• Ivana Filipović
  • Zorica Živković KBC "Dr Dragisa Misovic", Hospital for Children's Lung Diseases and TB, Belgrade, Serbia, Faculty of Pharmacy Novi Sad, Academy of Economics in Novi Sad, Novi Sad, Serbia
  • Snežana Zdjelar KBC "Dr Dragisa Misovic", Hospital for Gynecology and Obstetrics, Belgrade, Serbia
  • Olivera Ostojić KBC "Dr Dragisa Misovic", Hospital for Children's Lung Diseases and TB, Belgrade, Serbia,
  • Slađana Mihajlović KBC "Dr Dragisa Misovic", Hospital for Gynecology and Obstetrics, Belgrade, Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia


COVID19, newborns, immune system


The SARS-CoV-2 pandemic has strained the health care system, left catastrophic economic consequences on a global scale, disrupted social structures, especially in underdeveloped and developing countries. Fortunately, COVID19 in children remains less severe than in the adult population. According to current epidemiological data, only 2% of the population under the age of 18 has been severely affected by SARS-CoV-2. The immune system of newborns, infants, young children, preschool children and adolescents is not the same. Special attention should be paid here to the newborn's immune response. It has been suggested that increased susceptibility of older adults to COVID 19 may be associated with chronic low-grade systemic inflammation (inflammation) with higher levels of IL-6, TNF-α, and other congenital plasma cytokines. Differences in immune responses in neonates from adults are also attributed to other factors such as relative vitamin D deficiency in adults, increased comorbidities and endothelial damage, chronic altered density and distribution of ACE receptors, and cytomegalovirus infection. The current knowledge should be used in the best possible way in order to improve neonatal care and treatment during the COVID19 pandemic, but the acquired knowledge will certainly be of great help in understanding all the specifics of the neonatal period.


Kitano T, et al. The differential impact of pediatric COVID-19 between high-income countries and low- and middle-income countries: A systematic review of fatality and ICU admission in children worldwide. PLoS ONE. 2021;16:e0246326.

Kirmani, S. & Saleem, A. Impact of COVID-19 pandemic on paediatric services at a referral centre in Pakistan: lessons from a low-income and middle-income country setting. Arch. Dis. Child. 10.1136/archdischild-2020-319424 (2020)

Duke T, English M, Carai S, Qazi S. Paediatric care in the time of COVID-19 in countries with under-resourced healthcare systems. Arch. Dis. Child. 2020;105:616–617.

Klingenberg, C. et al. International Neonatal COVID-19 Consortium. COVID-19 preparedness-a survey among neonatal care providers in low- and middle-income countries. J. Perinatol.988–997 (2021).

Roberton T, et al. Early estimates of the indirect effects of the COVID-19 pandemic on maternal and child mortality in low-income and middle-income countries: a modelling study. Lancet Glob. Health. 2020;8:e901–e908.

Cyranoski D. Why children avoid the worst coronavirus complications might lie in their arteries. Nature. 2020;582:324–325.

Vousden, N. et al. The incidence, characteristics and outcomes of pregnant women hospitalized with symptomatic and asymptomatic SARS-CoV-2 infection in the UK from March to September 2020: a national cohort study using the UK Obstetric Surveillance System (UKOSS). Preprint at medRxiv10.1101/2021.01.04.21249195 (2021).

Götzinger, F., Santiago-Garcia, B., Fumadó-Pérez, V., Brinkmann, F. & Tebruegge, M. ptbnet COVID-19 Study Group. The ability of the neonatal immune response to handle SARS-CoV-2 infection. Lancet Child Adolesc Health. , e6–e7 (2021)

Gale, C. et al. Characteristics and outcomes of neonatal SARS-CoV-2 infection in the UK: a prospective national cohort study using active surveillance. Lancet Child Adolesc. Health10.1016/S2352-4642(20)30342-4 (2020).

Pareek M, et al. Ethnicity and COVID-19: an urgent public health research priority. Lancet. 2020;395:1421–1422.

Saheb Sharif-Askari N, et al. Airways expression of SARS-CoV-2 receptor, ACE2, and TMPRSS2 is lower in children than adults and increases with smoking and COPD. Mol. Ther. Methods Clin. Dev. 2020;18:1–6.

Soraya GV, Ulhaq ZS. Interleukin-6 levels in children developing SARS-CoV-2 infection. Pediatr. Neonatol. 2020;61:253–254.

