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Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure
Open accessAbstract
Proper management of COVID-19 mandates better understanding of disease pathogenesis. The sudden clinical deterioration 7-8 days after initial symptom onset suggests that severe respiratory failure (SRF) in COVID-19 is driven by a unique pattern of immune dysfunction. We studied immune responses of 54 COVID-19 patients, 28 of whom had SRF. All patients with SRF displayed either macrophage activation syndrome (MAS) or very low human leukocyte antigen D related (HLA-DR) expression accompanied by profound depletion of CD4 lymphocytes, CD19 lymphocytes, and natural killer (NK) cells. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production by circulating monocytes was sustained, a pattern distinct from bacterial sepsis or influenza. SARS-CoV-2 patient plasma inhibited HLA-DR expression, and this was partially restored by the IL-6 blocker Tocilizumab; off-label Tocilizumab treatment of patients was accompanied by increase in circulating lymphocytes. Thus, the unique pattern of immune dysregulation in severe COVID-19 is characterized by IL-6-mediated low HLA-DR expression and lymphopenia, associated with sustained cytokine production and hyper-inflammation.
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“the IL-6 receptor antagonist, tocilizumab, increased the number of circulating lymphocytes in COVID-19 patients122.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [122]
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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 · cited 1×
“This is mostly because severe COVID-19 is associated with hyper-cytokinemia (Guan et al., 2020; Huang et al., 2020).”
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 · cited 1×
“This is mostly because severe COVID-19 is associated with hyper-cytokinemia (Guan et al., 2020; Huang et al., 2020) .”
The third international consensus definitions for sepsis and septic shock (Sepsis-3).
Singer, M., Deutschman, C. S., Seymour, C. W., Shankar-Hari, M., Annane, D., Bauer, M., Bellomo, R., Bernard, G. R., Chiche, J.-D., Coopersmith, C. M., et al. (2016) · JAMA · doi:10.1001/jama.2016.0287 · Cited by 28,250
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
Fardet, L., Galicier, L., Lambotte, O., Marzac, C., Aumont, C., Chahwan, D., Coppo, P., & Hejblum, G. (2014) · Arthritis & Rheumatology · doi:10.1002/art.38690 · Cited by 1,508 · cited 1×
“HScore is proposed as a classification tool for secondary MAS, and values more than 169 are highly diagnostic (Fardet et al., 2014).”
Thevarajan, I., Nguyen, T. H. O., Koutsakos, M., Druce, J. D., Caly, L., van de Sandt, C. E., Jia, X., Nicholson, S. R., Catton, M. C., Cowie, B., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0819-2 · Cited by 993 · cited 1×
“Statistical comparisons are indicated by the arrows; ns: non-significant; *p < 0.05; **p < 0.01. of one case of COVID-19 of moderate severity (Thevarajan et al., 2020).”
BackgroundInfluentialDysregulation 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
COVID-19: a novel coronavirus and a novel challenge for critical care
Arabi, Y. M., Murthy, S., & Webb, S. A. R. (2020) · Intensive Care Medicine · doi:10.1007/s00134-020-05955-1 · Cited by 313 · cited 1×
“The risk of death of these patients is high, reaching even 60% (Arabi et al., 2020).”
Lukaszewicz, A., Grienay, M., Resche‐Rigon, M., Pirracchio, R., Faivre, V., Boval, B., & Payen, D. M. (2009) · Critical Care Medicine · doi:10.1097/ccm.0b013e3181ab858a · Cited by 288
on behalf of the Hellenic Sepsis Study Group, Kyriazopoulou, E., Leventogiannis, K., Norrby‐Teglund, A., Dimopoulos, G., Pantazi, A., Orfanos, S. E., Rovina, N., Tsangaris, I., Gkavogianni, T., et al. (2017) · BMC Medicine · doi:10.1186/s12916-017-0930-5 · Cited by 212 · cited 1×
“Immune responses of critically ill patients with sepsis can be classified into three patterns: macrophage-activation syndrome (MAS) (Kyriazopoulou et al., 2017) , sepsis-induced immunoparalysis characterized by low expression of the human leukocyte antigen D related (HLA-DR) on CD14 monocytes (Lukaszewicz et al., 2009…”
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Cited by
Sorted by citations
Items 301–400 of 1,002
Dalamaga, Μ., Christodoulatos, G. S., Karampela, Ι., Vallianou, N. G., & Apovian, C. M. (2021) · Current Obesity Reports · doi:10.1007/s13679-021-00436-y · Cited by 74
Tan, L., Kang, X., Ji, X., Li, G., Wang, Q. M., Li, Y., Wang, Q., & Miao, H. (2020) · Med · doi:10.1016/j.medj.2020.05.002 · Cited by 73
Ravichandran, S., Lee, Y., Grubbs, G., Coyle, E. M., Klenow, L., Akasaka, O., Koga, M., Adachi, E., Saito, M., Nakachi, I., et al. (2021) · Science Advances · doi:10.1126/sciadv.abf2467 · Cited by 71
Iron metabolism in infections: Focus on COVID-19
Girelli, D., Marchi, G., Busti, F., & Vianello, A. (2021) · Seminars in Hematology · doi:10.1053/j.seminhematol.2021.07.001 · Cited by 75
Hottz, E. D., Martins-Gonçalves, R., Palhinha, L., de Azevedo-Quintanilha, I. G., Campos, M. M., Sacramento, C. Q., Temerozo, J. R., Soares, V. C., Dias, S. D. S. G., Teixeira, L., et al. (2022) · Blood Advances · doi:10.1182/bloodadvances.2021006680 · Cited by 74
“12,48,49 This monocyte in fl ammatory program was also associated with poor outcomes in the patients with COVID-19 in our cohort (data not shown).”
