required that assess other types of passive immune therapies in the same patient setting. PRIMARY FUNDING SOURCE: U.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Neutralizing/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/therapeutic use , Aged , Alanine/adverse effects , Alanine/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Neutralizing/adverse effects , Antibodies, Neutralizing/blood , Antigens, Viral/blood , Antiviral Agents/adverse effects , Biomarkers/blood , COVID-19/blood , COVID-19/virology , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Male , Medical Futility , Middle Aged , RNA, Viral/blood , SARS-CoV-2 , Treatment Failure
13.
Ann Intern Med ; 175(5): 701-709, 2022 05.
Article in English | MEDLINE | ID: covidwho-1716081

ABSTRACT

BACKGROUND: Remdesivir is approved for the treatment of adults hospitalized with COVID-19. PURPOSE: To update a living review of remdesivir for adults with COVID-19. DATA SOURCES: Several electronic U.S. Food and Drug Administration, company, and journal websites from 1 January 2020 through 19 October 2021. STUDY SELECTION: English-language, randomized controlled trials (RCTs) of remdesivir for COVID-19. DATA EXTRACTION: One reviewer abstracted, and a second reviewer verified data. The Cochrane Risk of Bias Tool and GRADE (Grading of Recommendations Assessment, Development and Evaluation) method were used. DATA SYNTHESIS: Since the last update (search date 9 August 2021), 1 new RCT and 1 new subtrial comparing a 10-day course of remdesivir with control (placebo or standard care) were identified. This review summarizes and updates the evidence on the cumulative 5 RCTs and 2 subtrials for this comparison. Our updated results confirm a 10-day course of remdesivir, compared with control, probably results in little to no mortality reduction (5 RCTs). Updated results also confirm that remdesivir probably results in a moderate increase in the proportion of patients recovered by day 29 (4 RCTs) and may reduce time to clinical improvement (2 RCTs) and hospital length of stay (4 RCTs). New RCTs, by increasing the strength of evidence, lead to an updated conclusion that remdesivir probably results in a small reduction in the proportion of patients receiving ventilation or extracorporeal membrane oxygenation at specific follow-up times (4 RCTs). New RCTs also alter the conclusions for harms-remdesivir, compared with control, may lead to a small reduction in serious adverse events but may lead to a small increase in any adverse event. LIMITATION: The RCTs differed in definitions of COVID-19 severity and outcomes reported. CONCLUSION: In hospitalized adults with COVID-19, the findings confirm that remdesivir probably results in little to no difference in mortality and increases the proportion of patients recovered. Remdesivir may reduce time to clinical improvement and may lead to small reductions in serious adverse events but may result in a small increase in any adverse event. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs.


Subject(s)
Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , COVID-19 , Physicians , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/analogs & derivatives , Adult , Alanine/therapeutic use , COVID-19/drug therapy , Humans , United States
14.
CMAJ ; 194(7): E242-E251, 2022 02 22.
Article in English | MEDLINE | ID: covidwho-1714791

