ArticleGenome medicine2022
Loss of Y in leukocytes as a risk factor for critical COVID-19 in men.
Article in Genome medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Beyond sex determination: the Y chromosome in male cancers.Nature reviews. Cancer · 2026Review
- Loss of chromosome Y in hematopoietic cells: mechanisms and implications for human disease.MedScience · 2026Review
- Loss of Y chromosome in Alzheimer's patients co-occurs with somatic mutations beyond CHIP drivers.Life science alliance · 2026Article
- Knowledge gaps and research priorities to understand sex differences in immunity.PLoS biology · 2026Review
- Loss of Y chromosome and its implications in male amyotrophic lateral sclerosis: insights from the UK Biobank.BMC medicine · 2025Article
- Y-chromosome alteration and its impact on cancer progression and metastasis.Cellular & molecular biology letters · 2025Review
- Understanding sex and gender disparities in COVID-19 mortality: a narrative review beyond biology.Biology of sex differences · 2025Review
- Deciphering state-dependent immune features from multi-layer omics data at single-cell resolution.Nature genetics · 2025Article
- The effects of loss of Y chromosome on male health.Nature reviews. Genetics · 2025Review
- Interaction of low-density neutrophils with other immune cells in the mechanism of inflammation.Molecular medicine (Cambridge, Mass.) · 2025Review
- DNA methylation patterns contribute to changes of cellular differentiation pathways in leukocytes with LOY from patients with Alzheimer´s disease.Cellular and molecular life sciences : CMLS · 2025Article
- Transcript-specific enrichment enables profiling of rare cell states via single-cell RNA sequencing.Nature genetics · 2025Article
- A complex systems approach to mosaic loss of the Y chromosome.GeroScience · 2025Review
- Decoding sex differences in human immunity through systems immunology.Oxford open immunology · 2025Review
- Sex differences in disease: sex chromosome and immunity.Journal of translational medicine · 2024Review
- The impact of mosaic loss of the Y chromosome (mLOY) in men of advanced age.Biogerontology · 2024Review
- Chromosome-Y haplogroups in Asturias (Northern Spain) and their association with severe COVID-19.Molecular genetics and genomics : MGG · 2024Article
- Loss of Y in regulatory T lymphocytes in the tumor micro-environment of primary colorectal cancers and liver metastases.Scientific reports · 2024Article
- Loss of chromosome Y in regulatory T cells.BMC genomics · 2024Article
- Tumor Predisposing Post-Zygotic Chromosomal Alterations in Bladder Cancer-Insights from Histologically Normal Urothelium.Cancers · 2024Article
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Authors and funding
24 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe COVID-19 pandemic, which has a prominent social and economic impact worldwide, shows a largely unexplained male bias for the severity and mortality of the disease. Loss of chromosome Y (LOY) is a risk factor candidate in COVID-19 due to its prior association with many chronic age-related diseases, and its impact on immune gene transcription.
methodsPublicly available scRNA-seq data of PBMC samples derived from male patients critically ill with COVID-19 were reanalyzed, and LOY status was added to the annotated cells. We further studied LOY in whole blood for 211 COVID-19 patients treated at intensive care units (ICU) from the first and second waves of the pandemic. Of these, 139 patients were subject to cell sorting for LOY analysis in granulocytes, low-density neutrophils (LDNs), monocytes, and PBMCs.
resultsReanalysis of available scRNA-seq data revealed LDNs and monocytes as the cell types most affected by LOY. Subsequently, DNA analysis indicated that 46%, 32%, and 29% of critically ill patients showed LOY above 5% cut-off in LDNs, granulocytes, and monocytes, respectively. Hence, the myeloid lineage that is crucial for the development of severe COVID-19 phenotype is affected by LOY. Moreover, LOY correlated with increasing WHO score (median difference 1.59%, 95% HDI 0.46% to 2.71%, p=0.025), death during ICU treatment (median difference 1.46%, 95% HDI 0.47% to 2.43%, p=0.0036), and history of vessel disease (median difference 2.16%, 95% HDI 0.74% to 3.7%, p=0.004), among other variables. In 16 recovered patients, sampled during ICU stay and 93-143 days later, LOY decreased significantly in whole blood and PBMCs. Furthermore, the number of LDNs at the recovery stage decreased dramatically (median difference 76.4 per 10,000 cell sorting events, 95% HDI 55.5 to 104, p=6e-11).
conclusionsWe present a link between LOY and an acute, life-threatening infectious disease. Furthermore, this study highlights LOY as the most prominent clonal mutation affecting the myeloid cell lineage during emergency myelopoiesis. The correlation between LOY level and COVID-19 severity might suggest that this mutation affects the functions of monocytes and neutrophils, which could have consequences for male innate immunity.
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