Journal of Clinical and Diagnostic Research. 2022 Feb, Vol-16(2): KC01-KC07 1 1 DOI: 10.7860/JCDR/2022/51996.15940 Original Article Complementary/alternative medicine Section Evaluation of Efficacy and Safety of Clevira as an Add on Drug in Mild to Moderate COVID-19 Positive Patients- A Randomised Control Trial INTRODUCTION Coronaviruses, named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has caused a pandemic of COVID- 19. Coronaviruses cause mild to severe type of respiratory tract infections. Mild illnesses include some cases of the common cold, while severe illness can cause SARS virus (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Symptoms) virus, which has led to a death toll of more than 4 million globally [1,2]. Though vaccination has been initiated for Coronavirus Disease 2019 (COVID-19), the effectiveness of the same in controlling the upcoming mutant strains of SARS-CoV-2 is still a debate [3]. Hence, we are in need of a specific and effective antiviral therapy for SARS- CoV-2. Globally, there exists an urgent need for development of an alternative solutions for COVID-19. In a country like India, there is a rich source of herbs having antiviral and antipyretic activity and Ayurvedic interventions can also be more relevant in management of such pandemics [4]. In recent days the usage of many herbal formulations for various illnesses has increased worldwide and particularly for COVID-19 by the traditional Chinese medicines [5]. Ministry of Ayurveda, Yoga, Naturopathy, Unani, Siddha, Sowa-Rigpa and Homoeopathy (AYUSH), Government of India has also issued guidelines for boosting immunity with Ayurvedic interventions [6]. Clevira is one among them which is a polyherbal formulation consisting of many ingredients. Clevira is a proprietary Ayurvedic Medicine of apex laboratories pvt., Ltd., which has been approved by the government of India and AYUSH for its use in mild to moderate COVID-19 patients as an add on drug to the standard of care treatment [7]. The individual herbal ingredients used are known to have variety of medicinal properties against fever of viral origin and proven to have effective antipyretic, analgesic, antiviral and immuno regulatory properties. Composition of one clevira tablet includes extracts namely: Erandakarkati (Carica papaya)- Leaf- 100 mg, Mahanimba (Melia azedarach) Leaf- 100 mg, Kalmegh (Andrographis paniculata) Herb- 100 mg, Usira (Vettivera zizanoides) Root- 35 mg, Patola (Tricosanthus dioica) whole plant- 35 mg, Musta (Cyperus rotundus) Rhizome- 35 mg, Sunthi (Zingiber officinale) Rhizome- 35 mg, Maricha (Piper nigrum) Fruit- 35 mg, Grismachatraka (Mollugo cerviana) Whole plant- 35 mg, Guduchi (Tinospora cordifolia) Stem- 10 mg [8]. It has shown in vitro antiviral activity against Herpes Simplex Virus 1 and 2 [report attached as Annexure 1]. The antiviral activity of clevira Tablets-Granules and Syrup was carried out against HSV-1 and HSV-2 viruses. The 100 TCID50 (Median Tissue Culture Infectious Dose) virus concentration was used for HSV-1 and HSV-2 viruses. The results includes that the granules showed good percentage of cell protection (71.55%) and selectivity index (CC50/IC50) {Half maximal cytotoxic concentration/Half maximal inhibitory concentration} of 11.66 when compare to syrup (55.6%) and selectivity index of 4.81 against HSV-1 virus. The granules R NARAYANABABU 1 , S RAMESH KANNAN 2 , R LENIN 3 , M SAKTHIBALAN 4 , KM SUDHA 5 , K GOWTHAM 6 , ARTHER PAUL 7 , ESEKIA DAVID 8 Keywords: Andrographis paniculata, Antiviral, Coronavirus Disease 2019, Piper nigrum, Tinospora cordifolia ABSTRACT Introduction: Coronavirus Disease 2019 (COVID-19) has caused a devastating pandemic. Despite the worldwide efforts to find a therapeutic strategy and prophylaxis, we have not attained a complete success. Hence, there exists an urgent need for development of alternative solutions from Ayurveda system of medicine for COVID-19. Aim: To evaluate clevira, a polyherbal ayurvedic formulation, for its efficacy and safety in treatment of mild to moderate COVID- 19 patients as an add on drug. Materials and Methods: This randomised control trial was carried out from May 2020 to July 2020, in 100 patients (50 in test group and 50 in control group) confirmed with COVID- 19 infection (mild to moderate cases) by Reverse Transcription Polymerase Chain Reaction (RT-PCR) at a tertiary care Government Medical College and Hospital in Chennai, India. The test group received tablet clevira orally twice daily after food, in the morning and night for 14 days, as an add on, in addition to standard care of treatment as received by the control group. The primary outcome was assessment of clinical recovery, proportion of patients with swabs negative for COVID- 19 in RT-PCR and reduction of Viral cycle threshold ratio. The results of the both group were analysed and compared using Chi-square test and student’s t-test. Results: Significant improvement (p-value=0.0338) was seen in patients on day 5, who got treated with clevira as add on drug. An 86% (43) of patients turned out to be COVID-19 RT- PCR test negative on day 5 while in the control group 66% (33) of patients turned out to be negative. There was a statistically significant difference (p-value=0.0196) between the test and control groups on comparing the mean difference in CT value results between day 1 and day 5. Clevira when given in addition to the standard of care, showed a significant improvement in signs and symptoms of COVID-19 infection. Conclusion: Clevira, with its polyherbal ingredients show a significant antiviral action against coronavirus when given in addition to the standard of care medications suggested by Indian Council of Medical Research (ICMR), over a period of 14 days in treatment of mild to moderate COVID-19 patients.