Cellular immunity in patients with COVID-19: molecular biology, pathophysiology, and clinical implications
- Authors: Sсherbak S.G.1,2, Vologzhanin D.A.1,2, Golota A.S.2, Kamilova T.A.2, Makarenko S.V.1,2
-
Affiliations:
- Saint-Petersburg State University
- Saint-Petersburg City Hospital No 40 of Kurortny District
- Issue: Vol 13, No 2 (2022)
- Pages: 66-87
- Section: Reviews
- URL: https://journals.rcsi.science/clinpractice/article/view/106239
- DOI: https://doi.org/10.17816/clinpract106239
- ID: 106239
Cite item
Full Text
Abstract
The COVID-19 pandemic is caused by the SARS-CoV-2 coronavirus. From the viewpoint of factors critical to contain the virus, the neutralizing antibodies to SARS-CoV-2 garner most of the attention, however, it is essential to acknowledge that it is the level of the virus-specific T cell and B cell response that forms a basis for an effective neutralizing antibody response. T cell responses develop early and correlate with the protection, but they are relatively attenuated in the severe disease, in part due to lymphopenia. Understanding the role of different T cell subpopulations in the protection or the COVID-19 pathogenesis is critical to the prevention and treatment. The expression profile of different T cell subpopulations varies with the COVID-19 severity and is associated with the degree of T cell responses and the disease outcome. The structural changes in the genome, transcriptome, and proteome of SARS-CoV-2 promote the emergence of new variants of the virus and can reduce its interaction with antibodies and result in avoiding the neutralization. There is a strong correlation between the number of virus-specific CD4 T cells and neutralizing IgG antibody titers against SARS-CoV-2. During the primary viral infection, there is a wide variation in the cellular and humoral immune responses, patients with severe and prolonged symptoms showing highly imbalanced cellular and humoral immune responses. This review focuses on the generation and clinical significance of cellular immunity in the protection against severe acute infection and reinfection, as well as the potential involvement of seasonal coronavirus-specific cross-reactive T cells in response to SARS-CoV-2.
Full Text
##article.viewOnOriginalSite##About the authors
Sergey G. Sсherbak
Saint-Petersburg State University; Saint-Petersburg City Hospital No 40 of Kurortny District
Email: b40@zdrav.spb.ru
ORCID iD: 0000-0001-5036-1259
SPIN-code: 1537-9822
MD, PhD, Professor
Russian Federation, Saint Petersburg; Saint PetersburgDmitry A. Vologzhanin
Saint-Petersburg State University; Saint-Petersburg City Hospital No 40 of Kurortny District
Email: volog@bk.ru
ORCID iD: 0000-0002-1176-794X
SPIN-code: 7922-7302
MD, PhD
Russian Federation, Saint Petersburg; Saint PetersburgAleksandr S. Golota
Saint-Petersburg City Hospital No 40 of Kurortny District
Author for correspondence.
Email: golotaa@yahoo.com
ORCID iD: 0000-0002-5632-3963
SPIN-code: 7234-7870
MD, PhD, Аssociate Рrofessor
Russian Federation, Saint PetersburgTatyana A. Kamilova
Saint-Petersburg City Hospital No 40 of Kurortny District
Email: kamilovaspb@mail.ru
ORCID iD: 0000-0001-6360-132X
SPIN-code: 2922-4404
Cand. Sci. (Biol.)