Theoharides, T. C., & Kempuraj, D. (2023) · Cells · doi:10.3390/cells12050688 · Cited by 82
Peruzzi, B., Bencini, S., Capone, M., Mazzoni, A., Maggi, L., Salvati, L., Vanni, A., Orazzini, C., Nozzoli, C., Morettini, A., et al. (2020) · Immunology · doi:10.1111/imm.13254 · Cited by 72
Wang, Y., Zheng, J., Islam, M. S., Yang, Y., Hu, Y., & Chen, X. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.59534 · Cited by 71
Innate lymphoid cells and COVID-19 severity in SARS-CoV-2 infection
Silverstein, N. J., Wang, Y., Manickas-Hill, Z., Carbone, C., Dauphin, A., Boribong, B. P., Loiselle, M., Davis, J., Leonard, M. M., Kuri-Cervantes, L., et al. (2022) · eLife · doi:10.7554/elife.74681 · Cited by 73
Monocyte HLA‐DR Measurement by Flow Cytometry in COVID ‐19 Patients: An Interim Review
Benlyamani, I., Venet, F., Coudereau, R., Gossez, M., & Monneret, G. (2020) · Cytometry Part A · doi:10.1002/cyto.a.24249 · Cited by 75
Complement cascade in severe forms of COVID‐19: Recent advances in therapy
Benmansour, N. C., Carvelli, J., & Vivier, É. (2021) · European Journal of Immunology · doi:10.1002/eji.202048959 · Cited by 69
“Once the PRRs have been activated by the virus, an intracellular cascade is triggered, leading to the expression of proinflammatory cytokines, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) [7] and IL-1 .”
BackgroundInfluentialZheng, H., Rao, A., Đermadi, D., Toh, J., Jones, L. M., Donato, M., Liu, Y. E., Su, Y., Dai, C. L., Kornilov, S. A., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.03.002 · Cited by 69
“The modulation of monocyte responses, as reflected by gene expression, is compatible with the detrimental role of monocytes/macrophages in severe SARSCoV-2 infection associated with respiratory dysfunction (Giamarellos-Bourboulis et al., 2020).”
Self-citationA scoping review of the pathophysiology of COVID-19
Marik, P. E., Iglesias, J. I., Varón, J., & Kory, P. D. (2021) · International Journal of Immunopathology and Pharmacology · doi:10.1177/20587384211048026 · Cited by 74
“Transcriptional activation of macrophages with the robust production of cytokines continues beyond clearance of the virus.(23,43) This may be related to the failure of natural killer (NK) and cytotoxic T cell to remove activated macrophage, as a consequence of the development of an exhausted cell phenotype.”
BackgroundRole of Senescence and Aging in SARS-CoV-2 Infection and COVID-19 Disease
Lynch, S. M., Guo, G., Gibson, D. S., Bjourson, A. J., & Singh, T. (2021) · Cells · doi:10.3390/cells10123367 · Cited by 70
Rahman, M. A., Shanjana, Y., Tushar, M. I., Mahmud, T., Rahman, G. M. S., Milan, Z. H., Sultana, T., Chowdhury, A. M. L. H., Bhuiyan, M. A., Islam, M. R., et al. (2021) · PLoS ONE · doi:10.1371/journal.pone.0255379 · Cited by 71
“Therefore, elevated serum ferritin induces cytokine storms and severity of COVID-19 patients [56, 57].”
BackgroundAl‐Nesf, M. A., Abdesselem, H., Bensmail, I., Ibrahim, S. I., Saeed, W., Mohammed, S., Razok, A., Alhussain, H., Aly, R. M. A., Maslamani, M. A. R. S. A., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28639-4 · Cited by 69
SARS-CoV-2: A Master of Immune Evasion
Rubio‐Casillas, A., Redwan, E. M. M. M., & Uversky, V. N. (2022) · Biomedicines · doi:10.3390/biomedicines10061339 · Cited by 72
Natural Killer Cells in SARS-CoV-2 Infection: Pathophysiology and Therapeutic Implications
Vito, C. D., Calcaterra, F., Coianiz, N., Terzoli, S., Voza, A., Mikulak, J., Bella, S. D., & Mavilio, D. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.888248 · Cited by 69
The intersection of COVID-19 and cancer: signaling pathways and treatment implications
Zong, Z., Wei, Y., Ren, J., Zhang, L., & Zhou, F. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01363-1 · Cited by 74
Hasan, M. Z., Islam, S., Matsumoto, K., & Kawai, T. (2021) · Scientific Reports · doi:10.1038/s41598-021-96110-3 · Cited by 69
Mahmoudi, S., Rezaei, M. S., Mansouri, N., Marjani, M., & Mansouri, D. (2020) · Journal of Clinical Immunology · doi:10.1007/s10875-020-00824-4 · Cited by 66
“Two main aspects of this immune dysregulation are the overproduction of pro-inflammatory cytokines by monocytes and the dysregulation of lymphocytes characterized by CD4+ T cell and consequently B cell lymphopenia [10].”
