Early triple antiviral therapy for COVID-19.
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ABSTRACT:
SUBMITTER: Lee N
PROVIDER: S-EPMC7836694 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
Publications
Early triple antiviral therapy for COVID-19.
Lee Nelson N Ison Michael M Dunning Jake J
Lancet (London, England) 20201101 10261
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Project description:Since the first case was reported in Wuhan, Hubei Province, China on December 12, 2019, Coronavirus disease 2019 (COVID-19) has spread widely to other countries since January 2020. As of April 16, 2020, 10635 confirmed cases have been reported, with 230 deaths in Korea. COVID-19 patients may be asymptomatic or show various clinical manifestations, including acute symptoms such as fever, fatigue, sore throat; pneumonia presenting as acute respiratory distress syndrome; and multiple organ failure. As COVID-19 has such varied clinical manifestations and case fatality rates, no standard antiviral therapy regimen has been established other than supportive therapy. In the present guideline, we aim to introduce potentially helpful antiviral and other drug therapies based on in vivo and in vitro research and clinical experiences from many countries.
| S-EPMC7335642 | biostudies-literature
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| S-EPMC10644264 | biostudies-literature
Project description:Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk-factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data, and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific autoantibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.
2022-02-01 | E-MTAB-10129 | biostudies-arrayexpress
Project description:BackgroundBased on current evidence, recent guidelines of the National Institute of Health, USA indicated the use of remdesivir and dexamethasone for the treatment of COVID-19 patients with mild-moderate disease, not requiring high-flow oxygen. No therapeutic agent directed against the immunologic pathogenic mechanisms related to the cytokine release syndrome complicating the disease was indicated.ObjectivesThe purpose of this review was to assess the clinical impact of different therapies for COVID-19; thus, helping to identify the optimal management of the disease. To explain the rationale for the different therapeutic approaches, the characteristics of SARS-CoV-2, the pathogenesis of COVID-19, and the immune response triggered by SARS-CoV-2 infection were reported.MethodsThe efficacy assessment of the different treatments was performed by a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Available English language published articles including randomised controlled trials, open-label trials of antivirals and immune therapies extracted from Medline, Google Scholar, and MedRxiv databases were analysed. For inclusion, the primary end point of the trials had to be the efficacy as measured by the improvement of clinical features, or mortality, or the Intensive Care Unit Admission rate, or the discharge number. Case reports, paediatric studies, and studies without control group were excluded. The literature search was extended up to August 15, 2020.ResultsAfter the removal of duplicate articles, and the exclusion of studies not meeting the eligibility criteria, 2 trials of lopinavir/ritonavir, 1 of favipiravir, 3 of remdesivir, 1 of dexamethasone, 3 of hydroxychloroquine, 2 of colchicine, 6 of tocilizumab, 1 of sarilumab, 1 of siltuximab, 2 of anakinra, 3 of baricitinib, 1 of ruxolitinib, 1 of mavrilimumab, and 1 of itolizumab were suitable for the review. Among antivirals, only remdesivir significantly reduced the time to recovery, and mortality. Data for chloroquine and hydroxychloroquine were largely inconclusive. In a large trial, dexamethasone 6 mg/day reduced mortality by one-third. Trials of tocilizumab and sarilumab did not definitively demonstrate efficacy. Anakinra significantly reduced the mortality in 2 trials. Three retrospective trials on a cumulative number of 145 patients, reported the efficacy of baricitinib, with significant reduction of intensive care unit admission, and deaths. These results were recently confirmed by the ACTT-2 trial. Due to paucity of studies and to the small size clinical series, the results of other immune therapies were not conclusive.ConclusionsBeyond the supportive therapy, up to now the best therapeutic approach for COVID-19 may be a three-step combination therapy, including remdesivir 100 mg/day (200 mg loading dose on first day) in the first stage of the disease, and combined dexamethasone 6 mg/day plus baricitinib 4 mg/day to target the immune dysregulation triggered by the SARS-CoV-2 infection. The promising results of anakinra should be confirmed by the ongoing RCTs.
| S-EPMC7568461 | biostudies-literature
Project description:To address the COVID-19 pandemic, there has been an unprecedented global effort to advance potent neutralizing mAbs against SARS-CoV-2 as therapeutics. However, historical efforts to advance antiviral monoclonal antibodies (mAbs) for the treatment of other respiratory infections have been met with categorical failures in the clinic. By investigating the mechanism by which SARS-CoV-2 and similar viruses spread within the lung, along with available biodistribution data for systemically injected mAb, we highlight the challenges faced by current antiviral mAbs for COVID-19. We summarize some of the leading mAbs currently in development, and present the evidence supporting inhaled delivery of antiviral mAb as an early intervention against COVID-19 that could prevent important pulmonary morbidities associated with the infection.
| S-EPMC7833882 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now a global outbreak of disease. The antiviral treatment acts as one of the most important means of SARS-CoV-2 infection. Alteration of physiological characteristics in special populations may lead to the change in drug pharmacokinetics, which may result in treatment failure or increased adverse drug reactions. Some potential drugs have shown antiviral effects on SARS-CoV-2 infections, such as chloroquine, hydroxychloroquine, favipiravir, lopinavir/ritonavir, arbidol, interferon alpha, and remedsivir. Here, we reviewed the literature on clinical effects in COVID-19 patients of these antiviral agents and provided the potential antiviral agent options for pregnant women, elderly patients, liver or renal dysfunction patients, and severe or critically ill patients receiving renal replacement therapy or ECMO after SARS-CoV-2 infection.
