Evaluation of Immune Response to COVID-19 in Neonates

Document Type : Scientific Review

Authors

1 Department of Pediatrics, Neonatal Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

2 Department of Medical Laboratory Sciences, School of Paramedical Science, Shiraz University of Medical Sciences, Shiraz, Iran

3 Department of Pediatrics, Islamic Azad University of Yazd, Yazd, Iran

Abstract

Background: During the COVID-19 epidemic, many neonates were involved, but they had fewer complications and deaths than adults. Therefore, in this review study, we investigated the immune mechanisms of neonates in response to COVID-19.
Methods: We reviewed articles that evaluated the immune system, COVID-19, or SARS-COV2 in neonates. We searched the databases of Google Scholar, PubMed, Scopus, Web of Sciences, SciELO, and CNKI databases published up to December 2022.
Results: There are different immune mechanisms in response to COVID-19 in infants, which lead to a different response to COVID-19 compared to adults. The important mechanisms include lower expression of ACE2 receptor, abundant of naive T cells, absence of cytokine storm, abundant of immunosuppressive cells, less inflammatory reactions, breastmilk secretory IgA, transfer of IgG through the placenta, and absence of chronic comorbidities. Also, in comparison with pediatrics multisystem inflammatory syndrome in children (MIS‐C) doesn’t observe in neonates.
Conclusion: The exact immune mechanisms in response to COVID-19 in infants have not yet been discovered, but knowing the exact mechanisms can be effective in future treatments, the production of effective vaccines, and other viral treatments, so there is a need for more investigations in this field.

Keywords


Corresponding Author: Fatemeh Asadian

View Orcid in Profile
You can search for this author in PubMed     Google Scholar Profile

