Age-associated Ligand-receptor Interactions Imputed from Nasopharyngeal Transcriptomes of COVID-19 Patients

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has exhibited different clinical manifestations amongst various age cohorts. As the immune microenvironment may play a role in clinical progression, it is crucial to examine molecular interactions to gain insight into host response. Therefore, to elucidate any differences in host response related to age, the present study imputed ligand-receptor interactions within the nasopharyngeal immune microenvironment in patients affected with SARS-COV-2. Tissue purities, the proportion of non-immune cells in the tissue sample, of 467 nasopharyngeal transcriptome profiles were estimated using known mRNA expression signatures of stromal/immune cells. Using the purity estimates and bulk tissue expression values, non-negative linear regression was used to estimate average expression of each gene in the tissue/stroma compartments. The inferred expression profiles were annotated with a curated database of ligand-receptor interactions and assumed as reasonable proxies for the law of mass action, allowing for quantification of directional ligand-receptor complex concentrations under equilibrium. It was found that older patients (>60 years) exhibited decreased interactions with receptors selectin L receptor SELL and increased interactions with pro-inflammatory chemokine receptors CXCR2 and CCR1. Younger patients showed increased interactions with various members of the TNF receptor super family (TNFRSF). The interactions were further related to immune cell subtypes, with older patients predicted to have less CD8+ and CD4+ resting T cells but increased neutrophil proportions. Collectively, the results suggest certain ligand-receptor interactions of the nasopharyngeal immune microenvironment are age-associated in response to SARS-CoV-2.

KEYWORDS:

• COVID-19
• SARS-CoV-2
• nasopharyngeal
• transcriptome
• deconvolution
• interactions

Conflicts of interest

The authors have no conflicts of interest to declare

Availability of data and material

All data used in the present study is publicly available at the referenced data repositories.

Code availability

All analyses were performed with R and Python programming language. Code is available upon request.

Authors’ contributions

S.B. conceptualized the study and performed data analysis. S.Y. and S.B. wrote and edited the paper.

Ethics approval

The paper is exempt from ethical committee approval. All data used can be found online at the stated repositories, previously published by the referenced studies who received ethics approval from their respective ethics approval committees.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

No funding was received for this study. The content is solely the responsibility of the authors and does not necessarily represent the official view of Cooper Medical School of Rowan University.