Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies
Open accessAbstract
Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is the pathogen that causes coronavirus disease 2019 (COVID-19). As of 25 May 2020, the outbreak of COVID-19 has caused 347,192 deaths around the world. The current evidence showed that severely ill patients tend to have a high concentration of pro-inflammatory cytokines, such as interleukin (IL)-6, compared to those who are moderately ill. The high level of cytokines also indicates a poor prognosis in COVID-19. Besides, excessive infiltration of pro-inflammatory cells, mainly involving macrophages and T-helper 17 cells, has been found in lung tissues of patients with COVID-19 by postmortem examination. Recently, increasing studies indicate that the "cytokine storm" may contribute to the mortality of COVID-19. Here, we summarize the clinical and pathologic features of the cytokine storm in COVID-19. Our review shows that SARS-Cov-2 selectively induces a high level of IL-6 and results in the exhaustion of lymphocytes. The current evidence indicates that tocilizumab, an IL-6 inhibitor, is relatively effective and safe. Besides, corticosteroids, programmed cell death protein (PD)-1/PD-L1 checkpoint inhibition, cytokine-adsorption devices, intravenous immunoglobulin, and antimalarial agents could be potentially useful and reliable approaches to counteract cytokine storm in COVID-19 patients.
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
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.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Many treatments have been developed around the hyperinflammatory state seen in severe cases.
“A starting point for many therapeutic strategies has been the hyperinflammatory state in severe disease (Tang et al., 2020; Wang et al., 2020a).”
From COVID-19 and the human innate immune system (2021) · cites this paper as Tang et al., 2020
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30183-5 · Cited by 48,884 · see citing works
Clinical characteristics of coronavirus disease 2019 in China
Guan, W.-J., Ni, Z.-Y., Hu, Y., Liang, W.-H., Ou, C.-Q., He, J.-X., Liu, L., Shan, H., Lei, C.-L., Hui, D. S. C., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2002032 · Cited by 30,246 · see citing works
Self-citationA pneumonia outbreak associated with a new coronavirus of probable bat origin
Zhou, P., Yang, X.-L., Wang, X.-G., Hu, B., Zhang, L., Zhang, W., Si, H.-R., Zhu, Y., Li, B., Huang, C.-L., et al. (2020) · Nature · doi:10.1038/s41586-020-2012-7 · Cited by 21,969 · see citing works
Chen, N., Zhou, M., Dong, X., Qu, J., Gong, F., Han, Y., Qiu, Y., Wang, J., Liu, Y., Wei, Y., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30211-7 · Cited by 21,415 · see citing works
Wang, D., Hu, B., Hu, C., Zhu, F., Liu, X., Zhang, J., Wang, B., Xiang, H., Cheng, Z., Xiong, Y., et al. (2020) · JAMA · doi:10.1001/jama.2020.1585 · Cited by 20,148 · see citing works
La certeza de lo impredecible: Cultura Educación y Sociedad en tiempos de COVID19
Martínez González, M. (2020) · DSPACE System - Metalibrary (University of the Coast) · Cited by 18,463 · see citing works
Wu, Z., & McGoogan, J. M. (2020) · JAMA · doi:10.1001/jama.2020.2648 · Cited by 17,016 · see citing works
COVID-19: consider cytokine storm syndromes and immunosuppression
Mehta, P., McAuley, D. F., Brown, M., Sanchez, E., Tattersall, R. S., & Manson, J. J. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30628-0 · Cited by 9,664 · see citing works
Pathological findings of COVID-19 associated with acute respiratory distress syndrome
Xu, Z., Shi, L., Wang, Y., Zhang, J., Huang, L., Zhang, C., Liu, S., Zhao, P., Liu, H., Zhu, L., et al. (2020) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(20)30076-x · Cited by 8,545 · see citing works
Self-citationSmolen, J. S., Landewé, R., Bijlsma, J. W. J., Burmester, G., Chatzidionysiou, K., Dougados, M., Nam, J., Ramiro, S., Voshaar, M., van Vollenhoven, R., et al. (2017) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2016-210715 · Cited by 7,468 · see citing works
First case of 2019 novel coronavirus in the United States
Holshue, M. L., DeBolt, C., Lindquist, S., Lofy, K. H., Wiesman, J., Bruce, H., Spitters, C., Ericson, K., Wilkerson, S., Tural, A., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2001191 · Cited by 6,030 · see citing works
IL‐6 in inflammation, immunity, and disease
Tanaka, T., Narazaki, M., & Kishimoto, T. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016295 · Cited by 5,046 · see citing works
Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China
Qin, C., Zhou, L., Hu, Z., Zhang, S., Yang, S., Tao, Y., Xie, C., Ma, K., Shang, K., Wang, W., et al. (2020) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa248 · Cited by 4,775 · see citing works
Clinical and immunological features of severe and moderate coronavirus disease 2019
