Skip to content
2000
Volume 32, Issue 8
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-COV-2) is one of the biggest unsolved global problems of the 21st century for which there has been no definitive cure yet. Like other respiratory viruses, SARS-COV-2 triggers the host immunity dramatically, causing dysfunction in the immune system, both innate and adaptive, which is a common feature of COVID-19 patients. Evidence shows that in the early stages of COVID-19, the immune system is suppressed while it is overactive in severe patients characterized by excessive and prolonged inflammatory responses called “Cytokine Storm”. There are many elements in the immune system that undergo alterations as the disease progresses. Some significant changes in the innate immune system following infection with SARS-COV-2 include delayed or inhibited interferon type 1 production by the infected cells leading to elevated virus replication, excessive recruitment of activated monocytes and macrophages, decrease in eosinophil population (eosinopenia), consequent decrease in CD8+T lymphocyte proliferation, natural killer (NK) cell dysfunction, and increase in neutrophil infiltration (neutrophilia) and neutrophil extracellular trap (NET) formation. Moreover, hallmark alterations in the adaptive immune system in this process cause an overall decrease in the T lymphocyte number (lymphopenia) and changes in the activity of some lymphocyte subsets and a number of B cells. This review delves into the mentioned changes in the immune system following SARS-COV-2 infection and the implications thereof to guide the development of immunotherapies for patients with COVID-19.

Loading

Article metrics loading...

/content/journals/cmc/10.2174/0929867331666230918092749
2023-10-04
2025-04-21
Loading full text...

Full text loading...

References

  1. WuF. ZhaoS. YuB. ChenY-M. WangW. HuY. Complete genome characterisation of a novel coronavirus associated with severe human respiratory disease in Wuhan, China.BioRxiv202010.1101/2020.01.24.919183
    [Google Scholar]
  2. HollenbergM.D. EpsteinM. The innate immune response, microenvironment proteinases, and the COVID-19 pandemic: Pathophysiologic mechanisms and emerging therapeutic targets.Kidney Int. Suppl.2022121486210.1016/j.kisu.2021.12.001 35316977
    [Google Scholar]
  3. HuB. GuoH. ZhouP. ShiZ-L. Characteristics of SARS-CoV-2 and COVID-19.Nat. Rev. Microbiol.2020114 33024307
    [Google Scholar]
  4. ChenG. WuD. GuoW. CaoY. HuangD. WangH. WangT. ZhangX. ChenH. YuH. ZhangX. ZhangM. WuS. SongJ. ChenT. HanM. LiS. LuoX. ZhaoJ. NingQ. Clinical and immunological features of severe and moderate coronavirus disease 2019.J. Clin. Invest.202013052620262910.1172/JCI137244 32217835
    [Google Scholar]
  5. YinY. WunderinkR.G. MERS, SARS and other coronaviruses as causes of pneumonia.Respirology201823213013710.1111/resp.13196 29052924
    [Google Scholar]
  6. JesenakM. BrndiarovaM. UrbancikovaI. RennerovaZ. VojtkovaJ. BobcakovaA. OstroR. BanovcinP. Immune parameters and COVID-19 infection-associations with clinical severity and diseases prognosis.Front. Cell. Infect. Microbiol.20201036410.3389/fcimb.2020.00364 32695683
    [Google Scholar]
  7. WangD. HuB. HuC. ZhuF. LiuX. ZhangJ. WangB. XiangH. ChengZ. XiongY. ZhaoY. LiY. WangX. PengZ. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China.JAMA2020323111061106910.1001/jama.2020.1585 32031570
    [Google Scholar]
  8. ZhangH. PenningerJ.M. LiY. ZhongN. SlutskyA.S. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: Molecular mechanisms and potential therapeutic target.Intensive Care Med.202046458659010.1007/s00134‑020‑05985‑9 32125455
