Asymptomatic COVID-19 Individuals Tend to Establish Relatively Balanced Innate and Adaptive Immune Responses.

Miao Li, Yue Zhang, Jianhua Lu, Li Li, Huixia Gao, Cuiqing Ma, Erhei Dai, Lin Wei
Author Information
  1. Miao Li: Department of Immunology, Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Hebei Medical University, Shijiazhuang 050000, China.
  2. Yue Zhang: Department of Immunology, Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Hebei Medical University, Shijiazhuang 050000, China.
  3. Jianhua Lu: The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang 050000, China.
  4. Li Li: The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang 050000, China.
  5. Huixia Gao: The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang 050000, China.
  6. Cuiqing Ma: Department of Immunology, Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Hebei Medical University, Shijiazhuang 050000, China.
  7. Erhei Dai: The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang 050000, China.
  8. Lin Wei: Department of Immunology, Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Hebei Medical University, Shijiazhuang 050000, China.

Abstract

The sharp increase in the proportion of asymptomatic cases and the potential risk of virus transmission have greatly increased the difficulty of controlling the COVID-19 pandemic. The individual immune response is closely associated with clinical outcomes and pathogenic mechanisms of COVID-19. However, the clinical characteristics and immunophenotyping features of immune cells of asymptomatic individuals remain somewhat mysterious. To better understand and predict the disease state and progress, we performed a comprehensive analysis of clinical data, laboratory indexes and immunophenotyping features in 41 patients with SARS-CoV-2 (including 24 asymptomatic cases and 17 symptomatic individuals). Firstly, from the perspective of demographic characteristics, the rate of asymptomatic infection was significantly higher in those with younger age. Secondly, the laboratory test results showed that some indexes, such as CRP (acute phase reaction protein), D-Dimer and fibrinogen (the marker for coagulation) were lower in the asymptomatic group. Finally, symptomatic individuals were prone to establishing a non-protective immune phenotype by abnormally decreasing the lymphocyte count and percentage, abnormally increasing the Th17 percentage and decreasing Treg percentage, which therefore cause an increase in the neutrophil/lymphocyte ratio (NLR), monocytes/lymphocytes ratio (MLR) and Th17/Treg ratio. On the other hand, asymptomatic individuals tended to establish a more effective and protective immune phenotype by maintaining a normal level of lymphocyte count and percentage and a high level of NK cells. At the same time, asymptomatic individuals can establish a relatively balanced immune response through maintaining a low level of monocytes, a relatively low level of Th17 and high level of Treg, which therefore lead to a decrease in MNKR and Th17/Treg ratio and finally the avoidance of excessive inflammatory responses. This may be one of the reasons for their asymptomatic states. This study is helpful to reveal the immunological characteristics of asymptomatic individuals, understand immune pathogenesis of COVID-19 and predict clinical outcomes more precisely. However, owing to small sample sizes, a future study with larger sample size is still warranted.