| S-EPMC7396737 | biostudies-literature
Project description:Favipiravir, a broad-spectrum RNA-dependent RNA polymerase inhibitor, inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at significantly lower concentrations than the plasma trough levels achieved by the dosage adopted for influenza treatment and exhibits efficacy against coronavirus disease 2019 (COVID-19) pneumonia. Although high doses of favipiravir are required due to the molecule being a purine analog, its conversion into the active form in infected cells with active viral RNA synthesis enhances the antiviral specificity and selectivity as a chain terminator with lethal mutagenesis. Another characteristic feature is the lack of generation of favipiravir-resistant virus. COVID-19 pneumonia is caused by strong cell-mediated immunity against virus-infected cells, and the inflammatory response induced by adaptive immunity continues to peak for 3 to 5 days despite antiviral treatment. This has also been observed in herpes zoster (HZ) and cytomegalovirus (CMV) pneumonia. Inflammation due to an immune response may mask the effectiveness of favipiravir against COVID-19 pneumonia. Favipiravir significantly shortened the recovery time in patients with mild COVID-19 pneumonia by 3 days with the start of treatment by the 5th day of symptom onset. Since both CMV and COVID-19 pneumonia are caused by adaptive immunity and prevention of cytomegalovirus pneumonia is the standard treatment due to difficulties in treating refractory CMV pneumonia, COVID-19 pneumonia should be prevented with early treatment as well. In the present study, we have comprehensively reviewed the optimal antiviral therapy for COVID-19 based on clinical trials of favipiravir for the treatment of COVID-19 pneumonia and the concurrently established therapies for other viral infections, particularly HZ and CMV pneumonia. Optimally, antivirals should be administered immediately after COVID-19 diagnosis, similar to that after influenza diagnosis, to prevent COVID-19 pneumonia and complications resulting from microangiopathy.
| S-EPMC8806403 | biostudies-literature
Project description:The outbreak of COVID-19, caused by severe acute respiratory syndrome coronavirus 2, started in December 2019, Wuhan, China. We aimed to figure out the time-point and duration of using antiviral drugs for receiving the maximal effects in patients with COVID-19. In this study, we enrolled 129 confirmed COVID-19 mild to moderate patients who had been treated with antiviral drugs during their hospitalization in Wuhan Union Hospital China. The patients were divided into an early antiviral treatment group and late antiviral treatment group. The demographic data, laboratory tests, the virus clearance time, chest computed tomography scans, and so forth were extracted, calculated, and compared between two groups. Our data showed that the median time from illness onset to initiation of antiviral treatment was 6 days in all patients. The group with early antiviral treatment demonstrated 7 days shorter in the virus clearance time when compared to the group with late antiviral treatment. After virus clearance, the group with early antiviral treatment showed milder illness than the group with late antiviral treatment. Early antiviral treatment could effectively shorten the virus clearance time, and prevent the rapid progression of COVID-19. Therefore, the COVID-19 patients should receive combined therapies with antiviral treatment at an early stage.
| S-EPMC7300891 | biostudies-literature
Project description:The vaccine weapon has resulted in being essential in fighting the COVID-19 outbreak, but it is not fully preventing infection due to an alarming spreading of several identified variants of concern. In fact, the recent emergence of variants has pointed out how the SARS-CoV-2 pandemic still represents a global health threat. Moreover, oral antivirals also develop resistance, supporting the need to find new targets as therapeutic tools. However, cocktail therapy is useful to reduce drug resistance and maximize vaccination efficacy. Natural products and metal-drug-based treatments have also shown interesting antiviral activity, representing a valid contribution to counter COVID-19 outbreak. This report summarizes the available evidence which supports the use of approved drugs and further focuses on significant clinical trials that have investigated the safety and efficacy of repurposing drugs and new molecules in different COVID-19 phenotypes. To date, there are many individuals vulnerable to COVID-19 exhibiting severe symptoms, thus characterizing valid therapeutic strategies for better management of the disease is still a challenge.
| S-EPMC9687182 | biostudies-literature
Project description:ObjectiveThe use of remdesivir for pregnant patients with coronavirus disease 2019 (COVID-19) showed conflicting results in prior studies. We aimed to systematically review its efficacy and safety for this population from the existing literature.MethodsOn July 26, 2021, registries (ClinicalTrials.gov) and databases (MEDLINE, ScienceDirect, Cochrane Library, JSTOR, DOAJ, and medRxiv) were systematically searched for research articles investigating remdesivir use in pregnant people with COVID-19. Clinical outcome, hospitalization duration, laboratory outcome, mortality, and adverse events were investigated.ResultsWe obtained 13 observation studies with 113 pregnant people. In these studies, remdesivir improved the clinical condition of pregnant patients with COVID-19, especially those who had a better clinical status at baseline and received earlier remdesivir treatment. Most fetuses were delivered via cesarean section, primarily because of emergency causes. No vertical transmissions were noted. The most reported adverse event was transaminitis, in which 10-day remdesivir treatment yielded more incidence than the 5-day treatment.ConclusionsIn pregnancy, the use of Remdesivir in combination with other COVID-19 treatments is inconclusive but its use should be followed with careful monitoring of adverse reactions and transaminase enzyme levels. Further studies are required to confirm its finding.
| S-EPMC8802673 | biostudies-literature