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. 2023 Jun 16;24(12):10234.
doi: 10.3390/ijms241210234.

Antioxidant Genetic Variants Modify Echocardiography Indices in Long COVID

Milika Asanin  1   2 , Marko Ercegovac  1   3 , Gordana Krljanac  1   2 , Tatjana Djukic  1   4 , Vesna Coric  1   4 , Djurdja Jerotic  1   4 , Marija Pljesa-Ercegovac  1   4 , Marija Matic  1   4 , Ivana Milosevic  1   5 , Mihajlo Viduljevic  2 , Goran Stevanovic  1   5 , Jovan Ranin  1   5 , Tatjana Simic  1   4   6 , Zoran Bukumiric  1   7 , Ana Savic-Radojevic  1   4
Affiliations

Antioxidant Genetic Variants Modify Echocardiography Indices in Long COVID

Milika Asanin et al. Int J Mol Sci. .

Abstract

Although disturbance of redox homeostasis might be responsible for COVID-19 cardiac complications, this molecular mechanism has not been addressed yet. We have proposed modifying the effects of antioxidant proteins polymorphisms (superoxide dismutase 2 (SOD2), glutathione peroxidase 1 (GPX1), glutathione peroxidase 3 (GPX3) and nuclear factor erythroid 2-related factor 2, (Nrf2)) in individual susceptibility towards the development of cardiac manifestations of long COVID-19. The presence of subclinical cardiac dysfunction was assessed via echocardiography and cardiac magnetic resonance imaging in 174 convalescent COVID-19 patients. SOD2, GPX1, GPX3 and Nrf2 polymorphisms were determined via the appropriate PCR methods. No significant association of the investigated polymorphisms with the risk of arrhythmia development was found. However, the carriers of variant GPX1*T, GPX3*C or Nrf2*A alleles were more than twice less prone for dyspnea development in comparison with the carriers of the referent ones. These findings were even more potentiated in the carriers of any two variant alleles of these genes (OR = 0.273, and p = 0.016). The variant GPX alleles were significantly associated with left atrial and right ventricular echocardiographic parameters, specifically LAVI, RFAC and RV-EF (p = 0.025, p = 0.009, and p = 0.007, respectively). Based on the relation between the variant SOD2*T allele and higher levels of LV echocardiographic parameters, EDD, LVMI and GLS, as well as troponin T (p = 0.038), it can be proposed that recovered COVID-19 patients, who are the carriers of this genetic variant, might have subtle left ventricular systolic dysfunction. No significant association between the investigated polymorphisms and cardiac disfunction was observed when cardiac magnetic resonance imaging was performed. Our results on the association between antioxidant genetic variants and long COVID cardiological manifestations highlight the involvement of genetic propensity in both acute and long COVID clinical manifestations.

Keywords: GPX1; GPX3; Nrf2; SOD2; antioxidant genetic variants; cardiological manifestations; long COVID-19.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The association of antioxidant genetic variations and long COVID arrhythmia.
Figure 2
Figure 2
The association of antioxidant genetic variations and long COVID dyspnea.
Figure 3
Figure 3
The values of the left ventricular ejection fraction (EF), the left ventricular end-diastolic diameter (EDD) and end-systolic diameter (ESD), end-diastolic volume (EDV), end-systolic volume (ESV), as well as the values for left ventricular mass index (LVMI) and longitudinal strain (SL peak G) with respect to SOD2, GPX1 and GPX3 genotypes.
Figure 4
Figure 4
The values of right ventricle EF, GS and fractional area change (FAC) with respect to SOD2, GPX1 and GPX3 genotypes.
Figure 5
Figure 5
The values of left atrial volume index (LAVI) with respect to SOD2, GPX1 and GPX3 genotypes.
See this image and copyright information in PMC

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