Russian Federation, Saint PetersburgStanislav V. Makarenko
Saint-Petersburg State University; Saint-Petersburg City Hospital No 40 of Kurortny District
Email: st.makarenko@gmail.com
ORCID iD: 0000-0002-1595-6668
SPIN-code: 8114-3984
Russian Federation, Saint Petersburg; Saint Petersburg
References
- Khanolkar A. Elucidating T cell and B cell responses to SARS-CoV-2 in humans: gaining insights into protective immunity and immunopathology. Cells. 2021;11(1):67. doi: 10.3390/cells11010067
- Moss P. The T cell immune response against SARS-CoV-2. Nat Immunol. 2022;23(2):186–193. doi: 10.1038/s41590-021-01122-w
- Le Bert N, Tan AT, Kunasegaran K, et al. SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature. 2020;584(7821):457–462. doi: 10.1038/s41586-020-2550-z
- Zeng C, Evans JP, King T, et al. SARS-CoV-2 spreads through cell-to-cell transmission. Proc Natl Acad Sci USA. 2022;119(1):e2111400119. doi: 10.1073/pnas.2111400119
- Da Silva AR, Pallikkuth S, Williams E, et al. Differential T-Cell reactivity to endemic coronaviruses and SARS-CoV-2 in community and health care workers. J Infect Dis. 2021;224(1):70–80. doi: 10.1093/infdis/jiab176
- Bergamaschi L, Mescia F, Turner L, et al. Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease. Immunity. 2021;54(6):1257–1275. doi: 10.1016/j.immuni.2021.05.010
- Lucas C, Klein J, Sundaram ME, et al. Delayed production of neutralizing antibodies correlates with fatal COVID-19. Nat Med. 2021;27(7):1178–1186. doi: 10.1038/s41591-021-01355-0
- Swadling L, Diniz OM, Schmidt NM, et al. Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2. Nature. 2022;601(7891):110–117. doi: 10.1038/s41586-021-04186-8
- Liu G, Jiang X, Zeng X, et al. Analysis of lymphocyte subpopulations and cytokines in COVID-19-associated pneumonia and community-acquired pneumonia. J Immunol Res. 2021;2021:6657894. doi: 10.1155/2021/6657894
- Venet F, Gossez M, Bidar F, et al. T cell response against SARS-CoV-2 persists after one year in patients surviving severe COVID-19. EBioMedicine. 2022;78:103967. doi: 10.1016/j.ebiom.2022.103967
- Le Bert N, Clapham HE, Tan AT, et al. Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection. J Exp Med. 2021;218(5):e20202617. doi: 10.1084/jem.20202617
- Schultze JL, Aschenbrenner AC. COVID-19 and the human innate immune system. Cell. 2021;18-4(7):1671–1692. doi: 10.1016/j.cell.2021.02.029
- Bao C, Tao X, Cui W, et al. Natural killer cells associated with SARS-CoV-2 viral RNA shedding, antibody response and mortality in COVID-19 patients. Exp Hematol Oncol. 2021; 10(1):5. doi: 10.1186/s40164-021-00199-1
- Yu KK, Fischinger S, Smith MT, et al. Comorbid illnesses are associated with altered adaptive immune responses to SARS-CoV-2. JCI Insight. 2021;6(6):e146242. doi: 10.1172/jci.insight.146242
- King C, Sprent J. Dual nature of type I interferons in SARS-CoV-2-induced inflammation. Trends Immunol. 2021;42(4): 312–322. doi: 10.1016/j.it.2021.02.003
- Priyal M, Barmania F, Mellet J, et al. SARS-CoV-2 Variants, Vaccines, and Host Immunity. Front Immunol. 2022;12:809244. doi: 10.3389/fimmu.2021.809244
- Carissimo G, Xu W, Kwok I, et al. Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early marker for severe COVID-19. Nat Commun. 2020;11(1):1–12. doi: 10.1038/s41467-020-19080-6
- Remy KE, Mazer M, Striker DA, et al. Severe immunosuppression and not a cytokine storm characterizes COVID-19 infections. JCI Insight. 2020;5(17):e140329. doi: 10.1172/jci.insight.140329
