Abstract
Currently, an efficient treatment for COVID-19 is still unavailable, and people are continuing to die from complications associated with SARS-CoV-2 infection. Thus, the development of new therapeutic approaches is urgently needed, and one alternative is to target the mechanisms of autophagy. Due to its multifaceted role in physiological processes, many questions remain unanswered about the possible advantages of inhibiting or activating autophagy. Based on a search of the literature in this field, a novel analysis has been made to highlight the relation between the mechanisms of autophagy in antiviral and inflammatory activity in contrast with those of the pathogenesis of COVID-19. The present analysis reveals a remarkable coincidence between the uncontrolled inflammation triggered by SARS-CoV-2 and autophagy defects. Particularly, there is conclusive evidence about the substantial contribution of two concomitant factors to the development of severe COVID-19: a delayed or absent type I and III interferon (IFN-I and IFN-III) response together with robust cytokine and chemokine production. In addition, a negative interplay exists between autophagy and an IFN-I response. According to previous studies, the clinical decision to inhibit or activate autophagy should depend on the underlying context of the pathological timeline of COVID-19. Several treatment options are herein discussed as a guide for future research on this topic.
Highlights
The pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents an enormous challenge for the scientific community around the world
One possibility is to target autophagy, which could be responsible for the ineffective immune response that is unable to control viral replication and ends up promoting spiraling inflammation
In light of the literature considered here, it is plausible to propose the inhibition of autophagy in the first stage of COVID-19 to prevent SARS-CoV-2 from taking advantage of this process to replicate itself
Summary
The pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents an enormous challenge for the scientific community around the world. There are numerous reports on the origin of the new virus as well as the diagnosis, prevention, and treatment of its associated disease. The suggested therapeutic regimens have been subjected to clinical studies, finding positive outcomes in some cases and a lack of significance (compared to standard care) in others (Table 1). Since the drugs at this time administered to treat COVID-19 patients do not have significant efficacy to counteract the effects of the disease, new therapeutic options are urgently needed to control the infection to avoid fatal outcomes in hospitalized patients that have developed a severe infection
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