Abstract: Available online at IJTID Website: https://e-journal.unair.ac.id/IJTID/ Vol. 9 No. 3 September–December 2021 The Effects of N-Acetylcysteine as Adjuvant Therapy To Reduce TNF-Α Level And Increase SPO2/FIO2 Ratio In Improving Hypoxemia In COVID-19 Patients 1 1 1 1 Fitratul Ramadhan , Ngakan Putu Parsama Putra , Ungky Agus Setyawan , Susanthy Djajalaksana , Aditya Sri 1 2 Listyoko , Harun al Rasyid 1 Department of Pulmonology and Medical Respiration, Faculty of Medicine, Universitas Brawijaya-RSUD Dr Saiful Anwar, Malang Indonesia 2 Department of Public Health and Preventive Medicine, Faculty of Medicine, Universitas Brawijaya, Malang Indonesia Received: 22 stOctober 2021; Revised: 28 th November 2021; Accepted: 23 thDecember 2021 ABSTRACT Tumor Necrosis Factor Alpha (TNF-α) is a pro-inflammatory cytokine that plays a crucial role in COVID-19 disease progression. N-acetylcysteine (NAC) works throughout several GSH-mediated mechanisms and is known to eliminate oxidative stress in acute respiratory distress syndrome (ARDS) in COVID-19. This study aims to analyze the e ect of the N-Acetylcysteine as Adjuvant Therapy to reduce TNF-α levels and Increase SpO2/FiO2 ratio in Improving hypoxemia in COVID-19 Patients. This is a quasi-experimental, non-equivalent control group design study. There were 91 subjects selected using non-random sampling, which consisted of 75 patients in the NAC group and 16 patients in the control group. The TNF-α level was measured using the ELISA method, and SpO2/FiO2 ratio was calculated on day 1 (on admission) and day eight after NAC 5000mg/ 72 hours was given. Statistical analysis was conducted using Wilcoxon and Mann-Whitney U Test. There is a significant decrease in TNF-α level in the treatment group (median 1.49±5.22) (p=0.016) compared with the control group (median 1.64±1.99) (p=0.005). The Median SpO2/FiO2 ratio on day 1 is 163.70±69.64 in the control group and 121.49±40.41 in the treatment group (p=0.005). The Median SpO2/FiO2 ratio on day 8 is 249.69±132.26 in the control group and 151.29±59.18 in the treatment group (p=0.001). There is a positive correlation between serum TNF-α level and SpO2/FiO2 ratio after administration of adjuvant therapy NAC (r=0.240, p=0.038). There is a positive correlation and significant decrease of serum TNF-α and SpO2/FiO2 ratio after adjuvant NAC therapy, which improves hypoxemia in COVID-19 patients. Keywords: N-acetylcysteine, TNF-α, SpO2/FiO2 ratio ABSTRAK Tumor Necrosis Factor Alpha (TNF-α) merupakan sitokin proinflamasi yang berperan penting dalam perkembangan penyakit COVID-19. N-acetylcysteine (NAC) bekerja melalui beberapa mekanisme yang dimediasi GSH dan diketahui menghilangkan stres oksidatif pada acute respiratory distress syndrome (ARDS) pada COVID-19. Penelitian ini bertujuan untuk menganalisis pengaruh NAC sebagai terapi Adjuvant untuk menurunkan kadar TNF-α dan Meningkatkan rasio SpO2/FiO2 dalam Memperbaiki Hipoksemia pada Pasien COVID-19. Penelitian ini merupakan quasi-experimental, non-equivalent control group designed study. Subyek yang dipilih sebanyak 91 orang dengan non random sampling, yang terdiri dari 75 pasien pada kelompok NAC dan 16 pasien pada kelompok kontrol. Kadar TNFα diukur menggunakan metode ELISA dan Rasio SpO2/FiO2 diukur pada hari ke-1 (saat masuk) dan hari ke-8 setelah pemberian NAC 5000mg/72 jam. Analisis statistik dilakukan dengan menggunakan Wilcoxon dan Mann-Whitney U Test. Terdapat penurunan kadar TNF-α yang signifikan pada..