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A neutrophil activation signature predicts critical illness and mortality in COVID-19

Open access
Meizlish, Matthew L., Pine, Alexander B., Bishai, Jason D., Goshua, George, Nadelmann, Emily R., Simonov, Michael, Chang, C-Hong, Zhang, Hanming, Shallow, Marcus, Bahel, Parveen, Owusu, Kent, Yamamoto, Yu, Arora, Tanima, Atri, Deepak S., Patel, Amisha, Gbyli, Rana, Kwan, Jennifer, Won, Christine H., Dela Cruz, Charles, Price, Christina, Koff, Jonathan, King, Brett A., Rinder, Henry M., Wilson, F. Perry, Hwa, John, Halene, Stephanie, Damsky, William, van Dijk, David, Lee, Alfred I., Chun, Hyung J.·2021·Blood Advances

Abstract

Pathologic immune hyperactivation is emerging as a key feature of critical illness in COVID-19, but the mechanisms involved remain poorly understood. We carried out proteomic profiling of plasma from cross-sectional and longitudinal cohorts of hospitalized patients with COVID-19 and analyzed clinical data from our health system database of more than 3300 patients. Using a machine learning algorithm, we identified a prominent signature of neutrophil activation, including resistin, lipocalin-2, hepatocyte growth factor, interleukin-8, and granulocyte colony-stimulating factor, which were the strongest predictors of critical illness. Evidence of neutrophil activation was present on the first day of hospitalization in patients who would only later require transfer to the intensive care unit, thus preceding the onset of critical illness and predicting increased mortality. In the health system database, early elevations in developing and mature neutrophil counts also predicted higher mortality rates. Altogether, these data suggest a central role for neutrophil activation in the pathogenesis of severe COVID-19 and identify molecular markers that distinguish patients at risk of future clinical decompensation.

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Metadata

Authors
Meizlish, M. L., Pine, A. B., Bishai, J. D., Goshua, G., Nadelmann, E. R., Simonov, M., Chang, C.-H., Zhang, H., Shallow, M., Bahel, P., Owusu, K., Yamamoto, Y., Arora, T., Atri, D. S., Patel, A., Gbyli, R., Kwan, J., Won, C. H., Dela Cruz, C., Price, C., Koff, J., King, B. A., Rinder, H. M., Wilson, F. P., Hwa, J., Halene, S., Damsky, W., van Dijk, D., Lee, A. I., & Chun, H. J.
Venue
Blood Advances
Published
2021-02-26
Volume
5
Issue
5
Pages
1164-1177
ISSN
  • 2473-9529 (ISSN-L)
  • 2473-9537
OpenAlex
W3132811058
Cited by
316
References
48
FWCI
20.80
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: A neutrophil activation signature predicts critical illness and mortality in COVID-19. https://app.cochat.ai/papers/10.1182/bloodadvances.2020003568
The paper
Meizlish, M. L., Pine, A. B., Bishai, J. D., Goshua, G., Nadelmann, E. R., Simonov, M., Chang, C.-H., Zhang, H., Shallow, M., Bahel, P., Owusu, K., Yamamoto, Y., Arora, T., Atri, D. S., Patel, A., Gbyli, R., Kwan, J., Won, C. H., Dela Cruz, C., . . . Chun, H. J. (2021). A neutrophil activation signature predicts critical illness and mortality in COVID-19. Blood Advances. https://doi.org/10.1182/bloodadvances.2020003568

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.