The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Inflammasome activation at the crux of severe COVID-19
Open accessAbstract
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), results in life-threatening disease in a minority of patients, especially elderly people and those with co-morbidities such as obesity and diabetes. Severe disease is characterized by dysregulated cytokine release, pneumonia and acute lung injury, which can rapidly progress to acute respiratory distress syndrome, disseminated intravascular coagulation, multisystem failure and death. However, a mechanistic understanding of COVID-19 progression remains unclear. Here we review evidence that SARS-CoV-2 directly or indirectly activates inflammasomes, which are large multiprotein assemblies that are broadly responsive to pathogen-associated and stress-associated cellular insults, leading to secretion of the pleiotropic IL-1 family cytokines (IL-1β and IL-18), and pyroptosis, an inflammatory form of cell death. We further discuss potential mechanisms of inflammasome activation and clinical efforts currently under way to suppress inflammation to prevent or ameliorate severe COVID-19. This Progress article brings us up to date on the role of inflammasomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19, describing how they may be activated during infection and contribute to the overexuberant inflammatory response in severe disease, and the efforts being taken to target them therapeutically.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Dexamethasone in Hospitalized Patients with Covid-19
The RECOVERY Collaborative Group (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2021436 · Cited by 11,477
Endothelial cell infection and endotheliitis in COVID-19
Varga, Z., Flammer, A. J., Steiger, P., Haberecker, M., Andermatt, R., Zinkernagel, A. S., Mehra, M. R., Schuepbach, R. A., Ruschitzka, F., & Moch, H. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30937-5 · Cited by 6,358
The NLRP3 inflammasome: molecular activation and regulation to therapeutics
Swanson, K. V., Deng, M., & Ting, J. P.-Y. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0165-0 · Cited by 4,884
The trinity of COVID-19: immunity, inflammation and intervention
Tay, M. Z., Poh, C. M., Rénia, L., MacAry, P. A., & Ng, L. F. P. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-0311-8 · Cited by 4,360
Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores
Liu, X., Zhang, Z., Ruan, J., Pan, Y., Magupalli, V. G., Wu, H., & Lieberman, J. (2016) · Nature · doi:10.1038/nature18629 · Cited by 3,202
Self-citationChemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin
Wang, Y., Gao, W., Shi, X., Ding, J., Liu, W., He, H., Wang, K., & Shao, F. (2017) · Nature · doi:10.1038/nature22393 · Cited by 3,199
Pore-forming activity and structural autoinhibition of the gasdermin family
Ding, J., Wang, K., Liu, W., She, Y., Sun, Q., Shi, J., Sun, H., Wang, D.-C., & Shao, F. (2016) · Nature · doi:10.1038/nature18590 · Cited by 2,771
Autoantibodies against type I IFNs in patients with life-threatening COVID-19
Bastard, P., Rosen, L. B., Zhang, Q., Michailidis, E., Hoffmann, H.-H., Zhang, Y., Dorgham, K., Philippot, Q., Rosain, J., Béziat, V., et al. (2020) · Science · doi:10.1126/science.abd4585 · Cited by 2,662
AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC
Hornung, V., Ablasser, A., Charrel-Dennis, M., Bauernfeind, F., Horvath, G., Caffrey, D. R., Latz, E., & Fitzgerald, K. A. (2009) · Nature · doi:10.1038/nature07725 · Cited by 2,627
Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19
Liao, M., Liu, Y., Yuan, J., Wen, Y., Xu, G., Zhao, J., Cheng, L., Li, J., Wang, X., Wang, F., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0901-9 · Cited by 2,614
An inflammatory cytokine signature predicts COVID-19 severity and survival
Del Valle, D. M., Kim-Schulze, S., Huang, H.-H., Beckmann, N. D., Nirenberg, S., Wang, B., Lavin, Y., Swartz, T. H., Madduri, D., Stock, A., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-1051-9 · Cited by 2,605
Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages
Merad, M., & Martin, J. C. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-0331-4 · Cited by 2,472
Inflammatory caspases are innate immune receptors for intracellular LPS
Shi, J., Zhao, Y., Wang, Y., Gao, W., Ding, J., Li, P., Hu, L., & Shao, F. (2014) · Nature · doi:10.1038/nature13683 · Cited by 2,285
Ziegler, C. G. K., Allon, S. J., Nyquist, S. K., Mbano, I. M., Miao, V. N., Tzouanas, C. N., Cao, Y., Yousif, A. S., Bals, J., Hauser, B. M., et al. (2020) · Cell · doi:10.1016/j.cell.2020.04.035 · Cited by 2,284
Interleukin-1 in the pathogenesis and treatment of inflammatory diseases
Dinarello, C. A. (2011) · Blood · doi:10.1182/blood-2010-07-273417 · Cited by 2,248
Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
Zhang, Q., Bastard, P., Liu, Z., Le Pen, J., Moncada-Velez, M., Chen, J., Ogishi, M., Sabli, I. K. D., Hodeib, S., Korol, C., et al. (2020) · Science · doi:10.1126/science.abd4570 · Cited by 2,229
Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1
Mills, E. L., Ryan, D. G., Prag, H. A., Dikovskaya, D., Menon, D., Zaslona, Z., Jedrychowski, M. P., Costa, A. S. H., Higgins, M., Hams, E., et al. (2018) · Nature · doi:10.1038/nature25986 · Cited by 1,885
Hospitalization and mortality among Black patients and White patients with Covid-19.
