Abstract
SARS-CoV-2 coronavirus infection induces heterogeneous symptoms, ranging from asymptomatic to lethal forms. Severe forms usually occur in the elderly and/or individuals with comorbidities. Children generally remain asymptomatic to primary infection, suggesting that they may have an effective local innate immune response. IFN-I and -III have non-redundant protective roles against SARS-CoV-2, although sometimes damaging the host. The expression and role of anti-viral peptides during SARS-CoV-2 infection have thus far been little studied. We aimed to identify the innate immune molecules present at the SARS-CoV-2 entry point. We analyzed the mRNA levels of type I (IFN-α and -β) and type III (IFN-λ1-3) interferons and selected antiviral peptides (i.e., β-defensins 1-3, α-defensins [HNP1-3, HD5] pentraxin-3, surfactant protein D, the cathelicidin LL-37 and interleukin-26) in nasopharyngeal swabs from 226 individuals of various ages, either infected with SARS-CoV-2 (symptomatic or asymptomatic) or negative for the virus. We observed that infection induced selective upregulation of IFN-λ1 expression in pediatric subjects (≤15 years), whereas IFN-α, IFN-β, IFN-λ2/λ3, and β-defensin 1-3 expression was unaffected. Conversely, infection triggered upregulation of IFN-α, IFN-β, IFN-λ2/λ3, and β-defensin 1-3 mRNA expression in adults (15-65 years) and the elderly (≥ 65 years), but without modulation of IFN-λ1. The expression of these innate molecules was not associated with gender or symptoms. Expression of the interferon-stimulated genes IFITM1 and IFITM3 was upregulated in SARS-CoV-2-positive subjects and reached similar levels in the three age groups. Finally, age-related differences in nasopharyngeal innate immunity were also observed in SARS-CoV-2-negative subjects. This study shows that the expression patterns of IFN-I/-III and certain anti-viral molecules in the nasopharyngeal mucosa of SARS-CoV-2-infected subjects differ with age and suggests that susceptibility to SARS-CoV-2 may be related to intrinsic differences in the nature of mucosal anti-viral innate immunity.
Highlights
Severe acute respiratory syndrome related coronavirus 2 (SARSCoV-2), a recently emerged enveloped RNA betacoronavirus, is responsible for the current pandemic coronavirus disease 2019 (COVID-19)
IFNA, IFNB, INFL1, and IFNL2L3 mRNA levels were significantly higher in SARS-CoV-2-infected subjects than in SARS-CoV-2-negative subjects (Figures 1A–D), there was no difference according to gender (Figures S1A–D) or symptoms (Figure S1E–H) with equivalent SARS-CoV-2 cycle threshold (Ct) values in symptomatic and asymptomatic subjects. (Figures S2A, B)
We show that the expression profiles of IFN-I, IFNIII, and b-defensins in the nasopharyngeal mucosa of SARSCoV-2-infected subjects differ according to their age rather than sex or the presence of symptoms
Summary
Severe acute respiratory syndrome related coronavirus 2 (SARSCoV-2), a recently emerged enveloped RNA betacoronavirus, is responsible for the current pandemic coronavirus disease 2019 (COVID-19). SARS-CoV-2 is mainly transmitted through respiratory droplets and the nasal and nasopharyngeal mucosa are the preferred sites of viral entry. Epithelial cells in this area constitutively express the SARS-CoV-2 receptor angiotensinconverting enzyme 2 (ACE2) and its associated receptor transmembrane serine protease type II (TMPRSS2) [1,2,3]. The clinical manifestations of COVID-19 infection are very heterogeneous, ranging from asymptomatic to lethal forms, due to viral progression in the lower respiratory tract and to exacerbated inflammatory response. Children generally develop asymptomatic or moderate forms, and some studies suggest that this could be partly due to a more effective innate immune response during primary infection compared to adults and elderly [6]
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