- Peng Y, Mentzer AJ, Liu G, et al. Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19. Nat Immunol. 2020;21(11):1336–1345. doi: 10.1038/s41590-020-0782-6
- Mathew D, Giles JR, Baxter AE, et al. Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science. 2020;369(6508):eabc8511. doi: 10.1126/science.abc8511
- Laing AG, Lorenc A, del Barrio I, et al. A dynamic COVID-19 immune signature includes associations with poor prognosis. Nat Med. 2020;26(10):1623–1635. doi: 10.1038/s41591-020-1038-6
- Rodriguez L, Pekkarinen PT, Lakshmikanth T, et al. Systems-level immunomonitoring from acute to recovery phase of severe COVID-19. Cell Rep Med. 2020;1(5):100078. doi: 10.1016/j.xcrm.2020.100078
- Blanchard-Rohner G, Didierlaurent A, Tilmanne A, et al. Pediatric COVID-19: immunopathogenesis, transmission and prevention. Vaccines (Basel). 2021;9(9):1002. doi: 10.3390/vaccines9091002
- Garibaldi BT, Fiksel J, Muschelli J, et al. Patient trajectories among persons hospitalized for COVID-19: a cohort study. Ann Intern Med. 2021;174(1):33–41. doi: 10.7326/M20-3905
- Takahashi T, Ellingson MK, Wong P, et al. Sex differences in immune responses that underlie COVID-19 disease outcomes. Nature. 2020;588(7837):315–320. doi: 10.1038/s41586-020-2700-3
- Grifoni A, Sidney J, Vita R, et al. SARS-CoV-2 human T cell epitopes: Adaptive immune response against COVID-19. Cell Host Microbe. 2021;29(7):1076–1092. doi: 10.1016/j.chom.2021.05.010
- Braun, J. Loyal L, Frentsch M, et al. SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19. Nature. 2020;587(7833):270–274. doi: 10.1038/s41586-020-2598-9
- Sekine T, Perez-Potti A, Rivera-Ballesteros O, et al. Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19. Cell. 2020;183(1):158–168. doi: 10.1016/j.cell.2020.08.017
- Nguyen TH, Rowntree LC, Petersen J, et al. CD8(+) T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope display high naive precursor frequency and TCR promiscuity. Immunity. 2021;54(5):1066–1082. doi: 10.1016/j.immuni.2021.04.009
- Notarbartolo S, Ranzani V, Bandera A, et al. Integrated longitudinal immunophenotypic, transcriptional and repertoire analyses delineate immune responses in COVID-19 patients. Sci Immunol. 2021;6(62):eabg5021. doi: 10.1126/sciimmunol.abg5021
- Habel JR, Nguyen TH, van de Sandt CE, et al. Suboptimal SARS-CoV-2-specific CD8+ T cell response associated with the prominent HLA-A*02:01 phenotype. Proc Natl Acad Sci USA. 2020;117(39):24384–24391. doi: 10.1073/pnas.2015486117
- Campbell KM, Steiner G, Wells DK, et al. Prioritization of SARS-CoV-2 epitopes using a pan-HLA and global population inference approach. bioRxiv. 2020. doi: 10.1101/2020.03.30.016931
- Weingarten-Gabbay S, Klaeger S, Sarkizova S, et al. Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs. Cell. 2021;184(15):3962–3980. doi: 10.1016/j.cell.2021.05.046
- Kusnadi A, Ramírez-Suástegui C, Fajardo V, et al. Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8+ T cells. Sci Immunol. 2021; 6(55):eabe4782. doi: 10.1126/sciimmunol.abe4782
- Rydyznski-Moderbacher C, Ramirez SI, Dan JM, et al. Antigen-specific adaptive immunity to SARS-CoV-2 in acute COVID-19 and associations with age and disease severity. Cell. 2020;183(4):996–1012.e19. doi: 10.1016/j.cell.2020.09.038