Keywords

References

  1. Allergy. 2021 Mar;76(3):866-868 [PMID: 32479648]
  2. N Engl J Med. 2020 Mar 26;382(13):1199-1207 [PMID: 31995857]
  3. Maturitas. 2008 Sep-Oct;61(1-2):122-31 [PMID: 19437587]
  4. Immunopharmacol Immunotoxicol. 2012 Oct;34(5):727-39 [PMID: 22316060]
  5. Int J Infect Dis. 2020 Jul;96:131-135 [PMID: 32376308]
  6. JAMA. 2020 Apr 14;323(14):1406-1407 [PMID: 32083643]
  7. Natl Sci Rev. 2020 Jun;7(6):1003-1011 [PMID: 34676126]
  8. Emerg Infect Dis. 2020 May;26(5):1052-1054 [PMID: 32091386]
  9. Front Immunol. 2020 Nov 26;11:596553 [PMID: 33324414]
  10. Int Immunopharmacol. 2021 Aug;97:107828 [PMID: 34091116]
  11. Sci Immunol. 2021 Aug 10;6(62): [PMID: 34376481]
  12. Nat Immunol. 2005 Nov;6(11):1123-32 [PMID: 16200070]
  13. JAMA. 2020 Apr 7;323(13):1239-1242 [PMID: 32091533]
  14. N Engl J Med. 2020 Jun 11;382(24):2302-2315 [PMID: 32289214]
  15. Lancet Respir Med. 2020 Apr;8(4):420-422 [PMID: 32085846]
  16. Immunol Res. 2001;24(1):53-67 [PMID: 11485209]
  17. Nat Commun. 2021 Jul 5;12(1):4117 [PMID: 34226537]
  18. Vascul Pharmacol. 2002 Nov;39(4-5):247-56 [PMID: 12747964]
  19. J Pharm Anal. 2020 Apr;10(2):102-108 [PMID: 32282863]
  20. Front Mol Biosci. 2020 Jul 03;7:157 [PMID: 32719810]
  21. Bone Marrow Transplant. 1999 Jul;24(2):179-89 [PMID: 10455347]
  22. N Engl J Med. 2020 May 28;382(22):2158-2160 [PMID: 32329972]
  23. Blood. 2019 Feb 7;133(6):511-520 [PMID: 30523120]
  24. Infect Dis Immun. 2021 Apr 20;1(1):8-16 [PMID: 38630124]
  25. China CDC Wkly. 2020 May 8;2(19):332-336 [PMID: 34594651]
  26. Front Immunol. 2020 May 27;11:1206 [PMID: 32574269]
  27. Ann Allergy Asthma Immunol. 2000 Jul;85(1):9-18; quiz 18, 21 [PMID: 10923599]
  28. Lancet Infect Dis. 2020 Apr;20(4):400-402 [PMID: 32113509]
  29. Respir Med Case Rep. 2020 May 13;30:101090 [PMID: 32405454]
  30. Signal Transduct Target Ther. 2020 Mar 27;5(1):33 [PMID: 32296069]
  31. Antimicrob Agents Chemother. 2004 Oct;48(10):3905-11 [PMID: 15388451]
  32. Cell Mol Immunol. 2020 May;17(5):533-535 [PMID: 32203188]
  33. J Cell Physiol. 2021 Apr;236(4):2829-2839 [PMID: 32926425]
  34. Lancet. 2020 Feb 15;395(10223):497-506 [PMID: 31986264]
  35. Front Immunol. 2020 May 01;11:827 [PMID: 32425950]
  36. JAMA. 2021 Feb 2;325(5):489-492 [PMID: 33528529]
  37. MMWR Morb Mortal Wkly Rep. 2020 Apr 10;69(14):411-415 [PMID: 32271722]
  38. Blood. 1999 Aug 1;94(3):1021-7 [PMID: 10419894]
  39. J Immunol. 2020 Aug 15;205(4):892-898 [PMID: 32651218]
  40. J Interferon Cytokine Res. 2015 Apr;35(4):252-64 [PMID: 25714109]
  41. Nat Med. 2020 Aug;26(8):1205-1211 [PMID: 32546824]
  42. Lancet. 2020 Mar 28;395(10229):1033-1034 [PMID: 32192578]
  43. Rev Med Virol. 2020 May;30(3):e2107 [PMID: 32267987]
  44. Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13120-4 [PMID: 9789051]
  45. EMBO Mol Med. 2021 Jun 7;13(6):e14045 [PMID: 33961735]
  46. Int J Infect Dis. 2020 Jun;95:332-339 [PMID: 32334118]
  47. Cell Host Microbe. 2020 Jun 10;27(6):992-1000.e3 [PMID: 32320677]
  48. Front Immunol. 2020 Dec 16;11:610300 [PMID: 33391280]

Grants

  1. 20277738D/Key Research and Development Program of Hebei province (Special Project to People's Livelihood Science and Technology)

Word Cloud

Created with Highcharts 10.0.0asymptomaticimmuneindividualsCOVID-19levelclinicalpercentageratiocharacteristicsincreasecasesresponseoutcomesHoweverimmunophenotypingfeaturescellsunderstandpredictlaboratoryindexesSARS-CoV-2symptomaticphenotypeabnormallydecreasinglymphocytecountTh17TregthereforeTh17/Tregestablishmaintaininghighrelativelylowresponsesstudysamplesharpproportionpotentialriskvirustransmissiongreatlyincreaseddifficultycontrollingpandemicindividualcloselyassociatedpathogenicmechanismsremainsomewhatmysteriousbetterdiseasestateprogressperformedcomprehensiveanalysisdata41patientsincluding2417FirstlyperspectivedemographicrateinfectionsignificantlyhigheryoungerageSecondlytestresultsshowedCRPacutephasereactionproteinD-DimerfibrinogenmarkercoagulationlowergroupFinallyproneestablishingnon-protectiveincreasingcauseneutrophil/lymphocyteNLRmonocytes/lymphocytesMLRhandtendedeffectiveprotectivenormalNKtimecanbalancedmonocytesleaddecreaseMNKRfinallyavoidanceexcessiveinflammatorymayonereasonsstateshelpfulrevealimmunologicalpathogenesispreciselyowingsmallsizesfuturelargersizestillwarrantedAsymptomaticIndividualsTendEstablishRelativelyBalancedInnateAdaptiveImmuneResponses

Similar Articles

Cited By (6)