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Functional exhaustion of antiviral lymphocytes in COVID-19 patients
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In December 2019, a novel coronavirus was first reported in Wuhan, China. 1 It was named by the World Health Organization as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is responsible for coronavirus disease 2019 (COVID-19). Up to 28 February 2020, 79,394 cases have been confirmed according to China’s National Health Commission. Outside China, the virus has spread rapidly to over 36 countries and territories.
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“In ex vivo studies, NK cells from patients with COVID-19 displayed impaired cytotoxicity (64, 65)”
From SARS-CoV-2 variants of concern partially escape humoral but not T cell responses in COVID-19 convalescent donors and vaccine recipients (2021) · cites this paper as [64]
In the citing paper
“NK cells were shown to be decreased in patients with COVID-19 in association with disease severity (64).”
From SARS-CoV-2 variants of concern partially escape humoral but not T cell responses in COVID-19 convalescent donors and vaccine recipients (2021) · cites this paper as [64]
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“A characteristic feature of primary HLH but not sHLH/MAS is defective NK function which is also reported in COVID-19 infection, but by different mechanisms [40] .”
BackgroundCOVID-19: immunopathology and its implications for therapy
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InfluentialMathew, D., Giles, J. R., Baxter, A. E., Oldridge, D. A., Greenplate, A. R., Wu, J. E., Alanio, C., Kuri-Cervantes, L., Pampena, M. B., D’Andrea, K., et al. (2020) · Science · doi:10.1126/science.abc8511 · Cited by 1,509
“T cell exhaustion (12, 13) and increased inhibitory receptor expression on peripheral T cells have also been reported (7, 14), though these inhibitory receptors are also increased after T cell activation (15).”
BackgroundResultTargeting potential drivers of COVID-19: Neutrophil extracellular traps
Barnes, B. J., Adrover, J. M., Baxter-Stoltzfus, A., Borczuk, A., Cools-Lartigue, J., Crawford, J. M., Daßler-Plenker, J., Guerci, P., Huynh, C., Knight, J. S., et al. (2020) · Journal of Experimental Medicine · doi:10.1084/jem.20200652 · Cited by 1,486
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“The exhaustion markers return to normal in patients who have recovered or are convalescent (47, 48).”
BackgroundImmune response to SARS‐CoV‐2 and mechanisms of immunopathological changes in COVID‐19
Azkur, A. K., Akdiş, M., Azkur, D., Sokołowska, M., van de Veen, W., Brüggen, M., O’Mahony, L., Gao, Y., Nadeau, K. C., & Akdiş, C. A. (2020) · Allergy · doi:10.1111/all.14364 · Cited by 1,149
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“These results suggest that the functional exhaustion of cytotoxic lymphocytes is associated with the acute phase of SARS-CoV-2 infection [33].”
BackgroundResultInfluentialA dynamic COVID-19 immune signature includes associations with poor prognosis
Laing, A. G., Lorenc, A., del Molino del Barrio, I., Das, A., Fish, M., Monin, L., Muñoz-Ruiz, M., McKenzie, D. R., Hayday, T. S., Francos-Quijorna, I., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-1038-6 · Cited by 946
COVID-19: immunopathogenesis and Immunotherapeutics
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“Moreover, killer cell lectin-like receptor subfamily C member 1 receptor expression on cytotoxic lymphocytes, including NK and CD8 T cells, is elevated.(34,35) Thus, elevated exhaustion levels and reduced functional diversity of T cells may predict severe progression in patients with COVID-19.”
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“The cytokine storm is thought to be associated with lymphopenia in COVID-19 patients (Zheng et al., 2020).”
Biomarkers associated with COVID-19 disease progression
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COVID-19: Current understanding of its Pathophysiology, Clinical presentation and Treatment
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COVID-19 and the human innate immune system
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T cell responses in patients with COVID-19
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Immune response, inflammation, and the clinical spectrum of COVID-19
García, L. F. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01441 · Cited by 739
“(67) ↓ CD8, NK (NKG2CD107a IFNγgrzB) ↓↓ CD8, NK (NKG2CD107a IFNγgrzB)”
BackgroundInfluentialMulti-Omics Resolves a Sharp Disease-State Shift between Mild and Moderate COVID-19
Su, Y., Chen, D., Yuan, D., Lausted, C. G., Choi, J., Dai, C. L., Voillet, V., Duvvuri, V. R. S. K., Scherler, K., Troisch, P., et al. (2020) · Cell · doi:10.1016/j.cell.2020.10.037 · Cited by 605
“, 2020), lymphopenia (Cao, 2020), immune cell exhaustion (Zheng et al., 2020), and elevated levels of inflammatory cytokines (Del Valle et al.”
