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