Lindan CE, et al. Neuroimaging manifestations in children with SARS-CoV-2 infection: a multinational, multicentre collaborative study. Lancet Child Adolesc. Health. 2021;5:167–177.

Michelow, I. C., Oladokun, R. E., Torbunde, N. & Sam-Agudu, N. A. Things must not fall apart: the ripple effects of the COVID-19 pandemic on children in sub-Saharan Africa. Pediatr. Res.10.1038/s41390-020-01174-y (2020).

Ashish KC, et al. Effect of the COVID-19 pandemic response on intrapartum care, stillbirth, and neonatal mortality outcomes in Nepal: a prospective observational study. Lancet Glob. Health. 2020;8:e1273–e1281.

Olin A, et al. Stereotypic immune system development in newborn children. Cell. 2018;174:1277–1292.e14.

Dowling DJ, Levy O. Ontogeny of early life immunity. Trends Immunol. 2014;35:299–310.

Yuanyuan D, et al. Epidemiology of COVID-19 among children in China. Pediatrics. 2020;145:e20200702.

Pou C, et al. The repertoire of maternal anti-viral antibodies in human newborns. Nat. Med. 2019;25:591–596.

Fonseca W, Lukacs NW, Ptaschinski C. Factors affecting the immunity to respiratory syncytial virus: from epigenetics to microbiome. Front. Immunol. 2018;9:226.

Yoon HE, et al. Age-associated changes in the vascular renin-angiotensin system in mice. Oxid. Med. Cell Longev. 2016;2016:6731093.

South, A. M., Tomlinson, L., Edmonston, D., Hiremath, S. & Sparks, M. A. Controversies of renin–angiotensin system inhibition during the COVID-19 pandemic. Nat. Rev. Nephrol.10.1038/s41581-020-0279-4 (2020).

O’Hare FM, William Watson R, Molloy EJ. Toll-like receptors in neonatal sepsis. Acta Paediatr. 2013;102:572–578.

Levy, O. et al. The adenosine system selectively inhibits TLR-mediated TNF-alpha production in the human newborn. J. Immunol. : 1956–1966 (2006).

Chantry CJ, Howard CR, Auinger P. Full breastfeeding duration and associated decrease in respiratory tract infection in US children. Pediatrics. 2006;117:425–432.

Fox, A. et al. Evidence of a significant secretory-IgA-dominant SARS-CoV-2 immune response in human milk following recovery from COVID-19. medRxiv 20089995 10.1101/2020.05.04.20089995 (2020).

Kollmann TR, Kampmann B, Mazmanian SK, Marchant A, Levy O. Protecting the newborn and young infant from infectious diseases: lessons from immune ontogeny. Immunity. 2017;46:350–363.

Zimmermann, P. and Curtis, N. Why is COVID-19 less severe in children? A review of the proposed mechanisms underlying the age-related difference in severity of SARS-CoV-2 infections. Arch. Dis. Child. 10.1136/archdischild-2020-320338 (2020).

Walker KF, O’Donoghue K, Grace N. Maternal transmission of SARS-COV-2 to the neonate, and possible routes for such transmission: a systematic review and critical analysis. BJOG. 2020;127:1324–1336.

Carsetti R, et al. The immune system of children: the key to understanding SARS-CoV-2 susceptibility? Lancet Child Adolesc. Health. 2020;4:414–416.

Goenka, A. et al. Young infants exhibit robust functional antibody responses and restrained IFN-γ production to SARS-CoV-2. Cell Rep. Med. , 100327 (2021).

Godfred-Cato S, et al. COVID-19-associated multisystem inflammatory syndrome in children—United States, March–July 2020. MMWR Morb. Mortal. Wkly Rep. 2020;69:1074–1080.

Raschetti R, et al. Synthesis and systematic review of reported neonatal SARS-CoV-2 infections. Nat. Commun. 2020;11:5164.

Sankaran D, Nakra N, Cheema R, Blumberg D, Lakshminrusimha S. Perinatal SARS-CoV-2 infection and neonatal COVID-19: a 2021 update. Neoreviews. 2021;22:e284–e295.

Pawar R, et al. Neonatal multisystem inflammatory syndrome (MIS-N) associated with prenatal maternal SARS-CoV-2: a case series. Children. 2021;8:572.

Horby P, et al. Dexamethasone in hospitalized patients with Covid-19. N. Engl. J. Med. 2021;384:693–704.






Review Articles