Chen, G., Wu, D., Guo, W., Cao, Y., Huang, D., Wang, H., Wang, T., Zhang, X., Chen, H., Yu, H., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci137244 · Cited by 4,750 · see citing works
Toll-like receptors and their crosstalk with other innate receptors in infection and immunity
Kawai, T., & Akira, S. (2011) · Immunity · doi:10.1016/j.immuni.2011.05.006 · Cited by 3,658 · see citing works
Kidney disease is associated with in-hospital death of patients with COVID-19
Cheng, Y., Luo, R., Wang, K., Zhang, M., Wang, Z., Dong, L., Li, J., Yao, Y., Ge, S., & Xu, G. (2020) · Kidney International · doi:10.1016/j.kint.2020.03.005 · Cited by 2,957 · see citing works
MAPK signal pathways in the regulation of cell proliferation in mammalian cells
ZHANG, W., & LIU, H. T. (2002) · Cell Research · doi:10.1038/sj.cr.7290105 · Cited by 2,845 · see citing works
Smolen, J. S., Landewé, R., Bijlsma, J. W. J., Burmester, G. R., Dougados, M., Kerschbaumer, A., McInnes, I. B., Sepriano, A. R., van Vollenhoven, R., de Wit, M. P. T., et al. (2020) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2019-216655 · Cited by 2,753 · see citing works
Effective treatment of severe COVID-19 patients with tocilizumab
Xu, X., Han, M., Li, T., Sun, W., Wang, D., Fu, B., Zhou, Y., Zheng, X., Yang, Y., Li, X., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2005615117 · Cited by 2,636 · see citing works
Channappanavar, R., & Perlman, S. (2017) · Seminars in Immunopathology · doi:10.1007/s00281-017-0629-x · Cited by 2,524 · see citing works
Smolen, J. S., Aletaha, D., Barton, A. C., Burmester, G. R., Emery, P., Firestein, G. S., Kavanaugh, A., McInnes, I. B., Solomon, D. H., Strand, V., et al. (2018) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2018.1 · Cited by 2,480 · see citing works
Peiris, J., Chu, C., Cheng, V., Chan, K., Hung, I., Poon, L., Law, K., Tang, B., Hon, T., Chan, C., et al. (2003) · The Lancet · doi:10.1016/s0140-6736(03)13412-5 · Cited by 2,375 · see citing works
Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan
Li, X., Xu, S., Yu, M., Wang, K., Tao, Y., Zhou, Y., Shi, J. C., Zhou, M., Wu, B., Yang, Z., et al. (2020) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2020.04.006 · Cited by 2,237 · see citing works
Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury
Russell, C. D., Millar, J. E., & Baillie, J. K. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30317-2 · Cited by 2,007 · see citing works
Into the Eye of the Cytokine Storm
Tisoncik, J. R., Korth, M. J., Simmons, C. P., Farrar, J., Martin, T. R., & Katze, M. G. (2012) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.05015-11 · Cited by 1,940 · see citing works
Functional exhaustion of antiviral lymphocytes in COVID-19 patients
Zheng, M., Gao, Y., Wang, G., Song, G., Liu, S., Sun, D., Xu, Y., & Tian, Z. (2020) · Cellular & Molecular Immunology · doi:10.1038/s41423-020-0402-2 · Cited by 1,768 · see citing works
COVID-19: immunopathology and its implications for therapy
Cao, X. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-0308-3 · Cited by 1,609 · see citing works
Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province
Liu, K., Fang, Y.-Y., Deng, Y., Liu, W. Y., Wang, M., Ma, J.-P., Xiao, W. L., Wang, Y.-N., Zhong, M.-H., Li, C.-H., et al. (2020) · Chinese Medical Journal · doi:10.1097/cm9.0000000000000744 · Cited by 1,412 · see citing works
Channappanavar, R., Fehr, A. R., Vijay, R., Mack, M., Zhao, J., Meyerholz, D. K., & Perlman, S. M. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2016.01.007 · Cited by 1,400 · see citing works
Multiple organ infection and the pathogenesis of SARS
Gu, J., Gong, E., Zhang, B., Zheng, J., Gao, Z., Zhong, Y., Zou, W., Zhan, J., Wang, S., Xie, Z., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050828 · Cited by 1,379 · see citing works
Molecular and Biochemical Aspects of the PD-1 Checkpoint Pathway
Boussiotis, V. A. (2016) · New England Journal of Medicine · doi:10.1056/nejmra1514296 · Cited by 1,342 · see citing works
Tocilizumab treatment in COVID‐19: A single center experience
Luo, P., Liu, Y., Qiu, L., Liu, X., Liu, D., & Li, J. (2020) · Journal of Medical Virology · doi:10.1002/jmv.25801 · Cited by 1,235 · see citing works
Xiong, Y., Liu, Y., Cao, L., Wang, D., Guo, M., Jiang, A., Guo, D., Hu, W., Yang, J., Tang, Z., et al. (2020) · Emerging Microbes & Infections · doi:10.1080/22221751.2020.1747363 · Cited by 1,076 · see citing works
Clinical Features of 69 Cases With Coronavirus Disease 2019 in Wuhan, China
Wang, Z., Yang, B., Li, Q., Wen, L., & Zhang, R. (2020) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa272 · Cited by 1,063 · see citing works
Dysregulation of Immune Response in Patients with COVID-19 in Wuhan, ChinaPreprint
Qin, C., Zhou, L., Hu, Z., Zhang, S., Yang, S., Yu, T., Xie, C., Ma, K., Shang, K., Wang, W., et al. (2020) · SSRN Electronic Journal · doi:10.2139/ssrn.3541136 · Cited by 898 · see citing works
Intravenous immunoglobulin therapy: how does IgG modulate the immune system?