BackgroundSchön, M. P., Berking, C., Biedermann, T., Buhl, T., Erpenbeck, L., Eyerich, K., Eyerich, S., Ghoreschi, K., Goebeler, M., Ludwig, R. J., et al. (2020) · JDDG Journal der Deutschen Dermatologischen Gesellschaft · doi:10.1111/ddg.14169 · Cited by 67
Autoimmunity as the comet tail of COVID-19 pandemic
Talotta, R., & Robertson, E. S. (2020) · World Journal of Clinical Cases · doi:10.12998/wjcc.v8.i17.3621 · Cited by 69
Franzetti, M., Molinari, A. F., Borsa, N., Pandolfo, A., Molteni, C., Borghesi, L., Pontiggia, S., Evasi, G., Guiotto, L., Erba, M., et al. (2021) · The Journal of Immunology · doi:10.4049/jimmunol.2001126 · Cited by 67
“Because of their potent anti-inflammatory effects, agents that block IL-1 and IL-6 have been the focus of attention in this regard.”
BackgroundInfluentialPASCALE, G. D., Maio, F. D., Carelli, S., Angelis, G. D., Cacaci, M., Montini, L. M., Bello, G., Cutuli, S. L., Pintaudi, G., Tanzarella, E. S., et al. (2021) · Critical Care · doi:10.1186/s13054-021-03623-4 · Cited by 70
“Several factors in COVID-19 patients may account for this finding, such as complex immune dysregulation [38], administration of immunomodulatory drugs (e.”
BackgroundElgueta, D., Murgas, P., Riquelme, E. M., Yang, G., & Cancino, G. I. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.816619 · Cited by 70
“In particular, COVID-19 patients show elevated IL-6 in their serum (120), even prompting the consideration of anti-IL-6 antibodies as a treatment (121, 122).”
BackgroundCytokine Storm Signature in Patients with Moderate and Severe COVID-19
Kalinina, O., Головкин, А. С., Zaikova, E. K., Aquino, A. D., Bezrukikh, V. A., Melnik, O., Vasilieva, E. Y., Каронова, Т. Л., Kudryavtsev, I. V., & Shlyakhto, E. V. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23168879 · Cited by 69
“Meanwhile, reduced expression of HLA-DR on classical monocytes has characterized severe cases of SARS-CoV-2 infection and could correlate with inflammation response, including IL-6 overproduction [40,41].”
BackgroundEndothelial Dysfunction in COVID-19: Potential Mechanisms and Possible Therapeutic Options
Pelle, M. C., Zaffina, I., Lucà, S., Forte, V., Trapanese, V., Melina, M., Giofrè, F., & Arturi, F. (2022) · Life · doi:10.3390/life12101605 · Cited by 72
“Moreover, the inactivation of ADAMTS-13during sepsis may contribute to the prothrombotic state, due to insufficient cleavage of VWF [60].”
BackgroundInfluentialLiu, X., Cao, W., & Li, T. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01660 · Cited by 68
“Macrophage activation syndrome (MAS) was reported in several COVID-19 patients with severe respiratory failure, and the production of associated pro-inflammatory cytokines (IL-6 and TNFα) might contribute to hyper-inflammatory conditions (108).”
BackgroundOlajide, O. A., Iwuanyanwu, V. U., Lepiarz‐Raba, I., & Al‐Hindawi, A. A. (2021) · Inflammation · doi:10.1007/s10753-021-01464-5 · Cited by 67
“However, in the pro-inflammatory phase, SARS-CoV-2 activates the host’s immune system to trigger both adaptive and innate immune responses [11-13].”
BackgroundNanocurcumin improves Treg cell responses in patients with mild and severe SARS-CoV2
Tahmasebi, S., Saeed, B. Q., Temirgalieva, E., Yumashev, A. V., El-Esawi, M. A., Navashenaq, J. G., Valizadeh, H., Sadeghi, A., Aslani, S., Yousefi, M., et al. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119437 · Cited by 66
Schoeman, D., & Fielding, B. C. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.02086 · Cited by 66
Dynamic changes in monocytes subsets in COVID-19 patients
Qin, S., Jiang, Y., Wei, X., Liu, X., Guan, J., Chen, Y., Lu, H., Qian, J., Wang, Z., & Lin, X. (2020) · Human Immunology · doi:10.1016/j.humimm.2020.12.010 · Cited by 65
Buicu, A., Cernea, S., Benedek, I., Buicu, C.-F., & Benedek, T. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10081545 · Cited by 69
“In fact, patients with severe respiratory failure with COVID-19 seem to exhibit a unique pattern of immune dysfunction: macrophage activation syndrome (MAS); interleukin (IL)-6-mediated very low human leukocyte antigen D related (HLA-DR) expression, with severe depletion of CD4+ T cells, CD19+ T cells and NK cells; an…”
BackgroundDefining the role of natural killer cells in COVID-19
Lee, M. J., & Blish, C. A. (2023) · Nature Immunology · doi:10.1038/s41590-023-01560-8 · Cited by 65
Pathogenesis of COVID-19 from the Perspective of the Damage-Response Framework
Pirofski, L., & Casadevall, A. (2020) · mBio · doi:10.1128/mbio.01175-20 · Cited by 63
“inflammation of the airways (9), although neurological mechanisms and thromboem-”
BackgroundKaye, A. G., & Siegel, R. (2020) · PeerJ · doi:10.7717/peerj.10322 · Cited by 62
“Roughly three-quarters of patients in severe condition present with IL-6 mediated respiratory failure while the other quarter occurs predominately through IL-1β macrophage activation (Giamarellos-Bourboulis et al., 2020).”
