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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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Peres, K., Riera, R., Martimbianco, A., Ward, L., & Cunha, L. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00562 · Cited by 37
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The COVID-19 immune landscape is dynamically and reversibly correlated with disease severity
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“response with pro-inflammatory cytokines IL-1 β and IL-6 leading to tissue damage set the perfect stage for fungal infection and dissemination [11,12].”
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“Along with the cytokine storm, one can observe the disruption of the immune homeostasis with an exacerbated response from the innate immunity, like neutrophils and macrophages, and the impairment of natural killer (NK) and CD8+ T cells, both cytotoxic cells directly involved in viral elimination (Giamarellos-Bourbouli…”
BackgroundCOVID-19 Immunobiology: Lessons Learned, New Questions Arise
Kaklamanos, A., Belogiannis, K., Skendros, P., Gorgoulis, V. G., Vlachoyiannopoulos, P. G., & Tzioufas, A. G. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.719023 · Cited by 37
“SARS-CoV-2 can also infect antigen-presenting cells (APCs), inducing epigenetic changes that cause an HLA-II downregulation, as described in both monocytes/macrophages, and B cells (47), probably via an IL-6-dependent pathway (48).”
BackgroundCellular and molecular mechanisms in COVID-19 coagulopathy: role of inflammation and endotheliopathy
Cacciola, R. R., Cacciola, E. G., Vecchio, V., & Cacciola, E. (2021) · Journal of Thrombosis and Thrombolysis · doi:10.1007/s11239-021-02583-4 · Cited by 38
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“SARS-CoV-2 .”
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MAFB and MAF Transcription Factors as Macrophage Checkpoints for COVID-19 Severity
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“From an immunological perspective, severe COVID-19 patients display a robust immune dysregulation, including T cell and NK cell cytopenia, sustained cytokine production and hyper-inflammation (4).”
BackgroundA comprehensive review on sarilumab in COVID-19
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“The pattern of immune dysregulation is characterized by IL-6 induced low human leukocyte antigen– DR isotype (HLA-DR) expression and lymphopenia associated with continuous cytokine release [44].”
BackgroundEffects of Tocilizumab in COVID-19 patients: a cohort study
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“Previously approved for the treatment of severe or life-threatening chimeric antigen receptor (CAR) T cellinduced CRS, its ability to downregulate the immune system may have positive implications for COVID-19 [7, 8].”
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Glycoprotein Targeted CAR-NK Cells for the Treatment of SARS-CoV-2 Infection
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“Indeed, serum levels of inflammatory mediators and markers, including interleukin (IL)-6, C-reactive protein (CRP), IL-1β, IL-10, CXCL9, CXCL10, ferritin, and tumor necrosis factor-α (TNF-α) are elevated in cases of COVID-19 [2,20,21].”
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“2 function by significantly reducing human leukocyte D antigen expression (HLA-DR) combined with the depletion of natural killer (NK) cells, CD4 + lymphocytes, and CD19 + lymphocytes [16].”
Human endogenous retrovirus K in the respiratory tract is associated with COVID-19 physiopathology
Temerozo, J. R., Rodrigues, N. F., dos Santos, M. C., Hottz, E. D., Sacramento, C. Q., da Silva, A. D. P. D., Mandacaru, S. C., Moraes, E. C. D. S., Trugilho, M. R. O., Gesto, J. S. M., et al. (2022) · Microbiome · doi:10.1186/s40168-022-01260-9 · Cited by 45
“It was reported that MERS-CoV- and SARS-CoV-infected macrophages produce high levels of pro-inflammatory cytokines and chemokines [11, 12], and, more recently, that lung monocytes from patients with severe pneumonia caused by SARS-CoV-2 are potent producers of TNF-alpha and IL-6 [13].”
BackgroundCoronaviruses and Immunosuppressed Patients: The Facts During the Third Epidemic
Merli, M., Perricone, G., Lauterio, A., Prosperi, M., Travi, G., Roselli, E., Petrò, L., Carlis, L. G. D., Belli, L. S., & Puoti, M. (2020) · Liver Transplantation · doi:10.1002/lt.25806 · Cited by 38
“(2) Even though the pathophysiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still under investigation, the immune system appears to play a major role especially in patients with severe disease,(3) thus supporting previous observations.”