Schwab, I., & Nimmerjahn, F. (2013) · Nature reviews. Immunology · doi:10.1038/nri3401 · Cited by 820 · see citing works
Phenotypical and functional specialization of FOXP3+ regulatory T cells
Campbell, D. J., & Koch, M. A. (2011) · Nature Reviews Immunology · doi:10.1038/nri2916 · Cited by 773 · see citing works
Mechanism of NLRP3 inflammasome activation
Sutterwala, F. S., Haasken, S., & Cassel, S. L. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12458 · Cited by 736 · see citing works
Ramiro, S., Gaujoux-Viala, C., Nam, J. L., Smolen, J. S., Buch, M. H., Gossec, L., van der Heijde, D. M. F. M., Winthrop, K. L., & Landewé, R. (2014) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2013-204575 · Cited by 701 · see citing works
[Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia].
Chen, L., Liu, H., Liu, W. Y., Liu, J., Liu, K., Shang, J., Deng, Y., & Wei, S. (2020) · PubMed · doi:10.3760/cma.j.issn.1001-0939.2020.0005 · Cited by 690 · see citing works
Self-citationAn interferon‐γ‐related cytokine storm in SARS patients
Huang, K., Su, I., Theron, M., Wu, Y., Lai, S., Liu, C., & Lei, H. (2005) · Journal of Medical Virology · doi:10.1002/jmv.20255 · Cited by 679 · see citing works
Hydroxychloroquine: From Malaria to Autoimmunity
Ben‐Zvi, I., Kivity, S., Langevitz, P., & Shoenfeld, Y. (2011) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-010-8243-x · Cited by 616 · see citing works
Arabi, Y. M., Arifi, A. A., Balkhy, H. H., Najm, H. K., Al‐Dawood, A., Ghabashi, A., Hawa, H., Alothman, A. F., Al-Khaldi, A., & Raiy, B. A. (2014) · Annals of Internal Medicine · doi:10.7326/m13-2486 · Cited by 573 · see citing works
Totura, A. L., Whitmore, A. C., Agnihothram, S., Schäfer, A., Katze, M. G., Heise, M. T., & Baric, R. S. (2015) · mBio · doi:10.1128/mbio.00638-15 · Cited by 479 · see citing works
Chemokine up-regulation in SARS-coronavirus–infected, monocyte-derived human dendritic cells
Law, H., Cheung, C. Y., Ng, H. Y., Sia, S. F., Chan, Y. O., Luk, W., Nicholls, J. M., Peiris, M. J. S., & Lau, Y. (2005) · Blood · doi:10.1182/blood-2004-10-4166 · Cited by 467 · see citing works
Cheung, C. Y., Poon, L. L. M., Ng, I. H. Y., Luk, W., Sia, S. F., Wu, M. H. S., Chan, K., Yuen, K., Gordon, S., Guan, Y., et al. (2005) · Journal of Virology · doi:10.1128/jvi.79.12.7819-7826.2005 · Cited by 461 · see citing works
Newly described pattern recognition receptors team up against intracellular pathogens
Brož, P., & Monack, D. M. (2013) · Nature reviews. Immunology · doi:10.1038/nri3479 · Cited by 459 · see citing works
Zhou, J., Chu, H., Li, C., Wong, B. H., Cheng, Z., Poon, V. K., Sun, T., Lau, C. C.-Y., Wong, K. K. Y., Chan, J. Y. W., et al. (2013) · The Journal of Infectious Diseases · doi:10.1093/infdis/jit504 · Cited by 429 · see citing works
IL-10: A Multifunctional Cytokine in Viral Infections
Rojas, J. M., Avia, M., Martı́n, V., & Sevilla, N. (2017) · Journal of Immunology Research · doi:10.1155/2017/6104054 · Cited by 414 · see citing works
Lau, S. K. P., Lau, C. C. Y., Chan, K., Li, C. P. Y., Chen, H., Jin, D., Chan, J. F., Woo, P. C. Y., & Yuen, K. (2013) · Journal of General Virology · doi:10.1099/vir.0.055533-0 · Cited by 393 · see citing works
Cameron, M. J., Ran, L., Xu, L., Danesh, A., Bermejo-Martin, J. F., Cameron, C. M., Muller, M. P., Gold, W. L., Richardson, S. E., Poutanen, S. M., et al. (2007) · Journal of Virology · doi:10.1128/jvi.00527-07 · Cited by 386 · see citing works
Immunopathological characteristics of coronavirus disease 2019 cases in Guangzhou, China
Shi, Y., Tan, M., Chen, X., Liu, Y., Huang, J., Ou, J., & 邓西龙 (2020) · Immunology · doi:10.1111/imm.13223 · Cited by 376 · see citing works
The Diverse Function of PD-1/PD-L Pathway Beyond Cancer
Qin, W., Hu, L.-P., Zhang, X., Jiang, S., Li, J., Zhang, Z., & Wang, X. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02298 · Cited by 371 · see citing works
