Elevated mortality and upregulated SARS-CoV-2-associated pathways in innate and adaptive immune cells from individuals with Down syndrome

Q: How does Down syndrome affect COVID-19 mortality in hospitalized patients?

Down syndrome increases mortality after SARS-CoV-2 infection. DS patients had a 4.5-fold higher mortality rate in ages 0–30 and showed persistently higher mortality after adjusting for comorbidities, with a 22% increase in those over 30.

Q: What clinical differences were observed between DS and non-DS patients?

DS patients had higher comorbidity prevalence and more frequently required ventilatory support, ICU admission, and intubation compared with non-DS patients.

Q: Which immune pathways were upregulated in DS before the pandemic?

Gene expression analysis of pre-pandemic monocytes and T cells from DS individuals revealed upregulated SARS-CoV-2-associated pathways, including interferon signaling and cytokine interactions.

Sep 29, 2026

Uploaded by Kurz

Trisomy 21 elevates the risk of severe outcomes and mortality among hospitalized individuals with Down syndrome (DS) after SARS-CoV-2 infection. Using Brazilian SIVEP-Gripe data, 102,767 hospitalized COVID-19 patients were analyzed, including 1,115 DS and 101,652 non-DS (NDS). DS patients showed higher comorbidity prevalence and greater need for ventilatory support, ICU admission, and intubation. Mortality was 4.5-fold higher in DS patients aged 0–30, remained 2.22-fold higher after adjustment, and increased by 22% in those over 30. Pre-pandemic monocytes and T cells from DS displayed upregulated SARS-CoV-2-linked interferon and cytokine-interaction pathways, suggesting baseline immune dysregulation contributing to severity and informing targeted strategies.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Abstract

Clinical outcomes and mortality comparison

Immune transcriptomic pathway findings

Implications for targeted therapeutic strategies

OPEN ACCESS Citation: Victorino DB, Malheiros JM, TenCaten F, Cardoso Betta VH, Barbosa FFS, Ghneim K, et al. (2026) Elevated mortality and upregulated SARS-CoV-2-associated pathways in innate and adaptive immune cells from individuals with Down syndrome. PLoS One 21(1): e0338519. [https://doi.org/10.1371/](https://doi.org/10.1371/)[ ](https://doi.org/10.1371/)[journal.pone.0338519](journal.pone.0338519) Editor: Vinay Kumar, Pennsylvania State University Hershey Medical Center, UNITED STATES OF AMERICA Received: May 9, 2025 Accepted: November 24, 2025 Published: January 5, 2026 Copyright: © 2026 Victorino et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data availability statement: Brazilian Epidemiological Surveillance Information System Influenza (SIVEP-Gripe) from Ministry of Health for the year 2020, used in this RESEARCH ARTICLE Elevated mortality and upregulated SARS-CoV- 2-associated pathways in innate and adaptive immune cells from individuals with Down syndrome Daniella Balduino Victorino1, Jackeline Moraes Malheiros2, Felipe Ten-Caten3, Victor Hugo Cardoso Betta2, Felipe Farinha Saad Barbosa2, Khader Ghneim3, Fernanda Caroline Coirada3, Fernanda Romano Bruno3, Giuliana Xavier de Medeiros3, Cassia Silveira4, Christina Gavegnano5,6,7,8,9, Robert Balderas10, Ana Claudia Brandao11, Edward Yang12, Helder Nakaya11, Gabriela A. Wagner13, Luciene Covolan2,12, Susan Pereira Ribeiro3* 1 Sorbonne Université, Institut du Cerveau-Paris Brain Institute- ICM, Inserm, CNRS, AP-HP, Hôpital de la Pitié Salpêtrière, Paris, France, 2 Department of Physiology, Universidade Federal de Sao Paulo, Sao Paulo, Brazil, 3 Pathology Advanced Translational Research Unit (PATRU), Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, Georgia, United States of America, 4 Department of Infectious and Parasitic Diseases, School of Medicine, University of São Paulo, São Paulo, Brazil, 5 Atlanta VÁ Medical Center, Atlanta, Georgia, United States of America, 6 Emory University Department of Pathology, Atlanta, Georgia, United States of America, 7 Emory University Department of Pharmacology and Chemical Biology, Atlanta, Georgia, United States of America, 8 Emory University Center for Human Health, Atlanta, Georgia, United States of America, 9 Harvard University School of Medicine, Boston, Massachusetts, United States of America, 10 BD Biosciences, San Jose, California, United States of America, 11 Hospital Israelita Albert Einstein, São Paulo, Brazil, 12 Center for Research, Education and Innovation (CEPI), Instituto Jo Clemente, Sao Paulo, Brazil, 13 Departamento de Medicina Preventiva, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, Brazil * [susan.pereira.ribeiro@emory.edu](susan.pereira.ribeiro@emory.edu) Abstract Trisomy 21 increases the risk of severe outcomes and mortality in hospitalized individuals with Down syndrome (DS) following SARS-CoV-2 infection. Using data from the Brazilian Epidemiological Surveillance Information System Influenza (SIVEP-Gripe), we analyzed 102,767 hospitalized COVID-19 patients (1,115 DS and 101,652 non-DS, NDS) . DS patients had a higher prevalence of comorbidities and required ventilatory support, ICU admission, and intubation more frequently than NDS patients (p < 0. 001) . Mortality was 4.5 times higher in DS patients aged 0–30 years (26 . 3% vs. 5. 9%, p < 0. 001) and remained 2.22 times higher after adjusting for comorbidities. DS patients over 30 years also exhibited a 22% increase in mortality (PR 1.22, p < 0. 001) . Gene expression analysis of pre-pandemic monocytes and T cells from DS individuals revealed upregulated pathways linked to SARS-CoV-2 infection, including interferon signaling and cytokine interactions. This

FAQs

How does Down syndrome affect COVID-19 mortality in hospitalized patients?

Down syndrome increases mortality after SARS-CoV-2 infection. DS patients had a 4.5-fold higher mortality rate in ages 0–30 and showed persistently higher mortality after adjusting for comorbidities, with a 22% increase in those over 30.

What clinical differences were observed between DS and non-DS patients?

DS patients had higher comorbidity prevalence and more frequently required ventilatory support, ICU admission, and intubation compared with non-DS patients.

Which immune pathways were upregulated in DS before the pandemic?

Gene expression analysis of pre-pandemic monocytes and T cells from DS individuals revealed upregulated SARS-CoV-2-associated pathways, including interferon signaling and cytokine interactions.

Sep 29, 2026

Uploaded by Kurz