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Perspective

Severe COVID-19 is a T cell immune dysregulatory disorder triggered by SARS-CoV-2

ORCID Icon, , , , ORCID Icon &
Pages 557-565 | Received 04 Dec 2021, Accepted 03 May 2022, Published online: 26 May 2022

References

  • Tiwari R, Dhama K, Sharun K, et al. COVID-19: animals, veterinary and zoonotic links. Vet Q. 2020;40(1):169–182.
  • Segreto R, Deigin Y. The genetic structure of SARS-CoV-2 does not rule out a laboratory origin: SARS-COV-2 chimeric structure and furin cleavage site might be the result of genetic manipulation. Bioessays. 2021;43(3):e2000240.
  • Holmes EC, Goldstein SA, Rasmussen AL, et al. The origins of SARS-CoV-2: a critical review. Cell. 2021;184:2848–4856.
  • Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506.
  • Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 Cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271–280.e8.
  • Baek WK, Sohn SY, Mahgoub A, et al. a comprehensive review of severe acute respiratory syndrome Coronavirus 2. Cureus. 2020;12(5):e7943.
  • Weiss P, Murdoch DR. Clinical course and mortality risk of severe COVID-19. Lancet. 2020;395:1014–1015.
  • Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1014–1015.
  • Gao Y, Chen Y, Liu M, et al. Impacts of immunosuppression and immunodeficiency on COVID-19: a systematic review and meta-analysis. J Infect. 2020;81(2):e93–e95.
  • Kirby T. Evidence mounts on the disproportionate effect of COVID-19 on ethnic minorities. Lancet Respir Med. 2020;8(6):547–548.
  • Steyn N, Binny RN, Hannah K, et al. Māori and Pacific people in New Zealand have a higher risk of hospitalisation for COVID-19. N Z Med J. 2021;134(1175–8716 (Electronic):28–43.
  • Kaholokula JK, Samoa RA, Miyamoto RES, et al. COVID-19 special column: COVID-19 Hits Native Hawaiian and Pacific Islander communities the hardest. Hawaii J Health Soc Welf. 2020;79(5):144–146.
  • Bose T, Pant N, Pinna NK, et al. Does immune recognition of SARS-CoV2 epitopes vary between different ethnic groups? Virus Res. 2021;305:198579. .
  • Abedi V, Olulana O, Avula V, et al. Racial, economic, and health inequality and COVID-19 infection in the United States. J Racial Ethn Health Disparities. 2021;8(3):732–742.
  • Wong LR, Perlman S. Immune dysregulation and immunopathology induced by SARS-CoV-2 and related coronaviruses - are we our own worst enemy? Nat Rev Immunol. 2022;22(1):47–56.
  • Bouayad A. Innate immune evasion by SARS-CoV-2: comparison with SARS-CoV. Rev Med Virol. 2020;30(6):1–9.
  • Chouaki Benmansour N, Carvelli J, Vivier E. Complement cascade in severe forms of COVID-19: recent advances in therapy. Eur J Immunol. 2021;51(7):1652–1659.
  • Chen Z, John Wherry E. T cell responses in patients with COVID-19. Nat Rev Immunol. 2020;20(9):529–536.
  • Ameratunga R, Woon ST, Lea E, et al. The (apparent) antibody paradox in COVID-19. Expert Rev Clin Immunol. 2022;10:1–11.
  • Zhou Y, Liu Z, Li S, et al. Enhancement versus neutralization by SARS-CoV-2 antibodies from a convalescent donor associates with distinct epitopes on the RBD. Cell Rep. 2021;34(5):108699.
  • Negro F. Is antibody-dependent enhancement playing a role in COVID-19 pathogenesis? Swiss Med Wkly. 2020;150:w20249. eCollection 22020 Apr 20246.
  • Halstead SB, Katzelnick LC, Russell PK, et al. Ethics of a partially effective dengue vaccine: lessons from the Philippines. Vaccine. 2020;38(35):5572–5576.
  • Rothan HA, Byrareddy SN. The potential threat of multisystem inflammatory syndrome in children during the COVID-19 pandemic. Pediatr Allergy Immunol. 2021;32(1):17–22.
  • Sharma C, Ganigara M, Galeotti C, et al. Multisystem inflammatory syndrome in children and Kawasaki disease: a critical comparison. Nat Rev Rheumatol. 2021;17(12):731–748. Epub 42021 Oct 41529.
  • Ferreira AC, Soares VC, de Azevedo-quintanilha IG, et al. SARS-CoV-2 engages inflammasome and pyroptosis in human primary monocytes. Cell Death Discov. 2021;7(1):43.
