Conclusion
Our understanding of how children are affected by SARS-CoV-2 has evolved since the beginning of the pandemic, however, much remains to be learned. It is now clear that children are not as spared from this pandemic as originally thought. Children are often asymptomatic carriers that play an unfortunate role in the spread of this disease, and they are also more likely to become ill from SARS-CoV infection that previously thought. The increase in cases of MIS-C reveals that the delayed inflammatory response of COVID-19 can cause significant illness in children; Understanding how to prevent this hyperinflammatory response is critical and could have important implications for vaccine development. Because they are less likely to be affected by the acute infection, children may offer critical insight in immune modulation and containment of the acute phase of illness. Importantly, children have many years ahead of them; it remains to be seen whether SARS-CoV-2 infection or MIS-C have long-term health implications for these children. Many essential questions remain to be answered regarding the pediatric impact of COVID-19 and research remains critical as we continue to fight this pandemic.
Figure 1: Time course of symptoms and disease severity related to SARS-CoV-2 infection in adults (top) and children (bottom).
Figure 2: Summary of hypothesized age-related differences in SARS-CoV-2 infections in adults as compared to children. Areas of interest include viral entry, interferon and cytokine immune response, neutrophil activation, macrophage hyperstimulation, antibody production and T-cell responses.
Cited References
1. Oberfeld B, Achanta A, Carpenter K, Chen P, Gilette NM, Langat P, Said JT, Schiff AE, Zhou AS, Barczak AK, et al. SnapShot: COVID-19. Cell. 2020 [accessed 2020 May 12];81(4):954-954e1. http://www.sciencedirect.com/science/article/pii/S009286742030475X. doi:10.1016/j.cell.2020.04.013.
2. Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, Si H-R, Zhu Y, Li B, Huang C-L, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nat. 2020 [accessed 2020 May 12];579(7798):270–273. doi:10.1038/s41586-020-2012-7.
3. Liu Y, Gayle AA, Wilder-Smith A, Rocklöv J. The reproductive number of COVID-19 is higher compared to SARS coronavirus. J Travel Med. 2020 [accessed 2020 May 28];27(2). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074654/. doi:10.1093/jtm/taaa021.
4. Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, Zhang W, Wang Y, Bao S, Li Y, et al. SARS-CoV-2 infection in children. N Engl J Med. 2020 [accessed 2020 May 12];382(17):1663–1665. https://www-ncbi-nlm-nih-gov.ezp-prod1.hul.harvard.edu/pmc/articles/PMC7121177/. doi:10.1056/NEJMc2005073.
5. Furukawa NW, Brooks JT, Sobel J. Evidence supporting transmission of Severe Acute Respiratory Syndrome Coronavirus 2 while presymptomatic or asymptomatic. Emerg Infecti Dis J. 2020 [accessed 2020 May 28];26(7). https://wwwnc.cdc.gov/eid/article/26/7/20-1595_article. doi:10.3201/eid2607.201595.
6. Verity R, Okell LC, Dorigatti I, Winskill P, Whittaker C, Imai N, Cuomo-Dannenburg G, Thompson H, Walker PGT, Fu H, et al. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infecti Dis. 2020 [accessed 2020 May 25];20(6):669-677. http://www.sciencedirect.com/science/article/pii/S1473309920302437. doi:10.1016/S1473-3099(20)30243-7.
7. CDC COVID-19 Response Team. Severe outcomes among patients with coronavirus disease 2019 (COVID-19) — United States, February 12–March 16, 2020. Morb Mortal Wkly Rep. 2020 [accessed 2020 May 3];69(12). https://www.cdc.gov/mmwr/volumes/69/wr/mm6912e2.htm. doi:10.15585/mmwr.mm6912e2.