- Hadjadj J, Yatim N, Barnabei L, et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science. 2020;369(6504):718–724. doi: 10.1126/science.abc6027
- Dan JM, Mateus J, Kato Y, et al. Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection. Science. 2021;371(6529):eabf4063. doi: 10.1126/science.abf4063
- Wang Z, Yang X, Zhong J, et al. Exposure to SARS-CoV-2 generates T-cell memory in the absence of a detectable viral infection. Nat Commun. 2021;12(1):1724. doi: 10.1038/s41467-021-22036-z
- Choe PG, Kang CK, Suh HJ, et al. Waning antibody responses in asymptomatic and symptomatic SARS-CoV-2 infection. Emerging Infect Dis. 2021;27(1):327–329. doi: 10.3201/eid2701.203515
- Mateus J, Grifoni A, Tarke A, et al. Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans. Science. 2020;370(6512):89–94. doi: 10.1126/science.abd3871
- Sette A, Crotty S. Pre-existing immunity to SARS-CoV-2: the knowns and unknowns. Nat Rev Immunol. 2020;20(8):457–458. doi: 10.1038/s41577-020-0389-z
- Poon MM, Rybkina K, Kato Y, et al. SARS-CoV-2 infection generates tissue-localized immunological memory in humans. Sci Immunol. 2021;6(65):eabl9105. doi: 10.1126/sciimmunol.abl9105
- Szabo PA, Dogra P, Gray JI, et al. Longitudinal profiling of respiratory and systemic immune responses reveals myeloid cell-driven lung inflammation in severe COVID-19. Immunity. 2021;54(4):797–814.e6. doi: 10.1016/j.immuni.2021.03.005
- Zhao Y, Kilian C, Turner JE, et al. Clonal expansion and activation of tissue-resident memory-like Th17 cells expressing GM-CSF in the lungs of severe COVID-19 patients. Sci Immunol. 2021;6(56):eabf6692. doi: 10.1126/sciimmunol.abf6692
- Rha MS, Jeong HW, Ko JH, et al. PD-1-Expressing SARS-CoV-2-specific CD8 + T cells are not exhausted, but functional in patients with COVID-19. Immunity. 2021;54(1):44–52. doi: 10.1016/j.immuni.2020.12.002
- Tarke A, Sidney J, Kidd CK, et al. Comprehensive analysis of T cell immunodominance and immunoprevalence of SARS-CoV-2 epitopes in COVID-19 cases. Cell Rep Med. 2021;2(2):100204. doi: 10.1016/j.xcrm.2021.100204
- Boppana S, Qin K, Files JK, et al. SARS-CoV-2-specific circulating T follicular helper cells correlate with neutralizing antibodies and increase during early convalescence. PLoS Pathog. 2021;17(7):e1009761. doi: 10.1371/journal.ppat.1009761
- Verhagen J, van der Meijden ED, Lang V, et al. Human CD4+ T cells specific for dominant epitopes of SARS-CoV-2 Spike and Nucleocapsid proteins with therapeutic potential. Clin Exp Immunol. 2021;205(3):363–378. doi: 10.1111/cei.13627
- Nagler A, Kalaora S, Barbolin C, et al. Identification of presented SARS-CoV-2 HLA class I and HLA class II peptides using HLA peptidomics. Cell Rep. 2021;35(13):109305. doi: 10.1016/j.celrep.2021.109305
- Hu Zi, van der Ploeg K, Chakraborty S, et al. Early immune responses have long-term associations with clinical, virologic, and immunologic outcomes in patients with COVID-19. Res Sq. 2022;rs.3.rs-847082. doi: 10.21203/rs.3.rs-847082/v1
- Yamada T, Sato S, Sotoyama Y, et al. RIG-I triggers a signaling-abortive anti-SARS-CoV-2 defense in human lung cells. Nat Immunol. 2021;22(7):820–828. doi: 10.1038/s41590-021-00942-0
- Pairo-Castineira E, Clohisey S, Klaric L, et al. Genetic mechanisms of critical illness in COVID-19. Nature. 2021; 591(7848):92–98. doi: 10.1038/s41586-020-03065-y
