Type I and III IFN-mediated antiviral actions counteracted by SARS-CoV-2 proteins and host inherited factors

Abstract

SARS-CoV-2 is a recently identified coronavirus accountable for the current pandemic disease known as COVID-19. Different patterns of disease progression infer a diverse host immune response, with interferon (IFN) being pivotal. IFN-I and III are produced and released by virus-infected cells during the interplay with SARS-CoV-2, thus establishing an antiviral state in target cells. However, the efficacy of IFN and its role in the possible outcomes of the disease are not yet defined, as it is influenced both by factors inherent to the virus and to the host. The virus exhibits multiple strategies to counteract the innate immune response, including those shared by SARS-CoV and MERS-CoV and other novel ones. Inborn errors in the host may affect IFN-related effector proteins or decrease its levels in plasma upon neutralization by preexistent autoantibodies. This battle between the IFN response triggered upon SARS-CoV-2 infection, its magnitude and timing, and the efficacy of its antiviral tools in dispute against the viral evasion strategies together with the genetic factors of the host, generate a scenario whose fate contributes to defining the severity of COVID-19.

Type I Interferons in COVID-19 Pathogenesis

“…Different epidemiological factors account for an increased risk of COVID-19 severity, such as being elderly, being male, obesity and the presence of previous comorbidities, including cardiovascular and respiratory diseases, diabetes and cancer [ 36 , 37 ]. These observations indicate that host factors are predictive of disease progression and, together with viral factors, drive the pathogenesis, with interferons (IFNs) playing a crucial role [ 38 , 39 ]. Differences in immunological responses between males and females are well documented [ 40 ].…”

The Evolutionary Dance between Innate Host Antiviral Pathways and SARS-CoV-2

“…This might explain why COVID-19 causes more than just respiratory symptoms [ 30 , 35 ], being noted also for gastrointestinal and even neurological features such as loss of taste (ageusia) and smell (anosmia). These two closely related viruses were even found to interfere with host immune responses through different mechanisms [ 30 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. It is therefore not surprising that many therapeutics that showed promise in SARS-CoV-1 infection, such as the HIV protease inhibitors lopinavir and ritonavir [ 43 ] or combined therapy with IFN-α and the broad antiviral ribavirin [ 44 ], had no impact on COVID-19 [ 45 , 46 ], with further drug combinations required to see an effect [ 47 ].…”

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“…Of course, age and other diseases such as diabetes, or cardiovascular compromise, or immunosuppressant medication would be the main determinants of the clinical outcome of Sars-Covid-2 infections, but with a stronger baseline level of innate immunity, the outcome would also make these categories of patients more resilient to Sars-Covid-2 infection [12].…”