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Host-Microbe Multiomic Profiling Reveals Age-Dependent COVID-19 Immunopathology.

Hoang Van Phan¹, Alexandra Tsitsiklis¹, Cole P Maguire²

¹University of California San Francisco.

Medrxiv : the Preprint Server for Health Sciences

|February 26, 2024

Summary

Aging impairs immune responses to COVID-19, increasing viral load and inflammation. Older adults show delayed viral clearance and dysregulated immune signaling, highlighting potential therapeutic targets for severe coronavirus disease-2019.

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Quantitative Imaging of Lineage-specific Toll-like Receptor-mediated Signaling in Monocytes and Dendritic Cells from Small Samples of Human Blood

Quantitative Imaging of Lineage-specific Toll-like Receptor-mediated Signaling in Monocytes and Dendritic Cells from Small Samples of Human Blood

Published on: April 16, 2012

Area of Science:

Immunology
Virology
Gerontology

Background:

Age is a significant risk factor for severe COVID-19, but the underlying immune mechanisms are not fully understood.
Investigating age-related immune dysregulation is crucial for understanding COVID-19 severity and developing targeted therapies.

Approach:

Analyzed blood and nasal samples from 1,031 hospitalized COVID-19 patients (18-96 years).
Measured viral load, immune cell populations, inflammatory markers, and autoantibodies.
Utilized transcriptomics, metatranscriptomics, and mass cytometry for comprehensive profiling.

Key Points:

Older age correlated with higher SARS-CoV-2 viral load and slower viral clearance.
Aging led to increased type I interferon and pro-inflammatory gene expression, with impaired inflammation resolution.
Immune cell analysis revealed reduced naive T/B cells and increased monocytes and exhausted NK cells in older adults.
Reactivation of latent viruses (HSV, CMV) was observed in the upper airways of older patients.

Conclusions:

Aging causes significant immune dysregulation at multiple levels (transcriptional, protein, cellular) in COVID-19 patients.
Age-dependent inflammatory imbalances and impaired immune resolution contribute to severe disease.
Findings suggest novel therapeutic targets for mitigating age-related COVID-19 severity.