Immune checkpoint inhibitors PD-1, PDL-1 With IL-6 and TNF-alpha in SARS-COV-2 patients: single center study in Salahddin province

Abstract

Background: The coronavirus disease 2019(COVID-19) was identified in Wuhan, China, in December 2019. And on February 24, 2020, Iraq received a report of its first COVID-19 patient. A student from Iran who traveled there. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a zoonotic virus that causes this disease. They are contagious from humans to humans, from humans to animals, and from animals to animals. Although most COVID-19 individuals experience a mild sickness similar to the flu or show no symptoms, a minority number of patients experience severe pneumonia, ARDS, or multi-organ failure. Additionally, it appears to have a mortality rate of about 6.4%. Methodology: A total of (90) samples included in this study, which will be divided into three groups. The Case group will consist of 60 patients (30 sever and 30 moderate cases based on the disease severity as defined by the WHO guidelines) with positive PCR COVID-19 test results, and the Control group will be composed of 30 individuals with asymptomatic and PCR negative for SARS-cov-2. who were attended to the COVID-19 specialized ward in the salahddin province between December 2022 and February 2023, oropharyngeal swabs, SARS-CoV-2 nucleic acid (RT-PCR) was used to confirm the positive status, an ELISA test to detect concentration cytokines (IL-6, TNF-alpha, and immune checkpoint inhibitors including PD-1 and PDL-1). Results: The case group patients' blood levels of IL6, TNF-alpha, PD-1, and PDL-1 were considerably greater than those of the healthy control group. The level of IL6 being mean SD (58.71±39.52 vs 10.45±10.95) with P-value of 0.001) pg/ml. for TNF-alpha, (126.3±570.70 vs 73.1±413.48 with P-value of 0.001) pg/ml, PD-1level were (2.14± 91.833 vs 0.64± 30.284) with P-value of 0.001) ng/ml, and (5.977±4.449vs 0.837±0.348with P-value of 0.001) ng/ml for PDL-1. There was a significant variation in serum level of IL6 between severe and non-severe patients and control groups; for IL6 higher mean ± SD for the severing group. Increased level of IL6 inpatients showed significant correlation with PD-1 and PDL-1. Conclusion:  The increased serum levels of IL6 and increased level of PD-1,PDL-1compared to the control group, indicate the host’s immune responses against the coronavirus infection and the “cytokine storm “that caused by a sudden acute rise in circulating levels of different pro-inflammatory cytokines like IL-6 and may lead to acute lung injury and ARDS with death As a result, the serum concentration of these biomarkers could be considered a reflection of COVID-19 severity, and these findings point to different immuno-regulatory events during SARS-CoV-2 infection, which could be useful in early detection of severe COVID-19 infected patients, as well as early recognition of Cytokine Strom, which could lead to a better outcome.