Robust Innate Responses to SARS-CoV-2 in Children Resolve Faster Than in Adults Without Compromising Adaptive Immunity

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2021 Sep 29

PMID 34587479

Citations 47

Authors

Maria Vono

Angela Huttner

Sylvain Lemeille

Paola Martinez-Murillo

Benjamin Meyer

Stephanie Baggio

Shilpee Sharma

Anais Thiriard

Arnaud Marchant

Gert-Jan Godeke

Chantal Reusken

Catia Alvarez

Francisco Perez-Rodriguez

Isabella Eckerle

Laurent Kaiser

Natasha Loevy

Christiane S Eberhardt

Geraldine Blanchard-Rohner

Claire-Anne Siegrist

Arnaud M Didierlaurent

Affiliations

Soon will be listed here.

Abstract

SARS-CoV-2 infection in children is less severe than it is in adults. We perform a longitudinal analysis of the early innate responses in children and adults with mild infection within household clusters. Children display fewer symptoms than adults do, despite similar initial viral load, and mount a robust anti-viral immune signature typical of the SARS-CoV-2 infection and characterized by early interferon gene responses; increases in cytokines, such as CXCL10 and GM-CSF; and changes in blood cell numbers. When compared with adults, the antiviral response resolves faster (within a week of symptoms), monocytes and dendritic cells are more transiently activated, and genes associated with B cell activation appear earlier in children. Nonetheless, these differences do not have major effects on the quality of SARS-CoV-2-specific antibody responses. Our findings reveal that better early control of inflammation as observed in children may be key for rapidly controlling infection and limiting the disease course.

Citing Articles

Age-associated differences in mucosal and systemic host responses to SARS-CoV-2 infection.

Hurst J, Mohan A, Dalapati T, George I, Aquino J, Lugo D Nat Commun. 2025; 16(1):2383.

PMID: 40064870 PMC: 11894178. DOI: 10.1038/s41467-025-57655-3.

Early immune profiling reveals distinct inflammatory responses between children and adults few days after primary SARS-CoV-2 infection.

van de Garde M, Miranda-Bedate A, Nanlohy N, Jacobi R, Meijer A, Reukers D Front Immunol. 2024; 15:1359993.

PMID: 39624095 PMC: 11609154. DOI: 10.3389/fimmu.2024.1359993.

Variant-specific antibody profiling for tracking SARS-CoV-2 variant infections in children and adolescents.

Kuthning D, Raafat D, Holtfreter S, Gramenz J, Wittmann N, Broker B Front Immunol. 2024; 15:1434291.

PMID: 39257574 PMC: 11384586. DOI: 10.3389/fimmu.2024.1434291.

Innate immune signatures in the nasopharynx after SARS-CoV-2 infection and links with the clinical outcome of COVID-19 in Omicron-dominant period.

Cha H, Lee C, Kim S, Kang C, Choe P, Jeon Y Cell Mol Life Sci. 2024; 81(1):364.

PMID: 39172244 PMC: 11342914. DOI: 10.1007/s00018-024-05401-1.

A T-Cell-Derived 3-Gene Signature Distinguishes SARS-CoV-2 from Common Respiratory Viruses.

Li Y, Tao X, Ye S, Tai Q, You Y, Huang X Viruses. 2024; 16(7).

PMID: 39066192 PMC: 11281602. DOI: 10.3390/v16071029.

References

Muus C, Luecken M, Eraslan G, Sikkema L, Waghray A, Heimberg G . Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics. Nat Med. 2021; 27(3):546-559. PMC: 9469728. DOI: 10.1038/s41591-020-01227-z. View

Aykac K, Yayla B, Ozsurekci Y, Evren K, Oygar P, Lacinel Gurlevik S . The association of viral load and disease severity in children with COVID-19. J Med Virol. 2021; 93(5):3077-3083. PMC: 8014156. DOI: 10.1002/jmv.26853. View

Schouten L, van Kaam A, Kohse F, Veltkamp F, Bos L, de Beer F . Age-dependent differences in pulmonary host responses in ARDS: a prospective observational cohort study. Ann Intensive Care. 2019; 9(1):55. PMC: 6517452. DOI: 10.1186/s13613-019-0529-4. View

Pierce C, Sy S, Galen B, Goldstein D, Orner E, Keller M . Natural mucosal barriers and COVID-19 in children. JCI Insight. 2021; 6(9). PMC: 8262299. DOI: 10.1172/jci.insight.148694. View