8. Bi Q, Wu Y, Mei S, Ye C, Zou X, Zhang Z, Liu X, Wei L, Truelove SA, Zhang T, et al. Epidemiology and transmission of COVID-19 in 391 cases and 1286 of their close contacts in Shenzhen, China: a retrospective cohort study. Lancet Infecti Dis. 2020 [accessed 2020 May 19]. http://www.sciencedirect.com/science/article/pii/S1473309920302875. doi:10.1016/S1473-3099(20)30287-5.
9. Lu X, Xiang Y, Du H, Wong GW-K. SARS-CoV-2 infection in children – Understanding the immune responses and controlling the pandemic. Pediatr Allergy Immunol. 2020 [accessed 2020 May 4]. http://onlinelibrary.wiley.com/doi/abs/10.1111/pai.13267. doi:10.1111/pai.13267.
10. Wong GW, Fok TF. Severe acute respiratory syndrome (SARS) in children. Pediatr Pulmonol. 2004 [accessed 2020 May 12];37(Suppl 26):69–71. https://www-ncbi-nlm-nih-gov.ezp-prod1.hul.harvard.edu/pmc/articles/PMC7168116/. doi:10.1002/ppul.70056.
11. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020 [accessed 2020 May12];323(13):1239–1242. https://jamanetwork-com.ezp-prod1.hul.harvard.edu/journals/jama/fullarticle/2762130. doi:10.1001/jama.2020.2648.
12. Castagnoli R, Votto M, Licari A, Brambilla I, Bruno R, Perlini S, Rovida F, Baldanti F, Marseglia GL. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents: a systematic review. JAMA Pediatr. 2020 Apr 22 [accessed 2020 Apr 27]. https://doi.org/10.1001/jamapediatrics.2020.1467. doi:10.1001/jamapediatrics.2020.1467.
13. Bialek S, Gierke R, Hughes M, McNamara LA, Pilishvili T, Skoff T. Coronavirus disease 2019 in children — United States, February 12–April 2, 2020. Morb Mortal Wkly Rep. 2020; [accessed 2020 May 12]; 69(14):422–426. doi:10.15585/mmwr.mm6914e4.
14. Matricardi PM, Negro RWD, Nisini R. The first, holistic immunological model of COVID-19: implications for prevention, diagnosis, and public health measures. Pediatr Allergy Immunol. [accessed 2020 May 6]. http://onlinelibrary.wiley.com/doi/abs/10.1111/pai.13271. doi:10.1111/pai.13271.
15. Choi S-H, Kim HW, Kang J-M, Kim DH, Cho EY. Epidemiology and clinical features of coronavirus disease 2019 in children. Clin Exp Pediatr. 2020 [accessed 2020 May 12];63(4):125–132. doi:10.3345/cep.2020.00535.
16. Xia W, Shao J, Guo Y, Peng X, Li Z, Hu D. Clinical and CT features in pediatric patients with COVID‐19 infection: different points from adults. Pediatr Pulmonol. 2020 [accessed 2020 May 12];55(5):1169–1174. doi:10.1002/ppul.24718.
17. Ludvigsson JF. Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults. Acta Paediatr. 2020; [accessed 2020 May 12];109(6):1088–1095. doi:10.1111/apa.15270.
18. Belhadjer Z, Méot M, Bajolle F, Khraiche D, Legendre A, Abakka S, Auriau J, Grimaud M, Oualha M, Beghetti M, et al. Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic. Circulation. [accessed 2020 Jun 3]. https://www.ahajournals.org/doi/abs/10.1161/CIRCULATIONAHA.120.048360. doi:10.1161/CIRCULATIONAHA.120.048360.
19. Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020 [accessed 2020 May 11]. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31094-1/abstract. doi:10.1016/S0140-6736(20)31094-1.
20. Viner RM, Whittaker E. Kawasaki-like disease: emerging complication during the COVID-19 pandemic. The Lancet. 2020 [accessed 2020 May 18]. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31129-6/abstract. doi:10.1016/S0140-6736(20)31129-6.
21. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; [Accessed 2020 May 18];395(10223):497–506. doi:10.1016/S0140-6736(20)30183-5.
22. Morand A, Urbina D, Fabre A. COVID-19 and Kawasaki like disease: the known-known, the unknown-known and the unknown-unknown. 2020 [accessed 2020 May 11]. doi:10.20944/preprints202005.0160.v1.
23. Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF. The proximal origin of SARS-CoV-2. Nat Med. 2020 [accessed 2020 May 18];26(4):450–452. doi:10.1038/s41591-020-0820-9.
24. 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. 2020 [accessed 2020 May 18];181(2):281-292.e6. doi:10.1016/j.cell.2020.02.058.
25. Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh C-L, Abiona O, Graham BS, McLellan JS. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020 [accessed 2020 May 18];367(6483):1260–1263. doi:10.1126/science.abb2507.
26. Aguar JA, Tremblay BJ-M, Mansfield MJ, Woody O, Lobb B, Banerjee A, Chandiramohan A, Tiessen N, Dvorkin-Gheva A, Revill S, et al. Gene expression and in situ protein profiling of candidate SARS-CoV-2 receptors in human airway epithelial cells and lung tissue. bioRxiv. 2020 [accessed 2020 May 6]. https://www.biorxiv.org/content/10.1101/2020.04.07.030742v2.
27. Sungnak W, Huang N, Bécavin C, Berg M, Queen R, Litvinukova M, Talavera-López C, Maatz H, Reichart D, Sampaziotis F, et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med. 2020 [accessed 2020 May 18];26(5):681–687. doi:10.1038/s41591-020-0868-6.
28. Ziegler C, Allon SJ, Nyquist SK, Mbano I, Miao VN, Cao Y, Yousif AS, Bals J, Hauser BM, Feldman J, et al. SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human Airway epithelial cells and is enriched in specific cell subsets across tissues. Cell. 2020 [accessed 2020 Jun 4]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252096/. doi: 10.1016/j.cell.2020.04.035.
29. Lee IT, Nakayama T, Wu C-T, Goltsev Y, Jiang S, Gall PA, Liao C-K, Shih L-C, Schurch CM, McIlwain DR, et al. Robust ACE2 protein expression localizes to the motile cilia of the respiratory tract epithelia and is not increased by ACE inhibitors or angiotensin receptor blockers. medRxiv. 2020 [accessed 2020 Jun 4]. doi:10.1101/2020.05.08.20092866.
30. Schuler BA, Habermann AC, Plosa EJ, Taylor CJ, Jetter C, Kapp ME, Benjamin JT, Gulleman P, Nichols DS, Braunstein LZ, et al. Age-related expression of SARS-CoV-2 priming protease TMPRSS2 in the developing lung. bioRxiv. 2020 [accessed 2020 Jun 4]. doi:10.1101/2020.05.22.111187.
31. Wang A, Chiou J, Poirion OB, Buchanan J, Valdez MJ, Verheyden JM, Hou X, Guo M, Newsome JM, Kudtarkar P, et al. Single nucleus multiomic profiling reveals age-dynamic regulation of host genes associated with SARS-CoV-2 infection. bioRxiv. 2020 [accessed 2020 Jun 4]. doi:10.1101/2020.04.12.037580.
32. Radzikowska U, Ding M, Tan G, Zhakparov D, Peng Y, Wawrzyniak P, Wang M, Li S, Morita H, Altunbulakli C, et al. Distribution of ACE2, CD147, cyclophilins, CD26 and other SARS-CoV-2 associated molecules in human tissues and immune cells in health and disease. bioRxiv. 2020 [accessed 2020 Jun 4]. doi:10.1101/2020.05.14.090332.
33. Sun J, Hemler ME. Regulation of MMP-1 and MMP-2 production through CD147/extracellular matrix metalloproteinase inducer interactions. Cancer Res. 2001;61(5):2276–2281. https://cancerres.aacrjournals.org/content/61/5/2276.full-text.pdf.