Feng, Z., Diao, B., Wang, R., Wang, G., Wang, C., Tan, Y., Liu, L., Wang, C., Liu, Y., Liu, Y., et al. (2020) · medRxiv · doi:10.1101/2020.03.27.20045427 · Cited by 369 · see citing works
Yang, Z., Liu, J., Zhou, Y., Zhao, Q., Zhao, Q., & Liu, J. (2020) · Journal of Infection · doi:10.1016/j.jinf.2020.03.062 · Cited by 361 · see citing works
Self-citationLi, J., Guo, M., Tian, X., Wang, X., Yang, X., Wu, P., Liu, C., Xiao, Z., Qu, Y., Yin, Y., et al. (2020) · Med · doi:10.1016/j.medj.2020.07.002 · Cited by 352 · see citing works
Corticosteroid treatment of patients with coronavirus disease 2019 ( COVID ‐19)
Zha, L., Li, S., Lingling, P., Tefsen, B., Li, Y., French, N., Chen, L., Yang, G., & Villanueva, E. (2020) · The Medical Journal of Australia · doi:10.5694/mja2.50577 · Cited by 345 · see citing works
Michot, J., Albiges, L. K., Chaput, N., Saada, V., Pommeret, F., Griscelli, F., Balleyguier, C., Besse, B., Marabelle, A., Netzer, F., et al. (2020) · Annals of Oncology · doi:10.1016/j.annonc.2020.03.300 · Cited by 336 · see citing works
Emamifar, A., Hess, S., Gerke, O., et al. (2020) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2020-eular.2238 · Cited by 324 · see citing works
Menachery, V. D., Eisfeld, A. J., Schäfer, A., Josset, L., Sims, A. M., Proll, S. C., Fan, S., Li, C., Neumann, G., Tilton, S. C., et al. (2014) · mBio · doi:10.1128/mbio.01174-14 · Cited by 307 · see citing works
Sciascia, S., Aprà, F., Baffa, A., Baldovino, S., Boaro, D., Boero, R., Bonora, S., Calcagno, A., Cecchi, I., Cinnirella, G., et al. (2020) · PubMed · Cited by 303 · see citing works
Xu, B., Fan, C.-Y., Wang, A., Yi-long, Z. O. U., Yu, Y., He, C., Xia, W., Zhang, J., & Miao, Q. (2020) · Journal of Infection · doi:10.1016/j.jinf.2020.04.012 · Cited by 302 · see citing works
Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock
Alejandria, M. M., Lansang, M. A., Dans, L. F., & Mantaring, J. B. (2013) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd001090.pub2 · Cited by 301 · see citing works
Wan, S.-X., Yi, Q., Fan, S., Lv, J.-L., Zhang, X.-X., Guo, L., Lang, C.-H., Xiao, Q., Xiao, K., Yi, Z.-J., et al. (2020) · British Journal of Haematology · doi:10.1111/bjh.16659 · Cited by 299 · see citing works
Hyperimmune IV Immunoglobulin Treatment
Hung, I. F., To, K. K., Lee, C. K., Lee, K., Yan, W., Chan, K., Chan, W.-M., Ngai, C.-W., Law, K. I., Chow, F., et al. (2013) · CHEST Journal · doi:10.1378/chest.12-2907 · Cited by 287 · see citing works
Clinical review: Blood purification for sepsis
Rimmel�, T., & Kellum, J. A. (2011) · Critical Care · doi:10.1186/cc9411 · Cited by 279 · see citing works
Li, T., Qiu, Z., Zhang, L., Han, Y., He, W., Liu, Z., Ma, X., Fan, H., Lu, W., Xie, J., et al. (2004) · The Journal of Infectious Diseases · doi:10.1086/381535 · Cited by 279 · see citing works
Sepriano, A. R., Kerschbaumer, A., Smolen, J. S., van der Heijde, D. M. F. M., Dougados, M., van Vollenhoven, R., McInnes, I. B., Bijlsma, J. W. J., Burmester, G. R., de Wit, M. P. T., et al. (2020) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2019-216653 · Cited by 277 · see citing works
Dienz, O., Rud, J., Eaton, S. M., Lanthier, P. A., Burg, E., Drew, A., Bunn, J., Suratt, B. T., Haynes, L., & Rincón, M. (2012) · Mucosal Immunology · doi:10.1038/mi.2012.2 · Cited by 276 · see citing works
Treatment of Severe Acute Respiratory Syndrome With Glucosteroids
Chen, R.-C., Tang, X.-P., Tan, S.-Y., Bi-ling, L., Wan, Z. Y., Fang, J.-Q., & Zhong, N. (2006) · CHEST Journal · doi:10.1378/chest.129.6.1441 · Cited by 275 · see citing works
Hotchkiss, R. S., Colston, E., Yende, S. P., Angus, D. C., Moldawer, L. L., Crouser, E. D., Martin, G. S., Coopersmith, C. M., Brakenridge, S. C., Mayr, F., et al. (2019) · Critical Care Medicine · doi:10.1097/ccm.0000000000003685 · Cited by 253 · see citing works
Chen, J., & Subbarao, K. (2007) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141706 · Cited by 252 · see citing works