    [Google Scholar]
  9. WehbeZ. HammoudS.H. YassineH.M. FardounM. El-YazbiA.F. EidA.H. Molecular and biological mechanisms underlying gender differences in COVID-19 severity and mortality.Front. Immunol.20211265933910.3389/fimmu.2021.659339 34025658
    [Google Scholar]
  10. WehbeZ. HammoudS. SoudaniN. ZaraketH. El-YazbiA. EidA.H. Molecular insights into SARS COV-2 interaction with cardiovascular disease: Role of RAAS and MAPK signaling.Front. Pharmacol.20201183610.3389/fphar.2020.00836 32581799
    [Google Scholar]
  11. WangK. ChenW. ZhouY-S. LianJ-Q. ZhangZ. DuP. SARS-CoV-2 invades host cells via a novel route: CD147-spike protein.BioRxiv202010.1101/2020.03.14.988345
    [Google Scholar]
  12. WehbeZ. WehbeM. IratniR. PintusG. ZaraketH. YassineH.M. EidA.H. Repurposing ivermectin for COVID-19: Molecular aspects and therapeutic possibilities.Front. Immunol.20211266358610.3389/fimmu.2021.663586 33859652
    [Google Scholar]
  13. TajbakhshA. Gheibi HayatS.M. TaghizadehH. AkbariA. InabadiM. SavardashtakiA. JohnstonT.P. SahebkarA. COVID-19 and cardiac injury: clinical manifestations, biomarkers, mechanisms, diagnosis, treatment, and follow up. Exp. Rev.Anti-infective Ther.202119334535710.1080/14787210.2020.1822737
    [Google Scholar]
  14. Na-BangchangK. PorasuphatanaS. KarbwangJ. Perspective: repurposed drugs for COVID-19.Arch. Med. Sci. AMS20221851378139110.5114/aoms/152467
    [Google Scholar]
  15. Vahedian-AzimiA. MohammadiS.M. BanachM. BeniF.H. GuestP.C. Al-RasadiK. JamialahmadiT. SahebkarA. Improved COVID-19 outcomes following statin therapy: An updated systematic review and meta-analysis.BioMed Res. Int.20212021190177210.1155/2021/1901772
    [Google Scholar]
  16. DelvesP.J. RoittI.M. DelvesP.J. RoittI.M. The immune system. First of two parts.N. Engl. J. Med.20003431374910.1056/NEJM200007063430107 10882768
    [Google Scholar]
  17. ZhouY. FuB. ZhengX. WangD. ZhaoC. QiY. SunR. TianZ. XuX. WeiH. Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients.Natl. Sci. Rev.202076998100210.1093/nsr/nwaa041 34676125
    [Google Scholar]
  18. ZhuN. ZhangD. WangW. LiX. YangB. SongJ. ZhaoX. HuangB. ShiW. LuR. NiuP. ZhanF. MaX. WangD. XuW. WuG. GaoG.F. TanW. A novel coronavirus from patients with pneumonia in China, 2019.N. Engl. J. Med.2020382872773310.1056/NEJMoa2001017 31978945
    [Google Scholar]
  19. ZhouP. YangX-L. WangX-G. HuB. ZhangL. ZhangW. A pneumonia outbreak associated with a new coronavirus of probable bat origin.Nature20205797798270273
    [Google Scholar]
  20. YanR. ZhangY. LiY. XiaL. GuoY. ZhouQ. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2.Science202036764851444144810.1126/science.abb2762 32132184
    [Google Scholar]
  21. VelavanT.P. MeyerC.G. The COVID‐19 epidemic.Trop. Med. Int. Health202025327828010.1111/tmi.13383 32052514
    [Google Scholar]
  22. HarapanH. ItohN. YufikaA. WinardiW. KeamS. TeH. MegawatiD. HayatiZ. WagnerA.L. MudatsirM. Coronavirus disease 2019 (COVID-19): A literature review.J. Infect. Public Health202013566767310.1016/j.jiph.2020.03.019 32340833
    [Google Scholar]
  23. CongY. UlasliM. SchepersH. MautheM. V’kovskiP. KriegenburgF. ThielV. de HaanC.A.M. ReggioriF. Nucleocapsid protein recruitment to replication-transcription complexes plays a crucial role in coronaviral life cycle.J. Virol.2020944e01925e1910.1128/JVI.01925‑19 31776274
    [Google Scholar]
  24. SrinivasanS. CuiH. GaoZ. LiuM. LuS. MkandawireW. NarykovO. SunM. KorkinD. Structural genomics of SARS-CoV-2 indicates evolutionary conserved functional regions of viral proteins.Viruses202012436010.3390/v12040360 32218151
