Abstract: molecules Article The Impact of Severe COVID-19 on Plasma Antioxidants Neven Žarković 1, * , Anna Jastrzab ˛ 2 , Iwona Jarocka-Karpowicz 2 , Biserka Orehovec 3 , Bruno Baršić 4 , 5 3 Marko Tarle , Marta Kmet , Ivica Lukšić 5,6 , Wojciech Łuczaj 2 and Elżbieta Skrzydlewska 2 1 2 3 4 5 6 * Citation: Žarković, N.; Jastrzab, ˛ A.; Jarocka-Karpowicz, I.; Orehovec, B.; Baršić, B.; Tarle, M.; Kmet, M.; Lukšić, I.; Łuczaj, W.; Skrzydlewska, E. The Laboratory for Oxidative Stress (LabOS), Rud̄er Bošković Institute, HR-10000 Zagreb, Croatia Department of Analytical Chemistry, Medical University of Bialystok, 15-089 Bialystok, Poland Clinical Department of Laboratory Diagnostics, Clinical Hospital Dubrava, HR-10000 Zagreb, Croatia Department of Internal Medicine, Clinical Hospital Dubrava, HR-10000 Zagreb, Croatia Department of Maxillofacial Surgery, Clinical Hospital Dubrava, HR-10000 Zagreb, Croatia School of Medicine, University of Zagreb, HR-10000 Zagreb, Croatia Correspondence: zarkovic@irb.hr Abstract: Several studies suggested the association of COVID-19 with systemic oxidative stress, in particular with lipid peroxidation and vascular stress. Therefore, this study aimed to evaluate the antioxidant signaling in the plasma of eighty-eight patients upon admission to the Clinical Hospital Dubrava in Zagreb, of which twenty-two died within a week, while the other recovered. The differences between the deceased and the survivors were found, especially in the reduction of superoxide dismutases (SOD-1 and SOD-2) activity, which was accompanied by the alteration in glutathione-dependent system and the intensification of the thioredoxin-dependent system. Reduced levels of non-enzymatic antioxidants, especially tocopherol, were also observed, which correlated with enhanced lipid peroxidation (determined by 4-hydroxynonenal (4-HNE) and neuroprostane levels) and oxidative modifications of proteins assessed as 4-HNE-protein adducts and carbonyl groups. These findings confirm the onset of systemic oxidative stress in patients with severe SARSCoV-2, especially those who died from COVID-19, as manifested by strongly reduced tocopherol level and SOD activity associated with lipid peroxidation. Therefore, we propose that preventive and/or supplementary use of antioxidants, especially of lipophilic nature, could be beneficial for the treatment of COVID-19 patients. Impact of Severe COVID-19 on Plasma Antioxidants. Molecules 2022, 27, 5323. https://doi.org/10.3390/ Keywords: COVID-19; SARS-CoV-2; biomarkers; plasma; antioxidants; GSH system; Trx system; lipid peroxidation; 4-HNE-protein adducts molecules27165323 Academic Editor: Jean-Marc Sabatier Received: 19 July 2022