COVID-19 and thrombotic complications-the role of anticoagulants, antiplatelets and thrombolytics.

Coronavirus disease 2019 (COVID-19) is a global pandemic the world is dealing with currently. Clinical evidences suggest that the patients are predisposed to both venous and arterial thrombotic complications. This is because of severe inflammatory responses, injury to endothelium and activation of platelets leading to increased coagulation. Additionally, individuals who are already receiving antithrombotic drug therapy for various cardiovascular diseases and complications might contract the disease in which case, attention should be given to the choice and duration of the therapy besides close monitoring of biochemical blood parameters. Herein, we review the incidences of thrombotic complications and their outcomes in COVID-19 patients as reported till date, while understanding the prophylactic and therapeutic roles of anticoagulants, antiplatelets and thrombolytics in the management of this severe viral respiratory illness.

The safety, tolerability and mortality reduction efficacy of remdesivir; based on randomized clinical trials, observational and case studies reported safety outcomes: an updated systematic review and meta-analysis.

INTRODUCTION: Remdesivir, an experimental antiviral drug has shown to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), both in vitro and in vivo. The present systematic review and meta-analysis were performed to quantify the safety and tolerability of remdesivir, based on safety outcome findings from randomized controlled trials, observational studies and case reports of remdesivir in coronavirus disease 2019 (COVID-19) patients. METHODS: We have performed a systematic search in the PubMed, Google Scholar and Cochrane Library using specific keywords such as 'COVID-19' OR 'SARS CoV-2' AND 'Remdesivir'. The study endpoints include total adverse events (AEs), serious adverse events (SAEs), grade 3 and grade 4 AEs, mortality and drug tolerability. Statistical analysis was carried out by using Revman 5.4 software. RESULTS: Total 15 studies were included for systematic review, but only 5 randomized clinical trials (RCTs) (n = 13,622) were included for meta-analysis. Visual inspection of the forest plots for remdesivir 10-day versus placebo and remdesivir 10-day versus 5-day groups revealed that there is a significant difference in SAEs [10-day remdesivir versus control (odds ratio [OR] = 0.55, 0.40-0.74) p = 0.0001; I 2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 0.56, 0.38-0.84) p = 0.005; I 2 = 13%]. In grade 4 AEs, there is a significant difference in 10-day remdesivir versus control (OR = 0.32, 0.19-0.54) p = 0.0001; I 2 = 0%, but not in comparison to 5-day remdesivir (OR = 0.95, 0.59-1.54) p = 0.85; I 2 = 0%. But there is no significant difference in grade 3 AEs [remdesivir 10 day versus control (OR = 0.81, 0.59-1.11) p = 0.19; I 2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 1.24, 0.86-1.80) p = 0.25; I 2 = 0%], in total AEs [remdesivir 10 day versus control (OR = 1.07, 0.66-1.75) p = 0.77; I 2 = 79%; remdesivir 10 day versus 5 day (OR = 1.08, 0.70-1.68) p = 0.73; I 2 = 54%)], in mortality [10-day remdesivir versus control (OR = 0.93, 0.80-1.08) p = 0.32; I 2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 1.39, 0.73-2.62) p = 0.32; I 2 = 0%)] and tolerability [remdesivir 10 day versus control (OR = 1.05, 0.51-2.18) p = 0.89; I 2 = 65%, 10-day remdesivir versus 5-day remdesivir (OR = 0.86, 0.18-4.01) p = 0.85; I 2 = 78%]. DISCUSSION & CONCLUSION: Ten-day remdesivir was a safe antiviral agent but not tolerable over control in the hospitalized COVID-19 patients with a need of administration cautiousness for grade 3 AEs. There was no added benefit of 10- or 5-day remdesivir in reducing mortality over placebo. To avoid SAEs, we suggest for prior monitoring of liver function tests (LFT), renal function tests (RFT), complete blood count (CBC) and serum electrolytes for those with preexisting hepatic and renal impairments and patients receiving concomitant hepatotoxic or nephrotoxic drugs. Furthermore, a number of RCTs of remdesivir in COVID-19 patients are suggested. PLAIN LANGUAGE SUMMARY: Ten-day remdesivir is a safe antiviral drug with common adverse events in comparison to placebo.The rate of serious adverse events and grade 3 adverse events were significantly lower in 10-day remdesivir in comparison to placebo/5-day remdesivir.There was no significant difference in the rate of tolerability and mortality reduction in 10-day remdesivir over placebo/5-day remdesivir.There were no new safety signals reported in vulnerable populations, paediatric, pregnant and lactating women.

Famotidine Repurposing for Novel Corona Virus Disease of 2019: A Systematic Review.

BACKGROUND: COVID-19 caused by SARS-CoV-2 was declared as a global pandemic by the WHO. Famotidine is a histamine-2 (H2) receptor antagonist which blocks the H2 receptors in the parietal cells, decreasing gastric acid secretion. Our review aims to study all the available scientific evidence on famotidine research outcomes systematically to introspect its clinical efficacy and probable mechanisms and clinical efficacy against SARS-CoV-2. METHODOLOGY: An electronic search of PubMed, Scopus and Google Scholar was performed using MeSH terms "SARS CoV-2" OR "COVID-19" AND"FAMOTIDINE". Relevant informationwas extracted from studies reporting the efficacy of famotidine in COVID-19. RESULTS: We found a total of 32 studies, out of which only 14 were relevant and were included in our review.Molecular computational studies showed that famotidine selectively acts on viral replication proteases papain-like protease (PLpro) and 3-chymotrypsin-like protease (3CLpro). Additionally, it acts via inverse-agonism on the H2 receptors present in neutrophils and eosinophils which leads to inhibition of cytokine release. Clinical study findings have pointed toward significant improvements in COVID-19 patient-reported symptoms in non-hospitalized patients and reduction in intubation or death in critically ill patients associated with the usage of famotidine. However,in one of the studies,famotidine has failed to show any significant benefit in reducing mortality due to COVID-19. CONCLUSION: Famotidine has the potential to answer the ongoing global challenge owing to its selective action on viral replication. Additionally, clinical findings in COVID-19 patients support its efficacy to reduce clinical symptoms of COVID-19.We suggest that further optimally powered randomized clinical trials should be carried out to come up with definitive conclusions.

The Potential Therapeutic Role of Proton Pump Inhibitors in COVID-19: Hypotheses Based on Existing Evidences.

Although the major therapeutic uses of the proton pump inhibitors are in gastric-acid related diseases, evidences are suggestive of a pleiotropic nature of the compounds. We comment on the probable pathways and cellular machineries via which proton pump inhibitors could show beneficial therapeutic effects against SARS-CoV-2 based on the existing evidences. Proton pump inhibitors have shown antiviral potencies in various in vivo and in vitro studies. Some of the major possible ways through which they can act against SARS-CoV-2 are by exerting anti-inflammatory and anti-fibrotic effects, via vacuolar ATPase pumps leading to raised endolysosomal pH and by targeting endosomal complexes. The current pandemic has put forward a challenge to find treatment options. Although the potential roles of proton pump inhibitors against SARS-CoV-2 have been discussed in recent publications, the clinical evidences for their real-world effectiveness do not point towards a beneficial effect clearly yet. We suggest that although proton pump inhibitors should strongly be considered as potential therapeutic options for COVID-19, larger studies in the form of randomized controlled trials would be required to arrive at a definite conclusion.