Differential expression of lung-homing chemokine receptors in severe COVID-19: distinct profiles between Alpha and Omicron
5 affiliations
- 1Saveh School of Medical Sciences, Saveh,, Iran
- 2Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran
- 3Department of Internal Medicine, Ghaem Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- 4Department of Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- 5Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Abstract
Background: Severe Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is characterized by excessive pulmonary immune cell recruitment mediated by chemokine – chemokine receptor signaling. Variant-specific differences in lung-homing chemokine receptor expression remain insufficiently defined.
Methods: This retrospective case-control study analyzed Bronchoalveolar Lavage Fluid (BALF) samples from Intensive Care Unit (ICU) admitted patients with severe COVID-19 during the Alpha (hICU-α) and Omicron (hICU-Ο) waves, along with SARS-CoV-2 – negative controls. Messenger RNA expression of CXCR1, CXCR2, CXCR3, CCR2, and CCR6 was quantified by Real-Time quantitative Polymerase Chain Reaction (RT-qPCR). Protein expression of selected receptors was assessed by western blotting in available samples.
Results: CXCR1 expression was significantly increased in hICU-α patients compared with controls (p = 0.02) but not in hICU-Ο patients. CXCR2 expression was elevated in both hICU-α and hICU-Ο groups versus controls (p = 0.008 and p = 0.006, respectively) and was higher in hICU-α than hICU-Ο patients (p = 0.009). CXCR3 expression was increased in both COVID-19 groups compared with controls (p = 0.03 and p = 0.001). CCR6 expression was highest in hICU-Ο patients compared with hICU-α and controls (p = 0.04 and p = 0.001). Increased CXCR2 and CXCR3 protein expression was confirmed in hICU-Ο patients.
Conclusions: Severe COVID-19 is associated with variant-specific alterations in lung chemokine receptor expression, highlighting differential immune trafficking patterns during Alpha and Omicron waves.
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BibTeX
@article{mohammadi2026differential,
title = {{Differential expression of lung-homing chemokine receptors in severe COVID-19: distinct profiles between Alpha and Omicron}},
author = {Fatemeh Sadat Mohammadi and Afsane Fadaee and Alireza Shariati and Saman Soleimanpour and Vahideh Taherian and Ali Mirhosseini and Mehran Mohareri and Narges Valizadeh and Nazila Ariaee and Amir Mohammad Hashem Asnaashari and Seyed Abdolrahim Rezaee},
journal = {Clinics},
year = {2026},
month = oct,
doi = {10.1016/j.clinsp.2026.101228},
url = {https://doi.org/10.1016/j.clinsp.2026.101228},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Differential expression of lung-homing chemokine receptors in severe COVID-19: distinct profiles between Alpha and Omicron
AU - Fatemeh Sadat Mohammadi
AU - Afsane Fadaee
AU - Alireza Shariati
AU - Saman Soleimanpour
AU - Vahideh Taherian
AU - Ali Mirhosseini
AU - Mehran Mohareri
AU - Narges Valizadeh
AU - Nazila Ariaee
AU - Amir Mohammad Hashem Asnaashari
AU - Seyed Abdolrahim Rezaee
PY - 2026
DA - 2026/10/30
JO - Clinics
DO - 10.1016/j.clinsp.2026.101228
UR - https://doi.org/10.1016/j.clinsp.2026.101228
AB - Background: Severe Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is characterized by excessive pulmonary immune cell recruitment mediated by chemokine – chemokine receptor signaling. Variant-specific differences in lung-homing chemokine receptor expression remain insufficiently defined. Methods: This retrospective case-control study analyzed Bronchoalveolar Lavage Fluid (BALF) samples from Intensive Care Unit (ICU) admitted patients with severe COVID-19 during the Alpha (hICU-α) and Omicron (hICU-Ο) waves, along with SARS-CoV-2 – negative controls. Messenger RNA expression of CXCR1, CXCR2, CXCR3, CCR2, and CCR6 was quantified by Real-Time quantitative Polymerase Chain Reaction (RT-qPCR). Protein expression of selected receptors was assessed by western blotting in available samples. Results: CXCR1 expression was significantly increased in hICU-α patients compared with controls (p = 0.02) but not in hICU-Ο patients. CXCR2 expression was elevated in both hICU-α and hICU-Ο groups versus controls (p = 0.008 and p = 0.006, respectively) and was higher in hICU-α than hICU-Ο patients (p = 0.009). CXCR3 expression was increased in both COVID-19 groups compared with controls (p = 0.03 and p = 0.001). CCR6 expression was highest in hICU-Ο patients compared with hICU-α and controls (p = 0.04 and p = 0.001). Increased CXCR2 and CXCR3 protein expression was confirmed in hICU-Ο patients. Conclusions: Severe COVID-19 is associated with variant-specific alterations in lung chemokine receptor expression, highlighting differential immune trafficking patterns during Alpha and Omicron waves.
SN - 1807-5932
SN - 1980-5322
ER -