The signal pathways and treatment of cytokine storm in COVID-19
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“Other investigations showed that the PD-1- or NK group 2 member A-positive NK cells were also significantly increased in the peripheral blood of COVID-19 patients compared to healthy controls.(35,36) Several mechanisms may contribute to SARS-CoV-2-induced depletion and exhaustion of lymphocytes: (1) SARS-CoV-2 may dir…”
BackgroundImmunity, endothelial injury and complement-induced coagulopathy in COVID-19
Perico, L., Benigni, A., Casiraghi, F., Ng, L. F. P., Rénia, L., & Remuzzi, G. (2020) · Nature Reviews Nephrology · doi:10.1038/s41581-020-00357-4 · Cited by 616
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“In ex vivo studies, NK cells from COVID-19 patients displayed impaired cytotoxicity (64, 65), potentially due to cytokine dysregulation and high plasma levels of IL-6 and TNF-α (66).”
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Immunopathology of Hyperinflammation in COVID-19
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“impairment of NK-cell function, a feature of primary HLH, is described in association with COVID-19 disease [50].”
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“onset to admission 13 (9-18) 13 (10-18)* 9 (6-17) 13 (9-16) 13 (9-16) 14 (7-18) 15 (8-21) 17 (11-24)* 9 (6-18) 9 (6-23) 23 (12-54)* 7 (3-9)”
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“Along with IL-6, IFN-γ has been a reliable indicator of COVID-19 patient deterioration and ICU admission [37,38,41].”
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“Also other studies confirm the relevance of these features and their association with the COVID-19 positivity [8, 30, 32, 44], compared to other kinds of pneumonia [43].”
ResultTwo X-linked agammaglobulinemia patients develop pneumonia as COVID-19 manifestation but recover
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“In relation to CD8+ T cells, it has been revealed that these cells exhibit functional exhaustion patterns, such as the expression of NKG2A, PD-1, and TIM-3 (Zheng et al. 2020, Moon 2020).”
BackgroundResultInfluentialLiang, Y., Wang, M., Chien, C., Yarmishyn, A. A., Yang, Y.-P., Lai, W.-Y., Luo, Y., Lin, Y.-T., Chen, Y.-J., Chang, P., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01022 · Cited by 347
“As for adaptive immunity, it is known that the low levels of CD4+ and CD8+ T cells are related to the mortality of SARSCoV-2 patients (104, 105).”
BackgroundLymphopenia in COVID‐19: Therapeutic opportunities
Fathi, N., & Rezaei, N. (2020) · Cell Biology International · doi:10.1002/cbin.11403 · Cited by 324
“The study by M. Zheng et al. (2020) showed that the NK cells and CTLs were reduced significantly in patients with COVID‐19.”
BackgroundResultInfluentialAutoinflammatory and autoimmune conditions at the crossroad of COVID-19
Rodríguez, Y., Novelli, L., Rojas, M., Santis, M. D., Acosta‐Ampudia, Y., Monsalve, D. M., Ramírez-Santana, C., Costanzo, A., Ridgway, W. M., Ansari, A. A., et al. (2020) · Journal of Autoimmunity · doi:10.1016/j.jaut.2020.102506 · Cited by 319
“also been reported [71], as well as an increased expression of their inhibitory receptor NKG2A that likely contributes to their reduced cytolytic activity [72].”
Severe immunosuppression and not a cytokine storm characterizes COVID-19 infections
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“6) n 19 17 8 8 10 10 10 10 4 IL-8 Mean (SEM) 118 (21) 327.”
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“Severe COVID19 patients have depleted peripheral NK cell counts and increased neutrophil-to-lymphocyte ratio compared with mild cases and healthy controls.(21,22) Cellular immunity to coronavirus could be more sustained, and T helper cell responses are critical in the generation of neutralizing antibodies.”
BackgroundEarly predictors of clinical outcomes of COVID-19 outbreak in Milan, Italy
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“Furthermore, exhaustion markers, such as NKG2A receptors on NK cells and CD8+ T cells, are up-regulated in patients with COVID-19 [28, 31].”
