Oxidative Stress and Inflammation in COVID-19-Associated Sepsis: The Potential Role of Anti-Oxidant Therapy in Avoiding Disease Progression

Abstract

Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak emerged, countless efforts are being made worldwide to understand the molecular mechanisms underlying the coronavirus disease 2019 (COVID-19) in an attempt to identify the specific clinical characteristics of critically ill COVID-19 patients involved in its pathogenesis and provide therapeutic alternatives to minimize COVID-19 severity. Recently, COVID-19 has been closely related to sepsis, which suggests that most deceases in intensive care units (ICU) may be a direct consequence of SARS-CoV-2 infection-induced sepsis. Understanding oxidative stress and the molecular inflammation mechanisms contributing to COVID-19 progression to severe phenotypes such as sepsis is a current clinical need in the effort to improve therapies in SARS-CoV-2 infected patients. This article aims to review the molecular pathogenesis of SARS-CoV-2 and its relationship with oxidative stress and inflammation, which can contribute to sepsis progression. We also provide an overview of potential antioxidant therapies and active clinical trials that might prevent disease progression or reduce its severity.

Susceptibility of the patients infected with Sars-Cov2 to oxidative stress and possible interplay with severity of the disease

“…In previous studies, it has been revealed that ROS production and oxidative stress are associated with the replication and subsequent viral infection in this disease [ [11] , [12] , [13] , [14] , 28 ]. Many evidences also suggest that the overproduction of ROS and a deprived antioxidant system play a major role in the pathogenesis, progression, and severity of SARS-CoV-2 [ 8 , 15 , 16 , 21 ]. However, this evidence has mainly been supported by review manuscripts.…”

“…The inflammatory response has led researchers to believe that there might be possible differences in the redox profile of patients with COVID-19 [ 8 , 15 , 16 ], and thus, the use of antioxidants as a complementary therapeutic strategy in COVID-19 has been proposed [ [37] , [38] , [39] , [40] ]. Oxidative stress affects the immune system through altering the immune cell function and inflammatory response [ 21 ]. One of the possible mechanisms involved in the production of ROS and oxidative stress in COVID-19 is related to the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) [ 41 ].…”

“…Patients with mild disease symptoms exhibit rapid recovery, while those with moderate to severe disease exhibit high mortality and poor prognosis [ 20 ]. Previous evidence suggests that the severity and progression in hospitalized patients with COVID-19 may be related to the systemic changes in their redox profile [ 8 , [14] , [15] , [16] , 21 , 22 ], but it has not been confirmed through experimental or descriptive studies. The information regarding the redox parameters in this disease may help better understand the natural history of COVID-19 and provide support for the clinical decision-making.…”

Potential Medicinal Plants for the Treatment of Dengue Fever and Severe Acute Respiratory Syndrome-Coronavirus

“…It can cleave the coronaviral receptor ACE-2 to amplify infectivity as well as activate the viral spike protein for membrane fusion [ 169 ]. Similar to DENV studies, no reports have been published regarding the antioxidant and anti-inflammatory effects of the medicinal plants on SARS-CoV infectivity, even though oxidative stress and inflammation have been demonstrated to play significant roles in the disease progression [ 170 ]. It is strongly believed that medicinal compounds with good antioxidant and anti-inflammatory properties might reduce or prevent the disease severity.…”

G6PD deficiency, redox homeostasis, and viral infections: implications for SARS-CoV-2 (COVID-19)

“…Individuals with COVID-19 can exhibit cold-like symptoms; however, 15% of them have severe complications. These complications, which result in death, include sepsis, thromboembolism as well as multiple organ failure including injury of the lung, heart, liver, brain, and kidney [2][3][4]. Respiratory distress accompanied by a systemic inflammatory response, such as increased cytokine secretions, is common in individuals with severe COVID-19 [5][6][7].…”