Elucidating the role of alpha-1-antitrypsin, IL-6, TNF-α, TAS and MDA in the pathogenesis of covid-19 positive cases

• Main Author: Nazri, Nor Amirah Mohammad
• Format: Thesis
• Language: English
• Published: 2025
• Subjects: R Medicine; RC Internal medicine
• Online Access: http://eprints.usm.my/63351/

The study aimed to investigate the disparities in immune and oxidative stress responses in COVID-19 patients by analysing the levels of Alpha1-antitrypsin (A1AT) and its phenotype variants, as well as interleukin-6 (IL-6) and tumour necrosis factor (TNF-α), malondialdehyde (MDA), and total antioxidant status (TAS). This case-control study involved a total of 282 participants, including healthy controls, mild to moderate COVID-19 patients, and severe to critical COVID-19 patients, aged 18 to 80. COVID-19 blood samples were archived from the patients that hospitalized in Kelantan and Selangor between July 2021 and June 2023. During the same period, healthy control was recruited. The study found a significant difference in A1AT levels between control and severe COVID-19 patients (p<0.01), but not between control and mild to moderate patients (p=0.47) or between mild to moderate and severe to critical patients (p=0.33). IL-6 and TNF-alpha levels were significantly higher in COVID-19 patients than in controls (p<0.001), with no significant difference across different stages of COVID-19 disease. Additionally, TAS levels were reduced in patients with COVID-19 compared to those in the control group (p<0.001). Meanwhile, MDA levels significantly increased in COVID-19 patients compared to control patients (p<0.001). Both TAS and MDA showed no significant difference across the COVID-19 group. The analysis indicated that the PiMM phenotype emerged as the predominant phenotype among participants, regardless of their COVID-19 status or being part of the healthy control group. Additionally, this study identified some infrequently observed normal phenotypes, such as PiBM, PiCM, PiEM, and PiMX. Furthermore, participants did not exhibit variants associated with A1AT deficiency, notably PiS and PiZ. This research lays a foundational step toward understanding the genetic and biochemical underpinnings of COVID-19, paving the way for personalized medicine approaches in managing and treating this disease. Further studies are necessary to build on these findings, potentially leading to the development of targeted therapies and preventive strategies based on genetic predispositions and biochemical marker profiles.