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The immunology and immunotherapy for COVID-19

Published online by Cambridge University Press:  17 December 2021

Yixin Liu
Affiliation:
Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
Xinsheng Zhou
Affiliation:
Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
Xuan Liu*
Affiliation:
Department of Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou, China
Xiaotao Jiang*
Affiliation:
Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
*
Authors for correspondence: Xuan Liu, E-mail: liuxuan515@qq.com; Xiaotao Jiang, E-mail: jxt_go@foxmail.com
Authors for correspondence: Xuan Liu, E-mail: liuxuan515@qq.com; Xiaotao Jiang, E-mail: jxt_go@foxmail.com

Abstract

The ongoing global pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and significantly impacts the world economy and daily life. Symptoms of COVID-19 range from asymptomatic to fever, dyspnoea, acute respiratory distress and multiple organ failure. Critical cases often occur in the elderly and patients with pre-existing conditions. By binding to the angiotensin-converting enzyme 2 receptor, SARS-CoV-2 can enter and replicate in the host cell, exerting a cytotoxic effect and causing local and systemic inflammation. Currently, there is no specific treatment for COVID-19, and immunotherapy has consistently attracted attention because of its essential role in boosting host immunity to the virus and reducing overwhelming inflammation. In this review, we summarise the immunopathogenic features of COVID-19 and highlight recent advances in immunotherapy to illuminate ideas for the development of new potential therapies.

Type
Review
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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Footnotes

*

These authors contributed equally to this work.

References

Lu, H et al. (2020) Outbreak of pneumonia of unknown etiology in Wuhan, China: the mystery and the miracle. Journal of Medical Virology 92, 401402.CrossRefGoogle ScholarPubMed
Wang, C et al. (2020) A novel coronavirus outbreak of global health concern. The Lancet 395, 470473.CrossRefGoogle ScholarPubMed
World Health Organization(WHO) Coronavirus Disease (COVID-19) Dashboard. Available at https://covid19.who.int/ (Accessed on October 2021).Google Scholar
Andersen, KG et al. (2020) The proximal origin of SARS-CoV-2. Nature Medicine 26, 450452.CrossRefGoogle ScholarPubMed
Epidemiology Working Group for Ncip Epidemic Response Chinese Center for Disease Control Prevention (2020) The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China. Zhonghua Liu Xing Bing Xue Za Zhi 41, 145151.Google Scholar
Jung, SM et al. (2020) Real-time estimation of the risk of death from novel coronavirus (COVID-19) infection: inference using exported cases. Journal of Clinical Medicine 9, 523. doi: 10.3390/jcm9020523Google ScholarPubMed
Siddiqi, HK and Mehra, MR (2020) COVID-19 illness in native and immunosuppressed states: a clinical-therapeutic staging proposal. Journal of Heart and Lung Transplantation 39, 405407.CrossRefGoogle ScholarPubMed
World Health Organization; COVID-19 clinical management: living guidance. Available at https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1 (Accessed on September 2021).Google Scholar
Wu, A et al. (2020) Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China. Cell Host & Microbe 27, 325328.CrossRefGoogle ScholarPubMed
Hoffmann, M et al. (2020) SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181, 271280 e8.CrossRefGoogle ScholarPubMed
Cantuti-Castelvetri, L et al. (2020) Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. Science 370, 856860.CrossRefGoogle ScholarPubMed
Vankadari, N and Wilce, JA (2020) Emerging Wuhan (COVID-19) coronavirus: glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26. Emerging Microbes & Infections 9, 601604.CrossRefGoogle ScholarPubMed
Amraei, R et al. (2021) CD209L/L-SIGN and CD209/DC-SIGN act as receptors for SARS-CoV-2. ACS Central Science 7, 11561165.CrossRefGoogle ScholarPubMed
