# Genetic and Inflammatory Signatures Associated With Worse Prognosis in Hospitalized Patients With Severe SARS‐CoV‐2 Infection With and Without Diabetes

**Authors:** Marshall Yuan, Andrew Wassef, Davit Sargsyan, Vahe Nersisyan, Javier Cabrera, Ronald G. Nahass, Wael Hassan, Ah‐Ng Kong, Luigi Brunetti

PMC · DOI: 10.1002/jmv.70425 · Journal of Medical Virology · 2025-06-06

## TL;DR

This study identifies genetic and inflammatory markers linked to worse outcomes in hospitalized patients with severe SARS-CoV-2 infection, both with and without diabetes.

## Contribution

The study reveals specific gene expression patterns and potential biomarkers for severe disease in patients with and without diabetes.

## Key findings

- 18 genes were differentially expressed between patients with and without COVID-19.
- 431 genes were differentially expressed between patients with and without diabetes.
- Five genes were commonly differentially expressed in both comparisons.

## Abstract

Severe acute respiratory syndrome coronavirus 2 (SAR‐CoV‐2) presents with a diverse symptomology, ranging from asymptomatic to severe disease, but the mechanism of risk factors such as diabetes remains unelucidated. The current retrospective cohort study of 182 patients, with and without COVID‐19 and diabetes, analyzed leftover blood specimens for RNA sequencing and chemokine/cytokine, ACE2/DPP‐IV concentrations. After analysis, 14 223 genes had sufficient hits; 18 genes and 431 genes were differentially expressed between patients with and without COVID‐19 and patients with and without diabetes, respectively. Both analyses had differentially expressed five genes, GRASP, KRT8, MYZAP, PRKG1, and SMIM24. DPP‐IV concentrations were statistically lower in COVID‐19 patients versus non‐COVID‐19, but no significant differences in chemokine/cytokine expression and ACE2 concentrations were detected. This study provides insight into altered gene expression patterns in individuals with COVID‐19 with and without diabetes mellitus and highlights potential markers for severe disease and pathways for treatment targets.

## Linked entities

- **Genes:** TAMALIN (trafficking regulator and scaffold protein tamalin) [NCBI Gene 160622], KRT8 (keratin 8) [NCBI Gene 3856], MYZAP (myocardial zonula adherens protein) [NCBI Gene 100820829], PRKG1 (protein kinase cGMP-dependent 1) [NCBI Gene 5592], SMIM24 (small integral membrane protein 24) [NCBI Gene 284422]
- **Diseases:** diabetes mellitus (MONDO:0005015)

## Full-text entities

- **Genes:** PRKG1 (protein kinase cGMP-dependent 1) [NCBI Gene 5592] {aka AAT8, PKG, PKG1, PRKG1B, PRKGR1B, cGK}, ACE2 (angiotensin converting enzyme 2) [NCBI Gene 59272] {aka ACEH}, DPP4 (dipeptidyl peptidase 4) [NCBI Gene 1803] {aka ADABP, ADCP2, CD26, DPPIV, TP103}, TAMALIN (trafficking regulator and scaffold protein tamalin) [NCBI Gene 160622] {aka GRASP}, KRT8 (keratin 8) [NCBI Gene 3856] {aka CARD2, CK-8, CK8, CYK8, K2C8, K8}, SMIM24 (small integral membrane protein 24) [NCBI Gene 284422] {aka C19orf77, HSPC323, MARDI}, MYZAP (myocardial zonula adherens protein) [NCBI Gene 100820829] {aka CMD2K, Gup, MYOZAP}
- **Diseases:** Inflammatory (MESH:D007249), COVID-19 (MESH:D000086382), Diabetes (MESH:D003920)
- **Species:** Homo sapiens (human, species) [taxon 9606], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12143195/full.md

## References

93 references — full list in the complete paper: https://tomesphere.com/paper/PMC12143195/full.md

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Source: https://tomesphere.com/paper/PMC12143195