Mucosal gene expression in response to SARS-CoV-2 is associated with early viral load

Abstract

Little is known about the relationships between symptomatic early-time SARS-CoV-2 viral load and upper airway mucosal gene expression and immune response. To examine the association of symptomatic SARS-CoV-2 early viral load with upper airway mucosal gene expression, we profiled the host mucosal transcriptome from nasopharyngeal swab samples from 68 adults with symptomatic, mild-to-moderate COVID-19. We measured SARS-CoV-2 viral load using qRT-PCR. We then examined the association of SARS-CoV-2 viral load with upper airway mucosal immune response. We detected SARS-CoV-2 in all samples and recovered >80% of the genome from 85% of the samples from symptomatic COVID-19 adults. The respiratory virome was dominated by SARS-CoV-2, with limited co-detection of common respiratory viruses i.e., only the human Rhinovirus (HRV) being identified in 6% of the samples. We observed a significant positive correlation between SARS-CoV-2 viral load and interferon signaling (OAS2, OAS3, IFIT1, UPS18, ISG15, ISG20, IFITM1, and OASL), chemokine signaling (CXCL10 and CXCL11), and adaptive immune system (IFITM1, CD300E, and SIGLEC1) genes in symptomatic, mild-to-moderate COVID-19 adults, when adjusted for age, sex and race. Interestingly, the expression levels of most of these genes plateaued at a CT value of ~25. Overall, our data shows that early nasal mucosal immune response to SARS-CoV-2 infection is viral load dependent, which potentially could modify COVID-19 outcomes.

Rapid recall andde novoT cell responses during SARS-CoV-2 breakthrough infection

“…Phenotypically, both DR15-S 751 - and DP04-S 167 -specific cells exhibited a mixture of T CM -like (CD45RA - CCR7 + ) and T EM -like (CD45RA - CCR7 - ) profiles, with a transient increase in the relative proportion of CCR7 + cells occurring around the peak of T cell proliferation (Supp Figure 3A). Previously, nasopharyngeal swabs collected during mild/moderate COVID-19 revealed the upregulation of multiple inflammatory mediators, including the CXCR3 ligand CXCL10(Rajagopala et al, 2022), which may facilitate trafficking of activated T cells to the lung or nasal mucosa. S-specific CD4 + T cells showed upregulation of both CXCR3 and CCR5 during BTI, suggesting the potential for these cells to migrate to inflamed tissues (Figure 2D, Supp Figure 3B-C).…”