    [Google Scholar]
  25. DawoodA.A. Glycosylation, ligand binding sites and antigenic variations between membrane glycoprotein of COVID-19 and related coronaviruses.Vacunas20212211910.1016/j.vacun.2020.09.005 33041736
    [Google Scholar]
  26. Nieto-TorresJ.L. DeDiegoM.L. Verdiá-BáguenaC. Jimenez-GuardeñoJ.M. Regla-NavaJ.A. Fernandez-DelgadoR. Castaño-RodriguezC. AlcarazA. TorresJ. AguilellaV.M. EnjuanesL. Severe acute respiratory syndrome coronavirus envelope protein ion channel activity promotes virus fitness and pathogenesis.PLoS Pathog.2014105e100407710.1371/journal.ppat.1004077 24788150
    [Google Scholar]
  27. BeniacD.R. AndonovA. GrudeskiE. BoothT.F. Architecture of the SARS coronavirus prefusion spike.Nat. Struct. Mol. Biol.200613875175210.1038/nsmb1123 16845391
    [Google Scholar]
  28. LinL. LuL. CaoW. LiT. Hypothesis for potential pathogenesis of SARS-CoV-2 infection–a review of immune changes in patients with viral pneumonia.Emerg. Microbes Infect.20209172773210.1080/22221751.2020.1746199 32196410
    [Google Scholar]
  29. LiW. MooreM.J. VasilievaN. SuiJ. WongS.K. BerneM.A. SomasundaranM. SullivanJ.L. LuzuriagaK. GreenoughT.C. ChoeH. FarzanM. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus.Nature2003426696545045410.1038/nature02145 14647384
    [Google Scholar]
  30. ShangJ. YeG. ShiK. WanY. LuoC. AiharaH. GengQ. AuerbachA. LiF. Structural basis of receptor recognition by SARS-CoV-2.Nature2020581780722122410.1038/s41586‑020‑2179‑y 32225175
    [Google Scholar]
  31. LiF. Structure, function, and evolution of coronavirus spike proteins.Annu. Rev. Virol.20163123726110.1146/annurev‑virology‑110615‑042301 27578435
    [Google Scholar]
  32. WallsA.C. ParkY-J. TortoriciM.A. WallA. McGuireA.T. VeeslerD. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein.Cell2020181228192.e6
    [Google Scholar]
  33. HirotsuY. MaejimaM. ShibusawaM. AmemiyaK. NagakuboY. HosakaK. SuekiH. MochizukiH. TsutsuiT. KakizakiY. MiyashitaY. OmataM. Analysis of COVID-19 and non-COVID-19 viruses, including influenza viruses, to determine the influence of intensive preventive measures in Japan.J. Clin. Virol.202012910454310.1016/j.jcv.2020.104543 32663787
    [Google Scholar]
  34. de GaboryL. AlharbiA. KérimianM. LafonM.E. The influenza virus, SARS-CoV-2, and the airways: Clarification for the otorhinolaryngologist.Eur. Ann. Otorhinolaryngol. Head Neck Dis.2020137429129610.1016/j.anorl.2020.05.015 32507410
    [Google Scholar]
  35. ParkinJ. CohenB. An overview of the immune system.Lancet200135792701777178910.1016/S0140‑6736(00)04904‑7 11403834
    [Google Scholar]
  36. WannametheeS.G. LoweG.D.O. RumleyA. BruckdorferK.R. WhincupP.H. Associations of vitamin C status, fruit and vegetable intakes, and markers of inflammation and hemostasis.Am. J. Clin. Nutr.200683356757410.1093/ajcn.83.3.567 16522902
    [Google Scholar]
  37. SchnappaufO. ChaeJ.J. KastnerD.L. AksentijevichI. The pyrin inflammasome in health and disease.Front. Immunol.201910174510.3389/fimmu.2019.01745 31456795
    [Google Scholar]
  38. Al-SamkariH. BerlinerN. Hemophagocytic lymphohistiocytosis.Annu. Rev. Pathol.201813274910.1146/annurev‑pathol‑020117‑043625
    [Google Scholar]
  39. MehtaP. McAuleyD.F. BrownM. SanchezE. TattersallR.S. MansonJ.J. COVID-19: Consider cytokine storm syndromes and immunosuppression.Lancet2020395102291033103410.1016/S0140‑6736(20)30628‑0 32192578
    [Google Scholar]
