High Throughput Spatial Immune Mapping Reveals an Innate Immune Scar in Post-COVID-19 Brains

Overview

Journal Acta Neuropathol

Specialty Neurology

Date 2024 Jul 26

PMID 39060438

Authors

Marius Schwabenland

Dilara Hasavci

Sibylle Frase

Katharina Wolf

Nikolaus Deigendesch

Joerg M Buescher

Kirsten D Mertz

Benjamin Ondruschka

Hermann Altmeppen

Jakob Matschke

Markus Glatzel

Stephan Frank

Robert Thimme

Juergen Beck

Jonas A Hosp

Thomas Blank

Bertram Bengsch

Marco Prinz

Affiliations

Soon will be listed here.

Abstract

The underlying pathogenesis of neurological sequelae in post-COVID-19 patients remains unclear. Here, we used multidimensional spatial immune phenotyping and machine learning methods on brains from initial COVID-19 survivors to identify the biological correlate associated with previous SARS-CoV-2 challenge. Compared to healthy controls, individuals with post-COVID-19 revealed a high percentage of TMEM119P2RY12CD68Iba1HLA-DRCD11cSCAMP2 microglia assembled in prototypical cellular nodules. In contrast to acute SARS-CoV-2 cases, the frequency of CD8 parenchymal T cells was reduced, suggesting an immune shift toward innate immune activation that may contribute to neurological alterations in post-COVID-19 patients.

References

Zhang H, Zang C, Xu Z, Zhang Y, Xu J, Bian J . Data-driven identification of post-acute SARS-CoV-2 infection subphenotypes. Nat Med. 2022; 29(1):226-235. PMC: 9873564. DOI: 10.1038/s41591-022-02116-3. View

Sudre C, Murray B, Varsavsky T, Graham M, Penfold R, Bowyer R . Attributes and predictors of long COVID. Nat Med. 2021; 27(4):626-631. PMC: 7611399. DOI: 10.1038/s41591-021-01292-y. View

Soriano J, Murthy S, Marshall J, Relan P, Diaz J . A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis. 2021; 22(4):e102-e107. PMC: 8691845. DOI: 10.1016/S1473-3099(21)00703-9. View

Douaud G, Lee S, Alfaro-Almagro F, Arthofer C, Wang C, McCarthy P . SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature. 2022; 604(7907):697-707. PMC: 9046077. DOI: 10.1038/s41586-022-04569-5. View

Radke J, Meinhardt J, Aschman T, Chua R, Farztdinov V, Lukassen S . Proteomic and transcriptomic profiling of brainstem, cerebellum and olfactory tissues in early- and late-phase COVID-19. Nat Neurosci. 2024; 27(3):409-420. DOI: 10.1038/s41593-024-01573-y. View

Bowe B, Xie Y, Al-Aly Z . Postacute sequelae of COVID-19 at 2 years. Nat Med. 2023; 29(9):2347-2357. PMC: 10504070. DOI: 10.1038/s41591-023-02521-2. View

Davis H, Assaf G, McCorkell L, Wei H, Low R, Reem Y . Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine. 2021; 38:101019. PMC: 8280690. DOI: 10.1016/j.eclinm.2021.101019. View

Mossad O, Nent E, Woltemate S, Folschweiller S, Buescher J, Schnepf D . Microbiota-dependent increase in δ-valerobetaine alters neuronal function and is responsible for age-related cognitive decline. Nat Aging. 2023; 1(12):1127-1136. DOI: 10.1038/s43587-021-00141-4. View

Yin K, Peluso M, Luo X, Thomas R, Shin M, Neidleman J . Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2. Nat Immunol. 2024; 25(2):218-225. PMC: 10834368. DOI: 10.1038/s41590-023-01724-6. View

10.

Taquet M, Geddes J, Husain M, Luciano S, Harrison P . 6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records. Lancet Psychiatry. 2021; 8(5):416-427. PMC: 8023694. DOI: 10.1016/S2215-0366(21)00084-5. View

11.

Floro S, Carandini T, Pietroboni A, De Riz M, Scarpini E, Galimberti D . Role of Chitinase 3-like 1 as a Biomarker in Multiple Sclerosis: A Systematic Review and Meta-analysis. Neurol Neuroimmunol Neuroinflamm. 2022; 9(4). PMC: 9128043. DOI: 10.1212/NXI.0000000000001164. View

12.

Taquet M, Skorniewska Z, Hampshire A, Chalmers J, Ho L, Horsley A . Acute blood biomarker profiles predict cognitive deficits 6 and 12 months after COVID-19 hospitalization. Nat Med. 2023; 29(10):2498-2508. PMC: 10579097. DOI: 10.1038/s41591-023-02525-y. View

13.

Mizrahi B, Sudry T, Flaks-Manov N, Yehezkelli Y, Kalkstein N, Akiva P . Long covid outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study. BMJ. 2023; 380:e072529. PMC: 9832503. DOI: 10.1136/bmj-2022-072529. View

14.

Schwabenland M, Salie H, Tanevski J, Killmer S, Lago M, Schlaak A . Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions. Immunity. 2021; 54(7):1594-1610.e11. PMC: 8188302. DOI: 10.1016/j.immuni.2021.06.002. View

15.

Schwabenland M, Bruck W, Priller J, Stadelmann C, Lassmann H, Prinz M . Analyzing microglial phenotypes across neuropathologies: a practical guide. Acta Neuropathol. 2021; 142(6):923-936. PMC: 8498770. DOI: 10.1007/s00401-021-02370-8. View

16.

Eilertz D, Mitterer M, Buescher J . automRm: An R Package for Fully Automatic LC-QQQ-MS Data Preprocessing Powered by Machine Learning. Anal Chem. 2022; 94(16):6163-6171. PMC: 9047440. DOI: 10.1021/acs.analchem.1c05224. View

17.

Erny D, Dokalis N, Mezo C, Castoldi A, Mossad O, Staszewski O . Microbiota-derived acetate enables the metabolic fitness of the brain innate immune system during health and disease. Cell Metab. 2021; 33(11):2260-2276.e7. DOI: 10.1016/j.cmet.2021.10.010. View

18.

Schonberger K, Mitterer M, Glaser K, Stecher M, Hobitz S, Schain-Zota D . LC-MS-Based Targeted Metabolomics for FACS-Purified Rare Cells. Anal Chem. 2023; 95(9):4325-4334. PMC: 9996616. DOI: 10.1021/acs.analchem.2c04396. View

19.

Windhager J, Zanotelli V, Schulz D, Meyer L, Daniel M, Bodenmiller B . An end-to-end workflow for multiplexed image processing and analysis. Nat Protoc. 2023; 18(11):3565-3613. DOI: 10.1038/s41596-023-00881-0. View

20.

Hosp J, Dressing A, Blazhenets G, Bormann T, Rau A, Schwabenland M . Cognitive impairment and altered cerebral glucose metabolism in the subacute stage of COVID-19. Brain. 2021; 144(4):1263-1276. PMC: 8083602. DOI: 10.1093/brain/awab009. View