34. Ibrahim IM, Abdelmalek DH, Elfiky AA. GRP78: A cell’s response to stress. Life Sci. 2019 [accessed 2020 May 18];226:156–163. doi:10.1016/j.lfs.2019.04.022.
35. Sajuthi SP, DeFord P, Jackson ND, Montgomery MT, Everman JL, Rios CL, Pruesse E, Nolin JD, Plender EG, Wechsler ME, et al. Type 2 and interferon inflammation strongly regulate SARS-CoV-2 related gene expression in the airway epithelium. bioRxiv. 2020 [accessed 2020 May 6]. https://www.biorxiv.org/content/10.1101/2020.04.09.034454v1.
36. Arango Duque G, Descoteaux A. Macrophage cytokines: involvement in immunity and infectious diseases. Front Immunol. 2014 [accessed 2020 May 25];5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4188125/. doi:10.3389/fimmu.2014.00491.
37. Delves PJ, Roitt IM. The immune system. N Engl J Med. 2000;343(2):108–117. doi:10.1056/NEJM200007133430207.
38. Blanco-Melo D, Nilsson-Payant BE, Liu W-C, Uhl S, Hoagland D, Møller R, Jordan TX, Oishi K, Panis M, Sachs D, et al. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell. 2020;181(5):1036-1045.e9. doi:10.1016/j.cell.2020.04.026.
39. Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020;20(6):363–374. doi:10.1038/s41577-020-0311-8.
40. Mosaddeghi P, Negahdaripour M, Dehghani Z, Farahmandnejad M, Moghadami M, Nezafat N, Masoompour SM. Therapeutic approaches for COVID-19 based on the dynamics of interferon-mediated immune responses. Preprints. [accessed 2020 Jun 3]. doi:10.20944/preprints202003.0206.v1.
41. Maughan EF, Nigro E, Pennycuick A, Gowers KHC, Denais C, Gómez-López S, Lazarus KA, Butler CR, Lee DDH, Orr JC, et al. 2020. Cell-intrinsic differences between human airway epithelial cells from children and adults. bioRxiv. 2020 [accessed 2020 May 6]. https://www.biorxiv.org/content/10.1101/2020.04.20.027144v1.
42. Henry BM, Lippi G, Plebani M. Laboratory abnormalities in children with novel coronavirus disease 2019. Clin Chem Lab Med. 2020 [accessed 2020 May 29];1(ahead-of-print). https://www.degruyter.com/view/journals/cclm/ahead-of-print/article-10.1515-cclm-2020-0272/article-10.1515-cclm-2020-0272.xml. doi:10.1515/cclm-2020-0272.
43. Barnes BJ, Adrover JM, Baxter-Stoltzfus A, Borczuk A, Cools-Lartigue J, Crawford JM, Daßler-Plenker J, Guerci P, Huynh C, Knight JS, et al. Targeting potential drivers of COVID-19: neutrophil extracellular traps. J Exp Med. 2020;217(6). doi:10.1084/jem.20200652.
44. Zuo Y, Yalavarthi S, Shi H, Gockman K, Zuo M, Madison JA, Blair CN, Weber A, Barnes BJ, Egeblad M, et al. Neutrophil extracellular traps in COVID-19. JCI insight. 2020. doi:10.1172/jci.insight.138999.
45. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-1069. doi:10.1001/jama.2020.1585.
46. Fox SE, Akmatbekov A, Harbert JL, Li G, Brown Q, Vander Heide RS. Pulmonary and cardiac pathology in Covid-19: the first autopsy series from New Orleans. medRxiv. 2020 [accessed 2020 Jun 3]. doi:10.1101/2020.04.06.20050575v1.
47. Merad M, Martin JC. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat Rev Immunol. 2020;20(6):355–362. doi:10.1038/s41577-020-0331-4.