  40. LauroR. IrreraN. EidA.H. BittoA. Could antigen presenting cells represent a protective element during SARS-CoV-2 infection in children?Pathogens202110447610.3390/pathogens10040476 33920011
    [Google Scholar]
  41. TianW. ZhangN. JinR. FengY. WangS. GaoS. GaoR. WuG. TianD. TanW. ChenY. GaoG.F. WongC.C.L. Immune suppression in the early stage of COVID-19 disease.Nat. Commun.2020111585910.1038/s41467‑020‑19706‑9 33203833
    [Google Scholar]
  42. ArunachalamP.S. WimmersF. MokC.K.P. PereraR.A.P.M. ScottM. HaganT. SigalN. FengY. BristowL. Tak-Yin TsangO. WaghD. CollerJ. PellegriniK.L. KazminD. AlaaeddineG. LeungW.S. ChanJ.M.C. ChikT.S.H. ChoiC.Y.C. HuertaC. Paine McCulloughM. LvH. AndersonE. EdupugantiS. UpadhyayA.A. BosingerS.E. MaeckerH.T. KhatriP. RouphaelN. PeirisM. PulendranB. Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans.Science202036965081210122010.1126/science.abc6261 32788292
    [Google Scholar]
  43. TayM.Z. PohC.M. RéniaL. MacAryP.A. NgL.F.P. The trinity of COVID-19: Immunity, inflammation and intervention.Nat. Rev. Immunol.202020636337410.1038/s41577‑020‑0311‑8 32346093
    [Google Scholar]
  44. von MeijenfeldtF.A. HavervallS. AdelmeijerJ. LundströmA. RudbergA.S. MagnussonM. MackmanN. ThalinC. LismanT. Prothrombotic changes in patients with COVID‐19 are associated with disease severity and mortality.Res. Pract. Thromb. Haemost.20215113214110.1002/rth2.12462 33537537
    [Google Scholar]
  45. ZhouZ. RenL. ZhangL. ZhongJ. XiaoY. JiaZ. Overly exuberant innate immune response to SARS-CoV-2 infection.Cell Host Microbe202010.2139/ssrn.3551623
    [Google Scholar]
  46. WenW. SuW. TangH. LeW. ZhangX. ZhengY. Immune cell profiling of COVID-19 patients in the recovery stage by single-cell sequencing.Cell Discov.202061118
    [Google Scholar]
  47. ZhangD. GuoR. LeiL. LiuH. WangY. WangY. COVID‐19 infection induces readily detectable morphologic and inflammation‐related phenotypic changes in peripheral blood monocytes.J. Leukoc. Biol.202010911322 33040384
    [Google Scholar]
  48. JesenakM. BanovcinP. DiamantZ. COVID‐19, chronic inflammatory respiratory diseases and eosinophils—Observations from reported clinical case series.Allergy20207571819182210.1111/all.14353 32369190
    [Google Scholar]
  49. Flores-TorresA.S. Salinas-CarmonaM.C. SalinasE. Rosas-TaracoA.G. Eosinophils and respiratory viruses.Viral Immunol.201932519820710.1089/vim.2018.0150 31140942
    [Google Scholar]
  50. LiuY. YangY. ZhangC. HuangF. WangF. YuanJ. WangZ. LiJ. LiJ. FengC. ZhangZ. WangL. PengL. ChenL. QinY. ZhaoD. TanS. YinL. XuJ. ZhouC. JiangC. LiuL. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury.Sci. China Life Sci.202063336437410.1007/s11427‑020‑1643‑8 32048163
    [Google Scholar]
  51. SunD. ZhangD. TianR. LiY. WangY. CaoJ. TangY. ZhangN. ZanT. GaoL. HuangY. CuiC. WangD. ZhengY. LvG. The underlying changes and predicting role of peripheral blood inflammatory cells in severe COVID-19 patients: A sentinel?Clin. Chim. Acta202050812212910.1016/j.cca.2020.05.027 32417210
    [Google Scholar]
  52. XieG. DingF. HanL. YinD. LuH. ZhangM. The role of peripheral blood eosinophil counts in COVID‐19 patients.Allergy202176247148210.1111/all.14465 32562554
    [Google Scholar]
  53. YanB. YangJ. XieY. TangX. Relationship between blood eosinophil levels and COVID-19 mortality.World Allergy Organ. J.202114310052110.1016/j.waojou.2021.100521 33589865
    [Google Scholar]
  54. TanB.H.J. Host defense against intracellular pathogens.Los AngelesUniversity of California2004
    [Google Scholar]