Song, W et al. (2018) Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2. PLoS Pathogens 14, e1007236.CrossRefGoogle ScholarPubMed
Prasad, K et al. (2021) Genomics-guided identification of potential modulators of SARS-CoV-2 entry proteases, TMPRSS2 and cathepsins B/L. PLoS ONE 16, e0256141.CrossRefGoogle ScholarPubMed
Khateeb, J et al. (2021) Emerging SARS-CoV-2 variants of concern and potential intervention approaches. Critical Care 25, 244.CrossRefGoogle ScholarPubMed
South, AM et al. (2019) Fetal programming and the angiotensin-(1-7) axis: a review of the experimental and clinical data. Clinical Science 133, 5574.CrossRefGoogle ScholarPubMed
Zhang, H et al. (2020) Expression of the SARS-CoV-2 ACE2 receptor in the human airway epithelium. American Journal of Respiratory and Critical Care Medicine 202, 219229.CrossRefGoogle ScholarPubMed
Wruck, W and Adjaye, J (2020) SARS-CoV-2 receptor ACE2 is co-expressed with genes related to transmembrane serine proteases, viral entry, immunity and cellular stress. Scientific Reports 10, 21415.CrossRefGoogle ScholarPubMed
Wrapp, D et al. (2020) Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 367, 12601263.CrossRefGoogle ScholarPubMed
Shang, J et al. (2020) Structural basis of receptor recognition by SARS-CoV-2. Nature 581, 221224.CrossRefGoogle ScholarPubMed
V'Kovski, P et al. (2021) Coronavirus biology and replication: implications for SARS-CoV-2. Nature Reviews Microbiology 19, 155170.CrossRefGoogle ScholarPubMed
Li, X et al. (2020) Molecular immune pathogenesis and diagnosis of COVID-19. Journal of Pharmaceutical Analysis 10, 102108.CrossRefGoogle ScholarPubMed
Karthik, K et al. (2020) Role of antibody-dependent enhancement (ADE) in the virulence of SARS-CoV-2 and its mitigation strategies for the development of vaccines and immunotherapies to counter COVID-19. Human Vaccines & Immunotherapeutics 16, 30553060.CrossRefGoogle ScholarPubMed
Florindo, HF et al. (2020) Immune-mediated approaches against COVID-19. Nature Nanotechnology 15, 630645.CrossRefGoogle ScholarPubMed
Vabret, N et al. (2020) Immunology of COVID-19: current state of the science. Immunity 52, 910941.CrossRefGoogle ScholarPubMed
Chiappelli, F et al. (2020) COVID-19 immunopathology and immunotherapy. Bioinformation 16, 219222.CrossRefGoogle ScholarPubMed
Liu, J et al. (2020) Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine 55, 102763.CrossRefGoogle ScholarPubMed
Zhao, J et al. (2020) Antibody responses to SARS-CoV-2 in patients with novel coronavirus disease 2019. Clinical infectious Diseases 71, 20272034.CrossRefGoogle ScholarPubMed
World Health Organization. COVID-19 natural immunity: scientific brief, 10 May 2021. Available at https://www.who.int/publications/i/item/WHO-2019-nCoV-Sci_Brief-Natural_immunity-2021.1 (Accessed on October 2021).Google Scholar
Ju, B et al. (2020) Human neutralizing antibodies elicited by SARS-CoV-2 infection. Nature 584, 115119.CrossRefGoogle ScholarPubMed
Zhou, L et al. (2020) Cause analysis and treatment strategies of ‘recurrence’ with novel coronavirus pneumonia (COVID-19) patients after discharge from hospital. Chinese Journal of Tuberculosis and Respiratory Diseases 43, 281284.Google ScholarPubMed
Wiersinga, WJ et al. (2020) Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA 324, 782793.CrossRefGoogle ScholarPubMed
Wang, W et al. (2020) Definition and risks of cytokine release syndrome in 11 critically ill COVID-19 patients with pneumonia: analysis of disease characteristics. Journal of Infectious Diseases 222, 14441451.CrossRefGoogle ScholarPubMed
Conti, P et al. (2020) Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by coronavirus-19 (COVID-19 or SARS-CoV-2): anti-inflammatory strategies. Journal of Biological Regulators and Homeostatic Agents 34, 327331.Google ScholarPubMed
Chua, RL et al. (2020) COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis. Nature Biotechnology 38, 970979.CrossRefGoogle ScholarPubMed
Costela-Ruiz, VJ et al. (2020) SARS-CoV-2 infection: the role of cytokines in COVID-19 disease. Cytokine & Growth Factor Reviews 54, 6275.CrossRefGoogle ScholarPubMed
