Abstract: medRxiv preprint doi: https://doi.org/10.1101/2021.06.06.21258091; this version posted June 8, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Title: Safety and efficacy of antiviral therapy alone or in combination in COVID-19 - a randomized controlled trial (SEV COVID Trial) Authors: SEV COVID trial group: Budha O Singh1, Bikram Moirangthem1, Prasan Kumar Panda1 Yogesh Arvind Bahurupi2, Sarama Saha3, Girraj Saini4, Minakshi Dhar1, Mukesh Bairwa1, Venkatesh Srinivasa Pai1, Ankit Agarwal5, Girish Sindhwani6, Shailendra Handu7, Ravikant8 Affiliations: Department of Internal Medicine1, Community and Family Medicine2, Biochemistry3, Nursing4, Anesthesia and Critical Care Medicne5, Pulmonary Medicine6, Pharmacology7, and Director8, All India Institute of Medical Sciences (AIIMS), Rishikesh, Uttarakhand, India Corresponding Author: Prasan Kumar Panda Asst. Professor, Dept. of Internal Medicine, Sixth Floor, College Block, All India Institute of Medical Sciences (AIIMS), Rishikesh, India, 249203 Mob: +91-9868999488 Email: motherprasanna@rediffmail.com 1 | Page NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2021.06.06.21258091; this version posted June 8, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. ABSTRACT Background Definitive antiviral treatment is not available for COVID-19 infection except remdesivir that even with many doubts. Various combination antivirals have been tried. Methods A single-center, open-label, parallel-arm, stratified randomized controlled trial evaluated the therapeutic potential of hydroxychloroquine and lopinavir-ritonavir in combination with ribavirin in COVID-19. Enrolled patients in severe category were randomized into three groups: A: standard treatment, B: hydroxychloroquine+ribavirin+standard treatment, or C: lopinavir+ritonavir+ribavirin+standard treatment; while non-severe category into two groups: A: standard treatment or B: hydroxychloroquine+ribavirin. Combination antivirals was given for 10 days and followed for 28 days. The primary endpoints were safety, symptomatic and laboratory recovery of organ dysfunctions, and time to SARS-CoV-2 RT-PCR negative report. Results Total 111 patients randomized: 24, 23, and 24 in severe category A, B, and C respectively, and 20 in each non-severe group. Two patients receiving ribavirin experienced drug induced liver injury and another developed QT prolongation after hydroxychloroquine. In the severe category, 47.6%, 55%, and 30.09% in A, B, and C groups respectively showed symptomatic recovery compared to 93.3% and 86.7% in A and B groups respectively in the non-severe category at 72hrs (P>0.05). Conclusions The results failed to show statistical superiority of the antiviral combination therapies to that of the standard therapy in both the severe and non-severe categories in symptomatic adult patients of COVID-19. However, results do indicate the benefit of non-standard interventional combination therapy in severe disease. Furthermore, the dose of..