  55. GralinskiL.E. SheahanT.P. MorrisonT.E. MenacheryV.D. JensenK. LeistS.R. WhitmoreA. HeiseM.T. BaricR.S. Complement activation contributes to severe acute respiratory syndrome coronavirus pathogenesis.MBio201895e01753e1810.1128/mBio.01753‑18 30301856
    [Google Scholar]
  56. BarnesB.J. AdroverJ.M. Baxter-StoltzfusA. BorczukA. Cools-LartigueJ. CrawfordJ.M. Daßler-PlenkerJ. GuerciP. HuynhC. KnightJ.S. LodaM. LooneyM.R. McAllisterF. RayesR. RenaudS. RousseauS. SalvatoreS. SchwartzR.E. SpicerJ.D. YostC.C. WeberA. ZuoY. EgebladM. Targeting potential drivers of COVID-19: Neutrophil extracellular traps.J. Exp. Med.20202176e2020065210.1084/jem.20200652 32302401
    [Google Scholar]
  57. LiuY. DuX. ChenJ. JinY. PengL. WangH.H.X. LuoM. ChenL. ZhaoY. Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19.J. Infect.2020811e6e1210.1016/j.jinf.2020.04.002 32283162
    [Google Scholar]
  58. FuJ. KongJ. WangW. WuM. YaoL. WangZ. JinJ. WuD. YuX. The clinical implication of dynamic neutrophil to lymphocyte ratio and D-dimer in COVID-19: A retrospective study in Suzhou China.Thromb. Res.20201923810.1016/j.thromres.2020.05.006 32407937
    [Google Scholar]
  59. PaustS. SenmanB. Von AndrianU.H. Adaptive immune responses mediated by natural killer cells.Immunol. Rev.2010235128629610.1111/j.0105‑2896.2010.00906.x 20536570
    [Google Scholar]
  60. SunJ.C. BeilkeJ.N. LanierL.L. Adaptive immune features of natural killer cells.Nature2009457722955756110.1038/nature07665 19136945
    [Google Scholar]
  61. CerwenkaA. LanierL.L. Natural killer cells, viruses and cancer.Nat. Rev. Immunol.200111414910.1038/35095564 11905813
    [Google Scholar]
  62. PragerI. LiescheC. van OoijenH. UrlaubD. VerronQ. SandströmN. FasbenderF. ClausM. EilsR. BeaudouinJ. ÖnfeltB. WatzlC. NK cells switch from granzyme B to death receptor–mediated cytotoxicity during serial killing.J. Exp. Med.201921692113212710.1084/jem.20181454 31270246
    [Google Scholar]
  63. National Research Project for SARS Beijing Group. The involvement of natural killer cells in the pathogenesis of severe acute respiratory syndrome.Am. J. Clin. Pathol.2004121450751110.1309/WPK7Y2XKNF4CBF3R 15080302
    [Google Scholar]
  64. AcharyaD. LiuG. GackM.U. Dysregulation of type I interferon responses in COVID-19.Nat. Rev. Immunol.202020739739810.1038/s41577‑020‑0346‑x 32457522
    [Google Scholar]
  65. AielloA. FarzanehF. CandoreG. CarusoC. DavinelliS. GambinoC.M. LigottiM.E. ZareianN. AccardiG. Immunosenescence and its hallmarks: How to oppose aging strategically? A review of potential options for therapeutic intervention.Front. Immunol.201910224710.3389/fimmu.2019.02247 31608061
    [Google Scholar]
  66. DengY. LiuW. LiuK. FangY.Y. ShangJ. ZhouL. WangK. LengF. WeiS. ChenL. LiuH.G. Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 in Wuhan, China: A retrospective study.Chin. Med. J.2020133111261126710.1097/CM9.0000000000000824 32209890
    [Google Scholar]
  67. YangW. CaoQ. QinL. WangX. ChengZ. PanA. DaiJ. SunQ. ZhaoF. QuJ. YanF. Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19):A multi-center study in Wenzhou city, Zhejiang, China.J. Infect.202080438839310.1016/j.jinf.2020.02.016 32112884
    [Google Scholar]
  68. LiD. ChenY. LiuH. JiaY. LiF. WangW. Immune dysfunction leads to mortality and organ injury in patients with COVID-19 in China: insights from ERS-COVID-19 study.Signal Transduct. Target. Ther.2020511310.1038/s41392‑019‑0089‑y 32296011
    [Google Scholar]
  69. ChenJ. LauY.F. LamirandeE.W. PaddockC.D. BartlettJ.H. ZakiS.R. SubbaraoK. Cellular immune responses to severe acute respiratory syndrome coronavirus (SARS-CoV) infection in senescent BALB/c mice: CD4+ T cells are important in control of SARS-CoV infection.J. Virol.20108431289130110.1128/JVI.01281‑09 19906920