Huang, C et al. (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395, 497506.CrossRefGoogle ScholarPubMed
McGonagle, D et al. (2020) The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmunity Reviews 19, 102537.CrossRefGoogle ScholarPubMed
Blanco-Melo, D et al. (2020) Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell 181, 10361045 e9.CrossRefGoogle ScholarPubMed
Hadjadj, J et al. (2020) Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science 369, 718724.CrossRefGoogle ScholarPubMed
Ye, Q et al. (2020) The pathogenesis and treatment of the ‘cytokine storm’ in COVID-19. The Journal of Infection 80, 607613.CrossRefGoogle ScholarPubMed
Tay, MZ et al. (2020) The trinity of COVID-19: immunity, inflammation and intervention. Nature Reviews Immunology 20, 363374.CrossRefGoogle ScholarPubMed
Liao, YC et al. (2002) IL-19 induces production of IL-6 and TNF-alpha and results in cell apoptosis through TNF-alpha. Journal of Immunology 169, 42884297.CrossRefGoogle ScholarPubMed
Chen, RF et al. (2006) Role of vascular cell adhesion molecules and leukocyte apoptosis in the lymphopenia and thrombocytopenia of patients with severe acute respiratory syndrome (SARS). Microbes and Infection 8, 122127.CrossRefGoogle Scholar
Yao, S et al. (2021) Elevated serum levels of progranulin and soluble vascular cell adhesion molecule-1 in patients with COVID-19. Journal of inflammation Research 14, 47854794.CrossRefGoogle ScholarPubMed
Bellesi, S et al. (2020) Increased CD95 (Fas) and PD-1 expression in peripheral blood T lymphocytes in COVID-19 patients. British Journal of Haematology 191, 207211.CrossRefGoogle Scholar
Wang, F et al. (2020) Characteristics of peripheral lymphocyte subset alteration in COVID-19 pneumonia. Journal of Infectious Diseases 221, 17621769.CrossRefGoogle ScholarPubMed
Tavakolpour, S et al. (2020) Lymphopenia during the COVID-19 infection: what it shows and what can be learned. Immunology Letters 225, 3132.CrossRefGoogle Scholar
Huang, G et al. (2020) Prognostic value of leukocytosis and lymphopenia for coronavirus disease severity. Emerging Infectious Diseases 26, 18391841.CrossRefGoogle ScholarPubMed
Zhang, B et al. (2020) Immune phenotyping based on the neutrophil-to-lymphocyte ratio and IgG level predicts disease severity and outcome for patients with COVID-19. Frontiers in Molecular Biosciences 7, 157.CrossRefGoogle ScholarPubMed
Lippi, G and Plebani, M (2020) Laboratory abnormalities in patients with COVID-2019 infection. Clinical Chemistry and Laboratory Medicine 58, 11311134.CrossRefGoogle ScholarPubMed
Qin, C et al. (2020) Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clinical infectious Diseases 71, 762768.CrossRefGoogle Scholar
Xu, K et al. (2020) Management of corona virus disease-19 (COVID-19): the Zhejiang experience. Zhejiang da Xue Xue Bao. Yi Xue Ban 49, 147157.Google ScholarPubMed
Wilt, TJ et al. (2021) Remdesivir for adults with COVID-19 : a living systematic review for American college of physicians practice points. Annals of Internal Medicine 174, 209220.CrossRefGoogle ScholarPubMed
Hung, IF et al. (2020) Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet 395, 16951704.CrossRefGoogle ScholarPubMed
Mazewski, C et al. (2020) Type I interferon (IFN)-regulated activation of canonical and non-canonical signaling pathways. Frontiers in Immunology 11, 606456.CrossRefGoogle ScholarPubMed
Mesev, EV et al. (2019) Decoding type I and III interferon signalling during viral infection. 4, 914924.CrossRefGoogle Scholar
Ribero, MS et al. (2020) Interplay between SARS-CoV-2 and the type I interferon response. PLoS Pathogens 16, e1008737.CrossRefGoogle Scholar
Thoms, M et al. (2020) Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2. Science 369, 12491255. doi: 10.1126/science.abc8665.CrossRefGoogle ScholarPubMed
Liyana, A et al. (2019) The emerging role of human TBK1 in virus-induced autophagy. Autophagy 15, 917918.CrossRefGoogle ScholarPubMed