BackgroundFrederiksen, L. S. F., Zhang, Y., Foged, C., & Thakur, A. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01817 · Cited by 295
“In another study, the function of NK and CD8 T cells was exhausted with the increased expression of natural killer group 2 member A (NKG2A) in COVID19 patients (36).”
BackgroundCOVID-19 and Cancer: a Comprehensive Review
Gosain, R., Abdou, Y. G., Singh, A., Rana, N. K., Puzanov, I. J., & Ernstoff, M. S. (2020) · Current Oncology Reports · doi:10.1007/s11912-020-00934-7 · Cited by 295
Current status of potential therapeutic candidates for the COVID-19 crisis
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“…2020), immune injury (Chen et al., 2020b; Guan et al., 2020; Qin et al., 2020; Wang et al., 2020b; Xu et al., 2020; Yao et al., 2020; Liu et al., 2020b; Zheng et al., 2020), coagulation impairment (Han et al., 2020b; Tang et al., 2020a), and even death (Huang et al., 2020; Wang et al., 2020a) (Fig.”
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Body Localization of ACE-2: On the Trail of the Keyhole of SARS-CoV-2
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“Nevertheless, lymphocytes have an exhaustion phenotype with programmed cell death protein-1 (PD1), T cell immunoglobulin domain and mucin domain-3 (TIM3), and killer cell lectin-like receptor subfamily C member 1 (NKG2A) upregulation (337).”
BackgroundTwo distinct immunopathological profiles in autopsy lungs of COVID-19
Nienhold, R., Ciani, Y., Koelzer, V. H., Tzankov, A., Haslbauer, J. D., Menter, T., Schwab, N., Henkel, M., Frank, A., Zsikla, V., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18854-2 · Cited by 246
Unique immunological profile in patients with COVID-19
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“Similarly, an increased peripheral neutrophil-to-lymphocyte ratio was also observed in severe cases of COVID-19, and was likely associated with unfavorable prognosis [35].”
BackgroundRobust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19Preprint
Sekine, T., Perez‐Potti, A., Rivera‐Ballesteros, O., Strålin, K., Gorin, J., Olsson, A., Llewellyn‐Lacey, S., Kamal, H., Bogdanović, G., Muschiol, S., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.06.29.174888 · Cited by 272
Untimely TGFβ responses in COVID-19 limit antiviral functions of NK cells
Witkowski, M., Tizian, C., Ferreira‐Gomes, M., Niemeyer, D., Jones, T. C., Heinrich, F., Frischbutter, S., Angermair, S., Hohnstein, T., Mattiola, I., et al. (2021) · Nature · doi:10.1038/s41586-021-04142-6 · Cited by 254
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“In addition, T cell exhaustion or dysfunction has also been observed (Diao et al., 2020; Zheng et al., 2020a; Zheng et al., 2020b).”
Chemokines and chemokine receptors during COVID-19 infection
Khalil, B. A., Elemam, N. M., & Maghazachi, A. A. (2021) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2021.01.034 · Cited by 248
“Additionally, circulating CD8 T and NK cells displayed abnormal function and exhaustion, where a negative correlation between perforin content and serum cytokine levels was detected [5,7].”
Cunha, L. L., Perazzio, S. F., Azzi, J., Cravedi, P., & Riella, L. V. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01748 · Cited by 245
Belsky, J. A., Tullius, B. P., Lamb, M. G., Sayegh, R., Stanek, J. R., & Auletta, J. J. (2021) · Journal of Infection · doi:10.1016/j.jinf.2021.01.022 · Cited by 238
Deciphering the COVID‐19 cytokine storm: Systematic review and meta‐analysis
Mulchandani, R., Lyngdoh, T., & Kakkar, A. K. (2020) · European Journal of Clinical Investigation · doi:10.1111/eci.13429 · Cited by 251
Unraveling the Mystery Surrounding Post-Acute Sequelae of COVID-19
Ramakrishnan, R. K., Kashour, T., Hamid, Q. A., Halwani, R., & Tleyjeh, I. M. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.686029 · Cited by 246
“Notably, a marked decrease in the absolute number and functional exhaustion of anti-viral cytotoxic lymphocytes, including cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, were reported in patients with SARS-CoV-2 infection, particularly in those with severe disease (60, 61).”