Price-Haywood, E. G., Burton, J., Fort, D., & Seoane, L. (2020) · New England Journal of Medicine · doi:10.1056/nejmsa2011686 · Cited by 1,660
Immunology of COVID-19: Current State of the Science
Vabret, N., Britton, G. J., Gruber, C., Hegde, S., Kim, J., Kuksin, M., Levantovsky, R., Malle, L., Moreira, A., Park, M. D., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.05.002 · Cited by 1,623
Mechanisms and regulation of endothelial VEGF receptor signalling
Simons, M., Gordon, E., & Claesson-Welsh, L. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.87 · Cited by 1,498
Imai, Y., Kuba, K., Neely, G. G., Yaghubian-Malhami, R., Perkmann, T., van Loo, G., Ermolaeva, M., Veldhuizen, R., Leung, Y. H. C., Wang, H., et al. (2008) · Cell · doi:10.1016/j.cell.2008.02.043 · Cited by 1,356
Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells
Zhou, Z., He, H., Wang, K., Shi, X., Wang, Y., Su, Y., Wang, Y., Li, D., Liu, W., Zhang, Y., et al. (2020) · Science · doi:10.1126/science.aaz7548 · Cited by 1,317
Tomazini, B. M., Maia, I. S., Cavalcanti, A. B., Berwanger, O., Rosa, R. G., Veiga, V. C., Avezum, A., Lopes, R. D., Bueno, F. R., Silva, M. V. A. O., et al. (2020) · JAMA · doi:10.1001/jama.2020.17021 · Cited by 1,241
Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans
Arunachalam, P. S., Wimmers, F., Mok, C. K. P., Perera, R. A. P. M., Scott, M., Hagan, T., Sigal, N., Feng, Y., Bristow, L., Tak-Yin Tsang, O., et al. (2020) · Science · doi:10.1126/science.abc6261 · Cited by 1,186
FDA-approved disulfiram inhibits pyroptosis by blocking gasdermin D pore formation
Hu, J. J., Liu, X., Xia, S., Zhang, Z., Zhang, Y., Zhao, J., Ruan, J., Luo, X., Lou, X., Bai, Y., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0669-6 · Cited by 1,145
Self-citationThe Pore-Forming Protein Gasdermin D Regulates Interleukin-1 Secretion from Living Macrophages
Evavold, C. L., Ruan, J., Tan, Y., Xia, S., Wu, H., & Kagan, J. C. (2018) · Immunity · doi:10.1016/j.immuni.2017.11.013 · Cited by 1,115
Self-citationA dynamic COVID-19 immune signature includes associations with poor prognosis
Laing, A. G., Lorenc, A., del Molino del Barrio, I., Das, A., Fish, M., Monin, L., Muñoz-Ruiz, M., McKenzie, D. R., Hayday, T. S., Francos-Quijorna, I., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-1038-6 · Cited by 946
NINJ1 mediates plasma membrane rupture during lytic cell death
Kayagaki, N., Kornfeld, O. S., Lee, B. L., Stowe, I. B., O’Rourke, K., Li, Q., Sandoval, W., Yan, D., Kang, J., Xu, M., et al. (2021) · Nature · doi:10.1038/s41586-021-03218-7 · Cited by 857
Skendros, P., Mitsios, A., Chrysanthopoulou, A., Mastellos, D. C., Metallidis, S., Rafailidis, P., Ntinopoulou, M., Sertaridou, E., Tsironidou, V., Tsigalou, C., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci141374 · Cited by 786
Immune cell profiling of COVID-19 patients in the recovery stage by single-cell sequencing
Wen, W., Su, W., Tang, H., Le, W., Zhang, X., Zheng, Y., Liu, X., Xie, L., Li, J., Ye, J., et al. (2020) · Cell Discovery · doi:10.1038/s41421-020-0168-9 · Cited by 730
An endogenous caspase-11 ligand elicits interleukin-1 release from living dendritic cells