First case of COVID-19 in a patient with multiple myeloma successfully treated with tocilizumab
Zhang, X., Song, K., Tong, F., Fei, M., Guo, H., Lu, Z., Wang, J., & Zheng, C. (2020) · Blood Advances · doi:10.1182/bloodadvances.2020001907 · Cited by 250 · see citing works
Negative regulation of nuclear factor-kappaB activation and function by glucocorticoids
Almawi, W., & Melemedjian, O. (2002) · Journal of Molecular Endocrinology · doi:10.1677/jme.0.0280069 · Cited by 242 · see citing works
Middle East Respiratory Syndrome Coronavirus: A Case-Control Study of Hospitalized Patients
Al‐Tawfiq, J. A., Hinedi, K., Ghandour, J., et al. (2014) · Clinical Infectious Diseases · doi:10.1093/cid/ciu226 · Cited by 235 · see citing works
Potential benefits of precise corticosteroids therapy for severe 2019-nCoV pneumonia
Zhou, W., Liu, Y., Tian, D., Wang, C., Wang, S., Cheng, J., Hu, M., Fang, M., & Gao, Y. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0127-9 · Cited by 234 · see citing works
Ristimaki, A. P., Narko, K., & Hla, T. (1996) · Biochemical Journal · doi:10.1042/bj3180325 · Cited by 232 · see citing works
Xu, H., He, Y., Yang, X., Liang, L., Zhan, Z., Ye, Y., Yang, X., Lian, F., & Sun, L. (2007) · Lara D. Veeken · doi:10.1093/rheumatology/kem014 · Cited by 222 · see citing works
Hotchkiss, R. S., Colston, E., Yende, S. P., Crouser, E. D., Martin, G. S., Albertson, T. E., Bartz, R. R., Brakenridge, S. C., Delano, M. J., Park, P. K., et al. (2019) · Intensive Care Medicine · doi:10.1007/s00134-019-05704-z · Cited by 212 · see citing works
Clinical and immunologic features in severe and moderate forms of Coronavirus Disease 2019Preprint
Chen, G., Wu, D., Guo, W., et al. (2020) · medRxiv · doi:10.1101/2020.02.16.20023903 · Cited by 209 · see citing works
The Use of Antimalarial Drugs against Viral Infection
D’Alessandro, S., Scaccabarozzi, D., Signorini, L., Perego, F., Ilboudo, D. P., Ferrante, P., & Delbue, S. (2020) · Microorganisms · doi:10.3390/microorganisms8010085 · Cited by 174 · see citing works
Use of Tocilizumab for COVID-19-Induced Cytokine Release Syndrome
Radbel, J. M., Narayanan, N., & Bhatt, P. J. (2020) · CHEST Journal · doi:10.1016/j.chest.2020.04.024 · Cited by 172 · see citing works
Shapira, M. Y., Resnick, I. B., Chou, S., Neumann, A. U., Lurain, N. S., Stamminger, T., Caplan, O., Saleh, N., Efferth, T., Marschall, M., et al. (2008) · Clinical Infectious Diseases · doi:10.1086/587106 · Cited by 157 · see citing works
Nakanishi, H., Kawashima, Y., Kurima, K., Chae, J. J., Ross, A. M., Pinto-Patarroyo, G. P., Patel, S. K., Muskett, J. A., Ratay, J. S., Chattaraj, P., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1702946114 · Cited by 154 · see citing works
Tseng, C.-T. K., Perrone, L. A., Zhu, H., Makino, S., & Peters, C. J. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.12.7977 · Cited by 152 · see citing works
Anti‐Inflammatory and Immunoregulatory Functions of Artemisinin and Its Derivatives
Shi, C., Li, H., Yang, Y., & Hou, L. (2015) · Mediators of Inflammation · doi:10.1155/2015/435713 · Cited by 151 · see citing works
Shao, R., Fang, Y., Han, Y., Zhao, L., Jiang, Z., & Li, C. (2016) · Critical Care · doi:10.1186/s13054-016-1301-x · Cited by 148 · see citing works
Modeling the Early Events of Severe Acute Respiratory Syndrome Coronavirus Infection In Vitro
Yen, Y., Liao, F., Hsiao, C.-H., Kao, C., Chen, Y., & Wu‐Hsieh, B. A. (2006) · Journal of Virology · doi:10.1128/jvi.80.6.2684-2693.2006 · Cited by 140 · see citing works
Antimalarial Drugs as Immune Modulators: New Mechanisms for Old Drugs
An, J., Minie, M., Sasaki, T., Woodward, J. J., & Elkon, K. B. (2016) · Annual Review of Medicine · doi:10.1146/annurev-med-043015-123453 · Cited by 140 · see citing works
“Hydroxychloroquine in patients with COVID-19: A Systematic Review and meta-analysis.”
