Citation Information :
Akbar SM, Mahtab MA, Aguilar JC, Uddin MH, Khan MS, Yoshida O, Penton E, Gerardo GN, Hiasa Y. Role of Pegylated Interferon in Patients with Chronic Liver Diseases in the Context of SARS-CoV-2 Infection. Euroasian J Hepatogastroenterol 2021; 11 (1):27-31.
The coronavirus 2019 (COVID-19) pandemic has resulted in 168 million cases and about 3.5 million deaths (as of May 26, 2021) during the last 18 months. These 18 months of the COVID-19 pandemic have been characterized by phases or waves of new cases, the emergence of new variants of the deadly virus, and several new complications. After providing emergency approval to several drugs and adherence to several public health measures with frequent full and partial lockdowns, the incidence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could not be contained till now on a global basis. Although prophylactic vaccines have inspired optimism, the scarcity of vaccines and several vaccine-related regulations indicate that the vaccine\'s benefit would not be reaching the people of developing countries anytime soon. In the course of our clinical practice, we used pegylated interferon (Peg-IFN) in 35 patients with chronic liver diseases (CLD), and we found that only two of them were infected with SARS-CoV-2 that was mild in nature. These two patients with CLD have a mild course of disease cured without any specific therapy. Patients with CLD are usually immune-compromised. However, three CLD patients remained free of SARS-CoV-2 although they had COVID-19 patients among their family members. Next, we accomplished two studies for assessing the immune-modulatory capacities of Peg-IFN, 1 and 12 injections following administration of Peg-IFN. The data revealed that peripheral blood mononuclear cells (PBMCs) of Peg-IFN-administered CLD patients produced significantly higher levels of some cytokines of innate immunity in comparison with the cytokines produced by PBMC of CLD patients before Peg-IFN intake. The pattern of cytokine responses and absence of infection of SARS-CoV-2 in 33 of 35 CLD patients represent some preliminary observations indicating a possible role of Peg-IFN in patients with CLD. The study may be extended to other chronic infections and cancers in which patients receive Peg-IFN. The role of Peg-IFN for pre- or postexposure prophylaxis in the acquisition of SARS-CoV-2 infection and influencing the natural course of COVID-19 remains to be clarified.
Li Q, Guan X, Wu P, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med 2020;382(13):1199–1207. DOI: 10.1056/NEJMoa2001316.
Yan R, Zhang Y, Li Y, et al. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science 2020;367(6485):1444–1448. DOI: 10.1126/science.abb2762.
Huang Y, Yang C, Xu X-F, et al. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin 2020;41(9):1141–1149. DOI: 10.1038/s41401-020-0485-4.
Gao Z, Xu Y, Sun C, et al. A systematic review of asymptomatic infections with COVID-19. J Microbiol Immunol Infect 2021;54(1):12–16. DOI: 10.1016/j.jmii.2020.05.001.
Bi Q, Wu Y, Mei S, et al. Epidemiology and transmission of COVID-19 in 391 cases and 1286 of their close contacts in Shenzhen, China: a retrospective cohort study. Lancet Infect Dis 2020;20(8):911–919. DOI: 10.1016/S1473-3099(20)30287-5.
Xie P, Ma W, Tang H, et al. Severe COVID-19: a review of recent progress with a look toward the future. Front Public Health 2020;8:189. DOI: 10.3389/fpubh.2020.00189.
Wang X, Huang K, Jiang H, et al. Long-term existence of SARS-CoV-2 in COVID-19 patients: host immunity, viral virulence, and transmissibility. Virol Sin 2020;35(6):793–802. DOI: 10.1007/s12250-020-00308-0.
Sungnak W, Huang N, Becan C, et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med 2020;26(5):681–687. DOI: 10.1038/s41591-020-0868-6.
Mitjà O, Corbacho-Monné M, Ubals M, et al. A cluster-randomized trial of hydroxychloroquine for prevention of Covid-19. N Engl J Med 2021;384(5):417–427. DOI: 10.1056/NEJMoa2021801.
Molento MB. Ivermectin against COVID-19: the unprecedented consequences in Latin America. One Health 2021;13:100250. DOI: 10.1016/j.onehlt.2021.100250.
WHO Solidarity Trial Consortium; Pan H, Peto R, Henao-Restrepo AM, et al. Repurposed antiviral drugs for Covid-19-Interim WHO solidarity trial results. N Engl J Med 2021;384(6):497–511. DOI: 10.1056/NEJMoa2023184.
Zhao H, Zhang C, Zhu Q, et al. Favipiravir in the treatment of patients with SARS-CoV-2 RNA recurrent positive after discharge: a multicenter, open-label, randomized trial. Int Immunopharmacol 2021;97:107702. DOI: 10.1016/j.intimp.2021.107702.
WHO Ad Hoc Expert Group on the Next Steps for Covid-19 Vaccine Evaluation; Krause PR, Fleming TR, et al. Placebo-controlled trials of Covid-19 vaccines – why we still need them. N Engl J Med 2021;384(2):e2. DOI: 10.1056/NEJMp2033538.
