Dear Editor, Plasma mitochondrial DNA (mtDNA) fragment abundance has emerged as a biomarker in multiple human disorders, thus pointing to the prospect that mtDNA, like F I G U R E 1 RNA target bait-capture and bioinformatics protocol and nuclear mitochondrial (NUMT) identification. (A) DNA is isolated from plasma or tissue. In the figure, nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) are denoted by colour. DNA isolation and library preparation are applied to all sample DNA, regardless of nuclear or mitochondrial origin. A target bait-capture kit consists of biotinylated RNA probes complementary to the mitochondrial genome. The probes efficiently bind mtDNA but can also bind homologous NUMT, as illustrated by the DNA fragment half coloured as mitochondrial and half coloured as nuclear. Once enriched, samples are pooled and sequenced on a standard Illumina instrument. From there, a Workflow Description Language pipeline aligns the reads to the whole genome -nuclear and mitochondrial. Three custom C/C++ programs built on the htslib library then call mitochondrial and nuclear coverage, insert (the size of a fragment after end repair and sequencing adapter ligation), and variant calling. (B) Schematic depiction of how target-bait capture also leads to the sequencing of flanking regions of polymorphic NUMTs. (C) Integrated Genome Viewer (IGV) histograms depicting a specific polymorphic NUMT in a nontransfused patient whereas the second patient lacks this insertion at either t0 or t72 post-admittance. Subfigures (A) and (B) were prepared in Inkscape.

When the COVID19 pandemic first appeared in December of 2019, the pathophysiologic underpinnings of the disease were largely unknown. Scientists, physicians and government institutions from around the globe took an “all-hands on deck” approach with the hope of identifying potential therapies to treat as well as understand the pathophysiology of the disease [1]. Currently, more than 4800 clinical trials listed on clinicaltrails.gov have been performed or proposed around the world, many with subjects from vastly different ethnic and racial backgrounds, as well as different standard-of-care strategies [2]. Despite this effort, apart from monoclonal antibodies, few therapies have emerged as effective treatments of COVID-19; vaccines remain the best approach to control and mitigate the pandemic [3].

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