BackgroundImpact of PD-1 Blockade on Severity of COVID-19 in Patients with Lung Cancers
Luo, J., Rizvi, H. A., Egger, J. V., Preeshagul, I. R., Wolchok, J. D., & Hellmann, M. D. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0596 · Cited by 236
Baricitinib: A Review of Pharmacology, Safety, and Emerging Clinical Experience in COVID‐19
Jorgensen, S. C. J., Tse, C. L. Y., Burry, L. D., & Dresser, L. (2020) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.2438 · Cited by 233
“Our understanding of the pathogenesis of and immune response to COVID-19 is rapidly evolving and, like sepsis, relative immunodeficiency also appears to be at play.(9,44,46,58) At this time, we do not have a reliable way to gauge whether the overruling response is pro or antiinflammatory and this complicates deploymen…”
BackgroundRha, M., Jeong, H. W., Ko, J. H., Choi, S. J., Seo, I., Lee, J. S., Sa, M., Kim, A. R., Joo, E., Ahn, J. Y., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.12.002 · Cited by 227
“Although many studies have suggested exhausted phenotypes of CD8 T cells on the basis of increased PD-1 expression in patients with COVID-19 (De Biasi et al., 2020; Song et al., 2020; Zheng et al., 2020a; Zheng et al., 2020b), whether CD8 T cells truly become exhausted remains controversial.”
The Innate Immune System: Fighting on the Front Lines or Fanning the Flames of COVID-19?
McKechnie, J. L., & Blish, C. A. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.05.009 · Cited by 218
Intranasal vaccines for SARS-CoV-2: From challenges to potential in COVID-19 management
Chavda, V. P., Vora, L. K., Pandya, A., & Patravale, V. B. (2021) · Drug Discovery Today · doi:10.1016/j.drudis.2021.07.021 · Cited by 216
The Immune Response and Immunopathology of COVID-19
Mortaz, E., Tabarsi, P., Varahram, M., Folkerts, G., & Adcock, I. M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.02037 · Cited by 210
T‐cell responses and therapies against SARS‐CoV‐2 infection
Toor, S. M., Saleh, R., Nair, V. S., Taha, R. Z., & Elkord, E. (2020) · Immunology · doi:10.1111/imm.13262 · Cited by 208
COVID-19 is a systemic vascular hemopathy: insight for mechanistic and clinical aspects
Smadja, D. M., Mentzer, S. J., Fontenay, M., Laffan, M., Ackermann, M., Helms, J., Jonigk, D. D., Chocron, R., Pier, G. B., Gendron, N., et al. (2021) · Angiogenesis · doi:10.1007/s10456-021-09805-6 · Cited by 204
Carsetti, R., Zaffina, S., Mortari, E. P., Terreri, S., Corrente, F., Capponi, C., Palomba, P., Mirabella, M., Cascioli, S., Palange, P., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.610300 · Cited by 201
“Surviving T cells are functionally exhausted, and reduced T-cell count predicts an unfavorable clinical course (12, 13).”
BackgroundActivation or exhaustion of CD8+ T cells in patients with COVID-19
Rha, M., & Shin, E. (2021) · Cellular and Molecular Immunology · doi:10.1038/s41423-021-00750-4 · Cited by 201
“The functions of CD8+ T cells in patients with COVID-19 Several studies have reported that CD8+ T cells from patients with COVID-19 exhibit a decreased cytokine-producing capacity upon stimulation with PMA/ionomycin [23, 27].”
BackgroundWong, L.-Y. R., & Perlman, S. M. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00656-2 · Cited by 202
Viral persistence, reactivation, and mechanisms of long COVID
Chen, B. K., Jülg, B. D., Mohandas, S., Bradfute, S. B., & RECOVER Mechanistic Pathways Task Force (2023) · eLife · doi:10.7554/elife.86015 · Cited by 211
Could there be a link between oral hygiene and the severity of SARS-CoV-2 infections?
Sampson, V., Kamona, N., & Sampson, A. (2020) · BDJ · doi:10.1038/s41415-020-1747-8 · Cited by 205
The Impact of Pre-existing Comorbidities and Therapeutic Interventions on COVID-19
Callender, L. A., Curran, M., Bates, S. M., Mairesse, M., Weigandt, J., & Betts, C. J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01991 · Cited by 195
“For example, elevated programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) and T cell Ig and ITM domain (TIGIT) on CD8 T cells and increased NKG2A on NK cells (34, 35).”
