A Randomized, Controlled Study on the Safety and Efficacy of Maraviroc and/or Favipiravir vs Currently Used Therapy in Severe COVID-19 Adults. “COMVIVIR” Trial.

Abstract

Multiple studies have established that hyperinflammatory response induced by SARS CoV-2 is a main cause of complications and death in infected subjects. Such dysfunctional immune response has been described as a dysregulated and exacerbated production of cytokines and chemokines that attracts and activates inflammatory cells, which start and sustain pulmonary and systemic damage, thus causing complications that lead to multi organ failure and death. Therefore, we suggest that blocking key inflammation receptors could help to reduce migration and activation of T cells, monocytes/macrophages and neutrophils, thus mitigating the cytokine dysregulation and averting severe complications and death. Importantly, the optimum treatment for COVID-19 severe patients should combine a modulator of the immune response plus a direct antiviral drug against SARS-CoV-2, in order to address both the hyperinflammatory effects of the immune dysregulation and the viral load. Methods: Maraviroc (MVC), a CCR5 antagonist, and Favipiravir (FPV), an antiviral, will be evaluated single and combined, added to the treatment currently used at the Hospital General de México Dr. Eduardo Liceaga for severe COVID-19 patients. One hundred patients will be allocated in four arms [Current treatment only (CT), CT+MVC, CT+FPV, CT+MVC+FPV]. Percentage of patients free of mechanical ventilation or death at day 28, immunophenotyping and viral load will be compared between groups. Discussion: New immune focused therapies are targeting strong inflammation mediators such as IL-6 and IL1-β; nevertheless, to our best knowledge, only one study explores chemotaxis control. The use of a drug therapy that addresses both the regulation of the immune response and the inhibition of viral replication could at the same time, help to alleviate the hyperinflammatory condition and reduce the time of the viral clearance process, therefore improving treatment outcomes.

Therapeutic Advancement in Treatment and Prevention of Nipah Viral Infection: A Review

“…According to the available data, it has been observed that the median incubation period of individuals who were exposed to a single case of Nipah virus is approximately nine days, with a range of 6 to 11 days [9]. However, it is important to note that the time interval between exposure and the onset of illness can vary between 6 to 16 days, as reported in previous studies [10,11,12,4]. According to research conducted in Bangladesh, it has been determined that the median incubation period from the time of consuming raw date palm sap to the onset of illness is 7 days.…”

“…Favipiravir: is a ribonucleotide analog, is known for its ability to specifically target the viral RNA polymerase enzyme. By doing so, it effectively inhibits the replication and transcription processes of RNA viruses, resulting in broad-spectrum antiviral effects [11]. According to a study conducted by Dawes BE et al, it was demonstrated that the drug, when administered orally in in vivo simulation models using hamsters, at a dosage of 300 mg/kg/day twice daily, did not lead to any observed morbidity and resulted in a 100% survival rate [18].…”