Persistent neutrophil maturation deficits associate with cognitive impairment in individuals with post-acute sequelae of COVID-19
9 affiliations
- 1Cellular & Molecular Immunoregulation Group, International Clinical Research Center (ICRC), St. Anne’s University Hospital
- 2Department of Biology, Faculty of Medicine, Masaryk University
- 3International Clinical Research Center (ICRC), Faculty of Medicine, Masaryk University
- 4Institute of Hematology and Blood Transfusion
- 5Department of Molecular Biology and Genetics, Democritus University of Thrace
- 6Brain and Mind Research Program, Central European Institute of Technology, Masaryk University
- 7Department of Internal Medicine and Cardiology, University Hospital Brno and Faculty of Medicine of Masaryk University
- 8Department of Psychiatry, Faculty of Medicine, Masaryk University and University Hospital Brno
- 9First Department of Neurology, Faculty of Medicine, Masaryk University and St. Anne's University Hospital
Abstract
Introduction: Post-COVID-19 condition, or post-acute sequelae of COVID-19 (PASC), is characterized by persistent cognitive impairments and immune dysregulation. While neutrophils are critical in acute COVID-19, whether their long-term functional dysregulation contributes to PASC, remains unclear. Thus, we investigated the links between immune system changes, symptom severity and cognitive impairment in PASC.
Methods: In this cross-sectional study, we enrolled 40 individuals with self-reported issues with COVID-19 recovery (PASC) and 37 fully recovered (REC) volunteers. Participants were post-infection at either TP1 (from 6 up to 18 months post-infection, 7 PASC, 20 REC) or at TP2 (from 19 up to 36 months post-infection, 33 PASC, 17 REC). We evaluated the Newcastle post-COVID-19 Syndrome Follow Up Screening (NC) scores for symptom severity, and neuropsychological tests for memory, attention, and executive function. Peripheral blood was analyzed using multicolor flow cytometry, ELISA, clustering, and multivariate regression.
Results: PASC participants in both the TP1 cohort and the TP2 cohort, demonstrated increased NC scores and significant changes in neutrophil numbers and subset composition. In the TP1 cohort, the PASC group showed an increased frequency of activated CD16 ⁺ CD62L low neutrophils and a reduced frequency of CXCR4 ⁺ TREM-1 ⁺ CCR2 ⁺ polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). This was accompanied by elevated soluble TNF receptor 1 (sTNFR1) and decreased sTNFR2 and CXCL12. In the TP2 cohort, PMN-MDSC levels were comparable between REC and PASC groups, alongside increased emergency granulopoiesis regulators IL-3 and IL-6. Multivariate regression revealed significant associations between PMN-MDSC signatures, granulopoiesis-related markers, NC scores, and cognitive test scores in either the TP1 or the TP2 cohort. These results represent cross-sectional observations in participants assessed within the respective post-infection intervals, rather than longitudinal evidence of persistence. The results show that dysregulated granulopoiesis and neutrophil maturation are present even at 18 and 36 months in PASC individuals, potentially associating with overall symptom severity and cognitive impairment.
Conclusions: Despite limitations in cohort size, requiring validation of the associations in larger cohorts, our findings may contribute to the further understanding of PASC and future new transitional perspectives for PASC management.
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BibTeX
@article{papatheodorou2026persistent,
title = {{Persistent neutrophil maturation deficits associate with cognitive impairment in individuals with post-acute sequelae of COVID-19}},
author = {Ioanna Papatheodorou and Petra Lázničková and Tereza Feglarová and Gabriela Blažková and Kateřina Kuglerová and Michal Santocki and Martina Jurásková and Filip Kafka and Petros Kolovos and Lubomír Vojtišek and Martin Radvan and Patrik Bartys and David Ulčák and Irena Rektorová and Marcela Hortová Kohoutková and Eliška Bartečková and Jan Frič},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1885356},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1885356/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Persistent neutrophil maturation deficits associate with cognitive impairment in individuals with post-acute sequelae of COVID-19
AU - Ioanna Papatheodorou
AU - Petra Lázničková
AU - Tereza Feglarová
AU - Gabriela Blažková
AU - Kateřina Kuglerová
AU - Michal Santocki
AU - Martina Jurásková
AU - Filip Kafka
AU - Petros Kolovos
AU - Lubomír Vojtišek
AU - Martin Radvan
AU - Patrik Bartys
AU - David Ulčák
AU - Irena Rektorová
AU - Marcela Hortová Kohoutková
AU - Eliška Bartečková
AU - Jan Frič
PY - 2026
DA - 2026/11/02
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1885356
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1885356/full
AB - Introduction: Post-COVID-19 condition, or post-acute sequelae of COVID-19 (PASC), is characterized by persistent cognitive impairments and immune dysregulation. While neutrophils are critical in acute COVID-19, whether their long-term functional dysregulation contributes to PASC, remains unclear. Thus, we investigated the links between immune system changes, symptom severity and cognitive impairment in PASC. Methods: In this cross-sectional study, we enrolled 40 individuals with self-reported issues with COVID-19 recovery (PASC) and 37 fully recovered (REC) volunteers. Participants were post-infection at either TP1 (from 6 up to 18 months post-infection, 7 PASC, 20 REC) or at TP2 (from 19 up to 36 months post-infection, 33 PASC, 17 REC). We evaluated the Newcastle post-COVID-19 Syndrome Follow Up Screening (NC) scores for symptom severity, and neuropsychological tests for memory, attention, and executive function. Peripheral blood was analyzed using multicolor flow cytometry, ELISA, clustering, and multivariate regression. Results: PASC participants in both the TP1 cohort and the TP2 cohort, demonstrated increased NC scores and significant changes in neutrophil numbers and subset composition. In the TP1 cohort, the PASC group showed an increased frequency of activated CD16 ⁺ CD62L low neutrophils and a reduced frequency of CXCR4 ⁺ TREM-1 ⁺ CCR2 ⁺ polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). This was accompanied by elevated soluble TNF receptor 1 (sTNFR1) and decreased sTNFR2 and CXCL12. In the TP2 cohort, PMN-MDSC levels were comparable between REC and PASC groups, alongside increased emergency granulopoiesis regulators IL-3 and IL-6. Multivariate regression revealed significant associations between PMN-MDSC signatures, granulopoiesis-related markers, NC scores, and cognitive test scores in either the TP1 or the TP2 cohort. These results represent cross-sectional observations in participants assessed within the respective post-infection intervals, rather than longitudinal evidence of persistence. The results show that dysregulated granulopoiesis and neutrophil maturation are present even at 18 and 36 months in PASC individuals, potentially associating with overall symptom severity and cognitive impairment. Conclusions: Despite limitations in cohort size, requiring validation of the associations in larger cohorts, our findings may contribute to the further understanding of PASC and future new transitional perspectives for PASC management.
SN - 1664-3224
ER -