48. van Royen N, Hoefer I, Böttinger M, Hua J, Grundmann S, Voskuil M, Bode C, Schaper W, Buschmann I, Piek JJ. Local monocyte chemoattractant protein-1 therapy increases collateral artery formation in apolipoprotein E-deficient mice but induces systemic monocytic CD11b expression, neointimal formation, and plaque progression. Circ Res. 2003;92(2):218–225. doi:10.1161/01.res.0000052313.23087.3f.
49. De Martinis M, Modesti M, Ginaldi L. Phenotypic and functional changes of circulating monocytes and polymorphonuclear leucocytes from elderly persons. Immunol Cell Biol. 2004;82(4):415–420. doi:10.1111/j.0818-9641.2004.01242.x.
50. Albright JM, Dunn RC, Shults JA, Boe DM, Afshar M, Kovacs EJ. Advanced age alters monocyte and macrophage responses. Antioxid Redox Sign. 2016;25(15):805–815. doi:10.1089/ars.2016.6691.
51. Henderson LA, Canna SW, Schulert GS, Volpi S, Lee PY, Kernan KF, Caricchio R, Mahmud S, Hazen MM, Halyabar O, et al. On the alert for cytokine storm: immunopathology in COVID-19. Arthritis Rheumatol. [accessed 2020 May 14]; 2020;0(0):1-5. https://onlinelibrary.wiley.com/doi/abs/10.1002/art.41285. doi:10.1002/art.41285.
52. Grom AA, Mellins ED. Macrophage activation syndrome: advances towards understanding pathogenesis. Curr Opin Rheumatol. 2010;22(5):561–566. doi:10.1097/01.bor.0000381996.69261.71.
53. Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017;39(5):529–539. doi:10.1007/s00281-017-0629-x.
54. 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. Intensiv Care Med. 2020 [accessed 2020 May 19];46(5). https://pubmed.ncbi.nlm.nih.gov/32125452/. doi:10.1007/s00134-020-05991-x.
55. Schouten LR, van Kaam AH, Kohse F, Veltkamp F, Bos LD, de Beer FM, van Hooijdonk RT, Horn J, Straat M, Witteveen E, et al. Age-dependent differences in pulmonary host responses in ARDS: a prospective observational cohort study. Ann Intensiv Care. 2019;9(1):55. doi:10.1186/s13613-019-0529-4.
56. Flint SJ, Racaniello VR, Rall GF, Skalka AM. 2015. Princ Virol. 4th ed. Washington (DC): ASM Press; 2015.
57. Zhao J, Yuan Q, Wang H, Liu W, Liao X, Su Y, Wang X, Yuan J, Li T, Li J, et al. Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019. Clin Infect Dis. 2020 [accessed 2020 Jun 3]: doi:10.1093/cid/ciaa344.
58. Long Q-X, Liu B-Z, Deng H-J, Wu G-C, Deng K, Chen Y-K, Liao P, Qiu J-F, Lin Y, Cai X-F, et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med. 2020 [accessed 2020 Jun 3]: doi:10.1038/s41591-020-0897-1.
59. Galanti M, Shaman J. Direct observation of repeated infections with endemic coronaviruses. medRxiv. 2020 [accessed 2020 Jun 3]: doi.org/10.1101/2020.04.27.20082032.
60. Cao Y, Su B, Guo X, Sun W, Deng Y, Bao L, Zhu Q, Zhang X, Zheng Y, Geng C, et al. Potent neutralizing antibodies against SARS-CoV-2 identified by high-throughput single-cell sequencing of convalescent patients’ B cells. Cell. 2020. doi:10.1016/j.cell.2020.05.025.
61. Wu F, Zhao S, Yu B, Chen Y-M, Wang W, Song Z-G, Hu Y, Tao Z-W, Tian J-H, Pei Y-Y, et al. A new coronavirus associated with human respiratory disease in China. Nat. 2020;579(7798):265–269. doi:10.1038/s41586-020-2008-3.
