Use of baricitinib in treatment of COVID-19: a systematic review.

OBJECTIVE: To assess the role of baricitinib alone or in combination with other therapies as a treatment for patients with COVID-19. METHODS: Systematic literature search was conducted in the WHO COVID-19 coronavirus disease database to find clinical studies on use of baricitinib for treatment of COVID-19 between December 1, 2019 and September 30, 2021. Two independent set of reviewers identified the eligible studies fulfilling the inclusion criteria, relevant data was extracted and a qualitative synthesis of evidence performed. The risk of bias was evaluated with validated tools. RESULTS: A total of 267 articles were found to be eligible after primary screening of titles and abstracts. Following assessment of full texts, 19 studies were finally included for this systematic review, out of which 16 are observational, and 3 are interventional studies. Collating the results from these observational and interventional studies, baricitinib used as add-on to standard therapy, either alone or in combination with other drugs, was found to have favorable outcomes in hospitalized patients with moderate to severe COVID-19. Furthermore, ongoing trials indicate that the drug is being extensively studied across the world for its safety and efficacy in COVID-19. CONCLUSION: Baricitinib significantly improves clinical outcomes in hospitalized patients with COVID-19 pneumonia, and further evidence will establish the drug as a standard treatment among such patients.

An observational multi-centric COVID-19 sequelae study among health care workers.

Background: India has seen more than 43 million confirmed cases of COVID-19 as of April 2022, with a recovery rate of 98.8%, resulting in a large section of the population including the healthcare workers (HCWs), susceptible to develop post COVID sequelae. This study was carried out to assess the nature and prevalence of medical sequelae following COVID-19 infection, and risk factors, if any. Methods: This was an observational, multicenter cross-sectional study conducted at eight tertiary care centers. The consenting participants were HCWs between 12 and 52 weeks post discharge after COVID-19 infection. Data on demographics, medical history, clinical features of COVID-19 and various symptoms of COVID sequelae was collected through specific questionnaire. Finding: Mean age of the 679 eligible participants was 31.49 ± 9.54 years. The overall prevalence of COVID sequelae was 30.34%, with fatigue (11.5%) being the most common followed by insomnia (8.5%), difficulty in breathing during activity (6%) and pain in joints (5%). The odds of having any sequelae were significantly higher among participants who had moderate to severe COVID-19 (OR 6.51; 95% CI 3.46-12.23) and lower among males (OR 0.55; 95% CI 0.39-0.76). Besides these, other predictors for having sequelae were age (≥45 years), presence of any comorbidity (especially hypertension and asthma), category of HCW (non-doctors vs doctors) and hospitalisation due to COVID-19. Interpretation: Approximately one-third of the participants experienced COVID sequelae. Severity of COVID illness, female gender, advanced age, co-morbidity were significant risk factors for COVID sequelae. Funding: This work is a part of Indian Council for Medical Research (ICMR)- Rational Use of Medicines network. No additional financial support was received from ICMR to carry out the work, for study materials, medical writing, and APC.

Molnupiravir in COVID-19: A Scoping Review.

BACKGROUND: COVID-19, first detected in Wuhan, China, has evolved into a lifethreatening pandemic spread across six continents, with the global case count being more than 243 million, and mortality over 4.95 million, along with causing significant morbidity. It has initiated an era of research on repurposed drugs such as hydroxychloroquine, lopinavir/ritonavir, corticosteroids, remedesivir, ivermectin, alongside selective antivirals to treat or prevent COVID- 19. Molnupiravir is an orally available emerging antiviral drug considered highly promising for COVID-19. METHODS AND RESULTS: We have performed a scoping review for the use of molnupiravir against SARS-CoV-2 and COVID-19. It acts by inhibiting RNA-dependent RNA polymerase (RdRp), and exhibits broad-spectrum antiviral activity. Preclinical studies have evaluated the therapeutic efficacy as well as prophylactic activity of molnupiravir against SARS CoV-2 in various animal models that include ferrets, hamsters, mice, immunodeficient mice implanted with human lung tissue and cell cultures, in various doses ranging from 5-300 mg/kg, and results have been encouraging. Initial evidence of safety and efficacy from early phase clinical studies has been encouraging too, and recent results from a large phase 3 global trial have shown significant benefits among symptomatic outpatients. Other late-phase clinical trials are still underway with the aim of establishing molnulpiravir as a therapeutic option for COVID-19, particularly for non-hospitalized patients. CONCLUSION AND RELEVANCE: On the basis of the limited evidence available as of now, molnupiravir could prove to be a promising oral therapy, worthy of further exploration of its utility for both treatment and prevention of COVID-19 in humans. Elaborate clinical evaluation is further warranted to confirm whether the results are replicable to the clinical scenario among outpatients to reduce the chance of progression to more severe disease.

Continued use of azithromycin for mild COVID-19 in India: Evidence and implications?

Azithromycin is an antibiotic commonly used for treating respiratory, gastrointestinal infections besides enteric fever, otitis media etc. It's convenient short duration oral dosing regimens and good tolerability make it a popular drug in routine outpatient settings in primary to tertiary care. Pre-clinical studies have shown immunomodulatory and in vitro activity of azithromycin against SARS CoV-2, which has led to its widespread usage in COVID-19. However, subsequent reviews of observational studies assessing its efficacy in different grades of COVID-19, as well as data from well conducted randomised clinical trials (RCTs) in mild - moderate COVID-19 have shown no or very low quality evidence of benefit of the drug on various clinical outcome parameters. Still, the drug continues to be used indiscriminately in many parts of India for treatment of home isolated patients of mild COVID-19. Such injudicious use in the community should be stopped, otherwise there will be serious adverse consequences of development of resistance to this very useful antibiotic during this pandemic.

