Association between Glutathione S-Transferases Gene Variants and COVID-19 Severity in Previously Vaccinated and Unvaccinated Polish Patients with Confirmed SARS-CoV-2 Infection

Orlewska, Katarzyna; Klusek, Justyna; Zarębska-Michaluk, Dorota; Kocańda, Kamila; Oblap, R.; Cedro, Anna; Witczak, Bartosz; Klusek, Jolanta; Śliwczyński, Andrzej; Orlewska, Ewa

doi:10.3390/ijerph20043752

Cited by 6 publications

(4 citation statements)

References 26 publications

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“…A recent Polish study conducted by Orlewska K. et al reported that GSTP1 Ile/Val genotype was associated with higher risk of developing a severe form of the disease. However, they found that GSTM1 null and GSTT1 null genotypes had no significant association with risk of developing severe forms of COVID-19, which is in agreement with results of our study [47].…”

Section: Discussionsupporting

confidence: 92%

GPX3 Variant Genotype Affects the Risk of Developing Severe Forms of COVID-19

Markovic,

Ranin,

Bukumiric

et al. 2023

IJMS

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In SARS-CoV-2 infection, excessive activation of the immune system intensively increases reactive oxygen species levels, causing harmful hyperinflammatory and oxidative state cumulative effects which may contribute to COVID-19 severity. Therefore, we assumed that antioxidant genetic profile, independently and complemented with laboratory markers, modulates COVID-19 severity. The study included 265 COVID-19 patients. Polymorphism of GSTM1, GSTT1, Nrf2 rs6721961, GSTM3 rs1332018, GPX3 rs8177412, GSTP1 rs1695, GSTO1 rs4925, GSTO2 rs156697, SOD2 rs4880 and GPX1 rs1050450 genes was determined with appropriate PCR-based methods. Inflammation (interleukin-6, CRP, fibrinogen, ferritin) and organ damage (urea, creatinine, transaminases and LDH) markers, complete blood count and coagulation status (d-dimer, fibrinogen) were measured. We found significant association for COVID-19 progression for patients with lymphocytes below 1.0 × 109/L (OR = 2.97, p = 0.002). Increased IL-6 and CRP were also associated with disease progression (OR = 8.52, p = 0.001, and OR = 10.97, p < 0.001, respectively), as well as elevated plasma AST and LDH (OR = 2.25, p = 0.021, and OR = 4.76, p < 0.001, respectively). Of all the examined polymorphisms, we found significant association with the risk of developing severe forms of COVID-19 for GPX3 rs8177412 variant genotype (OR = 2.42, p = 0.032). This finding could be of particular importance in the future, complementing other diagnostic tools for prediction of COVID-19 disease course.

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Section: Discussionsupporting

confidence: 92%

GPX3 Variant Genotype Affects the Risk of Developing Severe Forms of COVID-19

Markovic,

Ranin,

Bukumiric

et al. 2023

IJMS

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“…Variants in GSTT1 and GSTM1 can affect PO detoxification, with null genotypes potentially increasing susceptibility to its toxic effects. GSTT1-/-genotype showed higher mortality in COVID-19 patients [15] while GSTP1 Ile/Val genotype was found to be associated with a higher risk of developing a severe form of COVID-19 in the population of vaccinated patients [16]. In our subsequent studies [17], we observed some notable differences between the MEBO and average populations, but the incidence of COVID-19 was significantly lower in the MEBO group compared to the average population.…”

Section: Discussionmentioning

confidence: 99%

Propylene Oxide in Exhaled Breath as a Marker for Discriminating TMAU-like Conditions from TMAU

Gabashvili

2024

Preprint

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Volatile Organic Compounds (VOCs) triggering respiratory irritation are implicated in conditions such as Trimethylaminuria (TMAU) and "people are allergic to me" (PATM) which occur in otherwise healthy individuals without clear syndromic associations. Despite the absence of established non-targeted non-challenge-based diagnostic procedures, recent studies have identified discriminatory VOCs associated with PATM using gas chromatography-mass spectrometry. Breath VOCs, originating from the bloodstream, hold promise for non-invasive diagnosis. We conducted breath analysis on 23 individuals exhibiting TMAU-like symptoms and identified a diverse array of volatile organic compounds (VOCs) that discriminate between different subgroups. Using logistic regression, we achieved an accuracy of 88%, with both precision and recall at 88-89%, in distinguishing TMAU-negative individuals from those who tested positive at some point in their lives, solely based on the presence of Propylene Oxide ((2R)-2-Methyloxirane and (2S)-2-Methyloxirane). However, due to the limited subset and missing data, it cannot serve as the sole discriminating biomarker. Inclusion of additional VOCs in the analysis increased accuracy of the model to 85-95%, with precision and recall ranging from 85% to 100%, depending on the combinations of VOCs used. Unsupervised learning algorithms generally grouped positively tested individuals together based on endogenous VOCs, while negatively tested individuals were clustered into two distinct groups. Toluene, previously found to be elevated in PATM individuals, was identified as a discriminatory marker for those previously diagnosed with TMAU, but had since tested negative while still experiencing symptoms. Other PATM biomarkers, such as p-Xylene and Hexanal, were generally higher in TMAU positive individuals and were good predictors of TMAU history when combined with other VOCs. Our analysis revealed that the TMAU-positive group exhibited a greater abundance of biomarkers indicative of advanced oxidative stress in their breath samples and primary oxidative stress in their air samples, likely originating from their skin. Conversely, the TMAU-negative group demonstrated a higher likelihood of biomarkers associated with secondary oxidative stress in their air samples. Our findings highlight the potential of breath analysis as a non-invasive diagnostic tool for idiopathic malodor conditions. They underscore the importance of analyzing exogenous chemicals for insights into metabolism, detoxification, and elimination of toxins. This approach could help eliminate unnecessary challenge tests and emphasize the role of metabolomics in understanding the mechanisms underlying these conditions.