BackgroundGadi, N., Wu, S., Spihlman, A. P., & Moulton, V. R. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.02147 · Cited by 188
“Their exhaustion is correlated with disease progression (27), as they are primary secretors of IFN-γ, TNF-α, colony stimulating factors (CSF), and many other cytokines (15, 27).”
BackgroundT Cells: Warriors of SARS-CoV-2 Infection
de Candia, P., Prattichizzo, F., Garavelli, S., & Matarese, G. (2020) · Trends in Immunology · doi:10.1016/j.it.2020.11.002 · Cited by 189
“Accordingly, protein expression of three exhaustion markers, that is, the CD28 family member programmed cell death marker 1 (PD-1), the receptor mucin domaincontaining protein-3 (TIM-3), and the ITIM-bearing receptor NKG2A [68–70] were increased in both peripheral CD4 and CD8 T cells from severe COVID-19 patients, a f…”
Innate immunological pathways in COVID-19 pathogenesis
Paludan, S. R., & Mogensen, T. H. (2022) · Science Immunology · doi:10.1126/sciimmunol.abm5505 · Cited by 188
“However, at the same time they also display markers of functional exhaustion and down-regulation of genes associated with cytoxicity (39, 41, 42), thus demonstrating a central similarity to HLH (43).”
ResultSelenium and selenoproteins in viral infection with potential relevance to COVID-19
Zhang, J., Saad, R., Taylor, E. W., & Rayman, M. P. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101715 · Cited by 191
““Functional exhaustion” of natural killer (NK) Cells and cytotoxic T-cells has also been identified as a factor in severe COVID-19 [65].”
I mmunosenescence and Inflammaging: Risk Factors of Severe COVID-19 in Older People
Pietrobon, A. J., Teixeira, F. M. E., & Sato, M. N. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.579220 · Cited by 187
“reported impaired NK function in severe COVID-19 patients, expressing higher levels of the NKG2A receptor, a cellular exhaustion marker, indicating impaired antiviral immunity (150).”
BackgroundHeming, M., Li, X., Räuber, S. J., Mausberg, A. K., Börsch, A., Hartlehnert, M., Singhal, A., Lu, I., Fleischer, M., Szepanowski, F., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.12.011 · Cited by 181
Islam, H., Chamberlain, T. C., Mui, A., & Little, J. P. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.677008 · Cited by 191
“IL-10mediated hyperactivation of CD8+ T cells despite an overall reduced cell count may also explain why some studies report functional exhaustion of T cells in severe COVID-19 cases (25) and significant inverse associations between serum IL-10 levels and T cell count (26).”
BackgroundHoagland, D. A., Møller, R., Uhl, S. A., Oishi, K., Frere, J. J., Golynker, I., Horiuchi, S., Panis, M., Blanco-Melo, D., Sachs, D. M., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.01.017 · Cited by 177
“This juxtaposition of low IFN-I and high chemokines may be responsible for enhanced infiltration of neutrophils and monocytes to the respiratory tract, resulting in COVID-19 (Coperchini et al., 2020; Zheng et al., 2020a).”
Natural Killer Cell Dysfunction and Its Role in COVID-19
van Eeden, C., Khan, L., Osman, M. S., & Tervaert, J. W. C. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176351 · Cited by 179
“SARS-CoV-2 [34,35,84] infection in most cases is characterised by mild symptoms of fever, tiredness and dry cough.”
BackgroundInfluentialWang, X., Xu, W., Hu, G., Xia, S., Sun, Z., Liu, Z., Xie, Y., Zhang, R., Jiang, S., & Lu, L. (2020) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-0498-4 · Cited by 175
“4, 5 Lymphocytopenia was also found in the Middle East respiratory syndrome (MERS) cases.”
