Inflammatory leptomeningeal cytokines mediate COVID-19 neurologic symptoms in cancer patients
Open accessAbstract
SARS-CoV-2 infection induces a wide spectrum of neurologic dysfunction that emerges weeks after the acute respiratory infection. To better understand this pathology, we prospectively analyzed of a cohort of cancer patients with neurologic manifestations of COVID-19, including a targeted proteomics analysis of the cerebrospinal fluid. We find that cancer patients with neurologic sequelae of COVID-19 harbor leptomeningeal inflammatory cytokines in the absence of viral neuroinvasion. The majority of these inflammatory mediators are driven by type II interferon and are known to induce neuronal injury in other disease states. In these patients, levels of matrix metalloproteinase-10 within the spinal fluid correlate with the degree of neurologic dysfunction. Furthermore, this neuroinflammatory process persists weeks after convalescence from acute respiratory infection. These prolonged neurologic sequelae following systemic cytokine release syndrome lead to long-term neurocognitive dysfunction. Our findings suggest a role for anti-inflammatory treatment(s) in the management of neurologic complications of COVID-19 infection.
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These additional neuropathological consequences of severe COVID include microvascular thrombi, neuron loss, cortical inflammation, and even direct brain infection in some cases.
“These include microvascular thrombi, neuron loss, cortical inflammation, and even direct brain infection in some cases (Lee et al., 2021; Remsik et al., 2021; Song et al., 2021; Yang et al., 2021).”
From Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation (2022) · cites this paper as Remsik et al., 2021
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- Authors
- Remsik, J., Wilcox, J. A., Babady, N. E., McMillen, T. A., Vachha, B. A., Halpern, N. A., Dhawan, V., Rosenblum, M., Iacobuzio-Donahue, C. A., Avila, E. K., Santomasso, B., & Boire, A.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Boire, Adrienne
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2021-02
- Volume
- 39
- Issue
- 2
- Pages
- 276-283.e3
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC7833316
- OpenAlex
- W3125423734
- Cited by
- 77
- References
- 50
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 8 · 2023: 13 · 2022: 25 · 2021: 20
- FWCI
- 7.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 372 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cancer Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Brain Tumor Association
- Terri Brodeur Breast Cancer Foundation
- Pershing Square Sohn Cancer Research Alliance
- Pew Charitable Trusts
- Damon Runyon Cancer Research Foundation
- National Cancer Institute
- Fiona and Stanley Druckenmiller Center for Lung Cancer Research
- Topics
- Health Sciences › Medicine › Neurology › Long-Term Effects of COVID-19
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Infectious Diseases › Infectious Encephalopathies and Encephalitis
- Keywords
- COVID-19 pandemic, SARS-CoV-2, neurological complications, cancer patients, leptomeningeal inflammation, cytokines, cerebrospinal fluid, interferon-gamma, matrix metalloproteinase-10, neuroinflammation, cytokine release syndrome, neurocognitive impairment, anti-inflammatory therapy
- MeSH terms
- Angiotensin-Converting Enzyme 2, COVID-19, Brain, Brain Diseases, Cerebrospinal Fluid Proteins, Humans, Neoplasms, Comorbidity, Cytokines, Inflammation Mediators, Neuroimaging
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