Recent Developments in the Understanding of Immunity, Pathogenesis and Management of COVID-19

Yegiazaryan, Aram; Abnousian, Arbi; Alexander, Logan J.; Badaoui, Ali; Flaig, Brandon; Sheren, Nisar; Aghazarian, Armin; Alsaigh, Dijla; Amin, Arman; Mundra, Akaash; Nazaryan, Anthony; Guilford, Frederick T.; Venketaraman, Vishwanath

doi:10.3390/ijms23169297

Cited by 7 publications

(15 citation statements)

References 141 publications

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“…The symptoms of COVID-19 may vary significantly, and the course of the disease can range from mild to severe. The most common symptoms include fever, cough, acute lung injury, and septic shock, and even acute respiratory distress syndrome (ARDS) [ 3 , 4 ]. However, many other symptoms, such as loss of taste or smell, sore throat, congestion or runny nose, headache, muscle or body aches, nausea or vomiting, and diarrhea, have been reported in individuals with COVID-19 [ 1 , 2 ].…”

Section: Introductionmentioning

confidence: 99%

Links between Vitamin K, Ferroptosis and SARS-CoV-2 Infection

et al. 2023

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Ferroptosis is a recently discovered form of programmed cell death. It is characterized by the accumulation of iron and lipid hydroperoxides in cells. Vitamin K is known to have antioxidant properties and plays a role in reducing oxidative stress, particularly in lipid cell membranes. Vitamin K reduces the level of reactive oxygen species by modulating the expression of antioxidant enzymes. Additionally, vitamin K decreases inflammation and potentially prevents ferroptosis. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading to coronavirus disease 2019 (COVID-19) is associated with oxidant–antioxidant imbalance. Studies have shown that intensified ferroptosis occurs in various tissues and cells affected by COVID-19. Vitamin K supplementation during SARS-CoV-2 infection may have a positive effect on reducing the severity of the disease. Preliminary research suggests that vitamin K may reduce lipid peroxidation and inhibit ferroptosis, potentially contributing to its therapeutic effects in COVID-19 patients. The links between ferroptosis, vitamin K, and SARS-CoV-2 infection require further investigation, particularly in the context of developing potential treatment strategies for COVID-19.

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Section: Introductionmentioning

confidence: 99%

Links between Vitamin K, Ferroptosis and SARS-CoV-2 Infection

et al. 2023

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“…In addition, Omicron cross-reactive T-cells and immune memory B-cells located throughout the body can be swiftly engaged upon encounter with a viral infection ( 70 ), producing an effective B and T cell-specific immune response ( 71 ). The immune memory B-cells produce large amounts of targeted antibodies to protect against the spread and replication of viruses, helping to prevent the onset of severe COVID-19 ( 72 , 73 ). Accordingly, children who received complete vaccination during the Omicron-dominant period experienced a reduced risk of severe SARS-CoV-2 infection.…”

Section: Discussionmentioning

confidence: 99%

The effect of COVID-19 vaccine to the Omicron variant in children and adolescents: a systematic review and meta-analysis

