# Investigation of Epstein-Barr virus coinfection and changes in the gene expression of angiotensin converting enzyme II in peripheral blood mononuclear cells in COVID-19 patients

**Authors:** Hossein Lajmiri, Nioosha Ahmadi, Saeedeh Ebrahimi, Hadi Razavi Nikoo, Mehrdad Farrokhnia, Elham Heidari, Elham Mousavi

PMC · DOI: 10.1016/j.bbrep.2025.102311 · 2025-10-19

## TL;DR

This study examines whether Epstein-Barr virus (EBV) co-infection affects gene expression in COVID-19 patients, focusing on ACE2 levels in blood cells.

## Contribution

The study provides new insights into EBV reactivation and ACE2 expression in PBMCs of COVID-19 patients.

## Key findings

- Only 2.18% of PBMCs were EBV-positive, indicating no active EBV infection in patients.
- ACE2 expression levels in PBMCs showed no significant difference between patients and healthy controls.

## Abstract

SARS-CoV-2, a respiratory virus, causes a range of symptoms from mild cold-like signs to severe conditions like pneumonia and death. Co-infections, such as with Epstein-Barr Virus (EBV), may exacerbate disease severity. EBV can remain latent in B-cells and cause symptoms including pharyngitis, fatigue, and lymphopenia upon reactivation. Studies indicate that gene expression changes in the renin-angiotensin system, particularly involving angiotensin-converting enzyme 2 (ACE2), play a role in SARS-CoV-2 infection, and EBV might increase ACE2 expression. This study investigated EBV prevalence in plasma and peripheral blood mononuclear cells (PBMCs) of COVID-19 patients using serological (ELISA) and molecular (real-time PCR) methods, while also assessing ACE2 expression levels compared to healthy controls. Blood samples were processed to isolate PBMCs and plasma. Results revealed no IgM antibodies against EBV in plasma and only 2.18 % of PBMCs were EBV-positive, indicating no active EBV infection. ACE2 expression levels in PBMCs showed no significant difference between patients and controls. The study concludes that EBV reactivation is unlikely in these COVID-19 patients and recommends further investigation of ACE2 expression in nasopharyngeal epithelial cells.

•SARS-CoV-2 causes symptoms ranging from mild cold-like to severe pneumonia.•Co-infections can increase COVID-19 severity and mortality risk.•EBV may worsen COVID-19 symptoms like fatigue and lymphopenia.•EBV might upregulate ACE2, potentially aiding viral infection.

SARS-CoV-2 causes symptoms ranging from mild cold-like to severe pneumonia.

Co-infections can increase COVID-19 severity and mortality risk.

EBV may worsen COVID-19 symptoms like fatigue and lymphopenia.

EBV might upregulate ACE2, potentially aiding viral infection.

## Linked entities

- **Genes:** ACE2 (angiotensin converting enzyme 2) [NCBI Gene 59272]
- **Diseases:** COVID-19 (MONDO:0100096), pneumonia (MONDO:0005249), lymphopenia (MONDO:0003783)

## Full-text entities

- **Genes:** REN (renin) [NCBI Gene 5972] {aka ADTKD4, HNFJ2, RTD}, ACE2 (angiotensin converting enzyme 2) [NCBI Gene 59272] {aka ACEH}
- **Diseases:** Co (MESH:D060085), EBV infection (MESH:D020031), death (MESH:D003643), fatigue (MESH:D005221), pharyngitis (MESH:D010612), COVID-19 (MESH:D000086382), pneumonia (MESH:D011014), infections (MESH:D007239), lymphopenia (MESH:D008231)
- **Species:** human gammaherpesvirus 4 (Epstein Barr virus, no rank) [taxon 10376], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12554797/full.md

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Source: https://tomesphere.com/paper/PMC12554797