ABSTRACT

BACKGROUND: The role of remdesivir in the treatment of patients in hospital with COVID-19 remains ill defined in a global context. The World Health Organization Solidarity randomized controlled trial (RCT) evaluated remdesivir in patients across many countries, with Canada enrolling patients using an expanded data collection format in the Canadian Treatments for COVID-19 (CATCO) trial. We report on the Canadian findings, with additional demographics, characteristics and clinical outcomes, to explore the potential for differential effects across different health care systems. METHODS: We performed an open-label, pragmatic RCT in Canadian hospitals, in conjunction with the Solidarity trial. We randomized patients to 10 days of remdesivir (200 mg intravenously [IV] on day 0, followed by 100 mg IV daily), plus standard care, or standard care alone. The primary outcome was in-hospital mortality. Secondary outcomes included changes in clinical severity, oxygen- and ventilator-free days (at 28 d), incidence of new oxygen or mechanical ventilation use, duration of hospital stay, and adverse event rates. We performed a priori subgroup analyses according to duration of symptoms before enrolment, age, sex and severity of symptoms on presentation. RESULTS: Across 52 Canadian hospitals, we randomized 1282 patients between Aug. 14, 2020, and Apr. 1, 2021, to remdesivir (n = 634) or standard of care (n = 648). Of these, 15 withdrew consent or were still in hospital, for a total sample of 1267 patients. Among patients assigned to receive remdesivir, in-hospital mortality was 18.7%, compared with 22.6% in the standard-of-care arm (relative risk [RR] 0.83 (95% confidence interval [CI] 0.67 to 1.03), and 60-day mortality was 24.8% and 28.2%, respectively (95% CI 0.72 to 1.07). For patients not mechanically ventilated at baseline, the need for mechanical ventilation was 8.0% in those assigned remdesivir, and 15.0% in those receiving standard of care (RR 0.53, 95% CI 0.38 to 0.75). Mean oxygen-free and ventilator-free days at day 28 were 15.9 (± standard deviation [SD] 10.5) and 21.4 (± SD 11.3) in those receiving remdesivir and 14.2 (± SD 11) and 19.5 (± SD 12.3) in those receiving standard of care (p = 0.006 and 0.007, respectively). There was no difference in safety events of new dialysis, change in creatinine, or new hepatic dysfunction between the 2 groups. INTERPRETATION: Remdesivir, when compared with standard of care, has a modest but significant effect on outcomes important to patients and health systems, such as the need for mechanical ventilation. Trial registration: ClinicalTrials.gov, no. NCT04330690.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/administration & dosage , COVID-19/drug therapy , Hospital Mortality , Length of Stay/statistics & numerical data , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/adverse effects , Aged , Alanine/administration & dosage , Alanine/adverse effects , Antiviral Agents/adverse effects , COVID-19/epidemiology , COVID-19/mortality , Canada/epidemiology , Comorbidity , Female , Humans , Male , Middle Aged , Pandemics , Respiration, Artificial/statistics & numerical data , SARS-CoV-2
16.
N Engl J Med ; 386(4): 305-315, 2022 01 27.
Article in English | MEDLINE | ID: covidwho-1585665

ABSTRACT

BACKGROUND: Remdesivir improves clinical outcomes in patients hospitalized with moderate-to-severe coronavirus disease 2019 (Covid-19). Whether the use of remdesivir in symptomatic, nonhospitalized patients with Covid-19 who are at high risk for disease progression prevents hospitalization is uncertain. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving nonhospitalized patients with Covid-19 who had symptom onset within the previous 7 days and who had at least one risk factor for disease progression (age ≥60 years, obesity, or certain coexisting medical conditions). Patients were randomly assigned to receive intravenous remdesivir (200 mg on day 1 and 100 mg on days 2 and 3) or placebo. The primary efficacy end point was a composite of Covid-19-related hospitalization or death from any cause by day 28. The primary safety end point was any adverse event. A secondary end point was a composite of a Covid-19-related medically attended visit or death from any cause by day 28. RESULTS: A total of 562 patients who underwent randomization and received at least one dose of remdesivir or placebo were included in the analyses: 279 patients in the remdesivir group and 283 in the placebo group. The mean age was 50 years, 47.9% of the patients were women, and 41.8% were Hispanic or Latinx. The most common coexisting conditions were diabetes mellitus (61.6%), obesity (55.2%), and hypertension (47.7%). Covid-19-related hospitalization or death from any cause occurred in 2 patients (0.7%) in the remdesivir group and in 15 (5.3%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.03 to 0.59; P = 0.008). A total of 4 of 246 patients (1.6%) in the remdesivir group and 21 of 252 (8.3%) in the placebo group had a Covid-19-related medically attended visit by day 28 (hazard ratio, 0.19; 95% CI, 0.07 to 0.56). No patients had died by day 28. Adverse events occurred in 42.3% of the patients in the remdesivir group and in 46.3% of those in the placebo group. CONCLUSIONS: Among nonhospitalized patients who were at high risk for Covid-19 progression, a 3-day course of remdesivir had an acceptable safety profile and resulted in an 87% lower risk of hospitalization or death than placebo. (Funded by Gilead Sciences; PINETREE ClinicalTrials.gov number, NCT04501952; EudraCT number, 2020-003510-12.).


