Abstract
Children with the new coronavirus disease 2019 (COVID-19) have milder symptoms and a better prognosis than adult patients. Several investigations assessed type I, II, and III interferon (IFN) signatures in SARS-CoV-2 infected adults, however no data are available for pediatric patients. TRIM28 and SETDB1 regulate the transcription of multiple genes involved in the immune response as well as of human endogenous retroviruses (HERVs). Exogenous viral infections can trigger the activation of HERVs, which in turn can induce inflammatory and immune reactions. Despite the potential cross-talks between SARS-CoV-2 infection and TRIM28, SETDB1, and HERVs, information on their expressions in COVID-19 patients is lacking. We assessed, through a PCR real time Taqman amplification assay, the transcription levels of six IFN-I stimulated genes, IFN-II and three of its sensitive genes, three IFN-lIIs, as well as of TRIM28, SETDB1, pol genes of HERV-H, -K, and -W families, and of env genes of Syncytin (SYN)1, SYN2, and multiple sclerosis-associated retrovirus (MRSV) in peripheral blood from COVID-19 children and in control uninfected subjects. Higher expression levels of IFN-I and IFN-II inducible genes were observed in 36 COVID-19 children with mild or moderate disease as compared to uninfected controls, whereas their concentrations decreased in 17 children with severe disease and in 11 with multisystem inflammatory syndrome (MIS-C). Similar findings were found for the expression of TRIM-28, SETDB1, and every HERV gene. Positive correlations emerged between the transcriptional levels of type I and II IFNs, TRIM28, SETDB1, and HERVs in COVID-19 patients. IFN-III expressions were comparable in each group of subjects. This preserved induction of IFN-λs could contribute to the better control of the infection in children as compared to adults, in whom IFN-III deficiency has been reported. The upregulation of IFN-I, IFN-II, TRIM28, SETDB1, and HERVs in children with mild symptoms, their declines in severe cases or with MIS-C, and the positive correlations of their transcription in SARS-CoV-2-infected children suggest that they may play important roles in conditioning the evolution of the infection.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), is a recently emerged coronavirus that has infected millions of people worldwide
1.7; 13.0 years); and 108 children (57 males, median age 5.2 years, interquartile range (IQR) 3.5; 12.6 years) for the detection of pol genes of human endogenous retroviruses (HERVs)-H, HERV-K, and HERV-W who were investigated as a control group in our previous studies [45,51,56]
An extensive body of literature underlines the importance of IFNs for the optimal control of SARS-CoV-2 infection, though several studies point to their potential involvement in the immunopathology of severe COVID-19
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), is a recently emerged coronavirus that has infected millions of people worldwide. Type I ISG products have immunomodulatory properties and are implicated in the development of the cytokine storm that can lead to fatal outcomes in COVID-19 patients [2,3,4]. CXCL9, CXCL10, and IDO1 are prevalently IFN-γ-induced chemokines Their expressions correlate with the tissue infiltration of inflammatory cells, in particular of T cells [6]. A third type of interferons (IFN-III), referred to as lambdas (IFNλs), in humans comprise four members: IFNλ1/IL-29, IFNλ2/IL-28A, IFNλ3/IL-28B, and IFNλ4. They bind to a unique heterodimeric receptor complex, which is restricted to epithelial cells and a subset of immune cells [7]. IFNλs play a major role in the antiviral protection of mucosa barriers [8]
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