Ayurveda, an ancient Indian system of medicine contains a vast repository of plants and herbs with therapeutic properties. In the fight against COVID-19, herbal extracts with robust scientific evidence of therapeutic efficacy against SARS-CoV-2 can support rapid recovery and reduce mortality due to COVID-19. Our study investigates the effectiveness of NOQ19, an Ayurvedic polyherbal formulation, in clinical improvement and rate of recovery from the SARS-CoV-2 infection. This multicentric trial demonstrates an early recovery among patients who took NOQ19 along with standard of care treatment, compared to those who received standard of care alone.
The study was conducted during the second wave of COVID-19 in India. Along with other upper respiratory symptoms, the chief complain presented by patients during the second wave was shortness of breath associated with low SpO2 levels, requiring oxygen support27,29. In our study, a significant clinical improvement was noted in patients among the NOQ19 arm who had experienced lower oxygen saturation and breathlessness at baseline. Patients who received NOQ19 with the standard of care treatment showed an improvement in terms of oxygen requirement, breathlessness and SpO2. Thus, despite lack of intergroup statistical significance, the clinical significance of these findings cannot be ignored.
The second wave of COVID-19 in India was twice as severe as the first wave and created immense pressure on the health infrastructure and economy of the country30. Of the total deaths reported in India, 59% deaths were reported during the second wave31.The study was conducted in a hospital, where as per current guidelines, only patients with significant symptoms or considerable comorbidities were included. In the current study, an early clinical recovery was observed among moderate patients. With improvement in oxygen levels and clinical markers, it was noted that patients in the NOQ19 arm were feeling much better than the placebo arm. Also, a lesser number of patients in the NOQ19 arm required hospitalization on day 7. Therefore, this ayurvedic drug can aid early discharge, allowing rational utilization of limited resources, reduced burden on the healthcare system and support management of the illness at home.
Previous studies on the same formulation NOQ19 have shown promising results with respect to rate of recovery and antiviral efficacy23–25. A review of Ayurvedic literature presents robust preclinical evidence for efficacy of multiple NOQ19 ingredients such as Ashwagandha (Withania somnifera) and Guduchi (Tinospora cordifolia), along with Amalaki (Phyllanthus emblica) in proliferation of B and T cells and activation of non-specific immunity32. In addition, several other components of NOQ19 have been highlighted for their antiviral properties previously8,33,34. Yashtimadhu (Glycyrrhiza glabra) contains glycyrrhizin, a strong antiviral compound. In a previous study, treatment with different concentrations of glycyrrhizin lowered SARS-CoV viral antigen in a cell culture. At a concentration of 4000mg/ ml, Glycyrrhizin completely blocked the viral replication35.
A key observation of our study was the improvement in oxygen levels and reduction in breathlessness among patients with COVID-19, when treated with NOQ19. An earlier study demonstrated the therapeutic efficacy of Vasaka (Adhatoda vasica), present in NOQ19, in an in vitro and in vivo model, via inhibiting the hypoxic response in both the models. A possible mechanism for this could be the reversal of mitochondrial dysfunction associated with hypoxic conditions like asthma, ARDS, etc.36. Presence of Vasaka (Adhatoda Vasica) in NOQ19 may be responsible for its antihypoxic effect on COVID-19 patients37. Guduchi (Tinospora cordifolia), also present in NOQ19, is another important component studied for improvement in breathlessness38. Another clinical trial on patients with COVID-19 showed early recovery and reduced length of hospital stay with an Ayurvedic regime consisting of Dasamoolkaduthrayam Kashaya and Guluchyadi Kwatham39. A similar observation was noted in our study. Further investigation of the above two rasayanas showed the presence of Bilwa (Aegle marmelos), Pippali (Piper longum), Vaska (Adhatoda vasica) and Guduchi (Tinospora cordifolia) which are also present in NOQ19. AYUSH-64, is a long researched drug for Malaria40. During the pandemic, the drug was also tested against SARS-CoV-2 proteins, in silico, and showed excellent binding properties against SARS-CoV-2 virus41. Patients who received AYUSH-64 along with standard of care treatment demonstrated a reduced period of hospitalization compared to those who received standard of care treatment alone42.
According to data collected by the Ministry of AYUSH via AYUSH Sanjivani App, 80% of Indians used traditional medicines and home based remedies for the management of COVID-1943. Shortage of hospital beds, paucity of clinical drugs, expensive treatments and the emergence of secondary infections created challenges for patients and healthcare professionals across India during the second wave. Given the large percentage of Indians who rely on traditional remedies, administering an Ayurvedic formulation like NOQ19 along with standard of care can increase adoption and provide a sustainable and effective option to overcome COVID-19 infection safely and quickly. This may also be relevant in societies where people are open towards therapeutic options from traditional systems of medicine.
The authors acknowledge the limitations of the study and present further scope to improve the limitations. One of the key limitations of the study was the small sample size. Due to the small sample size, several clinically significant findings were not statistically significant. Secondly, although the blood biomarkers were captured, eg. IL-6 and D-dimer, no significant difference was noticed among both the groups. A possible reason for this could be that the duration between the two measurements was not long enough to notice any significant difference. Further studies with larger sample size and relatively longer duration can investigate in depth efficacy and mechanism of action of NOQ19 in patients with COVID-19. The findings of this study create an interesting backdrop for exploring the role of the NOQ19 in moderate to severe COVID-19 patients on oxygen therapy.