    [Google Scholar]
  70. ZhaoJ. ZhaoJ. PerlmanS. T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice.J. Virol.201084189318932510.1128/JVI.01049‑10 20610717
    [Google Scholar]
  71. KoutsakosM. NguyenT.H.O. KedzierskaK. With a little help from T follicular helper friends: Humoral immunity to influenza vaccination.J. Immunol.2019202236036710.4049/jimmunol.1800986 30617117
    [Google Scholar]
  72. GrifoniA. WeiskopfD. RamirezS.I. MateusJ. DanJ.M. ModerbacherC.R. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals.Cell202018171489501.e15
    [Google Scholar]
  73. SaghafiN. RezaeeS.A. Momtazi-BorojeniA.A. TavasolianF. SathyapalanT. AbdollahiE. SahebkarA. The therapeutic potential of regulatory T cells in reducing cardiovascular complications in patients with severe COVID-19.Life Sci.202229412039210.1016/j.lfs.2022.120392
    [Google Scholar]
  74. De BiasiS. MeschiariM. GibelliniL. BellinazziC. BorellaR. FidanzaL. GozziL. IannoneA. Lo TartaroD. MattioliM. PaoliniA. MenozziM. MilićJ. FranceschiG. FantiniR. TonelliR. SitaM. SartiM. TrentiT. BrugioniL. CicchettiL. FacchinettiF. PietrangeloA. CliniE. GirardisM. GuaraldiG. MussiniC. CossarizzaA. Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with COVID-19 pneumonia.Nat. Commun.2020111343410.1038/s41467‑020‑17292‑4 32632085
    [Google Scholar]
  75. YeQ. WangB. MaoJ. The pathogenesis and treatment of the ‘Cytokine Storm’ in COVID-19.J. Infect.202080660761310.1016/j.jinf.2020.03.037 32283152
    [Google Scholar]
  76. SchmittV. RinkL. UciechowskiP. The Th17/Treg balance is disturbed during aging.Exp. Gerontol.201348121379138610.1016/j.exger.2013.09.003 24055797
    [Google Scholar]
  77. Nikolich-ZugichJ. KnoxK.S. RiosC.T. NattB. BhattacharyaD. FainM.J. SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes.Geroscience202042250551410.1007/s11357‑020‑00186‑0 32274617
    [Google Scholar]
  78. Kaffash FarkhadN. ReihaniH. sedaghat, A.; Moghadam, A.A.; Moghadam, A.B.; Tavakol-Afshari, J. Are mesenchymal stem cells able to manage cytokine storm in COVID-19 patients? A review of recent studies.Regen. Ther.20211815216010.1016/j.reth.2021.05.007 34124322
    [Google Scholar]
  79. QinC. ZhouL. HuZ. ZhangS. YangS. TaoY. XieC. MaK. ShangK. WangW. TianD.S. Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China.Clin. Infect. Dis.2020711576276810.1093/cid/ciaa248 32161940
    [Google Scholar]
  80. NeurathM.F. COVID-19 and immunomodulation in IBD.Gut20206971335134210.1136/gutjnl‑2020‑321269 32303609
    [Google Scholar]
  81. MahallawiW.H. KhabourO.F. ZhangQ. MakhdoumH.M. SulimanB.A. MERS-CoV infection in humans is associated with a pro-inflammatory Th1 and Th17 cytokine profile.Cytokine201810481310.1016/j.cyto.2018.01.025 29414327
    [Google Scholar]
  82. JossetL. MenacheryV.D. GralinskiL.E. AgnihothramS. SovaP. CarterV.S. YountB.L. GrahamR.L. BaricR.S. KatzeM.G. Cell host response to infection with novel human coronavirus EMC predicts potential antivirals and important differences with SARS coronavirus.MBio201343e00165e1310.1128/mBio.00165‑13 23631916
    [Google Scholar]
  83. FaureE. PoissyJ. GoffardA. FournierC. KipnisE. TitecatM. BortolottiP. MartinezL. DubucquoiS. DesseinR. GossetP. MathieuD. GueryB. Distinct immune response in two MERS-CoV-infected patients: Can we go from bench to bedside?PLoS One201492e8871610.1371/journal.pone.0088716 24551142
    [Google Scholar]
