دورية أكاديمية
Absolute quantification of plasma mitochondrial DNA by droplet digital PCR marks COVID-19 severity over time during intensive care unit admissions.
| العنوان: | Absolute quantification of plasma mitochondrial DNA by droplet digital PCR marks COVID-19 severity over time during intensive care unit admissions. |
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| المؤلفون: | Hepokoski ML; VA San Diego Healthcare System, San Diego, California.; Division of Pulmonary and Critical Care and Sleep Medicine, University of California San Diego, San Diego, California., Odish M; Division of Pulmonary and Critical Care and Sleep Medicine, University of California San Diego, San Diego, California., Lam MT; VA San Diego Healthcare System, San Diego, California.; Division of Pulmonary and Critical Care and Sleep Medicine, University of California San Diego, San Diego, California.; Salk Institute for Biological Sciences, La Jolla, California., Coufal NG; Department of Pediatrics, University of California San Diego, San Diego, California.; Rady Children's Hospital, San Diego, California., Rolfsen ML; Department of Medicine, School of Medicine, University of California San Diego, San Diego, California., Shadel GS; Salk Institute for Biological Sciences, La Jolla, California., Moyzis AG; Salk Institute for Biological Sciences, La Jolla, California., Sainz AG; Salk Institute for Biological Sciences, La Jolla, California.; Department of Pathology, Yale School of Medicine, New Haven, Connecticut., Takiar PG; Department of Medicine, School of Medicine, University of California San Diego, San Diego, California., Patel S; Division of Pulmonary and Critical Care and Sleep Medicine, University of California San Diego, San Diego, California., Leonard AJ; Department of Medicine, School of Medicine, University of California San Diego, San Diego, California., Samandari N; VA San Diego Healthcare System, San Diego, California., Hansen E; Department of Pediatrics, University of California San Diego, San Diego, California., Trescott S; Department of Pediatrics, University of California San Diego, San Diego, California., Nguyen C; Department of Pediatrics, University of California San Diego, San Diego, California., Jepsen K; Institute for Genomic Medicine, University of California San Diego, La Jolla, California., Cutter G; Department of Biostatistics, School of Public Health, The University of Alabama at Birmingham, Birmingham, Alabama., Gillespie MN; Department of Pharmacology, University of South Alabama, Mobile, Alabama., Spragg RG; Division of Pulmonary and Critical Care and Sleep Medicine, University of California San Diego, San Diego, California., Sasik R; Center for Computational Biology & Bioinformatics, University of California San Diego, La Jolla, California., Ix JH; VA San Diego Healthcare System, San Diego, California.; Division of Nephrology and Hypertension, University of California San Diego, San Diego, California. |
| المصدر: | American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2022 Jul 01; Vol. 323 (1), pp. L84-L92. Date of Electronic Publication: 2022 Jun 14. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901229 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1504 (Electronic) Linking ISSN: 10400605 NLM ISO Abbreviation: Am J Physiol Lung Cell Mol Physiol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Bethesda, MD : American Physiological Society, c1989- |
| مواضيع طبية MeSH: | COVID-19*/diagnosis , COVID-19*/genetics , Respiratory Distress Syndrome*/diagnosis , Respiratory Distress Syndrome*/genetics, Critical Illness ; DNA, Mitochondrial/genetics ; Humans ; Intensive Care Units ; Polymerase Chain Reaction ; Reproducibility of Results |
| مستخلص: | Increased plasma mitochondrial DNA concentrations are associated with poor outcomes in multiple critical illnesses, including COVID-19. However, current methods of cell-free mitochondrial DNA quantification in plasma are time-consuming and lack reproducibility. Here, we used next-generation sequencing to characterize the size and genome location of circulating mitochondrial DNA in critically ill subjects with COVID-19 to develop a facile and optimal method of quantification by droplet digital PCR. Sequencing revealed a large percentage of small mitochondrial DNA fragments in plasma with wide variability in coverage by genome location. We identified probes for the mitochondrial DNA genes, cytochrome B and NADH dehydrogenase 1, in regions of relatively high coverage that target small sequences potentially missed by other methods. Serial assessments of absolute mitochondrial DNA concentrations were then determined in plasma from 20 critically ill subjects with COVID-19 without a DNA isolation step. Mitochondrial DNA concentrations on the day of enrollment were increased significantly in patients with moderate or severe acute respiratory distress syndrome (ARDS) compared with those with no or mild ARDS. Comparisons of mitochondrial DNA concentrations over time between patients with no/mild ARDS who survived, patients with moderate/severe ARDS who survived, and nonsurvivors showed the highest concentrations in patients with more severe disease. Absolute mitochondrial DNA quantification by droplet digital PCR is time-efficient and reproducible; thus, we provide a valuable tool and rationale for future studies evaluating mitochondrial DNA as a real-time biomarker to guide clinical decision-making in critically ill subjects with COVID-19. |
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| معلومات مُعتمدة: | R01 GM127823 United States GM NIGMS NIH HHS; T32 HL134632 United States HL NHLBI NIH HHS; UL1 TR001442 United States TR NCATS NIH HHS; R01 HL113614 United States HL NHLBI NIH HHS; T32 CA009370 United States CA NCI NIH HHS; K08 NS109200 United States NS NINDS NIH HHS; IK2 BX004338 United States BX BLRD VA; P30 DK079337 United States DK NIDDK NIH HHS; F31 AG062099 United States AG NIA NIH HHS; K24 DK110427 United States DK NIDDK NIH HHS; P30 AI036214 United States AI NIAID NIH HHS; R01 AR069876 United States AR NIAMS NIH HHS; P30 CA014195 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: ARDS; COVID-19; mitochondrial DNA |
| المشرفين على المادة: | 0 (DNA, Mitochondrial) |
| تواريخ الأحداث: | Date Created: 20220614 Date Completed: 20220712 Latest Revision: 20240515 |
| رمز التحديث: | 20240515 |
| مُعرف محوري في PubMed: | PMC9273271 |
| DOI: | 10.1152/ajplung.00128.2022 |
| PMID: | 35699291 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1522-1504 |
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| DOI: | 10.1152/ajplung.00128.2022 |