Zanoni, I., Tan, Y., Di Gioia, M., Broggi, A., Ruan, J., Shi, J., Donado, C. A., Shao, F., Wu, H., Springstead, J. R., et al. (2016) · Science · doi:10.1126/science.aaf3036 · Cited by 583
Self-citationReduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera
Supasa, P., Zhou, D., Dejnirattisai, W., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H. M. E., Nutalai, R., Tuekprakhon, A., et al. (2021) · Cell · doi:10.1016/j.cell.2021.02.033 · Cited by 460
Immunological characteristics govern the transition of COVID-19 to endemicity
Lavine, J. S., Bjornstad, O. N., & Antia, R. (2021) · Science · doi:10.1126/science.abe6522 · Cited by 416
Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity
Larsen, M. D., de Graaf, E. L., Sonneveld, M. E., Plomp, H. R., Nouta, J., Hoepel, W., Chen, H.-J., Linty, F., Visser, R., Brinkhaus, M., et al. (2021) · Science · doi:10.1126/science.abc8378 · Cited by 408
SARS-CoV-2 triggers inflammatory responses and cell death through caspase-8 activation
Li, S., Zhang, Y., Guan, Z., Li, H., Ye, M., Chen, X., Shen, J., Zhou, Y., Shi, Z.-L., Zhou, P., et al. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00334-0 · Cited by 365
Proinflammatory IgG Fc structures in patients with severe COVID-19
Chakraborty, S., Gonzalez, J., Edwards, K., Mallajosyula, V., Buzzanco, A. S., Sherwood, R., Buffone, C., Kathale, N., Providenza, S., Xie, M. M., et al. (2021) · Nature Immunology · doi:10.1038/s41590-020-00828-7 · Cited by 326
Inflamm-aging: Why older men are the most susceptible to SARS-CoV-2 complicated outcomes
Bonafè, M., Prattichizzo, F., Giuliani, A., Storci, G., Sabbatinelli, J., & Olivieri, F. (2020) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2020.04.005 · Cited by 184
Aging impairs both primary and secondary RIG-I signaling for interferon induction in human monocytes
Molony, R. D., Nguyen, J. T., Kong, Y., Montgomery, R. R., Shaw, A. C., & Iwasaki, A. (2017) · Science Signaling · doi:10.1126/scisignal.aan2392 · Cited by 154
Song, X., Hu, W., Yu, H., Zhao, L., Zhao, Y., Zhao, X., Xue, H., & Zhao, Y. (2023) · Cytometry Part A · doi:10.1002/cyto.a.24285 · Cited by 117
Junqueira, C., Crespo, Â., Ranjbar, S., Ingber, J., Parry, B., Ravid, S., Lacerda, L. B. D., Lewandrowski, M., Clark, S., Ho, F., et al. (2021) · doi:10.1101/2021.03.06.21252796 · Cited by 70
Self-citation
Cited by
Cardiovascular Manifestation of the BNT162b2 mRNA COVID-19 Vaccine in Adolescents
Mansanguan, S., Charunwatthana, P., Piyaphanee, W., Dechkhajorn, W., Poolcharoen, A., & Mansanguan, C. (2022) · Tropical Medicine and Infectious Disease · doi:10.3390/tropicalmed7080196 · Cited by 83
NLRP3 inflammasome activation in COVID-19: an interlink between risk factors and disease severity
Amin, S., Aktar, S., Rahman, M. M., & Chowdhury, M. M. H. (2022) · Microbes and Infection · doi:10.1016/j.micinf.2021.104913 · Cited by 51
Metadata
- Authors
- Vora, S. M., Lieberman, J., & Wu, H.
- Venue
- Nature Reviews Immunology
- Published
- 2021-08-09
- Volume
- 21
- Issue
- 11
- Pages
- 694-703
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- OpenAlex
- W3191470838
- Cited by
- 325
- References
- 40
- FWCI
- 5.74
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
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.