Safety of hydroxychloroquine in healthcare workers for COVID-19 prophylaxis.

BACKGROUND & OBJECTIVES: Hydroxychloroquine (HCQ), reported to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in in vitro studies, has been recommended for prophylaxis of COVID-19 in healthcare workers (HCWs). The objective of this study was to assess short-term adverse events (AEs) of HCQ in HCWs. METHODS: This cross-sectional study among consenting HCWs taking prophylaxis and working in hospitals with COVID-19 patients used online forms to collect details of HCWs, comorbidities, prophylactic drugs used and AEs after the first dose of HCQ. Verification of dose and AEs was done by personal contact. Multivariate logistic regression analysis was done to determine the effect of age, gender and dose of HCQ on AE. RESULTS: Of the 1303 HCWs included, 98.4 per cent (n=1282) took HCQ and 66 per cent (n=861) took 800 mg as first day's dose. Among the 19.9 per cent (n=259) reporting AEs, 1.5 per cent (n=20) took treatment for AE, none were hospitalized and three discontinued HCQ. Gastrointestinal AEs were the most common (172, 13.2%), with less in older [odds ratio (OR) 0.56, 95% confidence interval (CI) 0.35-0.89], with more in females (OR 2.46, 95% CI 1.78-3.38) and in those taking a total dose of 800 mg on day one compared to a lower dose. Hypoglycaemia (1.1%, n=14), cardiovascular events (0.7%, n=9) and other AEs were minimal. INTERPRETATION & CONCLUSIONS: HCQ prophylaxis first dose was well tolerated among HCWs as evidenced by a low discontinuation. For adverse effects, a small number required treatment, and none required hospitalization. The study had limitations of convenience sampling and lack of laboratory and electrocardiography confirmation of AEs.

Approval of Itolizumab for COVID-19: A Premature Decision or Need of The Hour?

Itolizumab is a first-in-class anti-CD6 monoclonal antibody that was initially developed for various cancers and was later developed and approved in India for treatment of moderate to severe chronic plaque psoriasis in 2013. This drug is now being re-purposed for COVID-19. The potential utility of itolizumab in COVID-19, based on its unique mechanism of action in ameliorating cytokine release syndrome (CRS), was proposed first in Cuba with approval of a single-arm clinical trial and expanded access use. Subsequently, a phase II, open-label, randomized, placebo-controlled trial has been conducted in 30 COVID-19 patients in India after receiving regulatory permission. Based on the results, the Indian drug regulatory agency recently approved itolizumab in July 2020 for 'restricted emergency use' for the treatment of CRS in moderate to severe acute respiratory distress syndrome (ARDS) due to COVID-19. This has drawn sharp criticism within the scientific community, with the approval being granted on the basis of a relatively small phase II trial, without conduct of a conventional phase III trial, and lacking availability of the claimed supportive real-world evidence in the public domain to date. In a global scenario where finding a successful treatment for COVID-19 is of utmost priority, a biologic agent has been re-purposed and approved with a successfully completed RCT, in a country where cases and mortality due to COVID-19 are growing exponentially. However, instead of welcoming the approval with open arms, many doubts are being raised. This is an issue that needs to be considered and dealt with sensitively, as well as scientifically.

Diabetes care during COVID-19 lockdown at a tertiary care centre in India.

Providing scheduled consultations to persons with diabetes during the COVID-19 induced lockdowns posed a major challenge. With the clinicians occupied in COVID management, a strategy of using telemedicine and engaging a team of para-clinical doctors was devised. Telephonic follow up consults were given and diabetes care was efficiently delivered.

IL-6 Inhibitors in the Treatment of Serious COVID-19: A Promising Therapy?

At present, there are no proven agents for treatment of coronavirus disease (COVID-19). The available evidence has not allowed guidelines to clearly recommend any drugs outside the context of clinical trials. The novel coronavirus SARS-CoV-2 that causes COVID-19 invokes a hyperinflammatory state driven by multiple cells and mediators like interleukin (IL)-1, IL-6, IL-12, and IL-18, tumor necrosis factor alpha (TNFα), etc. Considering the proven role of cytokine dysregulation in causing this hyperinflammation in the lungs with IL-6 being a key driver, particularly in seriously ill COVID-19 patients, it is crucial to further explore selective cytokine blockade with drugs like the IL-6 inhibitors tocilizumab, sarilumab, and siltuximab. These targeted monoclonal antibodies can dampen the downstream IL-6 signaling pathways, which can lead to decreased cell proliferation, differentiation, oxidative stress, exudation, and improve clinical outcomes in patients with evident features of cytokine-driven inflammation like persistent fever, dyspnea and elevated markers. Preliminary evidence has come for tocilizumab from some small studies, and interim analysis of a randomized controlled trial; the latter also being available for sarilumab. International guidelines do include IL-6 inhibitors as one of the options available for severe or critically ill patients. There has been increased interest in evaluating these drugs with a series of clinical trials being registered and conducted in different countries. The level of investigation though perhaps needs to be further intensified as there is a need to focus on therapeutic options that can prove to be 'life-saving' as the number of COVID-19 fatalities worldwide keeps increasing alarmingly. IL-6 inhibitors could be one such treatment option, with generation of more evidence and completion of a larger number of systematic studies.