Xia, H et al. (2020) Evasion of type I interferon by SARS-CoV-2. Cell Reports 33, 108234.CrossRefGoogle ScholarPubMed
Fung, SY et al. (2021) SARS-CoV-2 main protease suppresses type I interferon production by preventing nuclear translocation of phosphorylated IRF3. International Journal of Biological Sciences 17, 15471554.CrossRefGoogle ScholarPubMed
Mordstein, M et al. (2010) Lambda interferon renders epithelial cells of the respiratory and gastrointestinal tracts resistant to viral infections. Journal of Virology 84, 56705677.CrossRefGoogle ScholarPubMed
Lazear, HM et al. (2019) Shared and distinct functions of type I and type III interferons. Immunity 50, 907923.CrossRefGoogle ScholarPubMed
Subbian, S and Ramasamy, S (2020) Critical determinants of cytokine storm and type I interferon response in COVID-19 pathogenesis. Clinical Microbiology Reviews 34, e00299–20.Google Scholar
Subbian, S (2021) The abstruse side of type I interferon immunotherapy for COVID-19 cases with comorbidities. Journal of Respiration 34, 49–59. doi: 10.3390/jor1010005.Google Scholar
Pdm, A et al. (2020) Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trial. Clinical Trials 9, 196206.Google Scholar
Zhang, XN et al. (2006) Hyper-activated IRF-1 and STAT1 contribute to enhanced interferon stimulated gene (ISG) expression by interferon alpha and gamma co-treatment in human hepatoma cells. Biochimica et Biophysica Acta 1759, 417425.CrossRefGoogle ScholarPubMed
Nezhad, FS et al. (2020) Therapeutic approaches for COVID-19 based on the dynamics of interferon-mediated immune responses. Preprints, 126. doi:10.20944/preprints202003.0206.v2Google Scholar
Li, C et al. (2021) Effect of a genetically engineered interferon-alpha versus traditional interferon-alpha in the treatment of moderate-to-severe COVID-19: a randomised clinical trial. Annals of Medicine 53, 391401.CrossRefGoogle ScholarPubMed
Van Gool, AR et al. (2003) Neuropsychiatric side effects of interferon-alfa therapy. Pharmacy World & Science: PWS 25, 1120.CrossRefGoogle ScholarPubMed
Seow, J et al. (2020) Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans. Nature Microbiology 5, 15981607.CrossRefGoogle ScholarPubMed
Briggs, N et al. (2021) Early but not late convalescent plasma is associated with better survival in moderate-to-severe COVID-19. 16, e0254453.CrossRefGoogle Scholar
Candia, PD et al. (2021) Effect of time and titer in convalescent plasma therapy for COVID-19. iScience 24, 102898.CrossRefGoogle ScholarPubMed
Cross, RW et al. (2021) Use of convalescent serum reduces severity of COVID-19 in nonhuman primates. Cell Reports 34, 108837.CrossRefGoogle ScholarPubMed
Acosta-Ampudia, Y et al. (2021) COVID-19 convalescent plasma composition and immunological effects in severe patients. Journal of Autoimmunity 118, 102598.CrossRefGoogle ScholarPubMed
Blake, A et al. (2021) Effect of monoclonal antibody treatment on clinical outcomes in ambulatory patients with coronavirus disease 2019. Open Forum Infectious Diseases 7, ofab315.Google Scholar
O'Brien, MP et al. (2021) Subcutaneous REGEN-COV antibody combination for COVID-19 prevention. medRxiv. doi: 10.1101/2021.06.14.21258567Google ScholarPubMed
Koenig, PA et al. (2021) Structure-guided multivalent nanobodies block SARS-CoV-2 infection and suppress mutational escape. Science 371, eabe6230. doi:10.1126/science.abe6230CrossRefGoogle Scholar
Rojas, M et al. (2020) Convalescent plasma in COVID-19: possible mechanisms of action. Autoimmunity Reviews 19, 102554.CrossRefGoogle ScholarPubMed
Concepción, MLRDL et al. (2021) High-dose intravenous immunoglobulins might modulate inflammation in COVID-19 patients. Life Science Alliance 4, e202001009.Google Scholar
Ali, S et al. (2021) Production of hyperimmune anti-SARS-CoV-2 intravenous immunoglobulin from pooled COVID-19 convalescent plasma. Immunotherapy 13, 397407.CrossRefGoogle ScholarPubMed
Chagla, Z (2021) The BNT162b2 (BioNTech/Pfizer) vaccine had 95% efficacy against COVID-19 ≥7 days after the 2nd dose. Annals of Internal Medicine 174, JC15.CrossRefGoogle ScholarPubMed
