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Volume 11
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10.3390/pr11020398
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Article

The Safety and Efficacy of the Protease Inhibitors Lopinavir/Ritonavir as Monotherapy or Combined with Interferon in COVID-19 Patients

by
Mahmoud Kandeel
1,2,*,
Mohamed A. Morsy
3,4,
Hany M. Abd El-Lateef
5,6,
Mohamed Marzok
7,8,
Hossam S. El-Beltagi
9,10,
Khalid M. Al Khodair
11,
Ibrahim Albokhadaim
1 and
Katharigatta N. Venugopala
3,12
1
Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia
2
Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt
3
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
4
Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia 61511, Egypt
5
Department of Chemistry, College of Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia
6
Department of Chemistry, Faculty of Science, Sohag University, Sohag 82524, Egypt
7
Department of Clinical Sciences, College of Veterinary Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia
8
Department of Surgery, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt
9
Agricultural Biotechnology Department, College of Agriculture and Food Sciences, King Faisal University, Al-Ahsa 31982, Saudi Arabia
10
Biochemistry Department, Faculty of Agriculture, Cairo University, Giza 12613, Egypt
11
Department of Anatomy, College of Veterinary Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia
12
Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, Durban 4000, South Africa
 
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Author to whom correspondence should be addressed.
Processes 2023, 11(2), 398; https://doi.org/10.3390/pr11020398
Submission received: 22 December 2022 / Revised: 17 January 2023 / Accepted: 19 January 2023 / Published: 28 January 2023
(This article belongs to the Section Pharmaceutical Processes)
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Abstract

Enzyme inhibitors are frequently used to treat viral illnesses. Protease inhibitors are a promising class for combating novel and life-threatening viral infections. This research aimed to evaluate the efficacy and safety of lopinavir/ritonavir monotherapy or lopinavir/ritonavir plus interferon for the treatment of COVID-19. The PubMed, Scopus, Web of Science, and Cochrane Library databases were searched for English articles with full texts available online. ReviewManager software was used to conduct a meta-analysis, subgroup analysis, and sensitivity analysis. Following the creation of the protocol, the collected sources were sorted into categories and evaluated for quality. Risk and hazard ratios and the random effects model were implemented, with statistical heterogeneity assigned using the Higgins I2 statistic. Lopinavir/ritonavir, with or without interferon, was associated with a nonsignificant higher mortality rate (odds ratio [OR] 1.29; 95% confidence interval [CI] 0.95 to 1.761; p = 0.1), as was clinical improvement (OR 1.2; 95% CI 0.8 to 1.84; p = 0.36). The difference in the length of hospital stay was in favor of the control group but statistically insignificant (standardized mean difference [SMD] 0.07; 95% CI −0.44 to 0.57; p = 0.79). The pooled data showed that lopinavir/ritonavir, with or without interferon, was associated with a significantly higher number of adverse events than placebo (OR 1.2; 95% CI 1.09 to 2.34; p = 0.02). Serious adverse events were insignificantly increased in the treated group over the control group (OR 1.2; 95% CI 0.96 to 2.12; p = 0.08). In the subgroup analysis, it was found that interferon used with lopinavir/ritonavir did not have a statistically significant effect on mortality rates (OR 1.75; 95% CI 0.87 to 3.55; p = 0.37), adverse effects (OR 1.20; 95% CI 0.75 to 1.91; p = 0.27), or serious adverse effects (OR 1.86; 95% CI 1.17 to 2.96; p = 0.33). Treatment with lopinavir/ritonavir alone or in combination with interferon for COVID-19 did not significantly outperform placebo in this study. Large randomized clinical trials are required to evaluate lopinavir/ritonavir in conjunction with interferon for the treatment of COVID-19. Such studies would benefit greatly from being conducted in a double-blind fashion at multiple locations.
Keywords: COVID-19; lopinavir; interferon; meta-analysis; ritonavir COVID-19; lopinavir; interferon; meta-analysis; ritonavir

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MDPI and ACS Style

Kandeel, M.; Morsy, M.A.; Abd El-Lateef, H.M.; Marzok, M.; El-Beltagi, H.S.; Al Khodair, K.M.; Albokhadaim, I.; Venugopala, K.N. The Safety and Efficacy of the Protease Inhibitors Lopinavir/Ritonavir as Monotherapy or Combined with Interferon in COVID-19 Patients. Processes 2023, 11, 398. https://doi.org/10.3390/pr11020398

AMA Style

Kandeel M, Morsy MA, Abd El-Lateef HM, Marzok M, El-Beltagi HS, Al Khodair KM, Albokhadaim I, Venugopala KN. The Safety and Efficacy of the Protease Inhibitors Lopinavir/Ritonavir as Monotherapy or Combined with Interferon in COVID-19 Patients. Processes. 2023; 11(2):398. https://doi.org/10.3390/pr11020398

Chicago/Turabian Style

Kandeel, Mahmoud, Mohamed A. Morsy, Hany M. Abd El-Lateef, Mohamed Marzok, Hossam S. El-Beltagi, Khalid M. Al Khodair, Ibrahim Albokhadaim, and Katharigatta N. Venugopala. 2023. "The Safety and Efficacy of the Protease Inhibitors Lopinavir/Ritonavir as Monotherapy or Combined with Interferon in COVID-19 Patients" Processes 11, no. 2: 398. https://doi.org/10.3390/pr11020398

APA Style

Kandeel, M., Morsy, M. A., Abd El-Lateef, H. M., Marzok, M., El-Beltagi, H. S., Al Khodair, K. M., Albokhadaim, I., & Venugopala, K. N. (2023). The Safety and Efficacy of the Protease Inhibitors Lopinavir/Ritonavir as Monotherapy or Combined with Interferon in COVID-19 Patients. Processes, 11(2), 398. https://doi.org/10.3390/pr11020398

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