Evaluating the efficacy and safety of a novel prophylactic nasal spray in the prevention of SARS-CoV-2 infection: A multi-centre, double blind, placebo-controlled, randomised trial.

Background The COVID-19 pandemic continues to devastate communities all over the world. The aim of this study was to evaluate the efficacy and safety of the test agent as a prophylaxis against SARS-CoV-2 infection in a population of high-risk healthcare workers. Methods The study was a multi-centre, prospective, double blind, randomized, placebo-controlled trial. Key eligibility criteria included absence of significant co-morbidity and no previous SARS-CoV-2 infection or vaccination. Participants were randomised to either the active agent nasal spray or placebo using computer generated random number tables. The nasal spray was administered 3 times daily over a 45 day course. The primary end point was the percentage of subjects who tested positive for IgGS (anti-spike, immunoglobulin G specific to the spike protein of SARS-CoV-2) at day 45. Results Between 16th April 2021 and 26th July 2021, 556 participants were analysed for the primary endpoint (275 Test; 281 Placebo). The test agent significantly reduced SARS-CoV-2 infection compared to placebo [36 cases (13.1%) Vs 97 cases (34.5%); OR 0.29 (95% CI; 0.18-0.45), p < 0.0001]. Fewer clinical symptoms were also seen in the test group [57 cases (17.6%) vs 112 cases (34.6%); OR 0.40, (95% CI; 0.27-0.59), p < 0.0001]. No harmful effects were associated with taking the test agent. Conclusion The test agent significantly reduced SARS-CoV-2 infection in healthcare workers, with 62% fewer infections when compared to placebo. It was found to be safe and well tolerated and offers a novel treatment option for prophylaxis against SARS-CoV-2 infection.

Modulation of neutrophil (dys)function by Ayurvedic herbs and its potential influence on SARS-CoV-2 infection.

For centuries, traditional medicines of Ayurveda have been in use to manage infectious and non-infectious diseases. The key embodiment of traditional medicines is the holistic system of approach in the management of human diseases. SARS-CoV-2 (COVID-19) infection is an ongoing pandemic, which has emerged as the major health threat worldwide and is causing significant stress, morbidity and mortality. Studies from the individuals with SARS-CoV-2 infection have shown significant immune dysregulation and cytokine overproduction. Neutrophilia and neutrophil to lymphocyte ratio has been correlated to poor outcome due to the disease. Neutrophils, component of innate immune system, upon stimulation expel DNA along with histones and granular proteins to form extracellular traps (NETs). Although, these DNA lattices possess beneficial activity in trapping and eliminating pathogens, NETs may also cause adverse effects by inducing immunothrombosis and tissue damage in diseases including Type 2 Diabetes and atherosclerosis. Tissues of SARS-CoV-2 infected subjects showed microthrombi with neutrophil-platelet infiltration and serum showed elevated NETs components, suggesting large involvement and uncontrolled activation of neutrophils leading to pathogenesis and associated organ damage. Hence, traditional Ayurvedic herbs exhibiting anti-inflammatory and antioxidant properties may act in a manner that might prove beneficial in targeting over-functioning of neutrophils and there by promoting normal immune homeostasis. In the present manuscript, we have reviewed and discussed pathological importance of NETs formation in SARS-CoV-2 infections and discuss how various Ayurvedic herbs can be explored to modulate neutrophil function and inhibit NETs formation in the context of a) anti-microbial activity to enhance neutrophil function, b) immunomodulatory effects to maintain neutrophil mediated immune homeostasis and c) to inhibit NETs mediated thrombosis.