دراسة علاقة مستوى انترلوكين1 الفا، انترلوكين1 بيتا، العامل النووي كابا بيتا و انترلوكين 6 مع الاختبارات الدموية والكيميائية في مرضى كوفيد 19

Studying the association of serum levels of IL-1 alpha, IL-1 beta, Nuclear Factor kappa B and IL-6 with hematological and biochemical parameters in SARS-CoV-2 patients

Abstract

Corona virus disease 2019 (COVID-19) is an infectious disease caused by a newly discovered coronavirus, SARS-CoV-2. The virus infects the cells along the airways of the lung, by attaching to angiotensin converting enzyme 2 receptor (ACE-2). The disease considered a major global health problem affecting, large number of the population around the world. Covid-19 disease is characterized by cytokine storm that is the major cause of disease manifestation and complications. Better understanding the key players this storm would feed in into better formulation of treatment protocols. The aim of this study was to study cytokine candidates, namely IL-1 alpha, IL-1 beta, Nuclear Factor Kappa beta and IL-6 levels, as well as other hematological and chemical parameters in SARS-CoV-2 patients. For this purpose, this cross-sectional study which included 65 Covid-19 patients (32 male and 33 female). All patients were admitted to Al-Amal Specialized Hospital for Communicable diseases, Al-Hakeem Hospital and Al Sader General Hospital in the period extending from December 2020 to February 2021. Their ages ranged between sixteen to ninety years old. The control groups included 23 healthy people (13 male and 10 female) with the same ages and gender of the patients were randomly selected from the local community. The control group was used in the cytokine study for setting up a local reference value. The demographic and clinical data were collected from patients through interview questionnaire. The patients were classified based on SpO2 percentage into mild/moderate group (< 90-94%) and severe/critical group (>90 %). Accordingly, 22 patients were mild/moderate and 43 patients severe/critical. Sera and whole blood were collected from each participant noting that the sera were used to determine serum IL-6, IL-1α, IL-1β and NF-κB levels as well as biochemical parameter for all samples, while whole blood was used for determination of complete blood count and for ESR. The ELISA was used to measure the concentration of serum Interleukins and the data were statistically analysed by software SPSS version 26.
The results of the study showed the sever/critical disease was seen in older age people (mean age 62.58 years). Therefore, the older age is considered a risk factor for developing Severe/critical form of Covid-19. The lymphocyte percent was significantly lower in severe/critical patients compared with mild/moderate group (p = 0.004). While, the ESR was significantly increased in severe/critical patients (p = 0.016). On the other hand, there were a significant association between biochemical marker (urea, albumin, ALT, AST, ALP, LDH, CRP, ferritin and D-dimer) and Covid-19 severity (p-value 0.001, 0.000, 0.016, 0.014, 0.012, 0.005, 0.003, 0.031, 0.001 respectively). There was a significant positive correlation between serum IL-1α levels with neutrophil (p = 0.010). Likely there was a significant positive correlation between serum IL-6 levels and creatinine level (p = 0.012). Whereas, the SpO2 percentage, lymphocyte and serum albumin were negatively correlated with IL-6 level (p = 0.002, 0.015, 0.034 respectively). In addition, the NF-κB had a negative correlation with RBC counts and haemoglobin levels (p = 0.034, 0.005 respectively). Finally, there was a positive correlation between the level of IL-1β with LDH and AST levels (p = 0.054, 0.049 respectively).
In conclusion, an increased risk of Covid-19 was associated with older age, comorbidities including; hypertension (increased systolic blood pressure) higher blood glucose level as well as decrease lymphocyte. Serum IL-6 level had a positive linear correlation with creatinine level and negative liner correlation with lymphocyte and albumin. Accordingly, IL-6 may have direct adverse effect on kidney and lung tissues in addition to bone marrow and the liver. The increased of IL-6 levels may be due to SARS-CoV-2, as a relationship was found between NF-κB and IL-6, while there is study indicating existence of relationship between ORF7a of SARS-CoV-2 and NF-κB which in turn responsible for upregulation of IL-6. The IL-1α serum level had a positive linear correlation with neutrophil and negative liner correlation with lymphocyte and albumin. Thus, IL-1α has a proinflammatory effect. The IL-1β had a positive linear correlation with AST and LDH level. These results may indicate that IL-1β is associated with tissue damage. On the other hand, the NF-κB level had a negative linear correlation with white blood cells and haemoglobin. These results may indicate that NF-κB has direct adverse effect on RBC counts and hemoglobin levels.