  • Yan X, Chen G, Jin Z, et al. Anti-SARS-CoV-2 IgG levels in relation to disease severity of COVID-19. J Med Virol. 2022;94(1):380–383.
  • Sandberg JK, Varnaitė R, Christ W, et al. SARS-CoV-2-specific humoral and cellular immunity persists through 9 months irrespective of COVID-19 severity at hospitalisation. Clin Transl Immunology. 2021;10(7):e1306.
  • Kowitdamrong E, Puthanakit T, Jantarabenjakul W, et al. Antibody responses to SARS-CoV-2 in patients with differing severities of coronavirus disease 2019. PloS one. 2020;15(10):e0240502.
  • Long QX, Liu BZ, Deng HJ, et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med. 2020;26(6):845–848.
  • Ibarrondo FJ, Fulcher JA, Goodman-Meza D, et al. Rapid Decay of Anti-SARS-CoV-2 Antibodies in persons with Mild Covid-19. N Engl J Med. 2020;383(11):1085–1087.
  • Ali AM, Ali KM, Fatah MH, et al. SARS-CoV-2 reinfection in patients negative for immunoglobulin G following recovery from COVID-19. New Microbes New Infect. 2021;43:100926.
  • Esenboga S, Ocak M, Akarsu A, et al. COVID-19 in Patients with Primary Immunodeficiency. J Clin Immunol. 2021;41(7):1515–1522.
  • Gupta S, Agrawal S, Sandoval A, et al. SARS-CoV-2-Specific and functional Cytotoxic CD8 Cells in primary antibody deficiency: natural infection and response to vaccine. J Clin Immunol. 2022;2:1–9.
  • Quinti I, Lougaris V, Milito C, et al. A possible role for B cells in COVID-19? Lesson from patients with agammaglobulinemia. J Allergy Clin Immunol. 2020;146(1):211–213 e214.
  • Jin H, Reed JC, Liu STH, et al. Three patients with X-linked agammaglobulinemia hospitalized for COVID-19 improved with convalescent plasma. J Allergy Clin Immunol Pract. 2020;8(10):3594–3596 e3593.
  • Mira E, Yarce OA, Ortega C, et al. Rapid recovery of a SARS-CoV-2-infected X-linked agammaglobulinemia patient after infusion of COVID-19 convalescent plasma. J Allergy Clin Immunol Pract. 2020;8(8):2793–2795.
  • Van Damme KFA, Tavernier S, Van Roy N, et al. Case report: convalescent Plasma, a Targeted Therapy for patients with CVID and Severe COVID-19. Front Immunol. 2020;11(1664–3224 (Electronic):596761.
  • Schiavetti I, Ponzano M, Signori A, et al. Severe outcomes of COVID-19 among patients with multiple sclerosis under anti-CD-20 therapies: a systematic review and meta-analysis. Mult Scler Relat Disord. 2022;57:103358. Epub 102021 Nov 103355.
  • Valk SJ, Piechotta V, Chai KL, et al. Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a rapid review. Cochrane Database Syst Rev. 2020;5(5):CD013600.
  • Hensley MK, Bain WG, Jacobs J, et al. Intractable Coronavirus Disease 2019 (COVID-19) and prolonged severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) replication in a chimeric antigen receptor-modified T-Cell Therapy recipient: a case study. Clin Infect Dis. 2021;73(3):e815–e821.
  • Chen L, Zody MC, Di Germanio C, et al. Emergence of multiple SARS-CoV-2 antibody escape variants in an immunocompromised host undergoing convalescent plasma treatment. mSphere. 2021;6(4):e0048021.
  • Lin WT, Hung SH, Lai CC, et al. The impact of neutralizing monoclonal antibodies on the outcomes of COVID-19 outpatients: a systematic review and meta-analysis of randomized controlled trials. J Med Virol. 2022;27(10):27623.
  • RECOVERY Collaborative Group. Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2022;399(10325):665–676.
  • Tan AT, Linster M, Tan CW, et al. Early induction of functional SARS-CoV-2-specific T cells associates with rapid viral clearance and mild disease in COVID-19 patients. Cell Rep. 2021;34(6):108728.
  • 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 e1019.
  • Casado JL, Häemmerle J, Vizcarra P, et al. SARS CoV-2 infections in health care workers with pre-existing T cell response: a prospective cohort study. Clin Microbiol Infect. 2021;27(6):916.e1–916.e4.
