Analysis of Immune Profiles Related to Disease Severity in COVID-19 by Flow Cytometry

Background: More than 768 million people have been affected by COVID-19. Identifying lymphocyte subsets and cytokine level abnormalities in COVID-19 patients is essential to gain new insights and data on immunity mechanisms against viral infections. Objectives: We used flow cytometry to determine the relationship between disease severity, lymphocyte subsets distribution, and cytokine level alterations in COVID-19 patients. Methods: Totally 94 COVID-19 patients (32 mild, 31 moderate, and 31 severe) and 27 healthy individuals were included in the cross-sectional study. The distribution of peripheral lymphocyte subsets and cytokine levels was assessed by flow cytometry. Results: The percentages of CD56+ Natural Killer (NK) cells in all patient groups and total T lymphocytes in moderate and severe groups were significantly lower than those in the control group (P < 0.001). Also, IL-2 (P < 0.001), IL-17A (P < 0.001), IL-4 (P < 0.001), IL-6 (P < 0.001), TNF-α (P = 0.004), IP-10 (P < 0.001), IFN-λ1 (IL-29) (P < 0.001), IFN-λ2/3 (IL-28A/B) (P = 0.011), IFN-β (P < 0.001), IL-10 (P < 0.001), and IFN-γ (P < 0.001) levels were statistically higher in patients than in the controls. Conclusions: Our data revealed that increased levels of certain cytokines in peripheral blood contribute to disease severity. Increased CRP (OR: 1.012, %95 CI: 1.002 - 1.023, P = 0.038) and IL-10 (OR: 1.068, %95 CI: 1.000 - 1.141, P = 0.049) levels, decreased CD56+ NK percentage (OR: 0.576, %95 CI: 0.376 - 0.882, P = 0.011) and lymphocyte count (OR: 0.02, %95 CI: 0.001 - 0.368, P = 0.009), and the presence of diabetes mellitus and mechanical ventilation were independent predictors of mortality.

[1]  D. Leaf,et al.  Therapeutic advances in COVID-19 , 2022, Nature Reviews Nephrology.

[2]  Ruchong Chen,et al.  Identification of Parameters Representative of Immune Dysfunction in Patients with Severe and Fatal COVID-19 Infection: a Systematic Review and Meta-analysis , 2022, Clinical Reviews in Allergy & Immunology.

[3]  Serpil Öcal SARS‐CoV‐2 and lung injury: Dysregulation of immune response but not hyperimmune response as in “cytokine storm syndrome” , 2021, The clinical respiratory journal.

[4]  J. Hsu,et al.  Interleukin-18 Is a Potential Biomarker to Discriminate Active Adult-Onset Still’s Disease From COVID-19 , 2021, Frontiers in Immunology.

[5]  B. Paiva,et al.  Immunological Biomarkers of Fatal COVID-19: A Study of 868 Patients , 2021, Frontiers in Immunology.

[6]  Guangwei Luo,et al.  The Inflammatory Factors Associated with Disease Severity to Predict COVID-19 Progression , 2021, The Journal of Immunology.

[7]  F. Conti,et al.  Autophagy Modulation in Lymphocytes From COVID-19 Patients: New Therapeutic Target in SARS-COV-2 Infection , 2020, Frontiers in Pharmacology.

[8]  P. Muñoz,et al.  Lymphocyte subsets early predict mortality in a large series of hospitalized COVID‐19 patients in Spain , 2020, Clinical and experimental immunology.

[9]  L. Cosmi,et al.  Cell‐mediated and humoral adaptive immune responses to SARS‐CoV‐2 are lower in asymptomatic than symptomatic COVID‐19 patients , 2020, European journal of immunology.

[10]  Chengliang Zhu,et al.  Descriptive, Retrospective Study of the Clinical Characteristics of Asymptomatic COVID-19 Patients , 2020, mSphere.

[11]  E. Zaboli,et al.  Apoptosis and immunophenotyping of peripheral blood lymphocytes in Iranian COVID‐19 patients: Clinical and laboratory characteristics , 2020, Journal of medical virology.

[12]  Daxian Wu,et al.  Lymphocyte subset alterations with disease severity, imaging manifestation, and delayed hospitalization in COVID-19 patients , 2020, BMC Infectious Diseases.

[13]  Nicolas Carlier,et al.  Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients , 2020, Science.

[14]  G. Mosayebi,et al.  Increased expression of CD8 marker on T-cells in COVID-19 patients , 2020, Blood Cells, Molecules, and Diseases.

[15]  Theodora Psaltopoulou,et al.  Hematological findings and complications of COVID‐19 , 2020, American journal of hematology.

[16]  G. Zini,et al.  Morphological anomalies of circulating blood cells in COVID‐19 , 2020, American journal of hematology.

[17]  Q. Ye,et al.  The pathogenesis and treatment of the `Cytokine Storm' in COVID-19 , 2020, Journal of Infection.

[18]  Mario Plebani,et al.  Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis , 2020, Clinical chemistry and laboratory medicine.

[19]  Q. Ye,et al.  The pathogenesis and treatment of the `Cytokine Storm' in COVID-19 , 2020, Journal of Infection.

[20]  R. Alizadeh-Navaei,et al.  Evaluation of Hepatic Enzymes Changes and Association with Prognosis in COVID-19 Patients , 2020, Hepatitis Monthly.

[21]  Allen M. Khakshooy,et al.  CoViD-19 Immunopathology and Immunotherapy , 2020, Bioinformation.

[22]  Zhiyong Ma,et al.  Characteristics of Peripheral Lymphocyte Subset Alteration in COVID-19 Pneumonia , 2020, The Journal of infectious diseases.

[23]  M. Girardis,et al.  SARS‐CoV‐2, the Virus that Causes COVID‐19: Cytometry and the New Challenge for Global Health , 2020, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[24]  D. Wang,et al.  The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak – an update on the status , 2020, Military Medical Research.

[25]  A. M. Leontovich,et al.  The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2 , 2020, Nature Microbiology.

[26]  K. Yuen,et al.  Clinical Characteristics of Coronavirus Disease 2019 in China , 2020, The New England journal of medicine.

[27]  H. Rothan,et al.  The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak , 2020, Journal of Autoimmunity.

[28]  Lijuan Xiong,et al.  Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients , 2020, EBioMedicine.

[29]  Yan Zhao,et al.  Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. , 2020, JAMA.

[30]  Ting Yu,et al.  Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study , 2020, The Lancet.

[31]  Y. Hu,et al.  Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China , 2020, The Lancet.

[32]  Qin Ning,et al.  Clinical and immunological features of severe and moderate coronavirus disease 2019 , 2020 .