A randomized placebo controlled clinical trial using Homoeopathy as an adjuvant to standard care in the management of COVID-19

Inappropriate use of ivermectin during the COVID-19 pandemic: primum non nocere!

Non-invasive respiratory support strategies in COVID-19

Background: With the COVID-19 pandemic, the need for pharmacological and clinical studies in the search for substances with anti-inflammatory action became evident. To perform a systematic review of randomized controlled trials that evaluated the efficacy and safety of quercetin as a treatment and prevention option for COVID-19 in humans relative to an active comparator, placebo, or standard care alone. Methods: The search for studies was carried out in the following databases: Medline via PubMed, LILACS, Science Direct, Web of Science, and Scopus via Capes periodicals with the descriptors: “Quercetin” AND ''COVID-19” AND “randomized controlled trial”. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Protocol registration number in the PROSPERO database: CRD42022359842, available: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022359842.Results: 455 articles were found, and after reading the titles, abstracts, and full text, only 8 randomized clinical trials were included. According to the Cochrane RoB 2 tool, most included studies have some concerns about the risk of bias. The use of quercetin in the treatment and prevention of COVID-19 contributed to the rapid evolution of patients compared to standard treatment and protected them against the development of COVID-19 compared to placebo. No adverse events were reported. Conclusion: It is inferred that drug supplementation with quercetin can help in the treatment and prevention of COVID-19, reducing recovery time, laboratory parameters and symptom manifestation, when compared to standard treatment. Thus, further research is needed to confirm the relationship between quercetin in the immune system and the development of COVID-19 in its most severe form. A systematic review carried out with randomized clinical trials for quercetin in COVID-19 is not yet available in the indexes, and this work is unprecedented.

The effect of quercetin on the prevention or treatment of COVID-19 and other respiratory tract infections in humans: A rapid review

Decision letter: Concentration-dependent mortality of chloroquine in overdose

The COVID-19 pandemic required the rapid development of COVID-19 vaccines and treatments, necessitating quick yet representative clinical trial enrollment to evaluate these preventive measures. However, misinformation around the COVID-19 pandemic and general concerns about clinical trial participation in the U.S. hindered clinical trial enrollment. This study assessed awareness of, willingness to participate in, and enrollment in COVID-19 vaccine and treatment clinical trials in Texas. A quota sample of 1,089 Texas residents was collected online from June – July 2022. Respondents were asked if they were aware of, willing to participate in, and had enrolled in clinical trials for COVID-19 vaccines or treatments. Overall, 45.8% of respondents reported being aware of clinical trials for COVID-19 treatments or vaccines, but only 21.7% knew how to enroll and only 13.2% had enrolled in a COVID-19 clinical trial. Respondents with bachelor’s or graduate degrees were more likely to be aware of clinical trials, more likely to have enrolled in trials, and more willing to participate in treatment trials. Women were less willing to participate and less likely to have enrolled in COVID-19 clinical trials than men. Respondents aged 55 years and older were more willing to participate, but less likely to have enrolled in COVID-19 clinical trials than 18-to-24-year-olds. Common reasons given for not participating in clinical trials included concerns that COVID-19 treatments may not be safe, government distrust, and uncertainty about what clinical trial participation would entail. Substantial progress is needed to build community awareness and increase enrollment in clinical trials.