Vakkila J, Thomson A, Vettenranta K, Sariola H, Saarinen-Pihkala U . Dendritic cell subsets in childhood and in children with cancer: relation to age and disease prognosis. Clin Exp Immunol. 2004; 135(3):455-61. PMC: 1808966. DOI: 10.1111/j.1365-2249.2003.02388.x. View

Cristiani L, Mancino E, Matera L, Nenna R, Pierangeli A, Scagnolari C . Will children reveal their secret? The coronavirus dilemma. Eur Respir J. 2020; 55(4). PMC: 7113798. DOI: 10.1183/13993003.00749-2020. View

Yonker L, Neilan A, Bartsch Y, Patel A, Regan J, Arya P . Pediatric Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Clinical Presentation, Infectivity, and Immune Responses. J Pediatr. 2020; 227:45-52.e5. PMC: 7438214. DOI: 10.1016/j.jpeds.2020.08.037. View

Mudd P, Crawford J, Turner J, Souquette A, Reynolds D, Bender D . Distinct inflammatory profiles distinguish COVID-19 from influenza with limited contributions from cytokine storm. Sci Adv. 2020; 6(50). PMC: 7725462. DOI: 10.1126/sciadv.abe3024. View

Henry B, Lippi G, Plebani M . Laboratory abnormalities in children with novel coronavirus disease 2019. Clin Chem Lab Med. 2020; 58(7):1135-1138. DOI: 10.1515/cclm-2020-0272. View

10.

Ng K, Faulkner N, Cornish G, Rosa A, Harvey R, Hussain S . Preexisting and de novo humoral immunity to SARS-CoV-2 in humans. Science. 2020; 370(6522):1339-1343. PMC: 7857411. DOI: 10.1126/science.abe1107. View

11.

Chen Y, Zuiani A, Fischinger S, Mullur J, Atyeo C, Travers M . Quick COVID-19 Healers Sustain Anti-SARS-CoV-2 Antibody Production. Cell. 2020; 183(6):1496-1507.e16. PMC: 7608032. DOI: 10.1016/j.cell.2020.10.051. View

12.

Liao Y, Smyth G, Shi W . featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics. 2013; 30(7):923-30. DOI: 10.1093/bioinformatics/btt656. View

13.

Wu H, Zhu H, Yuan C, Yao C, Luo W, Shen X . Clinical and Immune Features of Hospitalized Pediatric Patients With Coronavirus Disease 2019 (COVID-19) in Wuhan, China. JAMA Netw Open. 2020; 3(6):e2010895. PMC: 7272117. DOI: 10.1001/jamanetworkopen.2020.10895. View

14.

Corman V, Landt O, Kaiser M, Molenkamp R, Meijer A, Chu D . Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill. 2020; 25(3). PMC: 6988269. DOI: 10.2807/1560-7917.ES.2020.25.3.2000045. View

15.

Selva K, van de Sandt C, Lemke M, Lee C, Shoffner S, Chua B . Systems serology detects functionally distinct coronavirus antibody features in children and elderly. Nat Commun. 2021; 12(1):2037. PMC: 8016934. DOI: 10.1038/s41467-021-22236-7. View

16.

Bunyavanich S, Do A, Vicencio A . Nasal Gene Expression of Angiotensin-Converting Enzyme 2 in Children and Adults. JAMA. 2020; 323(23):2427-2429. PMC: 7240631. DOI: 10.1001/jama.2020.8707. View

17.

Heald-Sargent T, Muller W, Zheng X, Rippe J, Patel A, Kociolek L . Age-Related Differences in Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Levels in Patients With Mild to Moderate Coronavirus Disease 2019 (COVID-19). JAMA Pediatr. 2020; 174(9):902-903. PMC: 7393583. DOI: 10.1001/jamapediatrics.2020.3651. View

18.

Stringhini S, Wisniak A, Piumatti G, Azman A, Lauer S, Baysson H . Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study. Lancet. 2020; 396(10247):313-319. PMC: 7289564. DOI: 10.1016/S0140-6736(20)31304-0. View

19.

Bartsch Y, Wang C, Zohar T, Fischinger S, Atyeo C, Burke J . Humoral signatures of protective and pathological SARS-CoV-2 infection in children. Nat Med. 2021; 27(3):454-462. PMC: 8315827. DOI: 10.1038/s41591-021-01263-3. View

20.

van Tol S, Mogling R, Li W, Godeke G, Swart A, Bergmans B . Accurate serology for SARS-CoV-2 and common human coronaviruses using a multiplex approach. Emerg Microbes Infect. 2020; 9(1):1965-1973. PMC: 8284965. DOI: 10.1080/22221751.2020.1813636. View