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Loss of Y in leukoc...
Loss of Y in leukocytes as a risk factor for critical COVID-19 in men.
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- Bruhn-Olszewska, Bozena (author)
- Uppsala universitet,Cancerprecisionsmedicin,Science for Life Laboratory, SciLifeLab
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- Davies, Hanna (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Cancerprecisionsmedicin
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- Sarkisyan, Daniil (author)
- Uppsala universitet,Cancerprecisionsmedicin,Science for Life Laboratory, SciLifeLab
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Juhas, Ulana (author)
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Rychlicka-Buniowska, Edyta (author)
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Wójcik, Magdalena (author)
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Horbacz, Monika (author)
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Jąkalski, Marcin (author)
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Olszewski, Paweł (author)
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- Orzechowski Westholm, Jakub (author)
- Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab)
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- Smialowska, Agata (author)
- Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab)
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Wierzba, Karol (author)
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- Torinsson Naluai, Åsa, 1968 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Core Facilities, Genomics,Department of Laboratory Medicine,Core Facilities, Genomics
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- Jern, Niklas (author)
- Gothenburg University,Göteborgs universitet,Core Facilities,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Department of Laboratory Medicine
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- Andersson, Lars-Magnus, 1968 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine
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- Järhult, Josef D., 1975- (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper
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Filipowicz, Natalia (author)
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- Tiensuu Janson, Eva (author)
- Uppsala universitet,Onkologisk endokrinologi
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- Rubertsson, Sten (author)
- Uppsala universitet,Anestesiologi och intensivvård
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- Lipcsey, Miklós (author)
- Uppsala universitet,Hedenstiernalaboratoriet
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- Gisslén, Magnus, 1962 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine
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- Hultström, Michael, 1978- (author)
- Uppsala universitet,Integrativ Fysiologi,Anestesiologi och intensivvård
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- Frithiof, Robert (author)
- Uppsala universitet,Anestesiologi och intensivvård
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- Dumanski, Jan P. (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi,3P-Medicine Laboratory, Medical University of Gdańsk, Dębinki 7, 80-211, Gdańsk, Poland
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(creator_code:org_t)
- 2022-12-14
- 2022
- English.
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In: Genome medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 14:1
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https://uu.diva-port... (primary) (Raw object)
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https://doi.org/10.1...
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Abstract
Subject headings
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- The 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.Publicly 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.Reanalysis 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).We 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- Humans
- Male
- Chromosomes
- Human
- Y
- Leukocytes
- Mononuclear
- Pandemics
- Critical Illness
- COVID-19
- genetics
- Risk Factors
Publication and Content Type
- ref (subject category)
- art (subject category)
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Bruhn-Olszewska, ...
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Davies, Hanna
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Sarkisyan, Danii ...
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Juhas, Ulana
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Rychlicka-Buniow ...
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Wójcik, Magdalen ...
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show more...
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Horbacz, Monika
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Jąkalski, Marcin
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Olszewski, Paweł
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Orzechowski West ...
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Smialowska, Agat ...
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Wierzba, Karol
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Torinsson Naluai ...
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Jern, Niklas
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Andersson, Lars- ...
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Järhult, Josef D ...
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Filipowicz, Nata ...
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Tiensuu Janson, ...
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Rubertsson, Sten
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Lipcsey, Miklós
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Gisslén, Magnus, ...
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Hultström, Micha ...
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Frithiof, Robert
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Dumanski, Jan P.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Infectious Medic ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Genome medicine
- By the university
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University of Gothenburg
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Stockholm University
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Uppsala University