IntroductionThis study, for the first time to our knowledge, evaluated the efficacy of ropeginterferon alfa-2b, a long-acting pegylated interferon (IFN)-alfa, in the treatment of COVID-19.MethodsWe retrospectively evaluated ropeginterferon alfa-2b administered subcutaneously at a single dose of 250 µg for the treatment of mild and moderate COVID-19. Primary outcome was to compare the overall negative conversion time from the confirmed, last positive SARS-CoV-2 RT-PCR to the first RT-PCR negative conversion between patients receiving ropeginterferon alfa-2b plus standard of care (SOC) and those receiving SOC alone.ResultsThirty-five patients with mild COVID-19 and 37 patients with moderate disease were included. Of them, 19 patients received SOC plus ropeginterferon alfa-2b and 53 patients received SOC alone. All patients with moderate disease in the ropeginterferon alfa-2b group showed RT-PCR negative conversion within 8 days, while a significant portion of patients in the SOC alone group failed to do so. For patients with moderate disease and age ≤ 65 years old, the ropeginterferon alfa-2b group had statistically significant shorter median RT-PCR conversion time than the SOC alone group (7 vs. 11.5 days, p < 0.05).ConclusionsRopeginterferon alfa-2b showed the potential for the treatment of moderate COVID-19 patients. A randomized, controlled Phase III study is planned to further assess the effectiveness of ropeginterferon alfa-2b in COVID-19 patients.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01998-y.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is severe pneumonia caused by an enveloped, single-stranded RNA beta coronavirus, belonging to the coronaviridae family. SARSCoV- 2 is due to severe hyperinflammation in response to the coronavirus 2 infection. This results in overproduction of cytokines, chemokines, and growth factors by macrophages, such as interleukin- 1β (IL-1β), IL-2, IL-6, IL-8, IL-10, and tumour necrosis factor-α, which cause lung and multi-organ damage. Covid-19 pneumonia is characterized by diffuse alveolar damage due to direct infection of alveolar type II pneumocytes, pulmonary enema, interstitial infiltrates, microthrombi, and ventilation/perfusion mismatch. Covid-19 is a progressive disease which ultimately results in acute respiratory distress syndrome, respiratory failure, multi-organ failure, and death. The standard of care of Covid-19, includes high-flow nasal oxygen (HFNO), dexamethasone, remdesivir, and mechanical ventilation or extracorporeal membrane oxygenation in severe disease. However, the mortality is exceptionally high even with these therapies. IL-6 plays a key role in orchestrating the hyperinflammation and the cytokine storm, which lead to respiratory failure, and multi-organ failure. Interleukin-6 signalling is via the transmembrane IL-6 receptor-α (mIL-6Rα), and the soluble IL- 6Rα. Tocilizumab, and sarilumab are IL-6Rα antagonists, and have been issued an emergency use authorization (EUA) by the FDA. Both biologics are safe, and effective in the treatment of severe Covid-19, particularly in patients requiring HFNO, and mechanical ventilation. Another therapeutic approach to treat Covid-19 is to target the downstream JAK/STAT pathway which plays a critical role in promoting IL-6, and other cytokines in orchestrating acute respiratory distress syndrome. Baricite and tofacitinib have been granted EUA by the FDA. Both Janus kinase inhibitors have been shown to significantly decrease odds of mortality, and ICU admission. Additionally, JAK inhibitors significantly increase odds for patients’ discharge within 2 weeks. Tofacitinib has been reported to lead to a lower risk of respiratory failure or death through day 28 than placebo in hospitalized patients with Covid-19. Baricitinib in addition to standard of care, including dexamethasone was associated with reduced mortality in hospitalized adults with Covid-19. Baricitinib is effective in reducing mortality in patients with Covid-19, even in progressive disease stages on mechanical ventilation. Selective JAK inhibitors in addition to usual care are effective in the treatment of hospitalized patients with Covid-19, and in reducing mortality. Keywords: Covid-19; Cytokine storm; Interleukin-6; Janus kinase; JAKinibs; Baricitinib

GM-CSF in the treatment of COVID-19: a new conductor in the pathogenesis of cytokine storm?

BackgroundConvalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX).MethodsIn this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence.ResultsA total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis.ConclusionsConvalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.

The materials of the clinical trial "Multicenter, randomized, double-blind study of the efficacy and tolerability of FLAVOVIR® (capsules) in patients with moderate COVID-19 receiving basic therapy are presented". The investigational drug FLAVOVIR® (capsules) is a development of LLC "SPC "Ecopharm", presented for clinical study, in order to prove antiviral activity against SARS-CoV-2 viruses and to resolve the issue of the possibility of registering the drug in Ukraine as a direct-acting antiviral agent. FLAVOVIR® (capsules) is a new dosage form of the drug PROTEFLAZID® (drops), registered in Ukraine in 2001 and widely used. A clinical trial was conducted to confirm the predominant efficacy of FLAVOVIR® (capsules) in course doses against the background of standard baseline therapy in patients with COVID-19, moderate severity compared to placebo against the background of standard baseline therapy in patients with moderate COVID-19. Materials and methods. The study subjects were 162 patients with COVID-19 of moderate severity. Patients based on the method of block randomization in a ratio of 1:1:1 were divided into 3 groups of 54 patients. Patients of group I were prescribed the investigational drug FLAVOVIR® (capsules), orally 1 capsule 2 times a day for 14 days and, at the same time, placebo 1 capsule 2 times a day for 14 days (to ensure "double masking") against the background of standard basic therapy. Group II patients were prescribed the drug FLAVOVIR® (capsules), orally 2 capsules 2 times a day for 14 days against the background of standard basic therapy. Patients of group III were prescribed a placebo, capsules, orally 2 capsules 2 times a day for 14 days against the background of standard basic therapy. The effectiveness of treatment was evaluated taking into account the following primary efficacy variables: - time (in days) before the onset of an event characterized by the absence of hyperthermia (&lt;37.0 °C) for at least 3 days in the absence or minimal severity of ARVI symptoms (≤1 point on a verbal analog scale: 0–3 points) within a 14-day period of taking the drug; - the time (in days) until the elimination of SARS-CoV-2 viruses from the nasopharyngeal smear within the 14-day period of taking the drug. The tolerance of the studied drugs was assessed on the basis of the patient's subjective complaints, the presence and severity of adverse reactions/side effects, the data of an objective examination of the patient and laboratory examination. Conclusions. Treatment with FLAVOVIR® (capsules) was found to be effective in 94.4% of group I patients, in 94.4% of group II patients and in 70.4% of group III patients. No statistically significant difference in the efficacy of treatment by primary variable between groups I and II was found. A statistically significant difference was found between groups I and III and groups II and III. The hypothesis of the prevailing efficacy of FLAVOVIR® (capsules) in two dosages compared to placebo against the background of standard baseline therapy in patients with moderate COVID-19. The study showed that the drug FLAVOVIR® (capsules) is effective in the treatment of patients with COVID-19, with a high percentage of positive results in groups I and II. Statistically significant differences between groups I and III and groups II and III have been demonstrated. The results of the study confirm the hypothesis about the effectiveness of FLAVOVIR® (capsules) in the treatment of COVID-19, which is an important contribution to clinical practice and scientific research. The drug FLAVOVIR® (capsules), which has a high potential as an antiviral agent in the treatment of moderate COVID-19, requires further research and registration in Ukraine.

