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. 2022 May 12;11(5):954.
doi: 10.3390/antiox11050954.

Antioxidant Genetic Profile Modifies Probability of Developing Neurological Sequelae in Long-COVID

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

Antioxidant Genetic Profile Modifies Probability of Developing Neurological Sequelae in Long-COVID

Marko Ercegovac et al. Antioxidants (Basel). .

Abstract

Understanding the sequelae of COVID-19 is of utmost importance. Neuroinflammation and disturbed redox homeostasis are suggested as prevailing underlying mechanisms in neurological sequelae propagation in long-COVID. We aimed to investigate whether variations in antioxidant genetic profile might be associated with neurological sequelae in long-COVID. Neurological examination and antioxidant genetic profile (SOD2, GPXs and GSTs) determination, as well as, genotype analysis of Nrf2 and ACE2, were conducted on 167 COVID-19 patients. Polymorphisms were determined by the appropriate PCR methods. Only polymorphisms in GSTP1AB and GSTO1 were independently associated with long-COVID manifestations. Indeed, individuals carrying GSTP1 Val or GSTO1 Asp allele exhibited lower odds of long-COVID myalgia development, both independently and in combination. Furthermore, the combined presence of GSTP1 Ile and GSTO1 Ala alleles exhibited cumulative risk regarding long-COVID myalgia in carriers of the combined GPX1 LeuLeu/GPX3 CC genotype. Moreover, individuals carrying combined GSTM1-null/GPX1LeuLeu genotype were more prone to developing long-COVID "brain fog", while this probability further enlarged if the Nrf2 A allele was also present. The fact that certain genetic variants of antioxidant enzymes, independently or in combination, affect the probability of long-COVID manifestations, further emphasizes the involvement of genetic susceptibility when SARS-CoV-2 infection is initiated in the host cells, and also months after.

Keywords: antioxidant enzymes; glutathione transferases; long-COVID; neurological manifestations; polymorphisms.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) The frequency of acute COVID-19 manifestations in population of patients without and with long- COVID fatigue. (B) The frequency of acute COVID-19 manifestations in population of patients without and with long-COVID myalgia. (C) The frequency of acute COVID-19 manifestations in population of patients without and with long-COVID “brain fog”.
Figure 1
Figure 1
(A) The frequency of acute COVID-19 manifestations in population of patients without and with long- COVID fatigue. (B) The frequency of acute COVID-19 manifestations in population of patients without and with long-COVID myalgia. (C) The frequency of acute COVID-19 manifestations in population of patients without and with long-COVID “brain fog”.
Figure 2
Figure 2
(A). The association of genetic variations and long-COVID fatigue. (B) The association of genetic variations and long-COVID myalgia. (C). The association of genetic variations and long-COVID “brain fog”.
Figure 2
Figure 2
(A). The association of genetic variations and long-COVID fatigue. (B) The association of genetic variations and long-COVID myalgia. (C). The association of genetic variations and long-COVID “brain fog”.
See this image and copyright information in PMC

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