Antiviral Combination Clinically Better Than Standard Therapy in Severe but Not in Non-Severe COVID-19

Abstract: Clinical Pharmacology: Advances and Applications Dovepress open access to scientific and medical research Clinical Pharmacology: Advances and Applications For personal use only. Open Access Full Text Article ORIGINAL RESEARCH Antiviral Combination Clinically Better Than Standard Therapy in Severe but Not in Non-Severe COVID-19 Prasan Kumar Panda 1 Budha O Singh 1 Bikram Moirangthem 1 Yogesh Arvind Bahurupi 2 Sarama Saha 3 Girraj Saini 4 Minakshi Dhar 1 Mukesh Bairwa 1 Venkatesh Srinivasa Pai 1 Ankit Agarwal 5 Girish Sindhwani 6 Shailendra Handu 7 Ravi Kant 8 1 Department of Medicine (Infectious Disease Division), All India Institute of Medical Sciences (AIIMS), Rishikesh, India; 2Department of Community and Family Medicine, All India Institute of Medical Sciences (AIIMS), Rishikesh, India; 3Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Rishikesh, India; 4Department of Nursing, All India Institute of Medical Sciences (AIIMS), Rishikesh, India; 5 Department of Critical Care Medicine, All India Institute of Medical Sciences (AIIMS), Rishikesh, India; 6Department of Pulmonary Medicine, All India Institute of Medical Sciences (AIIMS), Rishikesh, India; 7Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Rishikesh, India; 8Department of General Surgery, All India Institute of Medical Sciences (AIIMS), Rishikesh, India Correspondence: Prasan Kumar Panda Department of Medicine (Infectious Disease Division), All India Institute of Medical Sciences (AIIMS), Sixth Floor, College Block, Rishikesh, 249203, India Tel +91 9868999488 Email motherprasanna@rediffmail.com Purpose: Definitive antiviral treatment is not available for COVID-19 infection, with the exception of remdesivir, which still evokes many doubts. Various monotherapy or combina­ tion therapies with antivirals or other agents have been tried. The present study aims to evaluate the therapeutic potential of hydroxychloroquine and lopinavir–ritonavir in combina­ tion with ribavirin in mild–severe COVID-19. Patients and Methods: A single-center, open-label, parallel-arm, stratified randomized controlled trial evaluated the therapeutic potential of combination antiviral therapies. Enrolled patients in the severe category were randomized into three groups: (A) standard treatment, (B) hydroxychloroquine+ribavirin+standard treatment, or (C) lopinavir+ritonavir +ribavirin+standard treatment; while the non-severe category comprised two groups: (A) standard treatment or (B) hydroxychloroquine+ribavirin. Combination antivirals were 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: In total, 111 patients were randomized: 24, 23, and 24 in severe categories A, B, and C, respectively, and 20 in each of the non-severe groups. Two patients receiving ribavirin experienced drug induced liver injury, and another developed QT prolongation after hydro­ xychloroquine. 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 72 hours (P>0.05). Conclusion: Though the results failed to show statistical superiority of the antiviral combination therapies to that of the standard therapy in both the severe and..