ResultCOVID-19: not a contraindication for surgery in patients with proximal femur fragility fractures
Morelli, I., Luceri, F., Giorgino, R., Accetta, R., Perazzo, P., Mangiavini, L., Maffulli, N., & Peretti, G. M. (2020) · Journal of Orthopaedic Surgery and Research · doi:10.1186/s13018-020-01800-9 · Cited by 37
“Our patients demonstrated a significant reduction in leukocyte and neutrophils count and an increase in lymphocyte relative count (Table 2) comparing POD1 and POD 5 ± 2, possibly explained by the time from surgery and by the COVID-19 infection resolution, with an improvement of the peculiar SARS-CoV-2-related lymphope…”
Koushki, K., Salemi, M., Miri, S. M., Arjeini, Y., Keshavarz, M., & Ghaemi, A. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112346 · Cited by 38
“Furthermore, elevated calprotectin (S100A8/S100A9) and accumulation of immature subsets of neutrophils with an immunosuppressive profile (G-MDSCs) were reported in blood and lungs of patients with severe COVID-19 infection [61,76,77].”
COVID-19 Coagulopathy: From Pathogenesis to Treatment
Alnima, T., Mulder, M. M. G., van Bussel, B. C. T., & Cate, H. T. (2022) · Acta Haematologica · doi:10.1159/000522498 · Cited by 38
Shifting the Immune Memory Paradigm: Trained Immunity in Viral Infections
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“At the same time, the cholesterol pathway metabolite mevalonate amplifies trained immunity through the insulin-like growth factor 1 receptor (IGF1R) and phosphatidylinositol-3-kinase (PI3K)/mTOR pathway (74).”
Self-citationCross, A. R., de Andrea, C. E., Villalba-Esparza, M., Landecho, M. F., Cerundolo, L., Weeratunga, P. N., Etherington, R. E., Denney, L., Ogg, G. S., Ho, L., et al. (2022) · JCI Insight · doi:10.1172/jci.insight.157837 · Cited by 40
“In keeping with this model, myeloid cell dysregulation is a hallmark of severe or progressive COVID-19 infection (34-37) and there is strong evidence for increased numbers of macrophages in COVID-19 lung tissue (6, 7, 30).”
BackgroundInnate Immunity in Protection and Pathogenesis During Coronavirus Infections and COVID-19
Malireddi, R. K. S., Sharma, B. R., & Kanneganti, T. (2024) · Annual Review of Immunology · doi:10.1146/annurev-immunol-083122-043545 · Cited by 39
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COVID‐19 and the liver – Lessons learned
Herta, T., & Berg, T. (2021) · Liver International · doi:10.1111/liv.14854 · Cited by 38
COVID-19 and Herpes Simplex Virus Infection: A Cross-Sectional Study
Shanshal, M., & Ahmed, H. S. (2021) · Cureus · doi:10.7759/cureus.18022 · Cited by 37
“COVID19 is associated with unique immune dysregulation, including CD4 cell and NK cell cytopenias and sustained inflammatory interleukin stimulation such as interleukin-6 (IL-6) and tumor necrosis factor-α [20].”
BackgroundHigashikuni, Y., Liu, W., Obana, T., & Sata, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222112081 · Cited by 38
Ghasemzadeh, M., Ahmadi, J., & Hosseini, E. (2022) · Thrombosis Research · doi:10.1016/j.thromres.2022.03.022 · Cited by 37
Invasive Aspergillosis in the Intensive Care Unit
Townsend, L., & Martín‐Loeches, I. (2022) · Diagnostics · doi:10.3390/diagnostics12112712 · Cited by 42
“These concerns were based on evidence that showed that SARS-CoV-2 is associated with endothelial dysfunction [45,46], while severe COVID-19 is associated with severe lymphopenia, potentially impairing the adaptive response to Aspergillus [47,48].”