- Adamo S, Michler J, Zurbuchen Y, et al. Signature of long-lived memory CD8+ T cells in acute SARS-CoV-2 infection. Nature. 2022;602(7895):148–155. doi: 10.1038/s41586-021-04280-x
- Kalfaoglu B, Almeida-Santos J, Tye CA, Satou Y. T-cell dysregulation in COVID-19. Biochem Biophys Res Commun. 2021;538:204–210. doi: 10.1016/j.bbrc.2020.10.079
- Sette A, Crotty S. Adaptive immunity to SARS-CoV-2 and COVID-19. Cell. 2021;184(4):861–880. doi: 10.1016/j.cell.2021.01.007
- Bilich T, Nelde A, Heitmann JS, et al. T cell and antibody kinetics delineate SARS-CoV-2 peptides mediating long-term immune responses in COVID-19 convalescent individuals. Sci Transl Med. 2021;13(590):eabf7517. doi: 10.1126/scitranslmed.abf7517
- Cohen KW, Linderman S, Moodie Z, et al. Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells. Cell Rep Med. 2021;2(7):100354. doi: 10.1016/j.xcrm.2021.100354
- Jung JH, Rha MS, Sa M, et al. SARS-CoV-2-specific T cell memory is sustained in COVID-19 convalescent patients for 10 months with successful development of stem cell-like memory T cells. Nat Commun. 2021;12(1):4043. doi: 10.1038/s41467-021-24377-1
- Laurén I, Havervall S, Ng H, et al. Long-term SARS-CoV-2-specific and cross-reactive cellular immune responses correlate with humoral responses, disease severity, and symptomatology. Immun Inflamm Dis. 2022;10(4):e595. doi: 10.1002/iid3.595
- Sagar M, Reifler K, Rossi M, et al. Recent endemic coronavirus infection is associated with less-severe COVID-19. J Clin Invest. 2021;131(1):e143380. doi: 10.1172/JCI143380
- Peng Y, Felce SL, Dong D, et al. An immunodominant NP 105-113-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease. Nat Immunol. 2022;23(1):50–61. doi: 10.1038/s41590-021-01084-z
- Ng KW, Faulkner N, Cornish GH, et al. Preexisting and de novo humoral immunity to SARS-CoV-2 in humans. Science. 2020;370(6522):1339–1343. doi: 10.1126/science.abe1107
- Lauring AS, Hodcroft EB. Genetic variants of SARS-CoV-2- what do they mean? JAMA. 2021;325(6):529–531. doi: 10.1001/jama.2020.27124
- Moeller NH, Shi K, Demir Ö, et al. Structure and dynamics of SARS-CoV-2 proofreading exoribonuclease ExoN. Proc Natl Acad Sci U S A. 2022;119(9):e2106379119. doi: 10.1073/pnas.2106379119
- SARS-CoV-2 variants of concern as of 7 April 2022. European Centre for Disease Prevention and Control. Available from: https://www.ecdc.europa.eu/en/covid-19/variants-concern. Accessed: 15.02.2022.
- Liu C, Ginn HM, Dejnirattisai W, et al. Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum. Cell. 2021;184(16):4220–4236. doi: 10.1016/j.cell.2021.06.020
- Legros V, Denolly S, Vogrig M, et al. A longitudinal study of SARS-CoV-2-infected patients reveals a high correlation between neutralizing antibodies and COVID-19 severity. Cell Mol Immunol. 2021;18(2):318–327. doi: 10.1038/s41423-020-00588-2
- Nyberg T, Ferguson NM, Nash SG, et al. Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study. Lancet. 2022;399(10332):1303–1312. doi: 10.1016/S0140-6736(22)00462-7
- Pulliam JR, van Schalkwyk C, Govender N, et al. Increased risk of SARS-CoV-2 reinfection associated with emergence of the Omicron variant in South Africa. Science. 2022;376(6593):eabn4947. doi: 10.1126/science.abn4947
- Ford CT, Machado JD, Janies DA. Predictions of the SARS-CoV-2 Omicron variant (B.1.1.529) spike protein receptor-binding domain structure and neutralizing antibody interactions. bioRxiv. 2021;2021.12.03.471024. doi: 10.1101/2021.12.03.471024
