Mitochondrial DNA Poly-C length heteroplasmy as a marker for risk of
Mitochondria play a central role in the innate and acquired response
against viral infections. Common mtDNA variants have been associated
with severe COVID-19 and mtDNA depletion. A poly C length variation has
been associated with mtDNA instability and increased risk for several
diseases. We studied 482 patients who required treatment in the
intensive care unit and age matched population controls. The 16184-16193
poly-C and 514-523 CA-repeats were determined by fluorescent capillary
electrophoresis and Sanger sequencing of PCR fragments. We found a
significantly higher frequency of 16184-16193 mtDNA poly-C heteroplasmy
in patients aged ≤60 compared to patients aged >60 years.
Poly-C heteroplasmy did not differ between the age control groups.
Poly-C heteroplasmy was associated with the presence of the 16223 T
allele, that was associated with the risk of critical COVID-19 at ≤60
years. In Conclusion, heteroplasmy in the poly-C tract of the mtDNA
control region might be a marker for critical COVID-19. The 16184-16193
heteroplasmy was linked to the 16223 T allele, that was significantly
increased among patients aged ≤60 years. This finding requires
validation in other cohorts and to determine the functional link between
length variation in the mitochondrial DNA control sequence and risk of
severe SARS-CoV-2 disease.