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Original Research Open Access

CALHM6: Expression Level in SARS-CoV-2 Patients and Its Trend as the Infection Progresses

  • 1National University of Sciences and Technology, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences (ASAB), Islamabad, Pakistan
  • 2Rawalpindi Medical University, Department of Pathology, Rawalpindi District, Rawalpindi, Punjab Province, Pakistan
  • 3Abdul Wali Khan University Mardan, Department of Biochemistry, Faculty of Chemical and Life Sciences, Mardan, Khyber Pakhtunkhwa Province, Pakistan
  • 4Bahria University, College of Medicine, Islamabad, Pakistan
  • 5National Institute of Health, Department of Virology, Pakistan, Islamabad
+ Affiliations - Affiliations

Corresponding Author

Aneela Javed, javedaneela19@gmail.com

Received Date: August 27, 2025

Accepted Date: December 31, 2025

Abstract

Background: This study investigates the role of Calcium Homeostasis Modulator 6 (CALHM6) in immune regulation during SARS-CoV-2 infection, with the aim of exploring its potential as a prognostic marker.

Methodology: Peripheral blood mononuclear cells (PBMCs) from 42 SARS-CoV-2 positive patients and 19 healthy controls were analyzed for CALHM6 expression. Clinical data were collected from patients admitted with low oxygen saturation (≤90%) and severe symptoms, and RNA was extracted at admission. Additionally, 18 SARS-CoV-2 positive patients were followed every two days, with RNA extracted on Days 1, 3, 5, 7, and 9 until they either succumbed or were discharged. CALHM6 expression was measured using RT-PCR and the 2−ΔΔCt method, and serum samples from eight SARS-CoV-2 positive and negative individuals were analyzed via ELISA.

Results: Out of the forty-two included patients, thirty (n=30) succumbed to SARS-CoV-2 (71.42%). Results revealed a significant reduction in CALHM6 mRNA expression in SARS-CoV-2 positive patients compared to healthy controls (p<0.0001) via qRT-PCR. This downregulation was consistent when CALHM6 levels were quantified using an ELISA kit (p=0.0025 **). Notably, 80% of discharged patients exhibited elevated CALHM6 expression at follow-up, and all showed an increase in expression at their final follow-up compared to Day 1. Moreover, the expression level of CALHM6 was elevated on the final follow-up of all discharged patients (100%, n=5) in comparison with the prior successive reading, meriting CALHM6 as a critical immune modulator. Out of the thirteen deceased patients during follow-ups (n=13), the expression level of CALHM6 decreased in eight patients and increased in five patients compared to their prior successive reading.

Conclusion: Our research is the first to demonstrate the association between CALHM6 and SARS-CoV-2. Further studies are needed to explore its potential as a therapeutic target for modulating immune response and calcium homeostasis to improve SARS-CoV-2 outcomes.

Keywords

SARS-CoV-2, CALHM6, ROS, Calcium homeostasis, ARDS, Immune modulator, Follow-up

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