Abstract COVID‐19 is a life‐threatening disease leading to bilateral pneumonia and respiratory failure. The underlying reasons why a smaller percentage of patients present with severe pulmonary symptoms whereas the majority is only mildly affected are to date not well understood. Comparing the immunological phenotype in healthy donors and patients with mild versus severe COVID‐19 shows that in COVID‐19 patients, NK‐/B‐cell activation and proliferation are enhanced independent of severity. As an important precondition for effective antibody responses, T‐follicular helper cells and antibody secreting cells are increased both in patients with mild and severe SARS‐CoV‐2 infection. Beyond this, T cells in COVID‐19 patients exhibit a stronger activation profile with differentiation toward effector cell phenotypes. Importantly, when looking at the rates of pulmonary complications in COVID‐19 patients, the chemokine receptor CCR4 is higher expressed by both CD4 and CD8 T cells of patients with severe COVID‐19. This raises the hypothesis that CCR4 upregulation on T cells in the pathogenesis of COVID‐19 promotes stronger T‐cell attraction to the lungs leading to increased immune activation with presumably higher pulmonary toxicity. Our study contributes significantly to the understanding of the immunological changes during COVID‐19, as new therapeutic agents, preferentially targeting the immune system, are highly warranted. Patients with mild COVID‐19 after SARS‐CoV2 infection exhibit increased T‐cell activation and induction of T‐cell exhaustion. During severe COVID‐19 patients show massive T‐cell activation and upregulation of homing receptors promoting hyperinflammation and increased lung trafficking.
【저자키워드】 COVID‐19, SARS‐CoV‐2, CCR4, Lung homing, T‐cell activation, 【초록키워드】 Pathogenesis, Respiratory failure, Pneumonia, antibody, T cells, severity, CCR4, lung, immune system, CD4, COVID‐19, T cell, immune activation, hyperinflammation, Lungs, Patient, Mild, therapeutic agents, receptor, differentiation, disease, Chemokine receptor, CD8 T cells, Hypothesis, CD8 T cell, immunological changes, proliferation, independent of, helper cells, Phenotypes, Activation, homing receptors, healthy donors, COVID‐19 patients, pulmonary complications, upregulation, antibody secreting cells, bilateral pneumonia, CD4 and CD8 T cells, chemokine receptor CCR4, immunological phenotype, pulmonary symptoms, pulmonary toxicity, SARS‐CoV2 infection, SARS‐CoV‐2 infection, T‐cell activation, T‐cell exhaustion, T‐follicular helper cells, responses, effective, homing, independent, healthy donor, raise, affected, significantly, lung trafficking, majority, contribute, expressed, promote, antibody secreting cell, COVID‐19 patient, effector cell, immunological change, NK‐/B‐cell, pulmonary complication, pulmonary symptom, T‐cell, T‐follicular helper cell, 【제목키워드】 lung, CD8, T cell, Patient, homing, activated, indicate,