Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications
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Abstract
Immune profiling of COVID-19 patients: Coronavirus disease 2019 (COVID-19) has affected millions of people globally, yet how the human immune system responds to and influences COVID-19 severity remains unclear. Mathew et al. present a comprehensive atlas of immune modulation associated with COVID-19. They performed high-dimensional flow cytometry of hospitalized COVID-19 patients and found three prominent and distinct immunotypes that are related to disease severity and clinical parameters. Arunachalam et al. report a systems biology approach to assess the immune system of COVID-19 patients with mild-to-severe disease. These studies provide a compendium of immune cell information and roadmaps for potential therapeutic interventions. Science , this issue p. eabc8511 , p. 1210
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COVID-19 results in hyperactivation of innate immune pathways, especially complement and TLR4-related pathways.
“They observed that COVID-19 results in hyperactivation of innate immune pathways, especially complement and TLR4-related pathways.”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [151]
The section on heterogeneous CD4 T-cell responses reports elevated inflammatory cytokines and myeloid-recruiting chemokines in a subgroup of COVID-19 patients, supporting a narrower claim of heightened inflammation. The passages do not establish hyperactivation of innate immune pathways, and searches for complement and TLR4 found no support for those specific pathways (page unavailable in our copy). (LLM, conf=0.82)
Experimental — accuracy not yet measuredMathew et al conducted deep immune profiling of T and B cells from 125 patients with COVID-19 versus healthy controls and identified 3 immune phenotypes associated with worse disease outcome.
“Mathew et al 151 conducted deep immune profiling of T and B cells obtained by flow cytometry from 125 patients with COVID-19 versus healthy controls and identified 3 immune phenotypes associated with worse disease outcome.”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [151]
The Discussion describes high-dimensional flow-cytometry profiling of B and T cells in approximately 125 patients and identifies three immunotypes. But it links immunotype 1—not all three—to more severe disease. The section on immunotypes and disease severity says immunotype 3 was associated with less severe pathology, so the claim overstates their association with worse outcomes. The cited passages provide no page numbers. (LLM, conf=0.90)
Experimental — accuracy not yet measuredSevere COVID-19 is characterized by increased circulating neutrophils and decreased lymphocytes.
“An increase in circulating neutrophils versus a decrease in lymphocytes has been appreciated as a hallmark of severe COVID-19”
From COVID-19 and the human innate immune system (2021) · cites this paper as Mathew et al., 2020
COVID-19 disease severity was inversely correlated with the frequency of naive T cells.
“COVID-19 disease severity was inversely correlated with the frequency of naive T cells (Mathew et al., 2020; Rydyznski Moderbacher et al., 2020).”
From Adaptive immunity to SARS-CoV-2 and COVID-19 (2021) · cites this paper as Mathew et al., 2020
The relative frequencies of circulating activated CD4+ and CD8+ T cells and plasmablasts are increased in Covid-19.
“The relative frequencies of circulating activated CD4+ and CD8+ T cells and plasmablasts are increased in Covid-19.92”
From Cytokine storm (2020) · cites this paper as [92]
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- Authors
- Mathew, D., Giles, J. R., Baxter, A. E., Oldridge, D. A., Greenplate, A. R., Wu, J. E., Alanio, C., Kuri-Cervantes, L., Pampena, M. B., D’Andrea, K., Manne, S., Chen, Z., Huang, Y. J., Reilly, J. P., Weisman, A. R., Ittner, C. A. G., Kuthuru, O., Dougherty, J., Nzingha, K., Han, N., Kim, J., Pattekar, A., Goodwin, E. C., Anderson, E. M., Weirick, M. E., Gouma, S., Arevalo, C. P., Bolton, M. J., Chen, F., Lacey, S. F., Ramage, H., Cherry, S., Hensley, S. E., Apostolidis, S. A., Huang, A. C., Vella, L. A., Unit, T. U. C. P., Betts, M. R., Meyer, N. J., Wherry, E. J., Alam, Z., Addison, M. M., Byrne, K. T., Chandra, A., Descamps, H. C., Kaminskiy, Y., Hamilton, J. T., Noll, J. H., Omran, D. K., Perkey, E., Prager, E. M., Pueschl, D., Shah, J. B., Shilan, J. S., & Vanderbeck, A. N.
- Affiliations
- University of Pennsylvania (US)
- Division of Translational Medicine and Human Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
- Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
- Thomas Jefferson University (US)
- Children's Hospital of Philadelphia (US)
- Corresponding author
- Mathew, Divij
- Giles, Josephine R.
- Baxter, Amy E.
- Oldridge, Derek A.
- Greenplate, Allison R.
- Wu, Jennifer E.
- Alanio, Cécile
- Betts, Michael R.
- Meyer, Nuala J.
- Wherry, E. John
- ORCID
- Mathew, Divij
- Giles, Josephine R.
- Baxter, Amy E.
- Oldridge, Derek A.
- Greenplate, Allison R.
- Wu, Jennifer E.
- Alanio, Cécile
- Kuri-Cervantes, Leticia
- Pampena, M. Betina
- D’Andrea, Kurt
- Manne, Sasikanth
- Chen, Zeyu
- Huang, Yinghui Jane
- Reilly, John P.
- Weisman, Ariel R.
- Kuthuru, Oliva
- Dougherty, Jeanette
- Nzingha, Kito
- Han, Nicholas
- Kim, Justin
- Pattekar, Ajinkya
- Anderson, Elizabeth M.
- Weirick, Madison E.
- Gouma, Sigrid
- Arevalo, Claudia P.
- Bolton, Marcus J.
- Lacey, Simon F.
- Ramage, Holly
- Cherry, Sara
- Hensley, Scott E.
- Apostolidis, Sokratis A.
- Huang, Alexander C.
- Vella, Laura A.
- Betts, Michael R.
- Meyer, Nuala J.
- Wherry, E. John
- Alam, Zahidul
- Addison, Mary M.
- Byrne, Katelyn T.
- Chandra, Aditi
- Descamps, Hélène C.
- Hamilton, Jacob T.
- Noll, Julia Han
- Omran, Dalia K.
- Perkey, Eric
- Pueschl, Dana
- Shah, Jennifer B.
- Vanderbeck, Ashley N.
- Venue
- Science
- Published
- 2020-09-04
- Volume
- 369
- Issue
- 6508
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC7402624
- OpenAlex
- W3041494167
- Cited by
- 1,509
- References
- 62
- Citations by year
- 2026: 42 · 2025: 63 · 2024: 132 · 2023: 212 · 2022: 350 · 2021: 515 · 2020: 194
- FWCI
- 41.83
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Science (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by-nd)
- Funders
- National Institutes of Health (AI105343, AI08263, CA230157, HL137006, HL137915, CA009140, CA234842)
- Mark Foundation For Cancer Research
- Cancer Research Institute
- Allen Foundation
- NHLBI (1R38HL143613)
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- COVID-19 pandemic, SARS-CoV-2, immune profiling, immunotypes, T cell activation, B cell activation, plasmablasts, lymphocyte activation, disease severity, clinical trajectories, high-dimensional cytometry, COVID-19 treatment, COVID-19 vaccines
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