BackgroundCD169-mediated restrictive SARS-CoV-2 infection of macrophages induces pro-inflammatory responses
Jalloh, S., Olejnik, J., Berrigan, J. L., Nisa, A., Suder, E. L., Akiyama, H., Lei, M., Ramaswamy, S., Tyagi, S., Bushkin, Y., et al. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010479 · Cited by 69
Kotsaki, A., Pickkers, P., Bauer, M. W., Calandra, T., Lupșe, M. S., Wiersinga, W. J., Meylan, S., Bloos, F., van der Poll, T., Slim, M. A., et al. (2022) · BMJ Open · doi:10.1136/bmjopen-2022-067251 · Cited by 63
“11 With the use of these biomarkers, the anticipated screening failure rate based on PROVIDE Study and the initial months of recruitment in ImmunoSep is anticipated to amount between 30% and 60%.”
MethodSelf-citationImmunosenescence and inflamm-ageing in COVID-19
Zinatizadeh, M. R., Zarandi, P. K., Ghiasi, M., Kooshki, H., Mohammadi, M., Amani, J., & Rezaei, N. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101818 · Cited by 69
“In these experiments, dependence on the amount of cytokines IL-6, IL-10, or TNF-α and blood lymphopenia was seen in disease, and IL-6 receptor antagonist tocilizumab raised the issue of lymphocytes in the blood of COVID-19 patients (Diao et al., 2020; Giamarellos-Bourboulis et al., 2020; Wan et al., 2020).”
BackgroundГоловкин, А. С., Kalinina, O., Bezrukikh, V. A., Aquino, A. D., Zaikova, E. K., Karonova, T. L., Melnik, O., Vasilieva, E., & Kudryavtsev, I. V. (2021) · Viruses · doi:10.3390/v13101966 · Cited by 64
Hallmarks of immune response in COVID-19: Exploring dysregulation and exhaustion
Mazzoni, A., Salvati, L., Maggi, L., Annunziato, F., & Cosmi, L. (2021) · Seminars in Immunology · doi:10.1016/j.smim.2021.101508 · Cited by 69
Pulmonary barotrauma in COVID-19: A systematic review and meta-analysis
Shrestha, D. B., Sedhai, Y. R., Budhathoki, P., Adhikari, A., Pokharel, N., Dhakal, R., Kafle, S., Mir, W. A. Y., Acharya, R., Kashiouris, M. G., et al. (2022) · Annals of Medicine and Surgery · doi:10.1016/j.amsu.2021.103221 · Cited by 62
“COVID-19 induces an elevated level of tumor necrosis factor alfa (TNF-alfa) and Interleukin-6 (IL-6) [32].”
Tincati, C., Cannizzo, E. S., Giacomelli, M., Badolato, R., Monforte, A. D., & Marchetti, G. C. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.580987 · Cited by 61
Lombardi, A., Trombetta, E., Cattaneo, A., Castelli, V., Palomba, E., Tirone, M., Mangioni, D., Lamorte, G., Manunta, M., Prati, D., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.560330 · Cited by 62
“The latter also demonstrated an inverse correlation between HLA-DR molecules and serum levels of IL-6 (10).”
BackgroundInfluentialLetafati, A., Ardekani, O. S., Naderisemiromi, M., Norouzi, M., Shafiei, M., Nik, S., & Mozhgani, S. (2024) · Virology Journal · doi:10.1186/s12985-024-02287-0 · Cited by 70
“Furthermore, numerous reports have suggested that the quantity of NK cells in the bloodstream is impacted by SARS-CoV-2 infection, with no variations in the distribution of NK cell subsets [103, 104].”
BackgroundFluoxetine as an anti-inflammatory therapy in SARS-CoV-2 infection
Creeden, J. F., Imami, A. S., Eby, H. M., Gillman, C., Becker, K. N., Reigle, J., Andari, E., Pan, Z. K., O’Donovan, S. M., McCullumsmith, R. E., et al. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111437 · Cited by 61
Bahrami, A., Vafapour, M., Moazzami, B., & Rezaei, N. (2020) · Journal of Paediatrics and Child Health · doi:10.1111/jpc.15048 · Cited by 61
Best-practice IgM- and IgA-enriched immunoglobulin use in patients with sepsis
Nierhaus, A., Berlot, G., Kindgen‐Milles, D., Müller, E. E., & Girardis, M. (2020) · Annals of Intensive Care · doi:10.1186/s13613-020-00740-1 · Cited by 62
Mazzoni, A., Maggi, L., Capone, M., Spinicci, M., Salvati, L., Colao, M. G., Vanni, A., Kiros, S. T., Mencarini, J., Zammarchi, L., et al. (2020) · European Journal of Immunology · doi:10.1002/eji.202048915 · Cited by 61
Chen, P., Lee, N., Cia, C.-T., Ko, W., & Hsueh, P. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.584956 · Cited by 62
“Of note, high levels of pro-inflammatory cytokine and IL-6 were noted in severe COVID-19 patients (Giamarellos-Bourboulis et al., 2020; Qin et al., 2020; Wang C. et al., 2020).”
