PreprintCited by 70Inflammasome and immune disordersCOVID-19 Clinical Research StudiesSARS-CoV-2 and COVID-19 Research

SARS-CoV-2 infects blood monocytes to activate NLRP3 and AIM2 inflammasomes, pyroptosis and cytokine release

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Junqueira, Caroline, Crespo, Ângela, Ranjbar, Shahin, Ingber, Jacob, Parry, Blair, Ravid, Sagi, Lacerda, Luna B. de, Lewandrowski, Mercedes +21 more·2021·medRxiv

Abstract

SARS-CoV-2 causes acute respiratory distress that can progress to multiorgan failure and death in some patients. Although severe COVID-19 disease is linked to exuberant inflammation, how SARS-CoV-2 triggers inflammation is not understood. Monocytes are sentinel blood cells that sense invasive infection to form inflammasomes that activate caspase-1 and gasdermin D (GSDMD) pores, leading to inflammatory death (pyroptosis) and processing and release of IL-1 family cytokines, potent inflammatory mediators. Here we show that ~10% of blood monocytes in COVID-19 patients are dying and infected with SARS-CoV-2. Monocyte infection, which depends on antiviral antibodies, activates NLRP3 and AIM2 inflammasomes, caspase-1 and GSDMD cleavage and relocalization. Signs of pyroptosis (IL-1 family cytokines, LDH) in the plasma correlate with development of severe disease. Moreover, expression quantitative trait loci (eQTLs) linked to higher GSDMD expression increase the risk of severe COVID-19 disease (odds ratio, 1.3, p<0.005). These findings taken together suggest that antibody-mediated SARS-CoV-2 infection of monocytes triggers inflammation that contributes to severe COVID-19 disease pathogenesis. One sentence summary: Antibody-mediated SARS-CoV-2 infection of monocytes activates inflammation and cytokine release.

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Crossref · 10.1101/2021.03.06.21252796

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  • In ageing patients, SARS-CoV-2 can enhance NLRP3 inflammasome activation, IL-1β and IL-18 levels, pyroptosis and DAMP release, further increasing inflammation and COVID-19 pathogenesis.

    “In ageing patients, SARS-CoV-2 can potentiate NLRP3 inflammasome activation and IL-1β and IL-18 levels, pyroptosis, and the release of DAMPs (including ATP), further heightening inflammation and COVID-19 pathogenesis74,75.”

    From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [74]

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Research works printed but not linked: 2

  1. X. X. Liu, Shiyu; Zhang, Zhibin; Wu, Hao; Lieberman, Judy, Channeling inflammation: Gasdermins in physiology and disease. Nature Reviews Drug Discovery, (In Press).
  2. E. Kyriazopoulou et al., Anakinra To Prevent Respiratory Failure In COVID-19 medRxiv, (2020).

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Authors
Junqueira, C., Crespo, Â., Ranjbar, S., Ingber, J., Parry, B., Ravid, S., Lacerda, L. B. D., Lewandrowski, M., Clark, S., Ho, F., Vora, S. M., Leger, V., Beakes, C., Margolin, J., Russell, N., Gehrke, L., Adhikari, U. D., Henderson, L., Janssen, E., Kwon, D., Sander, C., Abraham, J., Filbin, M., Goldberg, M. B., Wu, H., Mehta, G., Bell, S., Goldfeld, A. E., & Lieberman, J.
Affiliations
  • Boston Children's Hospital (US)
  • Massachusetts General Hospital (US)
  • Harvard University (US)
  • Massachusetts Institute of Technology (US)
  • Foundation for Liver Research (GB)
  • University of Cambridge (GB)
Corresponding author
  • Junqueira, Caroline
  • Lieberman, Judy
Venue
medRxiv
Publisher
openRxiv
Published
2021-03-08
OpenAlex
W3134550228
Cited by
70
References
66
Citations by year
2026: 2 · 2025: 8 · 2024: 5 · 2023: 11 · 2022: 30 · 2021: 14
Type
posted content
Language
en
Open access
Locations
  • medRxiv (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
Funders
  • Fast Grants
  • British Heart Foundation (RG/16/4/32218)
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico
  • National Institutes of Health (COVID-19)
  • National Institute of Allergy and Infectious Diseases (U19AI131135, R01AI124491)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Keywords
SARS-CoV-2, COVID-19 pandemic, monocytes, NLRP3 inflammasome, AIM2 inflammasome, pyroptosis, caspase-1, gasdermin D, IL-1 family cytokines, severe COVID-19, expression quantitative trait loci, inflammation

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