Hoffmann, D et al. (2021) CVnCoV and CV2CoV protect human ACE2 transgenic mice from ancestral B BavPat1 and emerging B.1.351 SARS-CoV-2. Nature Communications 12, 4048.CrossRefGoogle ScholarPubMed
Amanat, F et al. (2021) SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2. Cell 184, 39363948 e10.CrossRefGoogle ScholarPubMed
Chen, Y et al. (2021) Potent RBD-specific neutralizing rabbit monoclonal antibodies recognize emerging SARS-CoV-2 variants elicited by DNA prime-protein boost vaccination. Emerging Microbes & Infections 10, 13901403.CrossRefGoogle ScholarPubMed
Zhou, H et al. (2021) B.1.526 SARS-CoV-2 variants identified in New York City are neutralized by vaccine-elicited and therapeutic monoclonal antibodies. bioRxiv, doi: 10.1101/2021.03.24.436620.Google ScholarPubMed
Heath, PT et al. (2021) Safety and efficacy of NVX-CoV2373 COVID-19 vaccine. New England Journal of Medicine 385, 1172–1183. doi: 10.1056/NEJMoa2107659CrossRefGoogle ScholarPubMed
Wu, S et al. (2021) Safety, tolerability, and immunogenicity of an aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in adults: preliminary report of an open-label and randomised phase 1 clinical trial. The Lancet. Infectious Diseases 21, 1654–1664. doi: 10.1016/S1473-3099(21)00396-0CrossRefGoogle ScholarPubMed
Zhang, J et al. (2021) Boosting with heterologous vaccines effectively improves protective immune responses of the inactivated SARS-CoV-2 vaccine. Emerging Microbes and Infections 10, 1598–1608. doi: 10.1080/22221751.2021.1957401CrossRefGoogle ScholarPubMed
Routhu, NK et al. (2021) A modified vaccinia Ankara vector-based vaccine protects macaques from SARS-CoV-2 infection, immune pathology, and dysfunction in the lungs. Immunity 54, 542556 e9.CrossRefGoogle ScholarPubMed
Chen L, Y C et al. (2021) Assessing the importance of interleukin-6 in COVID-19. The Lancet. Respiratory Medicine 9, e13.CrossRefGoogle ScholarPubMed
FDA Approves Phase III Clinical Trial of Tocilizumab for COVID-19 Pneumonia https://www.cancernetwork.com/view/fda-approves-phase-iii-clinical-trial-tocilizumab-covid-19-pneumonia Accessed on September 2021.Google Scholar
Investigators, R-C et al. (2021) Interleukin-6 receptor antagonists in critically ill patients with COVID-19. New England Journal of Medicine 384, 14911502.CrossRefGoogle Scholar
Liu, B et al. (2020) Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)? Journal of Autoimmunity 111, 102452.CrossRefGoogle ScholarPubMed
Morrison A, R et al. (2020) Acute hypertriglyceridemia in patients with COVID-19 receiving tocilizumab. Journal of Medical Virology 92, 17911792.CrossRefGoogle ScholarPubMed
Martinon, F et al. (2002) The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Molecular Cell 10, 417426.CrossRefGoogle ScholarPubMed
Price, KN et al. (2020) COVID-19 and immunomodulator/immunosuppressant use in dermatology. Journal of the American Academy of Dermatology 82, e173ee75.CrossRefGoogle ScholarPubMed
Karki, R et al. (2021) Synergism of TNF-alpha and IFN-gamma triggers inflammatory cell death, tissue damage, and mortality in SARS-CoV-2 infection and cytokine shock syndromes. Cell 184, 149-168 e17.CrossRefGoogle ScholarPubMed
Mahajan, R et al. (2020) Eculizumab treatment for renal failure in a pediatric patient with COVID-19. Journal of Nephrology 33, 13731376.CrossRefGoogle Scholar
Ramesh, G et al. (2015) Anti-inflammatory effects of dexamethasone and meloxicam on Borrelia burgdorferi-induced inflammation in neuronal cultures of dorsal root ganglia and myelinating cells of the peripheral nervous system. Journal of Neuroinflammation 12, 240.CrossRefGoogle ScholarPubMed
Horby, P et al. (2021) Dexamethasone in hospitalized patients with COVID-19. New England Journal of Medicine 384, 693704.Google ScholarPubMed
Richardson, P et al. (2020) Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Lancet (London, England) 395, e30e31.CrossRefGoogle ScholarPubMed
Stebbing, J et al. (2020) COVID-19: combining antiviral and anti-inflammatory treatments. The Lancet. Infectious Diseases 20, 400402.CrossRefGoogle ScholarPubMed