BackgroundJohansen, M. D., Mahbub, R. M., Idrees, S., Nguyen, D. H., Miemczyk, S., Pathinayake, P. S., Nichol, K., Hansbro, N. G., Gearing, L. J., Hertzog, P. J., et al. (2022) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202108-1901oc · Cited by 61
Single-cell immune profiling reveals distinct immune response in asymptomatic COVID-19 patients
Zhao, X.-N., You, Y., Cui, X., Gao, H., Wang, G., Zhang, S., Lin, Y., Duan, L., Zhu, K.-L., Wang, Y., et al. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00753-7 · Cited by 64
GM-CSF: Master regulator of the T cell-phagocyte interface during inflammation
Ingelfinger, F., De Feo, D., & Becher, B. (2021) · Seminars in Immunology · doi:10.1016/j.smim.2021.101518 · Cited by 61
Immune reactivity during COVID-19: Implications for treatment
Claudio Napoli, A., Benincasa, G., Criscuolo, C., Faenza, M., Liberato, C., & Rusciano, M. (2021) · Immunology Letters · doi:10.1016/j.imlet.2021.01.001 · Cited by 60
COVID-19: Immunology, Immunopathogenesis and Potential Therapies
Bhardwaj, A., Sapra, L., Saini, C., Azam, Z., Mishra, P. K., Verma, B., Mishra, G. C., & Srivastava, R. K. (2021) · International Reviews of Immunology · doi:10.1080/08830185.2021.1883600 · Cited by 65
“This shows that IL-6 secreted by macrophages might be responsible for lymphopenia observed in severe COVID-19 patients [83].”
BackgroundJing, Y., Luo, L., Chen, Y., Westerberg, L. S., Zhou, P., Xu, Z. P., Herrada, A. A., Park, C.-S., Kubo, M., Mei, H., et al. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00749-3 · Cited by 61
“Flow cytometry analysis of PBMCs from symptomatic COVID-19 patients has shown a significant influx of granulocytemacrophage colony-stimulating factor (GM-CSF)-producing, activated CD4 T cells and CD14 HLA-DR inflammatory monocytes (IMs).(21,22) Multiple studies have shown reduced numbers of NK cells in the PBMC of COV…”
BackgroundBonnet, B., Cosme, J., Dupuis, C., Coupez, E., Adda, M., Calvet, L., Fabre, L., Saint-Sardos, P., Bereiziat, M., Vidal, M., et al. (2021) · EBioMedicine · doi:10.1016/j.ebiom.2021.103622 · Cited by 65
“In addition, mHLA-DR quantitative expression during hospitalization was also significantly correlated with the PaO2/FiO2 ratio thereby indicating, as previously described, a relation between the degree of monocyte dysregulation and the pulmonary involvement of ARDS [21].”
“Silent” Presentation of Hypoxemia and Cardiorespiratory Compensation in COVID-19
Bickler, P. E., Feiner, J., Lipnick, M. S., & McKleroy, W. (2020) · Anesthesiology · doi:10.1097/aln.0000000000003578 · Cited by 62
Deficiency of Tfh Cells and Germinal Center in Deceased COVID-19 Patients
Duan, Y.-Q., Xia, M.-H., Ren, L., Zhang, Y.-F., Ao, Q.-L., Xu, S.-P., Kuang, D., Liu, Q., Yan, B., Zhou, Y.-W., et al. (2020) · Current Medical Science · doi:10.1007/s11596-020-2225-x · Cited by 59
Combining Antivirals and Immunomodulators to Fight COVID-19
Feuillet, V., Canard, B., & Trautmann, A. (2020) · Trends in Immunology · doi:10.1016/j.it.2020.11.003 · Cited by 60
Tomić, S., Đokić, J., Stevanović, D., Ilić, N., Gruden‐Movsesijan, A., Dinić, M., Radojević, D., Bekić, M., Mitrović, N., Tomašević, R., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.614599 · Cited by 59
“In line with other reports (8, 17) we also found a reduced frequency of IFN-gproducing CD8 T and Th17 cells in COVID-19 patients, as well as their functional exhaustion marked by increased PD1 expression.”
