SARS-CoV-2 – Omicron variant exhibits an increased resilience to the antiviral type I interferon response


Expect more long term chronic diseases soon as a result of Omicron infections as preliminary unpublished data from 4 different ongoing studies are indicating the Omicron has evolved such that it is able to evade the human host’s innate and adaptive immunity systems by causing a wide range of disruptions and also dysregulation of the immune system so as to provide an environment that is conducive for its viral persistence

The published study that is not linked to the other 4 ongoing studies in the United States, that has been published on a preprint server and was conducted by German researchers from Justus-Liebig University, Goethe University, German Centre for Infection Research (DZIF) and the Fraunhofer Institute for Molecular Biology and Applied Ecology (IME) shows that Omicron variant has evolved to better exhibit an increased resilience to the antiviral type I interferon response.

Omicron (B.1.1.529) is a new variant of concern (VOC) of the pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19. Since its detection in South Africa in November 2021 (1), Omicron has rapidly spread in all countries where it was introduced, indicating elevated infectivity and a certain resistance to pre-existing immunity (2).

These features are due to an unprecedented number of mutations that are distinguishing Omicron from the original coronavirus that emerged in Wuhan, China, at the end of 2019, as well as from the subsequently appearing VOCs like e.g. Delta (B.1.617.2) (1).

Omicron exhibits a high resistance to neutralization by antibodies directed against the previously dominant lineages (3), an increased binding to the main virus receptor ACE2 (4), and a switch to the endosomal entry route (5). Moreover, it replicated more efficiently in cells of the upper respiratory tract (5), most likely contributing to its hyper-transmissibility (2).

Type I interferons (IFN-alpha/beta) constitute the first line of the innate immune defense against invading viruses (6). Upon infection, viral hallmark structures like e.g. doublestranded RNA are recognized by cellular sensors that, in turn, initiate a so-called antiviral signaling chain culminating in the induction of genes for IFN-beta and other cytokines.

Secreted IFN then binds to its cognate receptor in an autocrine and paracrine fashion to establish an antiviral state in the cell. SARS-CoV-2, like other highly pathogenic viruses (6), therefore evolved a series of countermeasures that suppress induction of IFNs or the IFN-stimulated signaling (7).

Despite the more than 15 viral proteins exhibiting IFN- antagonistic activity, infection by SARS-CoV-2 still induces a certain level of type I IFNs and other cytokines (8) and exogenously added IFN is inhibitory to viral replication (8–10).


Exogenously added IFNs were shown to restrict the original wt SARS-CoV-2 in cell culture (8–10), and in patients an early type I IFN therapy is associated with reduced mortality (12). This may also apply to the IFN that is endogenously produced by the infected individual, as the strength of the IFN response correlates with disease severity.

In children, a pre-activated IFN system that enables a rapid and strong antiviral response is controlling infection (13), whereas in the elderly the IFN system is less active and can be additionally hampered by neutralizing anti-IFN autoantibodies (14).

Thus, the ability of a virus to suppress IFN induction and antiviral IFN action are important determinants of COVID-19 risk, and the outcome of infection is dependent on the timing, amount and localization of IFN production.

Our results are in line with reports that the earlier VOC Alpha suppresses IFN induction more effectively than preceding wt SARS-CoV-2 isolates (15) and that the more pathogenic SARS-CoV-1 from 2003 is less IFN-sensitive than wt SARS-CoV-2 (9, 10).

Thus, IFN escape is an additional feature besides antibody escape, increased ACE2 affinity and endosomal entry that may contribute to the hyper-transmissibility of Omicron.


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