Singh, A. K., Singh, R., Singh, R., & Misra, A. (2020) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2020.05.017 · Cited by 130 · see citing works
Ferrey, A., Choi, G., Hanna, R. M., Chang, Y., Tantisattamo, E., Ivaturi, K., Park, E., Nguyen, L., Wang, B., Tonthat, S., et al. (2020) · American Journal of Nephrology · doi:10.1159/000507417 · Cited by 127 · see citing works
Ouyang, Y., Yin, J., Wang, W., et al. (2020) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa462 · Cited by 127 · see citing works
Hou, L., He, S., Li, X., Yang, Y., He, P., Zhou, Y., Zhu, F., Yang, Y., Li, Y., Tang, W., et al. (2011) · Arthritis & Rheumatism · doi:10.1002/art.30392 · Cited by 121 · see citing works
Clonally diverse CD38+HLA-DR+CD8+ T cells persist during fatal H7N9 disease
Wang, Z., Zhu, L., Nguyen, T. H. O., Wan, Y., Sant, S. A., Quiñones‐Parra, S. M., Crawford, J. C., Eltahla, A. A., Rizzetto, S., Bull, R. A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03243-7 · Cited by 121 · see citing works
Covid-19: US gives emergency approval to hydroxychloroquine despite lack of evidence
Lenzer, J. (2020) · BMJ · doi:10.1136/bmj.m1335 · Cited by 115 · see citing works
Immune suppressive properties of artemisinin family drugs
Hou, L., & Huang, H. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.07.002 · Cited by 97 · see citing works
Investigation of the immunosuppressive activity of artemether on T‐cell activation and proliferation
Wang, J., Tang, W., Shi, L., Wan, J., Zhou, R., Ni, J., Fu, Y., Yang, Y., Li, Y., & Zuo, J. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707137 · Cited by 94 · see citing works
Tynell, J., Westenius, V., Rönkkö, E., Munster, V. J., Melén, K., Österlund, P., & Julkunen, I. (2015) · Journal of General Virology · doi:10.1099/jgv.0.000351 · Cited by 90 · see citing works
Lau, J. T. F., Leung, P., Wong, E. L., Fong, C., Cheng, K.-F., Zhang, S. C., Lam, C. W. K., Wong, V. C. W., Choy, K. M., & Ko, W. M. (2005) · The Journal of Alternative and Complementary Medicine · doi:10.1089/acm.2005.11.49 · Cited by 85 · see citing works
Li, J., Guo, M., Tian, X., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.03.31.019216 · Cited by 83 · see citing works
Using Herbal Medicine as a Means of Prevention Experience During the SARS Crisis
Lau, T. F., Leung, P. C. K., Wong, E. L., et al. (2005) · The American Journal of Chinese Medicine · doi:10.1142/s0192415x05002965 · Cited by 79 · see citing works
Bruenger, F., Kizner, L., Weile, J., et al. (2015) · The International Journal of Artificial Organs · doi:10.5301/ijao.5000382 · Cited by 77 · see citing works
Wang, J., Hou, L., Yang, Y., et al. (2009) · Acta Pharmacologica Sinica · doi:10.1038/aps.2009.138 · Cited by 76 · see citing works
Chen, X., Ling, J., Mo, P., Zhang, Y., Jiang, Q., Ma, Z., Cao, Q., Hu, W., Zou, S., Chen, L., et al. (2020) · medRxiv · doi:10.1101/2020.03.03.20030437 · Cited by 75 · see citing works
Germi, R., Mariette, C., Alain, S., et al. (2013) · Antiviral Research · doi:10.1016/j.antiviral.2013.10.014 · Cited by 72 · see citing works
Wang, J., Tang, W., Zhou, R., et al. (2008) · British Journal of Pharmacology · doi:10.1038/bjp.2008.11 · Cited by 72 · see citing works
Li, B., Li, J., Pan, X., Ding, G., Cao, H., Jiang, W., Zheng, J., & Zhou, H. (2009) · International Immunopharmacology · doi:10.1016/j.intimp.2009.12.006 · Cited by 70 · see citing works
(2019) · Springer eBooks · doi:10.1007/978-3-030-22094-5 · Cited by 70 · see citing works
Artesunate Protects Against Sepsis-Induced Lung Injury Via Heme Oxygenase-1 Modulation
Cao, T., Jin, S., Fei, D., Kang, K., Jiang, L., Lian, Z.-Y., Pan, S., Zhao, M., & Zhao, M. (2015) · Inflammation · doi:10.1007/s10753-015-0290-2 · Cited by 66 · see citing works
Odièvre, M., de Marcellus, C., Pointe, H. D. L., et al. (2020) · American Journal of Hematology · doi:10.1002/ajh.25855 · Cited by 61 · see citing works
Huang, X., Xie, Z., Liu, F., et al. (2014) · International Immunopharmacology · doi:10.1016/j.intimp.2014.07.001 · Cited by 60 · see citing works
P2X7R: A potential key regulator of acute gouty arthritis
Tao, J., Zhang, Y., & Li, X.-P. (2013) · Seminars in Arthritis and Rheumatism · doi:10.1016/j.semarthrit.2013.04.007 · Cited by 55 · see citing works
FRI0335 THE EFFECT OF TOFACITINIB ON RESIDUAL PAIN IN PATIENTS WITH PSORIATIC ARTHRITIS
Dougados, M., van der Heijde, D. M. F. M., Bingham, C. O., Taylor, P. C., Fallon, L., Woolcott, J. C., Brault, Y., Wang, L., & Kessouri, M. (2020) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2020-eular.949 · Cited by 52 · see citing works
Wenisch, C., Linnau, K. F., Looaresuwan, S., et al. (1999) · The Journal of Infectious Diseases · doi:10.1086/314630 · Cited by 51 · see citing works