BackgroundResultInfluentialCellular and Humoral Immune Responses in Covid-19 and Immunotherapeutic Approaches
Hasan, A., Al‐Ozairi, E., Albaqsumi, Z., Ahmad, R., & Al‐Mulla, F. (2021) · ImmunoTargets and Therapy · doi:10.2147/itt.s280706 · Cited by 56
A randomised trial of anti-GM-CSF otilimab in severe COVID-19 pneumonia (OSCAR)
Patel, J., Bass, D., Beishuizen, A., Ruiz, X. B., Boughanmi, H., Cahn, A. P., Colombo, H. R., Criner, G. J., Davy, K., de Miguel‐Díez, J., et al. (2022) · European Respiratory Journal · doi:10.1183/13993003.01870-2021 · Cited by 59
Tackling COVID‐19 infection through complement‐targeted immunotherapy
Jodele, S., & Köhl, J. (2020) · British Journal of Pharmacology · doi:10.1111/bph.15187 · Cited by 58
Targeting Lipid Rafts—A Potential Therapy for COVID-19
Sviridov, D., Miller, Y. I., Ballout, R. A., Remaley, A. T., & Bukrinsky, M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.574508 · Cited by 59
“Lipid rafts host many receptors involved in immune and inflammatory responses and play a key role in regulation of inflammation (6), an important attribute given the role of unique pattern of immune and inflammatory responses in the clinical manifestations of COVID-19 (7, 8).”
BackgroundSingh, K., Mittal, S., Gollapudi, S., Butzmann, A., Kumar, J., & Ohgami, R. S. (2020) · International Journal of Laboratory Hematology · doi:10.1111/ijlh.13354 · Cited by 58
Liu, Y., Tan, W., Chen, H., Zhu, Y., Wan, L., Jiang, K., Guo, Y., Tang, K., Xie, C., Yi, H., et al. (2021) · BMC Infectious Diseases · doi:10.1186/s12879-021-05792-7 · Cited by 58
“This is in line with recent studies reporting that SARS-CoV-2–specific CD4 T cell responses predominate over CD8 T cell responses and that CD4 T cell cytopenias are a characteristic change in severe COVID-19 [23, 24].”
ResultA streamlined whole blood CyTOF workflow defines a circulating immune cell signature of COVID ‐19
Geanon, D., Lee, B. H., Gonzalez‐Kozlova, E., Kelly, G., Handler, D., Upadhyaya, B., Leech, J. M., de Real, R. M., Herbinet, M., Magen, A., et al. (2021) · Cytometry Part A · doi:10.1002/cyto.a.24317 · Cited by 60
Multiple Sclerosis and SARS-CoV-2: Has the Interplay Started?
Bellucci, G., Rinaldi, V., Buscarinu, M. C., Reniè, R., Bigi, R., Pellicciari, G., Morena, E., Romano, C., Marrone, A., Mechelli, R., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.755333 · Cited by 59
“Compared to other respiratory viruses, SARS-CoV-2 elicits a stronger, perduring, auto-aggressive inflammatory response (12), fueled by a massive cytokine release, causing coagulation dysfunction and multiorgan failure (13) in severe cases.”
BackgroundVick, S. C., Frutoso, M., Mair, F., Konecny, A., Greene, E., Wolf, C. R., Logue, J. K., Franko, N., Boonyaratanakornkit, J. B., Gottardo, R., et al. (2021) · Science Advances · doi:10.1126/sciadv.abj0274 · Cited by 58
Role of arachidonic cascade in COVID-19 infection: A review
Ripon, M. A. R., Bhowmik, D. R., Amin, M. T., & Hossain, M. S. (2021) · Prostaglandins & Other Lipid Mediators · doi:10.1016/j.prostaglandins.2021.106539 · Cited by 59
“Other major pro-inflammatory cytokines (TNF-α, IFN-ɣ, IL-2) and chemokines (CCL2, CCL3, and CCL4) are elevated, which underscore a potentially pathogenic TH1/2 program in COVID-19 [138,139].”
BackgroundZenarruzabeitia, O., Astarloa-Pando, G., Terrén, I., Orrantia, A., Pérez-Garay, R., Seijas, I., Arana, J. N., Imaz-Ayo, N., Pérez-Fernández, S., Arana‐Arri, E., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.655934 · Cited by 54
“Also, as previously published by others (10, 23, 24), we found a gradual decrease in HLA-DR expression levels in all monocyte subsets that correlated with the severity of the disease (Figure 4C).”
BackgroundResultGhasemzadeh, M., Ghasemzadeh, A., & Hosseini, E. (2021) · Human Immunology · doi:10.1016/j.humimm.2021.09.004 · Cited by 55
Toll-like receptor (TLRs) agonists and antagonists for COVID-19 treatments
Liu, Z., Yang, M., Yu, K., Lian, Z., & Deng, S. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.989664 · Cited by 58
Kinetics of antibody responses dictate COVID-19 outcomePreprint
Lucas, C. G. D. O., Klein, J., Sundaram, M. E., Liu, F., Wong, P., Silva, J. D. S., Mao, T., Oh, J. E., Tokuyama, M., Lu, P., et al. (2020) · medRxiv · doi:10.1101/2020.12.18.20248331 · Cited by 57
“Importantly, in contrast to the marked decreases in circulating T cells observed in COVID-19 patients (Giamarellos-Bourboulis et al., 2020; Huang et al., 2020; Mathew et al., 2020; Zhou et al., 2020a), circulating B cell do not seem to decrease (Chen et al., 2020a; Lucas et al., 2020).”
