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Review
. 2020;181(8):629-634.
doi: 10.1159/000508560. Epub 2020 Jun 19.

The Role of Genetic Sex and Mitochondria in Response to COVID-19 Infection

Affiliations
Review

The Role of Genetic Sex and Mitochondria in Response to COVID-19 Infection

Malgorzata Kloc et al. Int Arch Allergy Immunol. 2020.

Abstract

The difference between the female and male immune response to COVID-19 infection, and infections in general, is multifactorial. The well-known determiners of the immune response, such as X and Y chromosomes, sex hormones, and microbiota, are functionally interconnected and influence each other in shaping the organism's immunity. We focus our commentary on the interplay between the genetic sex and mitochondria and how this may affect a sex-dependent immune response in COVID-19 infection. Realizing the existence of these interactions may help in designing novel methods or fine-tuning the existing and routine therapies to fight COVID-19 and other infections.

Keywords: COVID-19; Immunity; Macrophages; Melatonin; SARS-CoV-2; X chromosome; Y chromosome.

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Conflict of interest statement

Authors do not have conflict of interest and have nothing to disclose.

Figures

Fig. 1
Fig. 1
Microgenderome effect on the immune system. The microorganisms acquired during birth, and from the environment (air and food) colonize the human body, especially the digestive system. After puberty, the sex hormones influence the abundance and variety of species inhabiting the male and female body; less variety in males than in females. The compounds produced by the microgendorome reciprocally influence the function of innate and adaptive immunity, and brain (adapted from Vemuri et al. [2]).
Fig. 2
Fig. 2
Effect of sex chromosomes on the immune-related functions. The X chromosome contains many immune response-related genes and 10% of all genomic miRNAs that regulate transcription, splicing, and degradation of many genes. It also, through the specification of female identity, directs maternal purging and transmission of mitochondria. Because in the female cells, the inactivation of one of the X chromosomes is random, the female body may contain different alleles of the same gene. For example, different alleles of viral receptor ACE2 may have a different affinity to the virus, which will affect the anti-viral immune response. The Y chromosome regulates many different immune-response functions, immune cell numbers, and immune cell phenotypes through the regulation of transcriptionally inert (heterochromatin) and active (euchromatin) status of X chromosome and autosomes.
Fig. 3
Fig. 3
Effect of mitochondria on the anti-viral immune response. The presence of the virus is sensed by the RIG-I that is a major sensor of viral RNA. This activates anti-viral MAVS protein present in the mitochondrial membrane. Activated MAVS, through the interaction with the virus inhibitory protein, viperin, affects the level of interferon, which in turn regulates virus replication. In addition, viruses can directly affect mitochondrial functions such as aerobic or anaerobic respiration, which in turn affect immune cell phenotypes and responses.

References

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