  • Weiskopf D, Schmitz KS, Raadsen MP, et al. Phenotype and kinetics of SARS-CoV-2-specific T cells in COVID-19 patients with acute respiratory distress syndrome. Sci Immunol. 2020;5(48):eabd2071.
  • Meckiff BJ, Ramirez-Suastegui C, Fajardo V, et al. Imbalance of regulatory and Cytotoxic SARS-CoV-2-Reactive CD4(+) T Cells in COVID-19. Cell. 2020;183(5):1340–1353 e1316.
  • Bacher P, Rosati E, Esser D, et al. Low-avidity CD4(+) T Cell responses to SARS-CoV-2 in unexposed individuals and humans with severe COVID-19. Immunity. 2020;53(6):1258–1271 e1255.
  • Golovkin A, Kalinina O, Bezrukikh V, et al. Imbalanced immune response of T-Cell and B-Cell subsets in patients with moderate and severe COVID-19. Viruses. 2021;13(10):1966.
  • Kroemer M, Boullerot L, Ramseyer M, et al. The quality of anti-SARS-CoV-2 T Cell responses predicts the neutralizing antibody titer in convalescent plasma donors. Front Public Health. 2022;10:816848. eCollection 812022.
  • 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 e114.
  • 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.
  • Cassaniti I, Percivalle E, Bergami F, et al. SARS-CoV-2 specific T-cell immunity in COVID-19 convalescent patients and unexposed controls measured by ex vivo ELISpot assay. Clin Microbiol Infect. 2021;27(7):1029–1034.
  • Chen J, Liu X, Zhang X, et al. Decline in neutralising antibody responses, but sustained T-cell immunity, in COVID-19 patients at 7 months post-infection. Clin Transl Immunology. 2021;10(7):e1319.
  • Bonifacius A, Tischer-Zimmermann S, Dragon AC, et al. COVID-19 immune signatures reveal stable antiviral T cell function despite declining humoral responses. Immunity. 2021;54(2):340–354 e346.
  • Swadling L, Diniz MO, Schmidt NM, et al. Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2. Nature. 2022;601(7891):110–117. .
  • Bastard P, Rosen LB, Zhang Q, et al. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science. 2020;370(6515):eabd4585.
  • Sacchi MC, Tamiazzo S, Stobbione P, et al. SARS-CoV-2 infection as a trigger of autoimmune response. Clinical Translational Science. 2021;14(3):898–907.
  • Kishimoto M, Ishikawa T, Odawara M. Subacute thyroiditis with liver dysfunction following coronavirus disease 2019 (COVID-19) vaccination: report of two cases and a literature review. Endocr J. 2022;10(10):EJ21–0629.
  • Poyrazoğlu HG, Kırık S, Sarı MY, et al. Acute demyelinating encephalomyelitis and transverse myelitis in a child with COVID-19. Turk J Pediatr. 2022;64(1):133–137.
  • Prete S, McShannic JD, Fertel BS, et al. Acute transverse myelitis progressing to permanent quadriplegia following COVID-19 infection. Am J Emerg Med. 2022;23(22):121–123.
  • Vannella KM, Oguz C, Stein SR, et al. Evidence of SARS-CoV-2-specific T-Cell-mediated Myocarditis in a MIS-A case. Front Immunol. 2021;12:779026. eCollection 772021.
  • Woon ST, Ameratunga R, Croxson M, et al. Follicular lymphoma in a X-linked lymphoproliferative syndrome carrier female. Scand J Immunol. 2008;68(2):153–158.
  • Ameratunga R, Lehnert K, Woon ST, et al. Review: diagnosing common variable immunodeficiency disorder in the Era of Genome Sequencing. Clin Rev Allergy Immunol. 2018;54(2):261–268.
  • Fliegauf M, Bryant VL, Frede N, et al. Haploinsufficiency of the NF-kappaB1 subunit p50 in common variable immunodeficiency. Am J Hum Genet. 2015;97(3):389–403.
  • Zhao Y, Liang W, Luo Y, et al. Personal protective equipment protecting healthcare workers in the Chinese epicentre of COVID-19. Clin Microbiol Infect. 2020;26(12):1716–1718.
  • Burgess S, Smith D, Kenyon JC, et al. Lightening the viral load to lessen covid-19 severity. BMJ. 2020;371:m4763.
  • Tsukagoshi H, Shinoda D, Saito M, et al. relationships between Viral load and the clinical course of COVID-19. Viruses. 2021;13(2):304.