Lu,

Zeng,

Yao

et al. 2024

Front. Public Health

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BackgroundOmicron (B.1.1.529), a variant of SARS-CoV-2, has emerged as a dominant strain in COVID-19 pandemic. This development has raised concerns about the effectiveness of vaccination to Omicron, particularly in the context of children and adolescents. Our study evaluated the efficacy of different COVID-19 vaccination regimens in children and adolescents during the Omicron epidemic phase.MethodsWe searched PubMed, Cochrane, Web of Science, and Embase electronic databases for studies published through March 2023 on the association between COVID-19 vaccination and vaccine effectiveness (VE) against SARS-CoV-2 infection in children and adolescents at the Omicron variant period. The effectiveness outcomes included mild COVID-19 and severe COVID-19. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was prospectively registered in PROSPERO (CRD42023390481).ResultsA total of 33 studies involving 16,532,536 children were included in the analysis. First, in children and adolescents aged 0–19 years, the overall VE of the COVID-19 vaccine is 45% (95% confidence interval [CI]: 40 to 50%). Subgroup analysis of VE during Omicron epidemic phase for different dosage regimens demonstrated that the VE was 50% (95% CI: 44 to 55%) for the 2-dose vaccination and 61% (95% CI: 45 to 73%) for the booster vaccination. Upon further analysis of different effectiveness outcomes during the 2-dose vaccination showed that the VE was 41% (95% CI: 35 to 47%) against mild COVID-19 and 71% (95% CI: 60 to 79%) against severe COVID-19. In addition, VE exhibited a gradual decrease over time, with the significant decline in the efficacy of Omicron for infection before and after 90 days following the 2-dose vaccination, registering 54% (95% CI: 48 to 59%) and 34% (95% CI: 21 to 56%), respectively.ConclusionDuring the Omicron variant epidemic, the vaccine provided protection against SARS-CoV-2 infection in children and adolescents aged 0–19 years. Two doses of vaccination can provide effective protection severe COVID-19, with booster vaccination additionally enhancing VE.

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“…Previous studies have found that the SARS-Cov-2 spike protein is associated with increased oxidative stress and reactive oxygen species within PBMCs [ 30 ]. Increased oxidative stress has also been found to be an important factor in COVID-19 infection and has even been shown to be involved with virus replication [ 31 ]. GSH is an antioxidant molecule that reduces oxidative stress on many cellular components [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Glutathione in Spike Protein of SARS-CoV-2 Induced Immunothrombosis and Cytokine Dysregulation

Norris,

Chorbajian,

Dawi

et al. 2024

Antioxidants

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Thrombotic microangiopathy has been identified as a dominant mechanism for increased mortality and morbidity in coronavirus disease 2019 (COVID-19). In the context of severe COVID-19, patients may develop immunothrombosis within the microvasculature of the lungs, which contributes to the development of acute respiratory distress syndrome (ARDS), a leading cause of death in the disease. Immunothrombosis is thought to be mediated in part by increased levels of cytokines, fibrin clot formation, and oxidative stress. Glutathione (GSH), a well-known antioxidant molecule, may have therapeutic effects in countering this pathway of immunothrombosis as decreased levels of (GSH) have been associated with increased viral replication, cytokine levels, and thrombosis, suggesting that glutathione supplementation may be therapeutic for COVID-19. GSH supplementation has never been explored as a means of treating COVID-19. This study investigated the effectiveness of liposomal glutathione (GSH) as an adjunctive therapy for peripheral blood mononuclear cells (PBMC) treated with SARS CoV-2 spike protein. Upon the addition of GSH to cell cultures, cytokine levels, fibrin clot formation, oxidative stress, and intracellular GSH levels were measured. The addition of liposomal-GSH to PBMCs caused a statistically significant decrease in cytokine levels, fibrin clot formation, and oxidative stress. The addition of L-GSH to spike protein and untreated PBMCs increased total intracellular GSH, decreased IL-6, TGF-beta, and TNF-alpha levels, decreased oxidative stress, as demonstrated through MDA, and decreased fibrin clot formation, as detected by fluorescence microscopy. These findings demonstrate that L-GSH supplementation within a spike protein-treated PBMC cell culture model reduces these factors, suggesting that GSH supplementation should be explored as a means of reducing mediators of immunothrombosis in COVID-19.

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Recent Developments in the Understanding of Immunity, Pathogenesis and Management of COVID-19

Cited by 7 publications

References 141 publications

Links between Vitamin K, Ferroptosis and SARS-CoV-2 Infection

Links between Vitamin K, Ferroptosis and SARS-CoV-2 Infection

The effect of COVID-19 vaccine to the Omicron variant in children and adolescents: a systematic review and meta-analysis

Evaluation of Glutathione in Spike Protein of SARS-CoV-2 Induced Immunothrombosis and Cytokine Dysregulation

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