IL-1 Mediates Tissue-Specific Inflammation and Severe Respiratory Failure in COVID-19
Renieris, G., Karakike, E., Gkavogianni, T., Droggiti, D.-E., Stylianakis, E., Andriopoulou, T., Spanou, V. M., Kafousopoulos, D., Netea, M. G., Eugen‐Olsen, J., et al. (2022) · Journal of Innate Immunity · doi:10.1159/000524560 · Cited by 35
Self-citationA Cross Entropy Test Allows Quantitative Statistical Comparison of t-SNE and UMAP Representations
Roca, C. P., Burton, O. T., Neumann, J., Tareen, S. H. K., Whyte, C. E., Gergelits, V., Veiga, R., Humblet‐Baron, S., & Liston, A. (2022) · Cell Reports Methods · doi:10.1016/j.crmeth.2022.100390 · Cited by 36
Oltean, M., Søfteland, J. M., Bagge, J., Ekelund, J., Felldin, M., Schult, A., Magnusson, J. M., Friman, V., & Karason, K. (2020) · Scandinavian Journal of Infectious Diseases · doi:10.1080/23744235.2020.1792977 · Cited by 36
Saridaki, M., Metallidis, S., Grigoropoulou, S., Vrentzos, E., Lada, M., Argyraki, K., Tsachouridou, Ο., Georgiadou, A., Vasishta, A., & Giamarellos‐Bourboulis, E. J. (2021) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-020-04145-7 · Cited by 36
Self-citationLiu, H., Wang, Z., Sun, H., Teng, T., Li, Y., Zhou, X., & Yang, Q. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.599334 · Cited by 35
“This finding is consistent with reports that treatment of COVID-19 patients with tocilizumab, which blocks IL-6-mediated signaling, restored circulating levels of lymphocytes to levels close to normal ranges (53).”
ResultCase Report: Use of Anakinra in Multisystem Inflammatory Syndrome During COVID-19 Pandemic
Paolera, S. D., Valencic, E., Piscianz, E., Moressa, V., Tommasini, A., Sagredini, R., Kiren, V., Comar, M., & Taddio, A. (2021) · Frontiers in Pediatrics · doi:10.3389/fped.2020.624248 · Cited by 36
Kageyama, Y., Nishizaki, Y., Aida, K., Yayama, K., Ebisui, T., Akiyama, T., & Nakamura, T. (2021) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2021.10942 · Cited by 37
Regulatory T Cells as Predictors of Clinical Course in Hospitalised COVID-19 Patients
Caldrer, S., Mazzi, C., Bernardi, M., Prato, M. G., Ronzoni, N., Rodari, P., Angheben, A., Piubelli, C., & Tiberti, N. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.789735 · Cited by 39
Mechanistic Insights Into the Immune Pathophysiology of COVID-19; An In-Depth Review
Shafqat, A., Shafqat, S., Alsalameh, S., Kashir, J., AlKattan, K. M., & Yaqinuddin, A. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.835104 · Cited by 37
“Accordingly, COVID-19 patient plasma inhibits HLA-DR expression on monocytes (56, 79, 80), and tocilizumab restores HLA-DR expression levels and nonclassical monocytes (81).”
BackgroundNelson, C. E., Namasivayam, S., Foreman, T. W., Kauffman, K. D., Sakai, S., Dorosky, D. E., Lora, N. E., Program, N. T. I., Brooks, K., Potter, E. L., et al. (2022) · Science Immunology · doi:10.1126/sciimmunol.abo0535 · Cited by 36
Could the fibromyalgia syndrome be triggered or enhanced by COVID-19?
Fialho, M. F. P., Brum, E. S., & Oliveira, S. M. (2023) · Inflammopharmacology · doi:10.1007/s10787-023-01160-w · Cited by 33
An 8-gene machine learning model improves clinical prediction of severe dengue progression
Liu, Y. E., Saul, S., Rao, A., Robinson, M., Rojas, O. L. A., Sanz, A. M., Verghese, M., Solis, D., Sibai, M., Huang, C., et al. (2022) · Genome Medicine · doi:10.1186/s13073-022-01034-w · Cited by 35
Immunological aspects of COVID-19: What do we know?
Velikova, T. V., Kotsev, S. V., Georgiev, D., & Batselova, H. (2020) · World Journal of Biological Chemistry · doi:10.4331/wjbc.v11.i2.14 · Cited by 35
Can Natural Killer Cells Be a Principal Player in Anti-SARS-CoV-2 Immunity?
