Comparison by Age of the Local Interferon Response to SARS-CoV-2 Suggests a Role for IFN-ε and -ω

Abstract

Children generally develop a mild disease after SARS-CoV-2 infection whereas older adults are at risk of developing severe COVID-19. Recent transcriptomic analysis showed pre-activated innate immunity in children, resulting in a more effective anti-SARS-CoV-2 response upon infection. To further characterize age-related differences, we studied type I and III interferon (IFN) response in SARS-CoV-2 infected and non-infected individuals of different ages. Specifically, levels of expression of type I (IFN-α, -β, -ε and -ω), type III (IFN-λ1, -λ2 and -λ3) IFNs and of the IFN-stimulated genes, ISG15 and ISG56 were quantified in nasopharyngeal cells from diagnostic swabs. Basal transcription of type I/III IFN genes was highest among children and decreased with age. Among SARS-CoV-2-infected individuals, only IFN-ε and -ω levels were significantly higher in children and young adults whereas ISGs were overexpressed in infected adults. The occurrence of symptoms in children and the need for hospitalization in adults were associated to higher transcription of several IFN genes. Starting from a pre-activated transcription level, the expression of type I and III IFNs was not highly up-regulated in children upon SARS-CoV-2 infection; young adults activated IFNs’ transcription at intermediate levels whereas older adults were characterized by higher ISGs and lower IFN-ε and -ω relative expression levels. Overall, our findings contribute to recognize components of a protective IFN response as a function of age, in the context of SARS-CoV-2 infection.

Low-Dose Interferon I and Iii-Based Nasal Sprays: A Good-Looking Covid-19 Vaccine Candidate?

“…Likewise, it is important to acknowledge the "double-edged sword"-like nature of Type I (i.e. IFN alpha-2b, beta-1, delta, epsilon, kappa, omega Given that children and young adults generally have first and second-line immune defences that are more robust in nature than old adults, and that the levels of interferon epsilon and interferon omega were found to be significantly higher during SARS-CoV-2 infections in young people than in old adults, and that SARS-CoV-2 was found to affect older people pronouncedly more disproportionately, it is likely that the two interferon sub-domains also play an outstanding role in maintaining a balance between anti-and pro-inflammatory immune factors whilst strongly stimulating the recruitment of NK cells, dendritic cells, as well as of B-and T-lymphocytes (Pierangeli et al, 2022).…”

Low-Dose Interferon I and III-Based Nasal Sprays: A Good-Looking COVID-19 Vaccine Candidate and a Therapy of the Future?

“…Severe disease generally occurs when the viral peak reaches the level where the disease has not started its clinical manifestations (Muge Cevik et al, 2020), and this could imply the increased abilities of the novel coronavirus to escape host immune sensing can often impair the immune system by resulting in the development of autoantibodies and/or the suppression of the quality and wellbeing of the immune system as a whole. Given that children and young adults generally have first and second-line immune defenses that are more robust in nature than old adults, and that the levels of interferon epsilon and interferon omega were found to be significantly higher during SARS-CoV-2 infections in young people than in old adults, and that SARS-CoV-2 was found to affect older people pronouncedly more disproportionately, it is likely that the two interferon sub-domains also play an outstanding role in maintaining a balance between anti-and pro-inflammatory immune factors whilst strongly stimulating the recruitment of NK cells, dendritic cells, as well as of B-and T-lymphocytes (Pierangeli et al, 2022). Nevertheless, the Omicron variant was found to affect younger people much more than the previous major variants, which possibly means that the new variant escaped interferon epsilon and omega signals significantly more.…”

Low-Dose Interferon I and III-Based Nasal Sprays: A Good-Looking COVID-19 Vaccine Candidate?

“…Severe disease generally occurs when the viral peak reaches the level where the disease has not started its clinical manifestations (Muge Cevik et al, 2020), and this could imply the increased abilities of the novel coronavirus to escape host immune sensing can often impair the immune system by resulting in the development of autoantibodies and/or the suppression of the quality and wellbeing of the immune system as a whole. Given that children and young adults generally have first and second-line immune defenses that are more robust in nature than old adults, and that the levels of interferon epsilon and interferon omega were found to be significantly higher during SARS-CoV-2 infections in young people than in old adults, and that SARS-CoV-2 was found to affect older people pronouncedly more disproportionately, it is likely that the two interferon sub-domains also play an outstanding role in maintaining a balance between anti-and pro-inflammatory immune factors whilst strongly stimulating the recruitment of NK cells, dendritic cells, as well as of B-and T-lymphocytes (Pierangeli et al, 2022). Nevertheless, the Omicron variant was found to affect younger people much more than the previous major variants, which possibly means that the new variant escaped interferon epsilon and omega signals significantly more.…”