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/therapeutic use , Adult , Aged , Aged, 80 and over , Alanine/adverse effects , Alanine/therapeutic use , Antiviral Agents/adverse effects , COVID-19/complications , COVID-19/mortality , Comorbidity , Disease Progression , Double-Blind Method , Female , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Outpatients , SARS-CoV-2/drug effects , Time-to-Treatment , Viral Load
17.
Eur J Pharmacol ; 914: 174615, 2022 Jan 05.
Article in English | MEDLINE | ID: covidwho-1549762

ABSTRACT

In this study, the therapeutic efficacy of quercetin in combination with remdesivir and favipiravir, were evaluated in severe hospitalized COVID-19 patients. Our main objective was to assess the ability of quercetin for preventing the progression of the disease into critical phase, and reducing the levels of inflammatory markers related to SARS-Cov-2 pathogenesis. Through an open-label clinical trial, 60 severe cases were randomly divided into control and intervention groups. During a 7-day period, patients in the control group received antivirals, i.e., remdesivir or favipiravir, while the intervention group was treated with 1000 mg of quercetin daily in addition to the antiviral drugs. According to the results, taking quercetin was significantly associated with partial earlier discharge and reduced serum levels of ALP, q-CRP, and LDH in the intervention group. Furthermore, although the values were in normal range, the statistical outputs showed significant increase in hemoglobin level and respiratory rate in patients who were taking quercetin. Based on our observations, quercetin is safe and effective in lowering the serum levels of ALP, q-CRP, and LDH as critical markers involved in COVID-19 severity. However, according to the non-significant borderline results in comparing the mortality, the ICU-admission rate, and the duration of ICU-admission, further studies can be helpful to compensate the limitations of our study and clarify the therapeutic potential of quercetin in COVID-19 treatments.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Amides , COVID-19 , Pyrazines , Quercetin , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/adverse effects , Alanine/administration & dosage , Alanine/adverse effects , Amides/administration & dosage , Amides/adverse effects , Antioxidants/administration & dosage , Antioxidants/adverse effects , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Biomarkers/blood , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/immunology , COVID-19/mortality , Drug Monitoring/methods , Drug Monitoring/statistics & numerical data , Female , Hemoglobins/analysis , Humans , Male , Middle Aged , Outcome and Process Assessment, Health Care , Patient Discharge/statistics & numerical data , Pyrazines/administration & dosage , Pyrazines/adverse effects , Quercetin/administration & dosage , Quercetin/adverse effects , Respiratory Rate/drug effects
18.
Sci Rep ; 11(1): 23205, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1545647

ABSTRACT

The association between pulmonary sequelae and markers of disease severity, as well as pro-fibrotic mediators, were studied in 108 patients 3 months after hospital admission for COVID-19. The COPD assessment test (CAT-score), spirometry, diffusion capacity of the lungs (DLCO), and chest-CT were performed at 23 Norwegian hospitals included in the NOR-SOLIDARITY trial, an open-labelled, randomised clinical trial, investigating the efficacy of remdesivir and hydroxychloroquine (HCQ). Thirty-eight percent had a CAT-score ≥ 10. DLCO was below the lower limit of normal in 29.6%. Ground-glass opacities were present in 39.8% on chest-CT, parenchymal bands were found in 41.7%. At admission, low pO2/FiO2 ratio, ICU treatment, high viral load, and low antibody levels, were predictors of a poorer pulmonary outcome after 3 months. High levels of matrix metalloproteinase (MMP)-9 during hospitalisation and at 3 months were associated with persistent CT-findings. Except for a negative effect of remdesivir on CAT-score, we found no effect of remdesivir or HCQ on long-term pulmonary outcomes. Three months after hospital admission for COVID-19, a high prevalence of respiratory symptoms, reduced DLCO, and persistent CT-findings was observed. Low pO2/FiO2 ratio, ICU-admission, high viral load, low antibody levels, and high levels of MMP-9 were associated with a worse pulmonary outcome.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , COVID-19/drug therapy , Hydroxychloroquine/adverse effects , Lung Diseases/pathology , Matrix Metalloproteinase 9/metabolism , SARS-CoV-2/drug effects , Viral Load , Adenosine Monophosphate/adverse effects , Aged , Alanine/adverse effects , Antibody Formation , Antimalarials/adverse effects , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , COVID-19/virology , Female , Hospitalization , Humans , Lung Diseases/chemically induced , Lung Diseases/enzymology , Lung Diseases/virology , Male , Middle Aged , Severity of Illness Index
19.
Mini Rev Med Chem ; 21(17): 2530-2543, 2021.
Article in English | MEDLINE | ID: covidwho-1504184