Ahmed, F. N., Jo, D., & Lee, S. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.586765 · Cited by 36
NK Cell–Derived IL-10 Supports Host Survival during Sepsis
Jensen, I. J., McGonagill, P. W., Butler, N. S., Harty, J. T., Griffith, T. S., & Badovinac, V. P. (2021) · The Journal of Immunology · doi:10.4049/jimmunol.2001131 · Cited by 38
Serum IgG4 level predicts COVID-19 related mortality
Della‐Torre, E., Lanzillotta, M., Strollo, M., Ramirez, G. A., Dagna, L., & Tresoldi, M. (2021) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2021.09.012 · Cited by 36
“Dear Editor, Intrinsic features of the humoral immune response including antigen specificity, antibody glycosylation, and subclass of immunoglobulin (Ig) G have been shown to influence the progression of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection and Coronavirus19 disease (COVID-19) outcome…”
Siemińska, I., Węglarczyk, K., Surmiak, M., Kurowska-Baran, D., Sanak, M., Siedlar, M., & Baran, J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.748097 · Cited by 39
“HLA–DR downregulation, typical for MDSCs, was also shown to immediately precede progression to severe respiratory failure (45).”
BackgroundResultShambat, S. M., Gómez-Mejía, A., Schweizer, T. A., Huemer, M., Chang, C., Acevedo, C., Bergadà-Pijuan, J., Vulin, C., Hofmaenner, D. A., Scheier, T., et al. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010176 · Cited by 34
“This hypercytokinemia is usually associated with mobilization of myeloid immune cells such as neutrophils and monocytes, further augmenting the tissue damage, thereby suggesting that the hypercytokinemia might be associated with disease severity [11,16,19].”
BackgroundResultCostanza, A., Amerio, A., Aguglia, A., Serafini, G., Amore, M., Hasler, R., Ambrosetti, J., Bondolfi, G., Sampogna, G., Berardelli, I., et al. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104606 · Cited by 35
Cryptococcosis among hospitalised patients with COVID ‐19: A multicentre research network study
Chastain, D. B., Kung, V. M., Golpayegany, S., Jackson, B., Franco‐Paredes, C., Barahona, L. V., Thompson, G. R., & Henao‐Martínez, A. F. (2022) · Mycoses · doi:10.1111/myc.13476 · Cited by 35
“lymphopenia,2,3 (2) vomocytosis of Cryptococcus spp.”
Red Blood Cell Morphologic Abnormalities in Patients Hospitalized for COVID-19
Marchi, G., Bozzini, C., Bertolone, L., Dima, F., Busti, F., Castagna, A., Stranieri, C., Pasini, A. M. F., Friso, S., Lippi, G., et al. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.932013 · Cited by 35
“The COVID-19 pandemic has boosted an unprecedented expansion of research, especially focused on the complex immunological response to severe respiratory syndrome coronavirus 2 (SARS-CoV-2) (Giamarellos-Bourboulis et al., 2020; Brodin 2021).”
BackgroundJeong, H., Lee, Y. W., Park, I. H., Noh, H., Kim, S., Kim, J., Jeon, D., Jang, H. J., Oh, J., On, D., et al. (2022) · Disease Models & Mechanisms · doi:10.1242/dmm.049632 · Cited by 36
“A recent study revealed that an excessive immune reaction in K18-hACE2 mice induced PANoptosis (Karki et al., 2021), and this signature was recapitulated in the intestine and spleen in our study (Fig.”
Nugroho, J., Wardhana, A. P., Mulia, E. P. B., Maghfirah, I., Rachmi, D. A., A’yun, M. Q., & Septianda, I. (2020) · Clinical Hemorheology and Microcirculation · doi:10.3233/ch-200978 · Cited by 34
“Bourboulis E, 2020 [13] Pros Sotiria Athens General Hospital and Attikon University General Hospital Athens, Greece March 3–30, 2020 54 (28 vs 26) 89.”
BackgroundNikoloudis, D., Kountouras, D., & Hiona, A. (2020) · PeerJ · doi:10.7717/peerj.10402 · Cited by 34
Bacteriophages Could Be a Potential Game Changer in the Trajectory of Coronavirus Disease (COVID-19)
Wojewodzic, M. W. (2020) · PHAGE · doi:10.1089/phage.2020.0014 · Cited by 35
“For instance, complex immune dysregulation in Covid-19 patients with severe respiratory failure has been observed.(50) During the writing of this communication, the first immunological reviews were published, in which the authors identified major gaps in knowledge that need to be addressed by the scientific community.”