BackgroundRetractedRethinking the role of hydroxychloroquine in the treatment of COVID‐19
Meyerowitz, E. A., Vannier, A., Friesen, M. G. N., Schoenfeld, S. R., Gelfand, J. A., Callahan, M. V., Kim, A. Y., Reeves, P. M., & Poznansky, M. C. (2020) · The FASEB Journal · doi:10.1096/fj.202000919 · Cited by 174
Potential benefits and risks of omega-3 fatty acids supplementation to patients with COVID-19
Rogero, M. M., Leão, M. D. C., Santana, T. M., Pimentel, M. V. D. M. B., Carlini, G. C. G., da Silveira, T. F. F., Gonçalves, R. C., & de Castro, I. A. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.07.005 · Cited by 181
“[28] observed lower levels of Cytotoxic CD8 lymphocytes in critically ill patients compared to mild ones.”
Is pregnancy a risk factor of COVID-19?
Phoswa, W. N., & Khaliq, O. P. (2020) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2020.06.058 · Cited by 173
“Several studies have associated increased NKG2A expression with normal pregnancy development [24,29,33].”
InfluentialSokołowska, M., Łukasik, Z. M., Agache, I. O., Akdiş, C. A., Akdiş, D., Akdiş, M., Barcik, W., Brough, H. A., Eiwegger, T., Eljaszewicz, A., et al. (2020) · Allergy · doi:10.1111/all.14462 · Cited by 170
Wu, H., Zhu, H., Yuan, C., Yao, C., Luo, W. P., Shen, X., Wang, J., Shao, J., & Xiang, Y. (2020) · JAMA Network Open · doi:10.1001/jamanetworkopen.2020.10895 · Cited by 168
“048), C4 complement (median [IQR], 18 [13-23] mg/dL vs 22 [16-30] mg/dL; P = .”
BackgroundMicrostructure, pathophysiology, and potential therapeutics of COVID‐19: A comprehensive review
Singh, S. P., Pritam, M., Pandey, B., & Yadav, T. P. (2021) · Journal of Medical Virology · doi:10.1002/jmv.26254 · Cited by 166
Gyöngyösi, M., Alcaide, P., Asselbergs, F. W., Brundel, B. J. J. M., Camici, G. G., Martins, P. A. D. C., Ferdinandy, P., Fontana, M., Girão, H., Gnecchi, M., et al. (2022) · Cardiovascular Research · doi:10.1093/cvr/cvac115 · Cited by 175
Peripheral CD4+ T cell subsets and antibody response in COVID-19 convalescent individuals
Gong, F., Dai, Y., Zheng, T., Cheng, L., Zhao, D., Wang, H., Liu, M., Pei, H., Jin, T., Yu, D., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci141054 · Cited by 160
“However, CD8+ T cells often exhibit exhausted phenotypes in this disease (7, 8), together with markedly reduced cell counts in some severe patients.”
BackgroundWang, X., Xu, W., Hu, G., Xia, S., Sun, Z., Liu, Z., Xie, Y., Zhang, R., Jiang, S., & Lu, L. (2020) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-0424-9 · Cited by 162
“Some studies reported that lymphocytopenia might be related to mortality, especially in patients with low levels of CD3, CD4, and CD8 T lymphocytes.(4,5) Lymphocytopenia was also found in the Middle East respiratory syndrome (MERS) cases.”
BackgroundRetracted
Metadata
- Authors
- Zheng, M., Gao, Y., Wang, G., Song, G., Liu, S., Sun, D., Xu, Y., & Tian, Z.
- Affiliations
- First Affiliated Hospital of Anhui Medical University (CN)
- Anhui Medical University (CN)
- University of Science and Technology of China (CN)
- Corresponding author
- Zheng, Meijuan
- Xu, Yuanhong
- Tian, Zhigang
- Venue
- Cellular & Molecular Immunology
- Published
- 2020-03-19
- Volume
- 17
- Issue
- 5
- Pages
- 533-535
- ISSN
- 1672-7681 (ISSN-L)
- 2042-0226
- PMC
- PMC7091858
- OpenAlex
- W3011508332
- Cited by
- 1,768
- References
- 11
- Citations by year
- 2026: 26 · 2025: 63 · 2024: 119 · 2023: 186 · 2022: 329 · 2021: 514 · 2020: 531
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Cellular and Molecular Immunology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81788101, 81771685)
- Chinese Academy of Sciences (XDB29030000, 81788101)
- Anhui Medical University (YJGG202002)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- COVID-19 pandemic, SARS-CoV-2, T cell exhaustion, T cell dysfunction
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, Antiviral Agents, Hepatitis C, Humans, Killer Cells, Natural, Pneumonia, Viral, Coronavirus Infections, Pandemics
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