Fan, M., Li, Y., Yao, C.-H., et al. (2018) · International Immunopharmacology · doi:10.1016/j.intimp.2018.10.015 · Cited by 48 · see citing works
Träger, K., Schütz, C., Fischer, G., et al. (2016) · Case Reports in Critical Care · doi:10.1155/2016/9852073 · Cited by 47 · see citing works
Huang, X., Liu, W. Q., Zhou, Y., Hao, C., Zhou, Y., Zhang, C., Sun, C., Luo, Z., & Tang, S. (2019) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2019.4387 · Cited by 44 · see citing works
Cen, Y., Liu, C., Li, X., Yan, Z., Kuang, M., Su, Y., Pan, X., Qin, R., Liu, X., Zheng, J., et al. (2016) · International Immunopharmacology · doi:10.1016/j.intimp.2016.06.007 · Cited by 41 · see citing works
Junxia, Wang, Li-Fei, et al. (2009) · 中国药理学报:英文版 · Cited by 41 · see citing works
Kuang, M., Cen, Y., Qin, R., Shang, S., Zhai, Z., Liu, C., Pan, X., & Zhou, H. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000489982 · Cited by 40 · see citing works
Checkpoint inhibitor therapy in preclinical sepsis models: a systematic review and meta-analysis
Busch, L. M., Sun, J., Cui, X., Eichacker, P. Q., & Torabi‐Parizi, P. (2020) · Intensive Care Medicine Experimental · doi:10.1186/s40635-019-0290-x · Cited by 39 · see citing works
Artemisinin protects mice against burn sepsis through inhibiting NLRP3 inflammasome activation
Long, H., Xu, B., Luo, Y., & Luo, K. (2015) · The American Journal of Emergency Medicine · doi:10.1016/j.ajem.2015.12.075 · Cited by 38 · see citing works
Case Report of a SARS-CoV-2 Infection in a Patient With Ulcerative Colitis on Tofacitinib
Jacobs, J. D., Clark‐Snustad, K., & Lee, S. (2020) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izaa093 · Cited by 36 · see citing works
Decoding the enigma of antiviral crisis: Does one target molecule regulate all?
Mahmud-Al-Rafat, A., Majumder, A., Rahman, K. M. T., Hasan, A. M. M., Islam, K. M. D., Taylor-Robinson, A. W., & Billah, M. M. (2019) · Cytokine · doi:10.1016/j.cyto.2018.12.008 · Cited by 34 · see citing works
Cheng, Z., Qi, R., Li, L., Liu, Q., Zhang, W., Zhou, X., Xu, D., Allen, T. D., Pan, S., & Liu, J. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.01.078 · Cited by 28 · see citing works
Self-citationHsu, C.-H., Hwang, K., Chao, C.-L., et al. (2006) · The American Journal of Chinese Medicine · doi:10.1142/s0192415x06004405 · Cited by 25 · see citing works
Bobade, D., Khandare, A. V., Deval, M., et al. (2018) · MicrobiologyOpen · doi:10.1002/mbo3.651 · Cited by 23 · see citing works
Artesunate and erythropoietin synergistically improve the outcome of experimental cerebral malaria
Du, Y., Chen, G., Zhang, X., Yu, C., Cao, Y., & Cui, L. (2017) · International Immunopharmacology · doi:10.1016/j.intimp.2017.05.008 · Cited by 22 · see citing works
Park, K. H., Yoon, Y. D., Han, S., et al. (2012) · International Immunopharmacology · doi:10.1016/j.intimp.2012.09.012 · Cited by 21 · see citing works
Ma, C., Wong, C. K., Wong, B. C. K., et al. (2008) · Journal of Medical Virology · doi:10.1002/jmv.21383 · Cited by 14 · see citing works
Hyperimmune IV Immunoglobulin Treatment of 2009 Influenza A(H1N1): Response
Hung, I. F., & Yuen, K. (2013) · CHEST Journal · doi:10.1378/chest.13-0571 · Cited by 9 · see citing works
Hu, Y., Li, M., Zhang, T., et al. (2016) · PubMed · Cited by 8 · see citing works
Idowu, A. O., Bhattacharyya, S., Gradus, S. M., Oyibo, W. A., George, Z., Black, C. M., Igietseme, J. U., & Azenabor, A. A. (2018) · International Journal of Medical Sciences · doi:10.7150/ijms.27350 · Cited by 5 · see citing works
Flagged first, then by citations
Research works printed but not linked: 9
- [11]Zhong-yong C Wei-bin Y Qiang W Guo-lin L Clinical significance of serum hs-CRP, IL-6, and PCT in diagnosis and prognosis of patients with COVID-19. Drugs Clin. (2020) 35: 417– 20. 10.7501/j.issn.1674-5515.2020.03.005 · DOI
- [12]Guohua L Ling L Min H Haibiao L Peifeng K Zishao Z Value of various inflammatory markers combined with lymphocyte subsets on clinical diagnosis of different clinical types of COVID-19. J Chong Med Univ. (2020). 10.13406/j.cnki.cyxb.002465. [Epub ahead of print]. · DOI
- [42]Zilong L Ruyuan H Wenyang J Tao F Qing G Clinical characteristics and immune function analysis of COVID-19. Med J Wuhan Univ. (2020) 41: 529– 32. 10.14188/j.1671-8852.2020.0126 · DOI
- [43]Jing X Ming-feng H Feng-de Z Ting Z Lei M Clinical manifestations and sero-immunological characteristics of 155 patients with COVID-19. Chin J Nosocomiol. (2020) 30: 2261– 5. 10.11816/cn.ni.2020-200577 · DOI
- [63]Firestein GS Budd R Gabriel SE McInnes IB O'Dell JR Kelley's Textbook of Rheumatology E-Book. Amsterdam: Elsevier Health Sciences (2012).