Islam MA, Mazumder MA, Akhter N, et al. Extraordinary survival benefits of severe and critical patients with COVID-19 by immune modulators: the outcome of a clinical trial in Bangladesh. Euroasian J Hepatogastroenterol 2020;10(2):68–75. DOI: 10.5005/jp-journals-10018-1327.
Chen P, Nirula A, Heller B, et al. SARS-CoV-2 neutralizing antibody LY-CoV555 in outpatients with Covid-19. N Engl J Med 2021;384(3):229–237. DOI: 10.1056/NEJMoa2029849.
Li X, Peng T. Strategy, progress, and challenges of drug repurposing for efficient antiviral discovery. Front Pharmacol 2021;12:660710. DOI: 10.3389/fphar.2021.660710.
Sultana J, Crisafulli S, Gabbay F, et al. Challenges for drug repurposing in the COVID-19 pandemic era. Front Pharmacol 2020;6;11:588654. DOI: 10.3389/fphar.2020.588654.
Parvathaneni V, Gupta V. Utilizing drug repurposing against COVID-19 – efficacy, limitations, and challenges. Life Sci 2020;259:118275. DOI: 10.1016/j.lfs.2020.118275.
Li T, Huang T, Guo C, et al. Genomic variation, origin tracing, and vaccine development of SARS-CoV-2: a systematic review. Innovation (N Y) 2021;2(2):100116. DOI: 10.1016/j.xinn.2021.100116.
Kwok HF. Review of Covid-19 vaccine clinical trials – a puzzle with missing pieces. Int J Biol Sci 2021;17(6):1461–1468. DOI: 10.7150/ijbs.59170.
Al-Mahtab M, Akbar SM, Aguilar JC, et al. Therapeutic potential of a combined hepatitis B virus surface and core antigen vaccine in patients with chronic hepatitis B. Hepatol Int 2013;7(4):981–989. DOI: 10.1007/s12072-013-9486-4.
Mf Akbar S, Al-Mahtab M, I Khan S. Nature of host immunity during hepatitis B virus infection and designing immune therapy. Euroasian J Hepatogastroenterol 2018;8(1):42–46. DOI: 10.5005/jp-journals-10018-1256.
Al Mahtab M, Akbar SMF, Aguilar JC, et al. Treatment of chronic hepatitis B naïve patients with a therapeutic vaccine containing HBs and HBc antigens (a randomized, open and treatment-controlled phase III clinical trial). PLoS One 2018;13(8):e0201236. DOI: 10.1371/journal.pone.0201236.
Wong MT, Chen SSL. Emerging roles of interferon-stimulated genes in the innate immune response to hepatitis C virus infection. Cell Mol Immunol 2016;13(1):11–35. DOI: 10.1038/cmi.2014.127.
Crosse KM, Monson EA, Beard MR, et al. Interferon-stimulated genes as enhancers of antiviral innate immune signaling. J Innate Immun 2018;10(2);85–93. DOI: 10.1159/000484258.
King C, Sprent J. Dual nature of type 1 interferons in SARS-CoV-2 induced inflammation. Trends Immunol 2021;42(4):312–322. DOI: 10.1016/j.it.2021.02.003.
Akbar SM, Yamamoto K, Miyakawa H, et al. Peripheral blood T-cell responses to pyruvate dehydrogenase complex in primary biliary cirrhosis: Role of antigen-presenting dendritic cells. Eur J Clin Invest 2001;31(7):639–546. DOI: 10.1046/j.1365-2362.2001.00847.x.
Akbar SM, Horiike N, Chen S, et al. Mechanism of restoration of immune responses of chronic hepatitis B patients during lamivudine therapy; increased antigen processing and presentation by dendritic cells. J Viral Hepat 2011;18(3):200–205. DOI: 10.1111/j.1365-2893.2010.01300.x.
Maqbool A, Khan NM. Analyzing barriers for implementation of public health and social measures to prevent the transmission of COVID-19 disease using DEMATEL method. Diabetes Metab Syndr 2020;14(5):887–892. DOI: 10.1016/j.dsx.2020.06.024.
Ravani SA, Agrawal GA, Leuva PA, et al. Rise of the phoenix: mucormycosis in COVID-19 times. Indian J Ophthalmol 2021;69(6):1563–1568. DOI: 10.4103/ijo.IJO_310_21.
Martinez MA. Lack of effectiveness of repurposed drugs for COVID-19 treatment. Front Immunol 2021;12:635371. DOI: 10.3389/fimmu.2021.635371.
Charting coronavirus vaccine around the world. Available from: https://vdata.nikkei.com/en/newsgraphics/coronavirus-vaccine-status/.
Pandit A, Bhalani N, Bhushan BLS, et al. Efficacy and safety of pegylated interferon alfa-2b in moderate COVID-19: a phase II, randomized, controlled, open-label study. Int J Infect Dis 2021;105:516–521. DOI: 10.1016/j.ijid.2021.03.015.