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“…Cytokine storm, endothelial dysfunction, oxidative stress, and cell death are the processes respon-sible for COVID-19 pathogenesis and organ damage in the severe form of the disease, including ocular lesions [25,26].…”

Section: Discussionmentioning

confidence: 99%

Retinal thickness in patients with elevated D-dimer and interleukin-6 levels as a result of SARS-CoV-2 infection

Kal,

Brzdęk,

Winiarczyk

et al. 2023

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Introduction:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to various health issues, including severe pneumonia, organ damage, as well as effects on the retina. Researchers have detected SARS-CoV-2 in the retinas of infected patients, and new imaging methods, such as optical coherence tomography (OCT), are being used to investigate its impact on the eye. Aim of the research: To document changes in retinal thickness (RT) and their association with saturation (SpO2), D-dimers, and interleukin-6 (IL-6) levels in coronavirus disease 2019 (COVID-19) patients hospitalized for bilateral pneumonia. Material and methods: This prospective study included COVID-19 patients assessed after 2 months (Group 1) and re-evaluated after 8 months from hospital discharge (Group 2). RT was automatically assessed with OCT. Group 2 RT measurements were compared with those of healthy subjects, and D-dimers, IL-6, and SpO2 levels on admission were correlated with RT in group 1. Results: Group 2 exhibited a significant decrease in RT compared to group 1 in specific macular regions, accompanied by an increase in certain areas. Moreover, Group 2 demonstrated increased RT compared to a control group in specific regions. A positive correlation was observed between SpO 2 ≤ 90% and RT in Group 1 in specific macular regions. Conclusions: RT in patients after SARS-CoV-2 infection is altered at the 6-month follow-up. Hypoxia, hypercoagulability, and inflammation in COVID-19 can collectively influence RT. StreszczenieWprowadzenie: SARS-CoV-2 może prowadzić do różnych problemów zdrowotnych, w tym ciężkiego zapalenia płuc, uszkodzenia narządów, jak również wpływać na siatkówkę. Badacze wykryli SARS-CoV-2 w siatkówkach zakażonych pacjentów i ustalili, że stosując nowe metody obrazowania, takie jak optyczna koherentna tomografia (OCT), można zbadać jego wpływ na oko. Cel pracy: Udokumentowanie zmian w grubości siatkówki u pacjentów z COVID-19 hospitalizowanych z powodu obustronnego zapalenia płuc oraz ustalenie, jaki wpływ na grubość siatkówki mają saturacja (SpO 2 ), poziom D-dimerów i interleukiny 6 (IL-6). Materiał i metody: Badanie prospektywne obejmowało pacjentów z COVID-19 ocenianych po 2 miesiącach (grupa 1.) i ustalili, że ponownie po 8 miesiącach od wypisu ze szpitala (grupa 2.). Grubość siatkówki była automatycznie mierzona za pomocą OCT. Pomiar grubości siatkówki w grupie 2. porównano z wynikami zdrowych osób, a poziomy D-dimerów, IL-6 i SpO 2 przy przyjęciu do szpitala były korelowane z grubością siatkówki w grupie 1. Wyniki: W grupie 2. wykazano istotne zmniejszenie grubości siatkówki w porównaniu z grupą 1. w kilku regionach plamki żółtej z jednoczesnym wzrostem w innych obszarach. W grupie 2 stwierdzono większą grubość siatkówki w porównaniu z grupą kontrolną w niektórych regionach. Wykazano dodatnią korelację między SpO 2 ≤ 90% a grubością siatkówki w grupie 1. w określonych regionach plamki żółtej. Wnioski: Grubość siatkówki mierzona po przebyciu zakażenia SARS-CoV-2 zmienia się po 6 miesiącach od zakażenia. ...

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Association between Glutathione S-Transferases Gene Variants and COVID-19 Severity in Previously Vaccinated and Unvaccinated Polish Patients with Confirmed SARS-CoV-2 Infection

Cited by 6 publications

References 26 publications

GPX3 Variant Genotype Affects the Risk of Developing Severe Forms of COVID-19

GPX3 Variant Genotype Affects the Risk of Developing Severe Forms of COVID-19

Propylene Oxide in Exhaled Breath as a Marker for Discriminating TMAU-like Conditions from TMAU

Retinal thickness in patients with elevated D-dimer and interleukin-6 levels as a result of SARS-CoV-2 infection

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