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus strain and the causative agent of COVID-19 was emerged in Wuhan, China, in December 2019 [1]. This pandemic situation and magnitude of suffering have led to global effort to find out effective measures for discovery of new specific drugs and vaccines to combat this deadly disease. In addition to many initiatives to develop vaccines for protective immunity against SARS-CoV-2, some of which are at various stages of clinical trials, researchers worldwide are currently using available conventional therapeutic drugs with the potential to combat the disease effectively in other viral infections and it is believed that these antiviral drugs could act as a promising immediate alternative. Remdesivir (RDV), a broad-spectrum anti-viral agent, initially developed for the treatment of Ebola virus (EBOV) and known to showed promising efficiency in in vitro and in vivo studies against SARS and MERS coronaviruses, is now being investigated against SARS-CoV-2. On May 1, 2020, The U.S. Food and Drug Administration (FDA) granted Emergency Use Authorization (EUA) for RDV to treat COVID- 19 patients [2]. A number of multicentre clinical trials are on-going to check the safety and efficacy of RDV for the treatment of COVID-19. Results of published double blind, and placebo-controlled trial on RDV against SARS-CoV-2, showed that RDV administration led to faster clinical improvement in severe COVID-19 patients compared to placebo. This review highlights the available knowledge about RDV as a therapeutic drug for coronaviruses and its preclinical and clinical trials against COVID-19.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , COVID-19/drug therapy , SARS-CoV-2/drug effects , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/pharmacology , Adenosine Monophosphate/therapeutic use , Alanine/adverse effects , Alanine/pharmacology , Alanine/therapeutic use , Animals , Antiviral Agents/adverse effects , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/virology , Humans , Randomized Controlled Trials as Topic
20.
Clin Transl Sci ; 15(2): 501-513, 2022 02.
Article in English | MEDLINE | ID: covidwho-1494654

ABSTRACT

On October 2020, the US Food and Drug Administration (FDA) approved remdesivir as the first drug for the treatment of coronavirus disease 2019 (COVID-19), increasing remdesivir prescriptions worldwide. However, potential cardiovascular (CV) toxicities associated with remdesivir remain unknown. We aimed to characterize the CV adverse drug reactions (ADRs) associated with remdesivir using VigiBase, an individual case safety report database of the World Health Organization (WHO). Disproportionality analyses of CV-ADRs associated with remdesivir were performed using reported odds ratios and information components. We conducted in vitro experiments using cardiomyocytes derived from human pluripotent stem cell cardiomyocytes (hPSC-CMs) to confirm cardiotoxicity of remdesivir. To distinguish drug-induced CV-ADRs from COVID-19 effects, we restricted analyses to patients with COVID-19 and found that, after adjusting for multiple confounders, cardiac arrest (adjusted odds ratio [aOR]: 1.88, 95% confidence interval [CI]: 1.08-3.29), bradycardia (aOR: 2.09, 95% CI: 1.24-3.53), and hypotension (aOR: 1.67, 95% CI: 1.03-2.73) were associated with remdesivir. In vitro data demonstrated that remdesivir reduced the cell viability of hPSC-CMs in time- and dose-dependent manners. Physicians should be aware of potential CV consequences following remdesivir use and implement adequate CV monitoring to maintain a tolerable safety margin.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/adverse effects , COVID-19/drug therapy , Cardiovascular Diseases/chemically induced , Pharmacovigilance , SARS-CoV-2 , Adenosine Monophosphate/adverse effects , Alanine/adverse effects , Databases, Factual , Humans , Myocytes, Cardiac/drug effects , Retrospective Studies , World Health Organization
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