  • Liu Y, Liu J, Plante KS, et al. The N501Y spike substitution enhances SARS-CoV-2 infection and transmission. Nature. 2022;602(7896):294–299. Epub 42021 Nov 41524.
  • Corti D, Purcell LA, Snell G, et al. Tackling COVID-19 with neutralizing monoclonal antibodies. Cell. 2021;184:3086–3108.
  • Hussey H, Davies MA, Heekes A, et al. Assessing the clinical severity of the Omicron variant in the Western Cape Province, South Africa, using the diagnostic PCR proxy marker of RdRp target delay to distinguish between Omicron and Delta infections - a survival analysis. Int J Infect Dis. 2022;27(22):121–129.
  • Hong Q, Han W, Li J, et al. Molecular basis of receptor binding and antibody neutralization of Omicron. Nature. 2022;28(10):022–04581.
  • Shah M, Woo HG. Omicron: a heavily mutated SARS-CoV-2 variant exhibits stronger binding to ACE2 and potently escapes approved COVID-19 therapeutic antibodies. Front Immunol. 2021;12:830527. eCollection 832021.
  • Cui Z, Liu P, Wang N, et al. Structural and functional characterizations of infectivity and immune evasion of SARS-CoV-2 Omicron. Cell. 2022;185(5):860–871.e813.
  • Meng B, Abdullahi A, Ferreira I, et al. Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts tropism and fusogenicity. Nature. 2022;603(7902):706–714.
  • Ameratunga R, Woon ST, Steele R, et al. Perspective: the nose and the stomach play a critical role in the NZACE2-Patari* (modified ACE2) drug treatment project of SARS-CoV-2 infection. Expert Rev Clin Immunol. 2021;17(6):553–560.
  • Ameratunga R, Longhurst H, Steele R, et al. Common variable immunodeficiency disorders, T-Cell responses to SARS-CoV-2 Vaccines, and the risk of chronic COVID-19. J Allergy Clin Immunol Pract. 2021;9(10):3575–3583.
  • Ameratunga R, Lehnert K, Leung E, et al. Inhaled modified angiotensin converting enzyme 2 (ACE2) as a decoy to mitigate SARS-CoV-2 infection. N Z Med J. 2020;133(1515):112–118.
  • Al-Aly Z, Xie Y, Bowe B. High-dimensional characterization of post-acute sequelae of COVID-19. Nature. 2021;594(7862):259–264.
  • Augustin M, Schommers P, Stecher M, et al. Post-COVID syndrome in non-hospitalised patients with COVID-19: a longitudinal prospective cohort study. Lancet Reg Health Eur. 2021;6(2666–7762):100122.
  • Liu W, R R, B-r F, et al. Predictors of nonseroconversion after SARS-CoV-2 infection. Emerg Infect Dis. 2021;27(9):2454–2458.
  • Kell DB, Laubscher GJ, Pretorius E. A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications. Biochem J. 2022;479(4):537–559.
  • Tian T, Wu J, Chen T, et al. Long-term follow-up of dynamic brain changes in patients recovered from COVID-19 without neurological manifestations. JCI Insight. 2022;7(4):e155827.
  • Bertoletti A, Le Bert N, Qui M, et al. SARS-CoV-2-specific T cells in infection and vaccination. Cell Mol Immunol. 2021;18(10):2307–2312.
  • Faggiano F, Rossi M, Cena T, et al. An outbreak of COVID-19 among mRNA-Vaccinated Nursing home residents. Vaccines (Basel). 2021;9:859.
  • Bergwerk M, Gonen T, Lustig Y, et al. Covid-19 breakthrough infections in vaccinated health care workers. N Engl J Med. 2021;385(16):1474–1484.
  • Pegu A, O’Connell S, Schmidt SD, et al. Durability of mRNA-1273 vaccine-induced antibodies against SARS-CoV-2 variants. Science. 2021;373(6561):1372–1377.
  • Goel RR, Painter MM, Apostolidis SA, et al. mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern. Science. 2021;374(6572):abm0829.
  • Vardhana S, Baldo L, Morice WG 2nd, et al. Understanding T-cell responses to COVID-19 is essential for informing public health strategies. Sci Immunol. 2022;24:eabo1303.
  • Brosh-Nissimov T, Orenbuch-Harroch E, Chowers M, et al. BNT162b2 vaccine breakthrough: clinical characteristics of 152 fully-vaccinated hospitalized COVID-19 patients in Israel. Clin Microbiol Infect. 2021;27(11):1652–1657.
