# Association of gender and main comorbidities with expression of lncRNAs and mRNAs in COVID-19 patients

**Authors:** Hassan Abolghasemi, Hamidreza Kheiri, Hamid Sedighian, Elham Behzadi, Reza Kachuei, Mozhgan Kheirandish, Masoud Arabfard, Abbas Ali Imani Fooladi

PMC · DOI: 10.1016/j.jgeb.2025.100650 · 2025-12-24

## TL;DR

This study explores how gender and comorbidities affect gene expression in COVID-19 patients, identifying potential biomarkers for disease outcomes.

## Contribution

The study identifies specific lncRNAs and mRNAs associated with gender and comorbidities in COVID-19 patients.

## Key findings

- Genes like ALAS2, CCL2, AHSP, and IL5 were identified as hub genes in immune response pathways.
- CCL2 showed high expression in patients with unfavorable outcomes.
- Heme/hemoglobin metabolism genes were enriched in multiple patient groups.

## Abstract

SARS-CoV-2 causes mortality in a considerable number of patients with COVID-19. The association of comorbidities and gender with the expression of lncRNAs and mRNAs in COVID-19 patients is not fully understood. The purpose of the present study was to explore this association.

We used Transcriptomics data for lncRNAs and mRNAs from the integrated Gene Expression Omnibus (GEO) to identify Differentially Expressed Genes (DEGs) using R software for statistical and data analysis. Then, we carried out Gene Ontology (GO) analysis and constructed a Protein-Protein Interaction (PPI) network to identify interactions between the genes.

In this study, we divided samples into four groups and compared Differentially Expressed lncRNAs (DEls) and DEGs. Genes enriched in immune response and cytokine pathways were identified by GO analysis. By considering the protein–protein interaction network, the hub genes were ALAS2, CCL2, AHSP, and IL5.

mRNAs and lncRNAs could be used to identify the effects of SARS-CoV-2 on defined parameters (such as gender, main comorbidities in recovery, and treatment stages). Heme/hemoglobin metabolism was enriched in groups 1, 2, and 4, with four common genes (ALAS2, AHSP, HBD, and CA1) that are associated with the immune response to infection. CCL2 was enriched in group 3 and its expression was remarkably high in patients with an unfavorable outcome compared to other cases. Also, while both IL-5 and ALAS2 were enriched in group 4, IL-5 appeared to have no significant role in COVID-19. Overall, we conducted a bioinformatics analysis to predict how mRNAs and lncRNAs interact in patients with different characteristics such as gender, underlying disease, and treatment or recovery stages. mRNAs and lncRNAs can be potential biomarkers to examine the effect of SARS-CoV-2 on defined parameters.

## Linked entities

- **Genes:** ALAS2 (5'-aminolevulinate synthase 2) [NCBI Gene 212], CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347], AHSP (alpha hemoglobin stabilizing protein) [NCBI Gene 51327], IL5 (interleukin 5) [NCBI Gene 3567], HBD (hemoglobin subunit delta) [NCBI Gene 3045], CA1 (carbonic anhydrase 1) [NCBI Gene 759]
- **Diseases:** COVID-19 (MONDO:0100096)

## Full-text entities

- **Genes:** CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, AHSP (alpha hemoglobin stabilizing protein) [NCBI Gene 51327] {aka EDRF, ERAF}, HBD (hypophosphatemic bone disease) [NCBI Gene 100187828], ALAS2 (5'-aminolevulinate synthase 2) [NCBI Gene 212] {aka ALAS-E, ALASE, ANH1, ASB, SIDBA1, XLDPP}, CA1 (carbonic anhydrase 1) [NCBI Gene 759] {aka CA-I, CAB, Car1, HEL-S-11}, IL5 (interleukin 5) [NCBI Gene 3567] {aka EDF, IL-5, TRF}
- **Diseases:** COVID-19 (MESH:D000086382), infection (MESH:D007239)
- **Species:** Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Homo sapiens (human, species) [taxon 9606]

## Figures

12 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12797059/full.md

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Source: https://tomesphere.com/paper/PMC12797059