  84. Galván-PeñaS. LeonJ. ChowdharyK. MichelsonD.A. VijaykumarB. YangL. MagnusonA.M. ChenF. Manickas-HillZ. Piechocka-TrochaA. WorrallD.P. HallK.E. GhebremichaelM. WalkerB.D. LiJ.Z. YuX.G. MathisD. BenoistC. Lavin-ParsonsK. ParryB. LilleyB. LodensteinC. McKaigB. CharlandN. KhannaH. MargolinJ. GonyeA. GushterovaI. LasalleT. SharmaN. RussoB.C. Rojas-LopezM. Sade-FeldmanM. ManakongtreecheepK. TantivitJ. ThomasM.F. Profound Treg perturbations correlate with COVID-19 severity.Proc. Natl. Acad. Sci.202111837e211131511810.1073/pnas.2111315118 34433692
    [Google Scholar]
  85. SamiR. FathiF. EskandariN. AhmadiM. ArefNezhad, R.; Motedayyen, H. Characterizing the immune responses of those who survived or succumbed to COVID-19: Can immunological signatures predict outcome?Cytokine202114015543910.1016/j.cyto.2021.155439 33524886
    [Google Scholar]
  86. AnghelinaD. ZhaoJ. TrandemK. PerlmanS. Role of regulatory T cells in coronavirus-induced acute encephalitis.Virology2009385235836710.1016/j.virol.2008.12.014 19141357
    [Google Scholar]
  87. GladstoneD.E. KimB.S. MooneyK. KarabaA.H. D’AlessioF.R. Regulatory T cells for treating patients with COVID-19 and acute respiratory distress syndrome: two case reports.Ann. Intern. Med.20201731085285310.7326/L20‑0681 32628535
    [Google Scholar]
  88. SadeghiA. TahmasebiS. MahmoodA. KuznetsovaM. ValizadehH. TaghizadiehA. NazemiyehM. Aghebati-MalekiL. Jadidi-NiaraghF. Abbaspour-AghdamS. RoshangarL. MikaeiliH. AhmadiM. Th17 and Treg cells function in SARS‐CoV2 patients compared with healthy controls.J. Cell. Physiol.202123642829283910.1002/jcp.30047 32926425
    [Google Scholar]
  89. DiaoB. WangC. TanY. ChenX. LiuY. NingL. ChenL. LiM. LiuY. WangG. YuanZ. FengZ. ZhangY. WuY. ChenY. Reduction and functional exhaustion of T cells in patients with coronavirus disease 2019 (COVID-19).Front. Immunol.20201182710.3389/fimmu.2020.00827 32425950
    [Google Scholar]
  90. XuZ. ShiL. WangY. ZhangJ. HuangL. ZhangC. LiuS. ZhaoP. LiuH. ZhuL. TaiY. BaiC. GaoT. SongJ. XiaP. DongJ. ZhaoJ. WangF.S. Pathological findings of COVID-19 associated with acute respiratory distress syndrome.Lancet Respir. Med.20208442042210.1016/S2213‑2600(20)30076‑X 32085846
    [Google Scholar]
  91. DemariaO. CornenS. DaëronM. MorelY. MedzhitovR. VivierE. Harnessing innate immunity in cancer therapy.Nature20195747776455610.1038/s41586‑019‑1593‑5 31578484
    [Google Scholar]
  92. ClayC.C. DonartN. FomukongN. KnightJ.B. OverheimK. TipperJ. Van WestrienenJ. HahnF. HarrodK.S. Severe acute respiratory syndrome-coronavirus infection in aged nonhuman primates is associated with modulated pulmonary and systemic immune responses.Immun. Ageing2014111410.1186/1742‑4933‑11‑4 24642138
    [Google Scholar]
  93. WangF. NieJ. WangH. ZhaoQ. XiongY. DengL. SongS. MaZ. MoP. ZhangY. Characteristics of peripheral lymphocyte subset alteration in COVID-19 pneumonia.J. Infect. Dis.2020221111762176910.1093/infdis/jiaa150 32227123
    [Google Scholar]
  94. ZhengH.Y. ZhangM. YangC.X. ZhangN. WangX.C. YangX.P. DongX.Q. ZhengY.T. Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients.Cell. Mol. Immunol.202017554154310.1038/s41423‑020‑0401‑3 32203186
    [Google Scholar]
  95. XuB. FanC. WangA. ZouY. YuY. HeC. XiaW. ZhangJ. MiaoQ. Suppressed T cell-mediated immunity in patients with COVID-19: A clinical retrospective study in Wuhan, China.J. Infect.2020811e51e6010.1016/j.jinf.2020.04.012 32315725
    [Google Scholar]