BackgroundCavalli, G., Farina, N., Campochiaro, C., Luca, G. D. D., Della‐Torre, E., Tomelleri, A., & Dagna, L. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.598308 · Cited by 35
Mechanisms of Dysregulated Humoral and Cellular Immunity by SARS-CoV-2
Taefehshokr, N., Taefehshokr, S., & Heit, B. (2020) · Pathogens · doi:10.3390/pathogens9121027 · Cited by 35
Effects of melatonin on protecting against lung injury (Review)
Wang, W., & Gao, J. (2021) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2021.9659 · Cited by 36
Gouda, A. S., Adbelruhman, F. G., Alenezi, H. S., & Mégarbane, B. (2021) · Saudi Journal of Biological Sciences · doi:10.1016/j.sjbs.2021.06.046 · Cited by 35
NK and T Cell Immunological Signatures in Hospitalized Patients with COVID-19
Bergantini, L., d’Alessandro, M., Cameli, P., Cavallaro, D., Gangi, S., Cekorja, B., Sestini, P., & Bargagli, E. (2021) · Cells · doi:10.3390/cells10113182 · Cited by 34
Innate Immune Response in SARS-CoV-2 Infection
Schiuma, G., Beltrami, S., Bortolotti, D., Rizzo, S., & Rizzo, R. (2022) · Microorganisms · doi:10.3390/microorganisms10030501 · Cited by 39
“It has been observed that severe COVID-19 present low expression of HLADR on monocytes [91] in correlation with ICU (Intensive Care Unit) need (Figure 5) [92,93], probably due to the antagonizing action of IL-6 (Figure 5) [94].”
BackgroundThe role of antigen-presenting cells in the pathogenesis of COVID-19
Farzi, R., Aghbash, P. S., Eslami, N., Azadi, A., Shamekh, A., Hemmat, N., Entezari‐Maleki, T., & Baghi, H. B. (2022) · Pathology - Research and Practice · doi:10.1016/j.prp.2022.153848 · Cited by 33
de Almeida, L., da Silva, A. L. N., Rodrigues, T. S., Oliveira, S., Ishimoto, A. Y., Seribelli, A. A., Becerra, A., Andrade, W. A., Ataide, M. A., Caetano, C. C. D. S., et al. (2022) · Science Advances · doi:10.1126/sciadv.abo5400 · Cited by 33
Immune correlates of protection for SARS-CoV-2, Ebola and Nipah virus infection
Escudero-Pérez, B., Lawrence, P., & Castillo‐Olivares, J. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1156758 · Cited by 37
Cardiac injuries in coronavirus disease 2019 (COVID-19)
Chen, C., Li, H., Hang, W., & Wang, D. W. (2020) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2020.06.002 · Cited by 32
“Considering the cytokines patterns in COVID-19 patients, certain cytokine antagonists and cytokine absorption might be also promising therapeutic strategies for rescuing SARSCoV-2-associated immune dysregulation in COVID-19 patients with FM [23].”
BackgroundCOVID-19: The Immune Responses and Clinical Therapy Candidates
Zhand, S., Jazi, M. S., Mohammadi, S., Rasekhi, R. T., Rostamian, G., Kalani, M. R., Rostamian, A., George, J., & Douglas, M. W. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21155559 · Cited by 35
“A number of studies are exploring the immune response to the SARS-CoV-2 [30], with most suggesting that the immune response is disturbed due to aberrant activation of monocytes/macrophages [31], elevation of pro-inflammatory cytokines [32], depletion of lymphocytes [33] and deployment of large numbers of neutrophils […”
BackgroundNaturally activated adaptive immunity in COVID‐19 patients
Yang, X., Dai, T., Zhou, X., Qian, H., Guo, R., Lei, L., Zhang, X., Zhang, D., Shi, L., Cheng, Y., et al. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.15771 · Cited by 64
Roussel, M., Ferrant, J., Reizine, F., Gallou, S. L., Dulong, J., Carl, S. H., Lesouhaitier, M., Grégoire, M., Bescher, N., Verdy, C., et al. (2021) · Cell Reports Medicine · doi:10.1016/j.xcrm.2021.100291 · Cited by 35
“Consistent with these data, it was shown that CD14 + HLA-DR low cells were increased in critical COVID-19 patients, 21,26,56–58 while CD14 low CD16 + monocytes, able to migrate to the lung, were correlated with the length of stay in the ICU.”
A review on the immune responses against novel emerging coronavirus (SARS-CoV-2)
Lotfi, R., Kalmarzi, R. N., & Roghani, S. A. (2021) · Immunologic Research · doi:10.1007/s12026-021-09198-0 · Cited by 35
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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