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Differential expression of lung-homing chemokine receptors in severe COVID-19: distinct profiles between Alpha and Omicron

Year: 2026

Type: article

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.

Source: Clinics

DOI: 10.1016/j.clinsp.2026.101228