Patients with post-COVID-19 condition show minor blood transcriptomic changes, with altered erythrocyte gene expression in a male subgroup

BackgroundThe mechanisms underlying persistent symptoms after non-severe COVID-19 remain unclear. This study aimed to investigate transcriptomic changes in peripheral blood cells of patients with post-COVID-19 condition (PCC) and assess if distinct clinical subtypes with specific gene signatures cou...

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Main Authors: Piia Karisola, Mari Kanerva, Aki Vuokko, Helena Liira, Shuyuan Wang, Kirsi Kvarnström, Mikko Varonen, Hille Suojalehto, Harri Alenius
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1500997/full
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author Piia Karisola
Mari Kanerva
Mari Kanerva
Aki Vuokko
Helena Liira
Shuyuan Wang
Kirsi Kvarnström
Mikko Varonen
Hille Suojalehto
Harri Alenius
Harri Alenius
author_facet Piia Karisola
Mari Kanerva
Mari Kanerva
Aki Vuokko
Helena Liira
Shuyuan Wang
Kirsi Kvarnström
Mikko Varonen
Hille Suojalehto
Harri Alenius
Harri Alenius
author_sort Piia Karisola
collection DOAJ
description BackgroundThe mechanisms underlying persistent symptoms after non-severe COVID-19 remain unclear. This study aimed to investigate transcriptomic changes in peripheral blood cells of patients with post-COVID-19 condition (PCC) and assess if distinct clinical subtypes with specific gene signatures could be identified.MethodsThe cohort included 111 PCC patients from the SARS-CoV-2 Omicron variant era, with 57 recovered (Recov) and 54 having prolonged symptoms indicative of PCC. The results were compared to 63 healthy controls (Ctrl) without known SARS-CoV-2 infection. Clinical data included patient assessments, laboratory results, comorbidities, and questionnaires on quality of life and functioning. Transcriptomic analysis and cellular deconvolution methods were used on total RNA from peripheral blood mononuclear cells (PBMCs).ResultsPCC patients had more comorbidities (mean 1.3) and more frequently (59%) at least one comorbidity than recovered patients (31%) and controls (24%). Overall, past COVID-19 illness or current PCC symptoms caused minimal changes in the blood cell transcriptome, with only 3–6 differentially expressed genes (DEGs) identified across comparisons. However, a subset of male PCC patients exhibited an increased fraction of deconvoluted erythroblasts and significant genome-wide gene expression changes, with 399 DEGs compared to recovered and control males. These genes were enriched in pathways related to heme metabolism and gas exchange in erythrocytes.ConclusionsPersistent symptoms in PCC are multifactorial and not directly linked to peripheral blood cell gene expression changes. However, a subgroup of male PCC patients shows distinct erythrocyte responses that may contribute to long-term symptoms.
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spelling doaj-art-8bd8423c29894b0eb22e3759d4abf5a32025-08-20T01:49:14ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-03-011610.3389/fimmu.2025.15009971500997Patients with post-COVID-19 condition show minor blood transcriptomic changes, with altered erythrocyte gene expression in a male subgroupPiia Karisola0Mari Kanerva1Mari Kanerva2Aki Vuokko3Helena Liira4Shuyuan Wang5Kirsi Kvarnström6Mikko Varonen7Hille Suojalehto8Harri Alenius9Harri Alenius10Human Microbiome (HUMI) Research Program, Faculty of Medicine, University of Helsinki, Helsinki, FinlandDepartment of Infection Control, TYKS Turku University Hospital, The Wellbeing Services County of Southwest Finland, Turku, FinlandOutpatient Clinic for Long-Term Effects of COVID-19, Helsinki University Central Hospital, Helsinki, FinlandOccupational Medicine, Finnish Institute of Occupational Health, Helsinki, FinlandOutpatient Clinic for Long-Term Effects of COVID-19, Helsinki University Central Hospital, Helsinki, FinlandHuman Microbiome (HUMI) Research Program, Faculty of Medicine, University of Helsinki, Helsinki, FinlandOutpatient Clinic for Long-Term Effects of COVID-19, Helsinki University Central Hospital, Helsinki, FinlandOutpatient Clinic for Long-Term Effects of COVID-19, Helsinki University Central Hospital, Helsinki, FinlandOccupational Medicine, Finnish Institute of Occupational Health, Helsinki, FinlandHuman Microbiome (HUMI) Research Program, Faculty of Medicine, University of Helsinki, Helsinki, FinlandInstitute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, SwedenBackgroundThe mechanisms underlying persistent symptoms after non-severe COVID-19 remain unclear. This study aimed to investigate transcriptomic changes in peripheral blood cells of patients with post-COVID-19 condition (PCC) and assess if distinct clinical subtypes with specific gene signatures could be identified.MethodsThe cohort included 111 PCC patients from the SARS-CoV-2 Omicron variant era, with 57 recovered (Recov) and 54 having prolonged symptoms indicative of PCC. The results were compared to 63 healthy controls (Ctrl) without known SARS-CoV-2 infection. Clinical data included patient assessments, laboratory results, comorbidities, and questionnaires on quality of life and functioning. Transcriptomic analysis and cellular deconvolution methods were used on total RNA from peripheral blood mononuclear cells (PBMCs).ResultsPCC patients had more comorbidities (mean 1.3) and more frequently (59%) at least one comorbidity than recovered patients (31%) and controls (24%). Overall, past COVID-19 illness or current PCC symptoms caused minimal changes in the blood cell transcriptome, with only 3–6 differentially expressed genes (DEGs) identified across comparisons. However, a subset of male PCC patients exhibited an increased fraction of deconvoluted erythroblasts and significant genome-wide gene expression changes, with 399 DEGs compared to recovered and control males. These genes were enriched in pathways related to heme metabolism and gas exchange in erythrocytes.ConclusionsPersistent symptoms in PCC are multifactorial and not directly linked to peripheral blood cell gene expression changes. However, a subgroup of male PCC patients shows distinct erythrocyte responses that may contribute to long-term symptoms.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1500997/fullpost-COVID-19 conditionSARS-CoV-2transcriptomicsbioinformaticserythrocyte (human)
spellingShingle Piia Karisola
Mari Kanerva
Mari Kanerva
Aki Vuokko
Helena Liira
Shuyuan Wang
Kirsi Kvarnström
Mikko Varonen
Hille Suojalehto
Harri Alenius
Harri Alenius
Patients with post-COVID-19 condition show minor blood transcriptomic changes, with altered erythrocyte gene expression in a male subgroup
Frontiers in Immunology
post-COVID-19 condition
SARS-CoV-2
transcriptomics
bioinformatics
erythrocyte (human)
title Patients with post-COVID-19 condition show minor blood transcriptomic changes, with altered erythrocyte gene expression in a male subgroup
title_full Patients with post-COVID-19 condition show minor blood transcriptomic changes, with altered erythrocyte gene expression in a male subgroup
title_fullStr Patients with post-COVID-19 condition show minor blood transcriptomic changes, with altered erythrocyte gene expression in a male subgroup
title_full_unstemmed Patients with post-COVID-19 condition show minor blood transcriptomic changes, with altered erythrocyte gene expression in a male subgroup
title_short Patients with post-COVID-19 condition show minor blood transcriptomic changes, with altered erythrocyte gene expression in a male subgroup
title_sort patients with post covid 19 condition show minor blood transcriptomic changes with altered erythrocyte gene expression in a male subgroup
topic post-COVID-19 condition
SARS-CoV-2
transcriptomics
bioinformatics
erythrocyte (human)
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1500997/full
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