تعدد الاشكال الجيني ومستويات بعض المعايير المناعية في الالتهاب الرئوي لمرضى كوفيد-19 وارتباطه بالفيروس الغدي كاصابة مشتركة

Gene Polymorphisms and Levels of some Immunological Markers in Patients with COVID-19 Pneumonia Associated with Adenovirus as Coinfection

abstract

Coronavirus 2019 is distinguished by the occurrence of a cytokines storm and excessive immune response through high secretion of cytokines and chemokines that there exists a deficit in the regulation of immune-associated tissue destruction when compared with the wound recovery as well as tissue restoration process that considered one of the most prominent methods used in virus, which determines the intensity of the illness.
One hundred fifty patients were diagnosed with infection related to the viral strain SARS-CoV-2 participated in this study, as their infection with the virus was confirmed through Real Time-Polymerase Chain Reaction (RT-PCR) of specific nasopharyngeal swab samples along with the rapid antigen, and the participants received health care in Imam Hussein Medical City from March until July 2022.
The average age was observed to be (44.04, 62.16 and 61.14 years) for three patients groups (Mild, Moderate and Severe) and the age range was between 20 to 79 years to control and mild groups, in comparison, 20 -89 years for moderate and severe groups. and the numbers of participants included 23 men and 27 women for control group, with 36 men and 14 women for mild group. Nonetheless, there were 31 men and 19 women within the moderate as well as severe groups. the preliminary results of this study imply that men participants of elderly status have had a greater probability of risk.
There were certainly exists a association amongst particular factors and the onset of symptoms brought on by COVID-19 (For human Spike protein COVID-19, Correlation=0.591, p =<0.001; and Adenovirus viral load, Correlation=0.457, p = <0.001; as well as the COVID-19 IgM the Correlation=0.249, p =0.021; while COVID-19 IgG is Correlation=0.347, p = <0.001 in addition to Interleukin 6 receptor (IL-6R) Correlation=0.695, p = <0.001 and monocyte–macrophage chemotactic receptor2 (CCR2) Correlation=0.564, p =<0.001). But Angiotensin-converting enzyme 2 (ACE2) and Coxsackievirus and adenovirus receptor (CAR) It has been proven that there truly exists an opposite relationship connecting certain factors with the apparition of symptoms tied to COVID-19. (Correlation of Angiotensin-converting enzyme 2 receptor equal to = – 0.34, and p =<0.001; Correlation Coxsackievirus and adenovirus receptor equal to = – 0.071, p =0.046 respectively). Each previous tests performed by enzyme-linked immunosorbent assay (ELISA) and enzyme-linked fluorescence assay (Vidas).
All COVID-19 patients groups and healthy control undergo experimental two SNPs for IL-6R gene and one SNP for CCR2 gene polymorphisms (rs4845374, rs2228145 and rs1799864 respectively), IL-6R genotypes in all patients groups compared with healthy control for two SNPs (rs4845374 and rs2228145) significantly positive correlation (p=0.0097, Correlation= 0.160 and p=0.0001, Correlation= 0.125) respectively with raise COVID-19 symptoms. and CCR2 genotypes in all patients groups compared with healthy control for SNP (rs1799864) had a significantly positive correlation (p =0.0001, Correlation= 0.564) with raised COVID-19 symptoms. All study SNPs performed by Sanger Sequencing and Allele specific primers.
Mutant TA genotype (rs4845374) SNP of IL-6R gene was more significantly frequent in mild, moderate and severe groups when comparing the groups participating in the experiment to the control group, (p=0.0183, 0.0364 and 0.0243) respectively; therefore, it was considered a protective factor, it demonstrated an odds ratio of (0.3375, 0.3816 and 0.3472) respectively in three patients groups. While Genotype AA mutant type was more frequent significantly in the severe group in comparison with other groups, (p =0.0324); therefore, with an odds ratio of (0.0420), it was regarded as a protective factor for the severe group. Allele A was more significantly frequent in mild, moderate and severe groups compared with the control group, (p =0.0044, 0.0157 and 0.0003) respectively; therefore, it was considered a protective factor, it demonstrated an odds ratio of (0.3162, 0.3720 and 0.2361) respectively in three groups.
Mutant AC genotype (rs2228145) SNP of IL-6R gene was more significantly frequent in mild, moderate and severe groups compared with the control group, (p =0.0001, 0.0103 and 0.0052) respectively; therefore, it was considered a protective factor, it demonstrated an odds ratio of (0.0952, 0.3333 and 0.2667) respectively in three groups. While Genotype CC mutant type was more significantly frequent in mild, moderate and severe groups compared with the control group, (p =0.0017, 0.0417 and 0.0024) respectively; therefore, with an odds ratio of (0.0086, 0.0462 and 0.0111) respectively in three groups, it was regarded as a protective factor for the severe group. Allele C was more significantly frequent in mild, moderate and the severe groups comparing with control group, (p =0.0001, 0.0024 and 0.0001) respectively; therefore, it was considered a protective factor, it demonstrated an odds ratio of (0.2045, 0.3750 and 0.2045) respectively in three groups.
Mutant GA genotype (rs1799864) SNP of CCR2 gene was more frequent in moderate and the severe groups in compared with the control group (p = 0.0573, 0.0051) respectively; therefore, it was odds ratio of (2.5455, 5.4118) respectively, therefore, it was regarded considered a risk factor for those with moderate and severe conditions. While the opposite occurs in the mild group in comparison with control group. Genotype AA mutant type was absent in patients group in comparison with control group. Allele A was more frequent in patients with moderate and the severe group (p= 0.3096,0.1140) respectively; therefore, it had an odds ratio of (1.3448,1.5820) respectively, in comparison with group control, which was regarded as simply a risk factor for both patient groups.
In conclusion, all viral parameters studied and immunological markers (except sACE2 and CAR receptor) the amounts of spike protein concentration, COVID-19 IgG, adenovirus viral load, IL-6R and CCR2 were raised in individuals suffered from COVID-19. and our concluded about gene polymorphisms that SNPs of IL-6R gene Considered as protective factors while Risk factors in SNP of CCR2 gene. nevertheless, it is essential to keep in mind that not all alterations in biological processes could be exclusively referred to these levels being elevated.