  96. VarnaitėR. GarcíaM. GlansH. MalekiK.T. SandbergJ.T. TynellJ. ChristW. LagerqvistN. AsgeirssonH. LjunggrenH.G. AhlénG. FrelinL. SällbergM. BlomK. KlingströmJ. Gredmark-RussS. Expansion of SARS-CoV-2–specific antibody-secreting cells and generation of neutralizing antibodies in hospitalized COVID-19 patients.J. Immunol.202020592437244610.4049/jimmunol.2000717 32878912
    [Google Scholar]
  97. HeB. WangJ. WangY. ZhaoJ. HuangJ. TianY. YangC. ZhangH. ZhangM. GuL. ZhouX. ZhouJ. The metabolic changes and immune profiles in patients with COVID-19.Front. Immunol.202011207510.3389/fimmu.2020.02075 32983157
    [Google Scholar]
  98. LiuJ. LiS. LiuJ. LiangB. WangX. WangH. LiW. TongQ. YiJ. ZhaoL. XiongL. GuoC. TianJ. LuoJ. YaoJ. PangR. ShenH. PengC. LiuT. ZhangQ. WuJ. XuL. LuS. WangB. WengZ. HanC. ZhuH. ZhouR. ZhouH. ChenX. YeP. ZhuB. WangL. ZhouW. HeS. HeY. JieS. WeiP. ZhangJ. LuY. WangW. ZhangL. LiL. ZhouF. WangJ. DittmerU. LuM. HuY. YangD. ZhengX. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients.EBioMedicine20205510276310.1016/j.ebiom.2020.102763 32361250
    [Google Scholar]
  99. YaoC. BoraS.A. ParimonT. ZamanT. FriedmanO.A. PalatinusJ.A. SurapaneniN.S. MatusovY.P. Cerro ChiangG. KassarA.G. PatelN. GreenC.E.R. AzizA.W. SuriH. SudaJ. LopezA.A. MartinsG.A. StrippB.R. GharibS.A. GoodridgeH.S. ChenP. Cell-type-specific immune dysregulation in severely Ill COVID-19 Patients.Cell Rep.202134110859010.1016/j.celrep.2020.108590 33357411
    [Google Scholar]
  100. FalletB. KyburzD. WalkerU.A. Mild course of Coronavirus disease 2019 and spontaneous severe acute respiratory syndrome coronavirus 2 clearance in a patient with depleted peripheral blood B‐cells due to treatment with rituximab.Arthritis Rheumatol.202072915811582
    [Google Scholar]
  101. Mattos-SilvaP. FelixN.S. SilvaP.L. RobbaC. BattagliniD. PelosiP. RoccoP.R.M. CruzF.F. Pros and cons of corticosteroid therapy for COVID-19 patients.Respir. Physiol. Neurobiol.202028010349210.1016/j.resp.2020.103492 32659271
    [Google Scholar]
  102. IpA. BerryD.A. HansenE. GoyA.H. PecoraA.L. SinclaireB.A. BednarzU. MarafeliasM. BerryS.M. BerryN.S. MathuraS. SawczukI.S. BiranN. GoR.C. SperberS. PiwozJ.A. BalaniB. CicognaC. SebtiR. ZuckermanJ. RoseK.M. TankL. JacobsL.G. KorcakJ. TimmapuriS.L. UnderwoodJ.P. SugalskiG. BarskyC. VargaD.W. AsifA. LandolfiJ.C. GoldbergS.L. Hydroxychloroquine and tocilizumab therapy in COVID-19 patients—An observational study.PLoS One2020158e023769310.1371/journal.pone.0237693 32790733
    [Google Scholar]
  103. CantiniF. NiccoliL. MatarreseD. NicastriE. StobbioneP. GolettiD. Baricitinib therapy in COVID-19: A pilot study on safety and clinical impact.J. Infect.202081231835610.1016/j.jinf.2020.04.017 32333918
    [Google Scholar]
  104. Kaffash FarkhadN. SedaghatA. ReihaniH. Adhami MoghadamA. Bagheri MoghadamA. Khadem GhaebiN. KhodadoustM.A. GanjaliR. TafreshianA.R. Tavakol-AfshariJ. Mesenchymal stromal cell therapy for COVID-19-induced ARDS patients: A successful phase 1, control-placebo group, clinical trial.Stem Cell Res. Ther.202213128310.1186/s13287‑022‑02920‑1 35765103
    [Google Scholar]
  105. Kaffash FarkhadN. MahmoudiA. MahdipourE. Regenerative therapy by using mesenchymal stem cells-derived exosomes in COVID-19 treatment. The potential role and underlying mechanisms.Regen. Ther.202220617110.1016/j.reth.2022.03.006 35340407
    [Google Scholar]
  106. FocosiD. AndersonA.O. TangJ.W. TuccoriM. Convalescent plasma therapy for COVID-19: State of the art.Clin. Microbiol. Rev.2020334e00072e2010.1128/CMR.00072‑20 32792417
    [Google Scholar]
/content/journals/cmc/10.2174/0929867331666230918092749
Loading
/content/journals/cmc/10.2174/0929867331666230918092749
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test