ResultJuan, R. S., Barbero, P. G. M., Fernández‐Ruiz, M., López‐Medrano, F., Lizasoaín, M., Hernández-Jiménez, P., Silva, J. T., Ruiz‐Ruigómez, M., Corbella, L., Rodríguez‐Góncer, I., et al. (2020) · EClinicalMedicine · doi:10.1016/j.eclinm.2020.100407 · Cited by 56
MATH+ protocol for the treatment of SARS-CoV-2 infection: the scientific rationale
Marik, P. E., Kory, P. D., Varón, J., Iglesias, J. I., & Meduri, G. U. (2020) · Expert Review of Anti-infective Therapy · doi:10.1080/14787210.2020.1808462 · Cited by 56
Maternal natural killer cells at the intersection between reproduction and mucosal immunity
Shmeleva, E. V., & Colucci, F. (2021) · Mucosal Immunology · doi:10.1038/s41385-020-00374-3 · Cited by 58
Innate Immune Response to SARS-CoV-2 Infection: From Cells to Soluble Mediators
Ricci, D., Etna, M. P., Rizzo, F., Sandini, S., Severa, M., & Coccia, E. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22137017 · Cited by 61
Liu, N., Jiang, C., Cai, P., Shen, Z., Sun, W., Xu, H. Y., Fang, M., Yao, X., Zhu, L., Gao, X., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109793 · Cited by 55
NK cell dysfunction in patients with COVID-19
Bi, J. (2022) · Cellular and Molecular Immunology · doi:10.1038/s41423-021-00825-2 · Cited by 56
SARS-CoV-2 and influenza: a comparative overview and treatment implications
Manzanares, L. D., & Contreras, O. M. (2020) · Boletín Médico del Hospital Infantil de México · doi:10.24875/bmhim.20000183 · Cited by 64
COVID-19 Outbreak: Pathogenesis, Current Therapies, and Potentials for Future Management
Hossain, M. F., Hasana, S., Mamun, A. A., Uddin, M. S., Wahed, M. I. I., Sarker, S., Behl, T., Ullah, I., Begum, Y., Bulbul, I. J., et al. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.563478 · Cited by 57
Delivery Routes for COVID-19 Vaccines
Park, J. H., & Lee, H. K. (2021) · Vaccines · doi:10.3390/vaccines9050524 · Cited by 53
“COVID-19 patients show lymphopenia, with decreased CD4 T cells, CD8 T cells, and B cells, as well as a preference for natural killer cells over CD8 T cells [20,21].”
BackgroundGamma Delta T Cells and Their Involvement in COVID-19 Virus Infections
von Massow, G., Oh, S. K. W., Lam, A. T., & Gustafsson, K. T. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.741218 · Cited by 55
“In Covid-19, IL-6, together with IL-10 seem to be the only cytokines consistently elevated among reports, while TNF-a is elevated in some reports (31, 34, 35).”
BackgroundProgrammed cell death: the pathways to severe COVID-19?
Bader, S. M., Cooney, J. P., Pellegrini, M., & Doerflinger, M. (2022) · Biochemical Journal · doi:10.1042/bcj20210602 · Cited by 55
Briquez, P. S., Rouhani, S. J., Yu, J., Pyzer, A. R., Trujillo, J., Dugan, H. L., Stamper, C. T., Changrob, S., Sperling, A. I., Wilson, P. C., et al. (2022) · Science Advances · doi:10.1126/sciadv.abn3777 · Cited by 55
Neutrophil Extracellular Traps in Airway Diseases: Pathological Roles and Therapeutic Implications
Jo, A., & Kim, D. W. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24055034 · Cited by 58
Hall, M. W., Joshi, I., Leal, L. O., & Ooi, E. E. (2020) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa904 · Cited by 54
“There have also been clinical reports of decreased immune cell populations including CD4, CD8, and natural killer (NK) cells in peripheral blood [19].”
The common risk factors for progression and mortality in COVID-19 patients: a meta-analysis
Zhang, L., Hou, J., Ma, F.-Z., Li, J., Xue, S., & Xu, Z. (2021) · Archives of Virology · doi:10.1007/s00705-021-05012-2 · Cited by 55
“For patients with malignancy or immunodeficiency, COVID-19 more often results in critical/fatal cases [67, 68].”
BackgroundCell Death in Coronavirus Infections: Uncovering Its Role during COVID-19
Paolini, A., Borella, R., Biasi, S. D., Neroni, A., Mattioli, M., Tartaro, D. L., Simonini, C., Franceschini, L., Cicco, G., Piparo, A. M., et al. (2021) · Cells · doi:10.3390/cells10071585 · Cited by 55
“In the severe disease, the restoration of normal levels of this molecule and the reappearance of the non-classical monocyte subset in the blood was observed in response to anti-IL-6R antibodies [35].”
BackgroundFeyaerts, D., Hedou, J. J., Gillard, J., Chen, H. M., Tsai, E. S., Peterson, L. S., Ando, K., Manohar, M., Do, E., Dhondalay, G. K., et al. (2022) · Cell Reports Medicine · doi:10.1016/j.xcrm.2022.100680 · Cited by 56
COVID‐19 immunopathology: From acute diseases to chronic sequelae
Arish, M., Qian, W. G., Narasimhan, H., & Sun, J. (2022) · Journal of Medical Virology · doi:10.1002/jmv.28122 · Cited by 55
“Several other innate cells are depleted in COVID‐19 cases such as DCs, eosinophils, and NK cells.(75,132,133) Also, among them, the most prominent depletion occurred in DCs, eosinophils, and NK cells and was associated with disease severity.”
