Concomitant use of dexamethasone and tetracyclines: a potential therapeutic option for the management of severe COVID-19 infection?

Introduction: The global coronavirus disease-2019 (COVID-19) pandemic has posed a critical challenge to the research community as well as to the healthcare systems. Severe COVID-19 patients are at a higher risk of developing serious complications and mortality. There is a dire need for safe and effective pharmacotherapy for addressing unmet needs of these patients. Concomitant use of dexamethasone and tetracyclines, by virtue of their immunomodulatory and other relevant pharmacological properties, offers a potential strategy for synergy aimed at improving clinical outcomes.Areas covered: Here we review the potential benefits of combining dexamethasone and tetracyclines (minocycline or doxycycline) for the management of severe COVID-19 patients. We have critically examined the evidence obtained from in silico, experimental, and clinical research. We have also discussed the plausible mechanisms, advantages, and drawbacks of this proposed combination therapy for managing severe COVID-19.Expert opinion: The concomitant use of dexamethasone and one of the tetracyclines among severe COVID-19 patients offers several advantages in terms of additive immunomodulatory effects, cost-effectiveness, wide-availability, and well-known pharmacological properties including adverse-effect profile and contraindications. There is an urgent need to facilitate pilot studies followed by well-designed and adequately-powered multicentric clinical trials to generate conclusive evidence related to utility of this approach.

Hydroxychloroquine for the treatment and prophylaxis of COVID-19: The journey so far and the road ahead.

As mortality and morbidity from novel coronavirus disease (COVID-19) continue to mount worldwide, the scientific community as well as public health systems are under immense pressure to contain the pandemic as well as to develop effective medical countermeasures. Meanwhile, desperation has driven prescribers, researchers as well as administrators to recommend and try therapies supported by little or no reliable evidence. Recently, hydroxychloroquine-sulfate (HCQS) has got significant media and political attention for the treatment as well as prophylaxis of COVID-19 despite the lack of convincing and unequivocal data supporting its efficacy and safety in these patients. This has unfortunately, yet foreseeably led to several controversies and confusion among the medical fraternity, the patient community as well as the general public. Based on the available studies, many with high risk of bias, relatively small sample sizes, and abbreviated follow-ups, HCQS is unlikely to be of dramatic benefit in COVID-19 patients and yet has the potential to cause harm, particularly when used in combination with azithromycin or other medications in high risk individuals with comorbidities. Although definitive data from larger well-controlled randomized trials will be forthcoming in the future, and we may be able to identify specific patient subpopulations likely to benefit from hydroxychloroquine, till that time it will be prudent to prescribe it within investigational trial settings with close safety monitoring. Here we review the current evidence and developments related to the use of HCQS in COVID-19 patients and highlight the importance of risk-benefit assessment and rational use of HCQS during this devastating pandemic.

Repurposing minocycline for COVID-19 management: mechanisms, opportunities, and challenges.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly grown into a public health emergency that has placed the national health systems as well as scientific research communities under enormous pressures. Drug repurposing or repositioning is a well-known strategy that seeks to deploy existing licensed drugs for newer indications and provides the quickest possible transition from bench to clinics for unmet therapeutic needs. Given the current, urgent, and dire need for effective therapies against novel coronavirus-19, this approach is particularly appealing. AREAS COVERED: Here, we review the significant anti-inflammatory, immunomodulatory, and antiviral properties of minocycline as potential mechanisms for efficacy against the novel coronavirus and highlight the promises and pitfalls of this approach. EXPERT OPINION: As compared to other agents being investigated for COVID-19, minocycline offers distinct advantages in terms of potential efficacy in patients with life-threatening acute respiratory distress syndrome (ARDS) and myocardial injury, well-known safety and interaction profile, relatively low costs, and widespread availability. We call upon public and private funders to facilitate urgent and rigorous research efforts before evidence-based recommendations for its widespread use can be made.