- [93]Xiaolin T Aiguo L Zhiyuan Z Jun D Xiaoguang C Chuanjin H Clinical observation on 16 cases of infectious atypical pneumonia treated by traditional Chinese Medicine. J Tradition Chin Med. (2003) 44: 506– 7. 10.13288/j.11-2166/r.2003.07.020 · DOI
- [94]Tan W Li S Yiyang C Yakun F Wei Y Xiaozheng D Clinical efficacy analysis of 50 cases of corona virus disease 2019 in traditional Chinese medicine. Jilin J Chin Med. (2020) 40: 281– 5. 10.13463/j.cnki.jlzyy.2020.03.001 · DOI
- [95]Kai-tao Y Ming-yu L Xin L Ji-han H Hong-bin C Retrospective clinical analysis on treatment of novel coronavirus-infected pneumonia with traditional chinese medicine Lianhua Qingwen. Chin J Exp Tradition Med Formul. (2020) 26: 8– 12. 10.13422/j.cnki.syfjx.20201099 · DOI
- [96]Wen-guang X Chang-qing A Chan-juan Z Ji-xian Z Min H Yu W Clinical study on 34 novel coronavirus pneumoniae treated with integrated traditional Chinese and Western Medicine. J Tradition Chin Med. (2020) 61: 375– 82. 10.13288/j.11-2166/r.2020.05.002 · DOI
Cited by
Sorted by citations
Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19
Woodruff, M. C., Ramonell, R. P., Nguyen, D. C., Cashman, K. S., Saini, A. S., Haddad, N. S., Ley, A. M., Kyu, S., Howell, J. C., Ozturk, T., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-00814-z · Cited by 791 · see citing works
COVID-19 and the human innate immune system
Schultze, J. L., & Aschenbrenner, A. C. (2021) · Cell · doi:10.1016/j.cell.2021.02.029 · Cited by 714 · see citing works
Evangelou, K., Veroutis, D., Paschalaki, K., Foukas, P. G., Lagopati, N., Dimitriou, M., Papaspyropoulos, A., Konda, B., Hazapis, O., Polyzou, A., et al. (2022) · European Respiratory Journal · doi:10.1183/13993003.02951-2021 · Cited by 98 · see citing works
Biomarkers of post-covid depression
Lorkiewicz, P., & Waszkiewicz, N. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10184142 · Cited by 102 · see citing works
Biologically informed deep learning to query gene programs in single-cell atlases
Lotfollahi, M., Rybakov, S., Hrovatin, K., Hediyeh-zadeh, S., Talavera-López, C., Misharin, A. V., & Theis, F. J. (2023) · Nature Cell Biology · doi:10.1038/s41556-022-01072-x · Cited by 100 · see citing works
Lu, R. X. Z., Lai, B. F. L., Rafatian, N., Gustafson, D., Campbell, S. B., Banerjee, A., Kozak, R., Mossman, K., Mubareka, S., Howe, K. L., et al. (2022) · Lab on a Chip · doi:10.1039/d1lc00817j · Cited by 58 · see citing works
- Authors
- Tang, Y., Liu, J., Zhang, D., Xu, Z., Ji, J., & Wen, C.
- Affiliations
- Zhejiang Chinese Medical University (CN)
- Corresponding author
- Ji, Jinjun
- Wen, Chengping
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2020-07-10
- Volume
- 11
- Pages
- 1708-1708
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC7365923
- OpenAlex
- W3041667892
- Cited by
- 1,094
- References
- 133
- Citations by year
- 2026: 28 · 2025: 52 · 2024: 96 · 2023: 166 · 2022: 334 · 2021: 353 · 2020: 65
- FWCI
- 10.84
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Natural Science Foundation of Zhejiang Province
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
- Keywords
- cytokine storm, COVID-19 pandemic, SARS-CoV-2, interleukin-6, inflammatory cytokines, lymphocyte exhaustion, tocilizumab, IL-6 inhibitors, corticosteroids, PD-1/PD-L1 inhibitors, intravenous immunoglobulin, antimalarial drugs, macrophages, Th17 cells, lung pathology, mortality
- MeSH terms
- Betacoronavirus, Artesunate, COVID-19, SARS-CoV-2, Interleukin-6 Inhibitors, Adrenal Cortex Hormones, Animals, Antimalarials, Hemoperfusion, Humans, Hydroxychloroquine, Pneumonia, Viral, Interleukin-6, Immunoglobulins, Intravenous, Coronavirus Infections, Mice, Pandemics, Programmed Cell Death 1 Receptor, Antibodies, Monoclonal, Humanized
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