Use of Intravenous Immunoglobulins in Sepsis Therapy—A Clinical View
Jarczak, D., Kluge, S., & Nierhaus, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21155543 · Cited by 59
Townsend, L., Dyer, A. H., Naughton, A., Kiersey, R., Holden, D., Gardiner, M., Dowds, J., O’Brien, K., Bannan, C., Nadarajan, P., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.676932 · Cited by 58
“Panlymphopenia is also prominent, with CD4+ T cells particularly affected (11, 12).”
BackgroundSARS-CoV-2/COVID-19: Evolving Reality, Global Response, Knowledge Gaps, and Opportunities
Osuchowski, M. F., Aletti, F. M., Cavaillon, J., Flohé, S. B., Giamarellos‐Bourboulis, E. J., Huber-Lang, M. S., Relja, B., Skirecki, T., Szabó, A., & Maegele, M. (2020) · Shock · doi:10.1097/shk.0000000000001565 · Cited by 50
Self-citationImmunesenescence: A Predisposing Risk Factor for the Development of COVID-19?
Hazeldine, J., & Lord, J. M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.573662 · Cited by 55
“Whilst more studies are required, emerging data implies a role for IL-6 in driving the SARS-CoV-2-mediated remodeling of the monocyte pool (117, 118), with one group demonstrating a significant reduction in the expression of genes”
BackgroundResultInfluentialTocilizumab for Severe Worsening COVID-19 Pneumonia: a Propensity Score Analysis
on behalf of the Foch COVID-19 Study Group, Roumier, M., Paule, R., Vallée, A., Rohmer, J., Ballester, M. C., Brun, A., Cerf, C., Chabi, M.-L., Chinet, T., et al. (2020) · Journal of Clinical Immunology · doi:10.1007/s10875-020-00911-6 · Cited by 53
Marcos‐Jiménez, A., Sánchez‐Alonso, S., Alcaraz‐Serna, A., Esparcia, L., López‐Sanz, C., Sampedro-Nuñez, M. A., Mateu‐Albero, T., Sánchez‐Cerrillo, I., Martínez‐Fleta, P., Gabrie, L., et al. (2020) · European Journal of Immunology · doi:10.1002/eji.202048858 · Cited by 52
“Regarding NK cells, several authors have studied the different lymphoid subsets in COVID-19 patients(22-25) and found no differences in the proportion of whole NK cells.”
Background
Metadata
- Authors
- Giamarellos-Bourboulis, E. J., Netea, M. G., Rovina, N., Akinosoglou, K., Antoniadou, A., Antonakos, N., Damoraki, G., Gkavogianni, T., Adami, M.-E., Katsaounou, P., Ntaganou, M., Kyriakopoulou, M., Dimopoulos, G., Koutsodimitropoulos, I., Velissaris, D., Koufargyris, P., Karageorgos, A., Katrini, K., Lekakis, V., Lupse, M., Kotsaki, A., Renieris, G., Theodoulou, D., Panou, V., Koukaki, E., Koulouris, N., Gogos, C., & Koutsoukou, A.
- Affiliations
- University of Bonn (DE)
- National and Kapodistrian University of Athens (GR)
- University of Patras (GR)
- ORCID
- Netea, Mihai G.
- Rovina, Nikoletta
- Akinosoglou, Karolina
- Antoniadou, Anastasia
- Antonakos, Nikolaos
- Damoraki, Georgia
- Gkavogianni, Theologia
- Katsaounou, Paraskevi
- Kyriakopoulou, Magdalini
- Koutsodimitropoulos, Ioannis
- Velissaris, Dimitrios
- Koufargyris, Panagiotis
- Lekakis, Vasileios
- Kotsaki, Antigone
- Koukaki, Evangelia
- Koulouris, Nikolaos
- Koutsoukou, Antonia
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2020-06
- Volume
- 27
- Issue
- 6
- Pages
- 992-1000.e3
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC7172841
- OpenAlex
- W3016288338
- Cited by
- 2,045
- References
- 16
- Citations by year
- 2026: 39 · 2025: 73 · 2024: 141 · 2023: 228 · 2022: 412 · 2021: 640 · 2020: 508
- FWCI
- 58.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Funders
- European Research Council (833247)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Pfizer
- National and Kapodistrian University of Athens
- Astellas Pharma US
- Horizon 2020 (847422)
- Meso Scale Diagnostics
- Gilead Sciences
- 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 › Hematology › Autoimmune and Inflammatory Disorders Research
- Keywords
- COVID-19 pandemic, severe respiratory failure, immune dysregulation, macrophage activation syndrome, HLA-DR expression, lymphopenia, CD4 depletion, natural killer cells, monocyte cytokine production, interleukin-6, TNF-α, tocilizumab, hyperinflammation, cytokine storm
- MeSH terms
- COVID-19, Aged, Female, HLA-DR Antigens, Humans, Inflammation, Killer Cells, Natural, Lymphopenia, Macrophage Activation, Male, Monocytes, Pneumonia, Viral, Respiratory Insufficiency, Interleukin-6, Coronavirus Infections, Pandemics, Antibodies, Monoclonal, Humanized
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