AUTHOR=Shoraka Shahrzad , Mohebbi Seyed Reza , Hosseini Seyed Masoud , Zali Mohammad Reza 

TITLE=Comparison of plasma mitochondrial DNA copy number in asymptomatic and symptomatic COVID-19 patients

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1256042

DOI=10.3389/fmicb.2023.1256042

ISSN=1664-302X

ABSTRACT=<sec id="sec1"><title>Introduction</title><p>Since the beginning of the COVID-19 pandemic, a wide clinical spectrum, from asymptomatic infection to mild or severe disease and death, have been reported in COVID-19 patients. Studies have suggested several possible factors, which may affect the clinical outcome of COVID-19. A pro-inflammatory state and impaired antiviral response have been suggested as major contributing factors in severe COVID-19. Considering that mitochondria have an important role in regulating the immune responses to pathogens, pro-inflammatory signaling, and cell death, it has received much attention in SARS-CoV-2 infection. Recent studies have demonstrated that high levels of cell-free mitochondrial DNA (<italic>cf</italic>-mtDNA) are associated with an increased risk of COVID-19 intensive care unit (ICU) admission and mortality. However, there have been few studies on <italic>cf</italic>-mtDNA in SARS-CoV-2 infection, mainly focusing on critically ill COVID-19 cases. In the present study, we investigated <italic>cf</italic>-mtDNA copy number in COVID-19 patients and compared between asymptomatic and symptomatic cases, and assessed the clinical values. We also determined the <italic>cf</italic>-nuclear DNA (<italic>cf</italic>-nDNA) copy number and mitochondrial transcription factor A (TFAM) mRNA level in the studied groups.</p></sec><sec id="sec2"><title>Materials and methods</title><p>Plasma and buffy coat samples were collected from 37 COVID-19 patients and 33 controls. Briefly, after total DNA extraction, plasma <italic>cf</italic>-mtDNA, and <italic>cf</italic>-nDNA copy numbers were measured by absolute qPCR using a standard curve method. Furthermore, after total RNA extraction from buffy coat and cDNA synthesis, TFAM mRNA levels were evaluated by qPCR.</p></sec><sec id="sec3"><title>Results</title><p>The results showed that <italic>cf</italic>-mtDNA levels in asymptomatic COVID-19 patients were statistically significantly higher than in symptomatic cases (<italic>p</italic> value = 0.01). However, <italic>cf</italic>-nDNA levels were higher in symptomatic patients than in asymptomatic cases (<italic>p</italic> value = 0.00). There was no significant difference between TFAM levels in the buffy coat of these two groups (<italic>p</italic> value &gt; 0.05). Also, <italic>cf</italic>-mtDNA levels showed good diagnostic potential in COVID-19 subgroups.</p></sec><sec id="sec4"><title>Conclusion</title><p><italic>cf</italic>-mtDNA is probably important in the outcome of SARS-CoV-2 infection due to its role in inflammation and immune response. It can also be a promising candidate biomarker for the diagnosis of COVID-19 subgroups. Further investigation will help understanding the COVID-19 pathophysiology and effective diagnostic and therapeutic strategies.</p></sec>