Introduction Lopinavir in combination with ritonavir is approved for the treatment of HIV and has recently been subject to a clinical trial in severe COVID-19. Areas covered This evaluation is of LOTUS China (the Lopinavir Trial for Suppression of SARS-Cov-2 in China), which was a randomized trial in hospitalized subjects with COVID-9 in a respiratory sample and pneumonia. As, in severe COVID-19, lopinavir/ritonavir had no beneficial effects but increased gastrointestinal adverse effects, this combination should not be used at this stage of COVID-19. Expert opinion In my opinion, the rationale for undertaking a trial of lopinavir/ritonavir in COVID-19 was poor. The analysis of a modified intention to treat group analysis in LOTUS China may have introduced bias. After LOTUS China, there is probably no future for lopinavir in the treatment of severe COVID-19, but some clinical trials for prevention or in various stages of COVID-19 have recently started or are ongoing. The major limitation of these trials is that as lopinavir does not inhibit COVID-19, it is unlikely to prevent infection, reduce viral load, or reduce the severity. However, these trials may be worthwhile in finally determining whether lopinavir has any role in preventing or treating COVID-19.

Objective To evaluate the quality of the clinical trial literatures published on the treatment of COVID-19 with find out the shortcomings and put forward corresponding suggestions, in order to promote TCM against COVID-19. Methods COVID-19, New Coronavirus Pneumonia, TCM, Medicine, Clinical Trial, Lianhua Qingwen, Huoxiang Zhengqi, Jinhua Qinggan, and other keywords were used to search relevant literatures in CNKI and PubMed database. Among the all the screened relevant literatures on the treatment of COVID-19 with the literature quality was assessed according to evaluation criteria of clinical trial literatures. Results A total of 463 papers related to the treatment of COVID-19 with TCM were obtained. 440 papers on theoretical research on the network pharmacology mechanism of Chinese medicine treatment of COVID-19 were excluded. Among the 23 articles included in the quality analysis, there are 3 randomized controlled studies, 1 multi-center prospective randomized controlled trial, 2 disease case report trials, and 5 uncontrolled single arm studies, 5 controlled trials and 7 retrospective studies. In the period of more than half a year, although many clinical trial documents of TCM for the treatment of COVID-19 have been published, the clinical trial design reflected in most TCM clinical trials were not standardized. There are problems in randomness and rationality, such as no control group, no randomization design, only case studies, no blinding method in controlling bias, and insufficient objectivity in the evaluation criteria of efficacy. All of these need to be improved. Conclusion The treatment of new coronavirus pneumonia with TCM still requires more and standardized clinical trial verifications and publications to generate strong evidence-based results, such as adding control groups, increasing sample size, and using blinding methods to increase the credibility of clinical trials.

Objective:Moxibustion has been widely used in the prevention and treatment of COVID-19. However, there is no systematic review of current topics and clinical findings on moxibustion for COVID-19. We conducted this scoping review to systematically summarize and analyze the themes and findings of published articles, and to provide an overview of current knowledge and practice of moxibustion for COVID-19.Methods:PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, SinoMed, Wan Fang Data, and VIP databases were searched from inception until April 2022. The relevant data were presented through bar graphs, structured tables, and figures along with descriptive statistics and analysis. This scoping review was conducted based on the PRISMA-ScR Checklist.Results:A total of 76 articles were reviewed: 47 reviews, 19 clinical research studies, seven systematic reviews (all were protocols), and three guidelines. All the studies were conducted by Chinese researchers and published from January 1, 2020 to March 14, 2022. The feasibility of moxibustion in the prevention and treatment of mild or moderate COVID-19 is based on the consensus of therapeutic mechanisms and effectiveness. The most adopted approach was the suspended and gentle moxibustion, and the most frequently applied or recommended acupoints were found to be ST36, CV8, CV6, CV4, CV12, GV14, BL13, LI4, ST25, and LR3.Conclusions:As a convenient and safe traditional Chinese medicine (TCM) therapy with its specific feature, moxibustion has been significantly effective at ameliorating mild or moderate symptoms among COVID-19 patients. Further large-scale, well-designed research and international cooperation are still warranted in clinical evaluations of moxibustion.Graphical abstract:http://links.lww.com/AHM/A35.

Doctors race to understand epilepsy in the time of COVID-19