- Tarke A, Coelho CH, Zhang Z, et al. SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron. Cell. 2022;185(5):847–859.e11. doi: 10.1016/j.cell.2022.01.015
- Woldemeskel BA, Garliss CC, Blankson JN. SARS-CoV-2 mRNA vaccines induce broad CD4+ T cell responses that recognize SARS-CoV-2 variants and HCoV-NL63. J Clin Invest. 2021;131(10):e149335. doi: 10.1172/JCI149335
- De Silva TI, Liu G, Lindsey BB, et al. The impact of viral mutations on recognition by SARS-CoV-2 specific T-cells. Science. 2021;24(11):103353. doi: 10.1016/j.isci.2021.103353
- Zhang Y, Chen Y, Li Y, et al. The ORF8 protein of SARS-CoV-2 mediates immune evasion through down-regulating MHC-Ι. Proc Natl Acad Sci USA. 2021;118(23):e2024202118. doi: 10.1073/pnas.2024202118
- Tarke A, Sidney J, Methot N, et al. Impact of SARS-CoV-2 variants on the total CD4+ and CD8+ T cell reactivity in infected or vaccinated individuals. Cell Rep Med. 2021;2(7):100355. doi: 10.1016/j.xcrm.2021.100355
- Guo L, Wang G, Wang Y, et al. SARS-CoV-2-specific antibody and T-cell responses 1 year after infection in people recovered from COVID-19: a longitudinal cohort study. Lancet Microbe. 2022;3(5):e348–e356 doi: 10.1016/S2666-5247(22)00036-2
- Lauro R, Irrera N, Eid AH, Bitto A. Could antigen presenting cells represent a protective element during SARS-CoV-2 infection in children? Pathogens. 2021;10(4):476. doi: 10.3390/pathogens10040476
- Fung SY, Yuen KS, Ye ZW, et al. A tug-of-war between severe acute respiratory syndrome coronavirus 2 and host antiviral defence: lessons from other pathogenic viruses. Emerg Microbes Infect. 2020;9(1):558–570. doi: 10.1080/22221751.2020.1736644
- Kaneko N, Kuo HH, Boucau J, et al. Loss of Bcl-6-expressing T follicular helper cells and germinal centers in COVID-19. Cell. 2020;183(1):143–157. doi: 10.1016/j.cell.2020.08.025
- Ni L, Ye F, Cheng ML, et al. Detection of SARS-CoV-2-specific humoral and cellular immunity in COVID-19 convalescent individuals. IImmunity. 2020;52(6):971–977. doi: 10.1016/j.immuni.2020.04.023
- Long QX, Tang XJ, Shi QL, et al. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med. 2020;26(8):1200–1204. doi: 10.1038/s41591-020-0965-6
- Turner JS, Kim W, Kalaidina E, et al. SARS-CoV-2 infection induces long-lived bone marrow plasma cells in humans. Nature. 2021;595(7867):421–425. doi: 10.1038/s41586-021-03647-4
- Hartley GE, Edwards ES, Aui PM, et al. Rapid generation of durable B cell memory to SARS-CoV-2 spike and nucleocapsid proteins in COVID-19 and convalescence. Sci Immunol. 2020; 5(54):eabf8891. doi: 10.1126/sciimmunol.abf8891
- Gaebler C, Wang Z, Lorenzi JC, et al. Evolution of antibody immunity to SARS-CoV-2. Nature. 2021;591(7851):639–644. doi: 10.1038/s41586-021-03207-w
- Zaman MS, Sizemore RC. Diverse manifestations of COVID-19: some suggested mechanisms. Int J Environ Res Public Health. 2021;18(18):9785. doi: 10.3390/ijerph18189785
- Zhang JY, Wang XM, Xing X, et al. Single-cell landscape of immunological responses in patients with COVID-19. Nature Immunol. 2020;21(9):1107–1118. doi: 10.1038/s41590-020-0762-x
- Saini SK, Hersby DS, Tamhane T, et al. SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8(+) T cell activation in COVID-19 patients. Sci Immunol. 2021;6(58):eabf7550. doi: 10.1126/sciimmunol.abf7550