  1. Ludvigsson JF. Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults. Acta Paediatr [Internet]. 2020;109(6):1088–95.
  2. Bahrami R, Neamatzadeh H, Akbarian E. COVID-19 and Renal Complications in Neonates and Pediatrics. World J Peri Neonatol [Internet]. 2021;3(2):48–9.
  3. Dong Y, Mo X, Hu Y, Qi X, Jiang F, Jiang Z, et al. Epidemiology of COVID-19 Among Children in China. Pediatrics [Internet]. 2020;145(6).
  4. Bahrami, R., Ekraminasab, S., Asadian F. A Survey on Cardiac Complications of COVID-19 in Infants. World J Peri Neonatol [Internet]. 2021;4(1):50–9.
  5. Nishiga M, Wang DW, Han Y, Lewis DB, Wu JC. COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives. Nat Rev Cardiol [Internet]. 2020;17(9):543–58.
  6. Tan W, Aboulhosn J. The cardiovascular burden of coronavirus disease 2019 (COVID-19) with a focus on congenital heart disease. Int J Cardiol [Internet]. 2020;309:70–7.
  7. Hu H, Ma F, Wei X, Fang Y. Coronavirus fulminant myocarditis treated with glucocorticoid and human immunoglobulin. Eur Heart J [Internet]. 2021;42(2):206.
  8. Wei M, Yuan J, Liu Y, Fu T, Yu X, Zhang Z-J. Novel Coronavirus Infection in Hospitalized Infants Under 1 Year of Age in China. 2020;323(13):1313–4.
  9. Walls AC, Park Y-J, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell [Internet]. 2020;181(2):281–92.
  10. Tang NL-S, Chan PK-S, Wong C-K, To K-F, Wu AK-L, Sung Y-M, et al. Early enhanced expression of interferon-inducible protein-10 (CXCL-10) and other chemokines predicts adverse outcome in severe acute respiratory syndrome. Clin Chem [Internet]. 2005;51(12):2333–40.
  11. Chowdhury MA, Hossain N, Kashem MA, Shahid MA, Alam A. Immune response in COVID-19: A review. J Infect Public Health. 2020;13(11):1619–29.
  12. Chaussabel D, Pascual V, Banchereau J. Assessing the human immune system through blood transcriptomics. BMC Biol. 2010;8(1):84.
  13. Mokhtari T, Hassani F, Ghaffari N, Ebrahimi B, Yarahmadi A, Hassanzadeh G. COVID-19 and multiorgan failure: A narrative review on potential mechanisms. J Mol Histol [Internet]. 2020;51(6):613–28.
  14. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med [Internet]. 2020;46(5):846–8.
  15. Karakike E, Giamarellos-Bourboulis EJ. Macrophage activation-like syndrome: a distinct entity leading to early death in sepsis. Front Immunol [Internet]. 2019;10:55.
  16. Ramos-Casals M, Brito-Zerón P, López-Guillermo A, Khamashta MA, Bosch X. Adult haemophagocytic syndrome. Lancet [Internet]. 2014;383(9927):1503–16.
  17. Ekraminasab S, Manzourolhojeh M. Prevalence of Sepsis among Iranian Newborns with Jaundice: A Meta-Analysis Based on Cross-Sectional Studies. World J Peri Neonatol [Internet]. 2022;4(2):115–23.
  18. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. 2020;395(10223):497–506.
  19. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet [Internet]. 2020;395(10229):1033–4.
  20. Fu Y, Cheng Y, Wu Y. Understanding SARS-CoV-2-Mediated Inflammatory Responses: From Mechanisms to Potential Therapeutic Tools. Virol Sin [Internet]. 2020;35(3):266–71.
  21. Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. 2020;395(10223):473–5.
  22. Elahi S. Neonatal and Children’s Immune System and COVID-19: Biased Immune Tolerance versus Resistance Strategy. J Immunol [Internet]. 2020;205(8):1990–7.
  23. Xydakis MS, Dehgani-Mobaraki P, Holbrook EH, Geisthoff UW, Bauer C, Hautefort C, et al. Smell and taste dysfunction in patients with COVID-19. Vol. 20, The Lancet. Infectious diseases. United States; 2020. p. 1015–6.
  24. Sungnak W, Huang N, Bécavin C, Berg M, Queen R, Litvinukova M, et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med [Internet]. 2020;26(5):681–7.
  25. Schuler BA, Habermann AC, Plosa EJ, Taylor CJ, Jetter C, Negretti NM, et al. Age-determined expression of priming protease TMPRSS2 and localization of SARS-CoV-2 in lung epithelium. J Clin Invest [Internet]. 2021;131(1).
  26. Mannheim J, Gretsch S, Layden JE, Fricchione MJ. Characteristics of Hospitalized Pediatric Coronavirus Disease 2019 Cases in Chicago, Illinois, March-April 2020. J Pediatric Infect Dis Soc [Internet]. 2020;9(5):519–22.
  27. Pierce CA, Preston-Hurlburt P, Dai Y, Aschner CB, Cheshenko N, Galen B, et al. Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients. Sci Transl Med [Internet]. 2020;12(564).
  28. Filippatos F, Tatsi EB, Michos A. Immune response to SARS-CoV-2 in children: A review of the current knowledge. Pediatr Investig [Internet]. 2021;5(3):217–28.
  29. Mahallawi WH, Khabour OF, Zhang Q, Makhdoum HM, Suliman BA. MERS-CoV infection in humans is associated with a pro-inflammatory Th1 and Th17 cytokine profile. Cytokine [Internet]. 2018;104:8–13.
  30. Dunsmore G, Koleva P, Ghobakhloo N, Sutton R, Ambrosio L, Meng X, et al. Lower Abundance and Impaired Function of CD71+ Erythroid Cells in Inflammatory Bowel Disease Patients During Pregnancy. J Crohns Colitis [Internet]. 2019;13(2):230–44.
  31. Elahi S. Neglected Cells: Immunomodulatory Roles of CD71(+) Erythroid Cells. Trends Immunol [Internet]. 2019;40(3):181–5.
  32. Kalafat E, Heath P, Prasad S, O Brien P, Khalil A. COVID-19 vaccination in pregnancy. Am J Obstet Gynecol [Internet]. 2022;227(2):136–47.
  33. Santano R, Vidal M, Melero NR, Parras D, Serra P, Santamaria P, et al. Maternal and neonatal immune response to SARS-CoV-2 , IgG transplacental transfer and cytokine pro fi le. 2022;2(September):1–15.
  34. Conti MG, Terreri S, Piano Mortari E, Albano C, Natale F, Boscarino G, et al. Immune Response of Neonates Born to Mothers Infected With SARS-CoV-2. JAMA Netw open [Internet]. 2021;4(11):e2132563.
  35. Garazzino S, Montagnani C, Donà D, Meini A, Felici E, Vergine G, et al. Multicentre Italian study of SARS-CoV-2 infection in children and adolescents, preliminary data as at 10 April 2020. Euro Surveill  Bull Eur sur les Mal Transm = Eur  Commun Dis Bull [Internet]. 2020;25(18).
  36. Baghalsafa, F., Neamatzadeh, H., Ekraminasab S. Death of a 3 Month-Old Infected Infant with Dilated Cardiomyopathy after COVID-19 Infection: A Case Report. World J Peri Neonatol [Internet]. 2021;4(1):60–4.
  37. Golshan-Tafti M, Ekraminasab S, Bahrami R, Asadian F. Mortality Rate in Hospitalized Pediatric Patients with COVID-19 Infection in Iran: A Systematic Review and Meta-Analysis. World J Peri Neonatol [Internet]. 2022;5(1):30–9.
  38. Kollmann TR, Kampmann B, Mazmanian SK, Marchant A, Levy O. Protecting the Newborn and Young Infant from Infectious Diseases: Lessons from Immune Ontogeny. Immunity [Internet]. 2017;46(3):350–63.
  39. Sette A, Crotty S. Pre-existing immunity to SARS-CoV-2: the knowns and unknowns. Nat Rev Immunol [Internet]. 2020;20(8):457–8.
  40. Riollano-Cruz M, Akkoyun E, Briceno-Brito E, Kowalsky S, Reed J, Posada R, et al. Multisystem inflammatory syndrome in children related to COVID-19: A New York City experience. J Med Virol [Internet]. 2021;93(1):424–33.
  41. Lookzadeh MH, Ekraminasab S, Baghalsafa F. Outcome of a Neonate Born to a Mother with COVID-19: A Case Report of Vertical Transmission. World J Peri Neonatol [Internet]. 2022;4(2):124–9.
  42. Smith C, Odd D, Harwood R, Ward J, Linney M, Clark M, et al. Deaths in children and young people in England after SARS-CoV-2 infection during  the first pandemic year. Nat Med [Internet]. 2022;28(1):185–92.