Zhou, T et al. (2021) Challenges and advances in clinical applications of mesenchymal stromal cells. Journal of Hematology & Oncology 14, 24.CrossRefGoogle ScholarPubMed
Jamshidi, E et al. (2021) Proposed mechanisms of targeting COVID-19 by delivering mesenchymal stem cells and their exosomes to damaged organs. Stem Cell Reviews and Reports 17, 176192.CrossRefGoogle ScholarPubMed
Xu, X et al. (2021) Evaluation of the safety and efficacy of using human menstrual blood-derived mesenchymal stromal cells in treating severe and critically ill COVID-19 patients: an exploratory clinical trial. Clinical and Translational Medicine 11, e297.CrossRefGoogle ScholarPubMed
Racchetti, G and Meldolesi, J (2021) Extracellular vesicles of mesenchymal stem cells: therapeutic properties discovered with extraordinary success. Biomedicines 9, 667. doi: 10.3390/biomedicines9060667.CrossRefGoogle ScholarPubMed
Gang, M et al. (2020) CAR-modified memory-like NK cells exhibit potent responses to NK-resistant lymphomas. Blood 136, 23082318.CrossRefGoogle ScholarPubMed
Ma, M et al. (2021) CAR-NK cells effectively target the D614 and G614 SARS-CoV-2-infected cells. bioRxiv. doi: 10.1101/2021.01.14.426742.Google ScholarPubMed
Schulien, I et al. (2021) Characterization of pre-existing and induced SARS-CoV-2-specific CD8(+) T cells. Nature Medicine 27, 7885.CrossRefGoogle ScholarPubMed
Rha M, S et al. (2021) PD-1-expressing SARS-CoV-2-specific CD8(+) T cells are not exhausted, but functional in patients with COVID-19. Immunity 54, 4452 e3.CrossRefGoogle Scholar
Zheng, M et al. (2020) Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cellular & Molecular Immunology 17, 533535.CrossRefGoogle ScholarPubMed
Awadasseid, A et al. (2021) Potential protective role of the anti-PD-1 blockade against SARS-CoV-2 infection. Biomedicine & Pharmacotherapy 142, 111957.CrossRefGoogle ScholarPubMed
Riva, G et al. (2020) COVID-19: room for treating T cell exhaustion? Critical Care (London, England) 24, 229.CrossRefGoogle ScholarPubMed
Alamri, A et al. (2021) A missing link: engagements of dendritic cells in the pathogenesis of SARS-CoV-2 infections. International Journal of Molecular Sciences 22, 1118.CrossRefGoogle ScholarPubMed
Cervantes-Barragan, L et al. (2007) Control of coronavirus infection through plasmacytoid dendritic-cell-derived type I interferon. Blood 109, 11311137.CrossRefGoogle ScholarPubMed
Tang, N et al. (2020) Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. Journal of Thrombosis and Haemostasis: JTH 18, 844847.CrossRefGoogle ScholarPubMed
Meizlish, ML et al. (2021) Intermediate-dose anticoagulation, aspirin, and in-hospital mortality in COVID-19: a propensity score-matched analysis. American Journal of Hematology 96, 471479.CrossRefGoogle ScholarPubMed
Gupta, S et al. (2021) Low dose lung radiotherapy for COVID-19 pneumonia: a potential treatment. Respiratory Medicine 186, 106531.CrossRefGoogle ScholarPubMed
Rodel, F et al. (2007) Radiobiological mechanisms in inflammatory diseases of low-dose radiation therapy. International Journal of Radiation Biology 83, 357366.CrossRefGoogle ScholarPubMed
Sharma, DN et al. (2021) Low-dose radiation therapy for COVID-19 pneumonia: a pilot study. The British Journal of Radiology 94, 20210187.CrossRefGoogle ScholarPubMed
Dhawan, G et al. (2020) Low dose radiation therapy as a potential life saving treatment for COVID-19-induced acute respiratory distress syndrome (ARDS). Radiotherapy & Oncology 147, 212216.CrossRefGoogle Scholar
Verbist, KC and Klonowski, KD (2012) Functions of IL-15 in anti-viral immunity: multiplicity and variety. Cytokine 59, 467478.CrossRefGoogle ScholarPubMed
Knudson, KM et al. (2019) Mechanisms involved in IL-15 superagonist enhancement of anti-PD-L1 therapy. Journal for Immunotherapy of Cancer 7, 82.CrossRefGoogle ScholarPubMed
Wilz, SW (2021) A clinical trial of IL-15 and IL-21 combination therapy for COVID-19 is warranted. Cytokine & Growth Factor Reviews 58, 4950.CrossRefGoogle ScholarPubMed