  • Shroff RT, Chalasani P, Wei R, et al. Immune responses to two and three doses of the BNT162b2 mRNA vaccine in adults with solid tumors. Nat Med. 2021;27(11):2002–2011. Epub 42021 Sep 41530.
  • Mlcochova P, Kemp S, Dhar MS, et al. SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion. Nature. 2021;599(7883):114–119.
  • Tea F, Ospina Stella A, Aggarwal A, et al. SARS-CoV-2 neutralizing antibodies: longevity, breadth, and evasion by emerging viral variants. PLoS Med. 2021;18(7):e1003656.
  • 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.
  • Ameratunga R. Assessing disease severity in common variable immunodeficiency disorders (CVID) and CVID-like disorders. Front Immunol. 2018;9:2130.
  • Ameratunga R, Woon ST. Perspective: evolving concepts in the diagnosis and understanding of common variable immunodeficiency disorders (CVID). Clin Rev Allergy Immunol. 2020;59(1):109–121.
  • Ameratunga R, Allan C, Woon ST. Defining common variable immunodeficiency disorders in 2020. Immunol Allergy Clin North Am. 2020;40(3):403–420.
  • Ameratunga R, Allan C, Lehnert K, et al. Perspective: application of the American college of medical genetics variant interpretation criteria to common variable immunodeficiency disorders. Clin Rev Allergy Immunol. 2021;61(2):226–235. Epub 12021 Apr 12015.
  • Ameratunga R, Gillis D, Steele R. Diagnostic criteria for common variable immunodeficiency disorders. J Allergy Clin Immunol Pract. 2016;4(5):1017–1018.
  • Ameratunga R, Ahn Y, Jordan A, et al. Keeping it in the family: the case for considering late-onset combined immunodeficiency a subset of common variable immunodeficiency disorders. Expert Rev Clin Immunol. 2018;14(7):549–556.
  • Ameratunga R, Ahn Y, Steele R, et al. The natural history of untreated primary hypogammaglobulinemia in adults: implications for the diagnosis and treatment of common variable immunodeficiency disorders (CVID). Front Immunol. 2019;10:1541.
  • Ameratunga R, Woon ST, Steele R, et al. Common Variable Immunodeficiency disorders as a model for assessing COVID-19 vaccine responses in immunocompromised patients. Front Immunol. 2021;12:798389. eCollection 792021.
  • Amodio D, Ruggiero A, Sgrulletti M, et al. Humoral and cellular response following vaccination with the BNT162b2 mRNA COVID-19 vaccine in patients affected by primary immunodeficiencies. Front Immunol. 2021;12:727850.
  • Salinas AF, Mortari EP, Terreri S, et al. SARS-CoV-2 vaccine induced atypical immune responses in antibody defects: everybody does their best. J Clin Immunol. 2021;41(8):1709–1722.
  • Bergman P, Blennow O, Hansson L, et al. Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial. EBioMedicine. 2021;74:103705. Epub 102021 Nov 103730.
  • Steiner S, Schwarz T, Corman VM, et al. SARS-CoV-2 T Cell response in severe and fatal COVID-19 in primary antibody deficiency patients without specific humoral immunity. Front Immunol. 2022;13:840126. eCollection 842022.
  • Björkander S, Du L, Zuo F, et al. SARS-CoV-2 specific B- and T-cell immunity in a population-based study of young Swedish adults. J Allergy Clin Immunol. 2022;149(1):65–75.
  • Jones JM, Stone M, Sulaeman H, et al. Estimated US infection- and vaccine-induced SARS-CoV-2 seroprevalence based on blood donations. JAMA. 2021;326(14):1400–1409.
  • Ameratunga R, Woon ST, Jordan A, et al. Perspective: diagnostic laboratories should urgently develop T cell assays for SARS-CoV-2 infection. Expert Rev Clin Immunol. 2021;17(5):421–430.
  • Ameratunga R, Woon ST, Koopmans W, et al. Cellular and molecular characterisation of the hyper immunoglobulin M syndrome associated with congenital rubella infection. J Clin Immunol. 2009;29(1):99–106.
  • Ameratunga R, Chen CJ, Koopmans W, et al. Identification of germinal centres in the lymph node of a patient with hyperimmunoglobulin M syndrome associated with congenital rubella. J Clin Immunol. 2014;34(7):796–803.
  • Ameratunga R, Lederman HM, Sullivan KE, et al. Defective antigen-induced lymphocyte proliferation in the X-linked hyper-IgM syndrome. J Pediatr. 1997;131(1 Pt 1):147–150.

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