62. Zhao J, Zhao J, Legge K, Perlman S. Age-related increases in PGD(2) expression impair respiratory DC migration, resulting in diminished T cell responses upon respiratory virus infection in mice. Journal Clin Investig. 2011;121(12):4921–4930. doi:10.1172/JCI59777.
63. Yager EJ, Ahmed M, Lanzer K, Randall TD, Woodland DL, Blackman MA. Age-associated decline in T cell repertoire diversity leads to holes in the repertoire and impaired immunity to influenza virus. J Exp Med. 2008;205(3):711–723. doi:10.1084/jem.20071140.
64. Linton P-J, Li SP, Zhang Y, Bautista B, Huynh Q, Trinh T. Intrinsic versus environmental influences on T-cell responses in aging. Immunol Rev. 2005;205:207–219. doi:10.1111/j.0105-2896.2005.00266.x.
65. Haynes BF, Markert ML, Sempowski GD, Patel DD, Hale LP. The role of the thymus in immune reconstitution in aging, bone marrow transplantation, and HIV-1 infection. Annu Rev Immunol. 2000;18:529–560. doi:10.1146/annurev.immunol.18.1.529.
66. Weiskopf D, Weinberger B, Grubeck-Loebenstein B. The aging of the immune system. Transpl Intern. 2009;22(11):1041–1050. doi:10.1111/j.1432-2277.2009.00927.x.
67. Zheng M, Gao Y, Wang G, Song G, Liu S, Sun D, Xu Y, Tian Z. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol. 2020;17(5):533–535. doi:10.1038/s41423-020-0402-2.
68. Li Y, Guo F, Cao Y, Li L, Guo Y. Insight into COVID-2019 for pediatricians. Pediatr Pulmonol. 2020 [accessed 2020 Jun 3];55(5):E1–E4. doi:10.1002/ppul.24734.
69. Guo X, Guo Z, Duan C, Chen Z, Wang G, Lu Y, Li M, Lu J. Long-term persistence of IgG antibodies in SARS-CoV infected healthcare workers. medRxiv. 2020 [accessed 2020 Jun 3]: doi:10.1101/2020.02.12.20021386.
70. Jones VG, Mills M, Suarez D, Hogan CA, Yeh D, Segal JB, Nguyen EL, Barsh GR, Maskatia S, Mathew R. COVID-19 and Kawasaki disease: novel virus and novel case. Hosp Pediatr. 2020 [accessed 2020 May 6]: https://hosppeds.aappublications.org/content/early/2020/04/06/hpeds.2020-0123. doi:10.1542/hpeds.2020-0123.
71. Pain CE, Felsenstein S, Cleary G, Mayell S, Conrad K, Harave S, Duong P, Sinha I, Porter D, Hedrich CM. Novel paediatric presentation of COVID-19 with ARDS and cytokine storm syndrome without respiratory symptoms. Lancet Rheumatol. 2020 [accessed 2020 May 18]: https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30137-5/abstract. doi:10.1016/S2665-9913(20)30137-5.
72. Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M, Ciuffreda M, Bonanomi E, D’Antiga L. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet. 2020;395(10239):1771–1778. doi:10.1016/S0140-6736(20)31103-X.
73. Yurttutan S, İpek S, Güllü UU. Why the SARS‐Cov‐2 has prolonged spreading time in children? Pediatr Pulmonol. 2020 [accessed 2020 Jun 4]: doi:10.1002/ppul.24795.
74. Selva KJ, van de Sandt CE, Lemke MM, Lee CY, Shoffner SK, Chua BY, Nguyen THO, Rowntree LC, Hensen L, Koutsakos M, et al. Distinct systems serology features in children, elderly and COVID patients. medRxiv. 2020 [accessed 2020 Jun 4]: doi:10.1101/2020.05.11.20098459.