Impacts of Myeloid and Lymphoid Clonal Hematopoiesis on Risks and Outcomes of Critical COVID-19
Bibliographic record
Abstract
Despite recent advances in the pathogenic understanding of coronavirus disease 2019 (COVID- 19), the full spectrum of risk factors for severe disease remains uncertain. The phenomenon of clonal hematopoiesis (CH), caused by somatic mutations in hematopoietic stem cells, is associated with impaired immune function and cardiopulmonary disease risks. Demographic and inflammatory similarities between CH and COVID-19 suggest that it may predispose to critical illness. Differential roles of common, myeloid CH drivers (M-CH) and unconventional lymphoid forms of CH (L-CH) have been suggested to influence the clinical severity of COVID-19, but the prevalence of these variant types has not yet been compared among affected patients. We therefore hypothesized that CH is associated with risks and outcomes of critical COVID-19, and these associations are influenced by distinct CH subtypes. We identified M- and L-CH variants in a Canadian cohort of critically ill COVID-19 patients using whole-genome and targeted sequencing of peripheral blood samples. We compared the prevalence of the different forms of CH to previously published estimates in multinational populations; and performed targeted sequencing with peripheral blood samples of age-matched controls recruited from similar communities as the COVID-19 cohort. We additionally compared laboratory parameters and clinical outcomes between COVID-19 patients with and without CH. We found that both M- and L-CH are prevalent in critical COVID-19 and appeared to be overrepresented among patients over 50 years of age compared to matched controls, suggesting that these variants are under-recognized risk factors for critical illness. However, CH may hold limited prognostic value after admission to the intensive care unit, as it was not significantly associated with critical COVID-19 outcomes. Future work will aim to expand upon our observations using larger cohorts of patients with critical and non- critical forms of COVID-19; and confirm whether commonly mutated CH genes are causally associated with COVID-19 severity through inflammatory, interferon, or adaptive immune pathways. Ultimately, it is hoped that this research will enhance understanding of the pathogenesis of critical COVID-19 and inform innovative, personalized approaches to its risk stratification and management.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".