- Wellington D, Yin Z, Kessler BM, Dong T. Immunodominance complexity: lessons yet to be learned from dominant T cell responses to SARS-COV-2. Curr Opin Virol. 2021;50:183–191. doi: 10.1016/j.coviro.2021.08.009
- Lineburg KE, Grant EJ, Swaminathan S, et al. CD8 + T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope cross-react with selective seasonal coronaviruses. Immunity. 2021;11;54(5):1055–1065. doi: 10.1016/j.immuni.2021.04.006
- Logunov DY, Dolzhikova IV, Shcheblyakov DV, et al. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia. Lancet. 2021;397(10275): 671–681. doi: 10.1016/S0140-6736(21)00234-8
- Sahin U, Muik A, Vogler I, et al. BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans. Nature. 2021;595(7868):572–577. doi: 10.1038/s41586-021-03653-6
- Baden LR, Sahly HM, Essink B, et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2021; 384(5):403–416. doi: 10.1056/NEJMoa2035389
- Oberhardt V, Luxenburger H, Kemming J, et al. Rapid and stable mobilization of CD8+ T cells by SARS-CoV-2 mRNA vaccine. Nature. 2021;597(7875):268–273. doi: 10.1038/s41586-021-03841-4
- Skelly DT, Harding AC, Gilbert-Jaramillo J, et al. Two doses of SARS-CoV-2 vaccination induce robust immune responses to emerging SARS-CoV-2 variants of concern. Nat Commun. 2021;12(1):5061. doi: 10.1038/s41467-021-25167-5
- Mazzoni A, Di Lauria N, Maggi L, et al. First-dose mRNA vaccination is sufficient to reactivate immunological memory to SARS-CoV-2 in subjects who have recovered from COVID-19. J Clin Invest. 2021;131(12):e149150. doi: 10.1172/JCI149150
- McLean G, Kamil J, Lee B, et al. The impact of evolving SARS-CoV-2 mutations and variants on COVID-19 vaccines. mBio. 2022;13(2):e0297921. doi: 10.1128/mbio.02979-21
- Haranaka M, Baber J, Ogama Y, et al. A randomized study to evaluate safety and immunogenicity of the BNT162b2 COVID-19 vaccine in healthy Japanese adults. Nat Commun. 2021;12(1):7105. doi: 10.1038/s41467-021-27316-2
- Skowronski DM, de Serres G. Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine. N Engl J Med. 2021;384(16):1576–1577. doi: 10.1056/NEJMc2036242
- Keller MD, Harris KM, Jensen-Wachspress MA, et al. SARS-CoV-2-specific T cells are rapidly expanded for therapeutic use and target conserved regions of the membrane protein. Blood. 2020;136(25):2905–2917. doi: 10.1182/blood.2020008488
- Basar R, Uprety N, Ensley E, et al. Generation of glucocorticoid-resistant SARS-CoV-2 T cells for adoptive cell therapy. Cell Rep. 2021;36(3):109432. doi: 10.1016/j.celrep.2021.109432
- Cooper RS, Fraser AR, Smith L, et al. Rapid GMP-compliant expansion of SARS-CoV-2-specific T cells from convalescent donors for use as an allogeneic cell therapy for COVID-19. Front Immunol. 2021;11:598402. doi: 10.3389/fimmu.2020.598402
- Pérez-Martínez A, Mora-Rillo M, Ferreras C, et al. Phase I dose-escalation single centre clinical trial to evaluate the safety of infusion of memory T cells as adoptive therapy in COVID-19 (RELEASE). Clinical Medicine. 2021;39:101086. doi: 10.1016/j.eclinm.2021.101086
- Gladstone DE, Kim BS, Mooney K, et al. Regulatory T cells for treating patients with COVID-19 and acute respiratory distress syndrome: two case reports. Ann Intern Med. 2020;173(10): 852–853. doi: 10.7326/L20-0681
- Baeten P, van Zeebroeck L, Kleinewietfeld M, et al. Improving the efficacy of regulatory T cell therapy. Clin Rev Allergy Immunol. 2022;62(2):363–381. doi: 10.1007/s12016-021-08866-1