Combining Antivirals and Immunomodulators to Fight COVID-19. Issue 1 (January 2021)

• Record Type: Journal Article
• Authors: Feuillet, Vincent; Canard, Bruno; Trautmann, Alain
• Is Part Of: Trends in immunology. Volume 42:Issue 1(2021)
• Page Start: 31
• Page End: 44
• Publication Date: 2021-01
• Subjects: COVID-19 -- SARS-CoV-2 -- antiviral molecules -- immunomodulators -- IFNα/β -- cytokine storm; Immunology -- Periodicals; 571.96
• DOI: 10.1016/j.it.2020.11.003
• Languages: English
• ISSNs: 1471-4906

Abstract

Abstract : The majority of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals remain paucisymptomatic, contrasting with a minority of infected individuals in danger of death. Here, we speculate that the robust disease resistance of most individuals is due to a swift production of type I interferon (IFNα/β), presumably sufficient to lower the viremia. A minority of infected individuals with a preexisting chronic inflammatory state fail to mount this early efficient response, leading to a delayed harmful inflammatory response. To improve the epidemiological scenario, we propose combining: (i) the development of efficient antivirals administered early enough to assist in the production of endogenous IFNα/β; (ii) potentiating early IFN responses; (iii) administering anti-inflammatory treatments when needed, but not too early to interfere with endogenous antiviral responses. Highlights: Although the coronavirus disease 2019 (COVID-19) pandemic is exceptional, lessons may be learned from previous outbreaks (coronavirus, dengue, influenza viruses), especially when considering drug design and cytokine storms. We propose that efficient treatments for COVID-19 patients should combine antivirals and immunomodulators. This combination and, especially the use of immunomodulators, might be adapted according to the disease stage. Among the repurposed antiviral drugs currently being tested against COVID-19, none shows high potency. We posit that the innate type 1 interferon (IFNα/β)-dependent antiviral immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection should be amplified. To this end, we propose two putative approaches: the inhibition of transforming growth factor (TGFβ) signaling, and perhaps, the administration of 1, 8-cineole. We suggest that an early diagnosis during COVID-19 is essential when aiming to purposely combine antivirals with the use of an immunomodulator (e.g., a drug to potentiate IFNα/β), ideally early in the disease course to lower the risk of cytokine storm manifestation. When the disease becomes severe, the new combination should prioritize targeting of the cytokine storm.