Coronavirus disease 2019, multisystem inflammatory syndrome in children, apolipoprotein E4, and race

Abstract

Kaushik et al presented a series of 33 children from New York City hospitals diagnosed with multisystem inflammatory syndrome in children (MIS-C); 81% had antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).1Kaushik S. Aydin S.I. Derespina K.R. Bansal P.B. Kowalsky S. Trachtman R. et al.Multisystem inflammatory syndrome in children associated with severe acute respiratory syndrome coronavirus 2 infection (MIS-C): a multi-institutional study from New York City.J Pediatr. 2020; 224: 24-29Abstract Full Text Full Text PDF PubMed Scopus (232) Google Scholar Similarly, Carter et al, reported on a series of 25 children diagnosed with MIS-C from the United Kingdom; 68% were SARS-CoV-2 seropositive.2Carter M.J. Fish M. Jennings A. Doores K.J. Wellman P. Seow J. et al.Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection.Nat Med. 2020; 26: 1701-1707Crossref PubMed Scopus (205) Google Scholar The children in both groups exhibited a cytokine profile consistent with a robust innate immune response. At the same time, emerging evidence suggests the hypothesis that the apolipoprotein E4 (apoE4) genotype can predict coronavirus disease 2019 (COVID-19) severity in adults.3Goldstein M.R. Poland G.A. Graeber C.W. Does apolipoprotein E genotype predict COVID-19 severity?.QJM. 2020; 113: 537-538Crossref Scopus (13) Google Scholar,4Kuo C.L. Pilling L.C. Atkins J.L. Masoli J.A.H. Delgado J. Kuchel G.A. et al.ApoE E4 genotype predicts severe COVID-19 in the UK Biobank Community Cohort.J Gerontol A Biol Sci Med Sci. 2020; 20: 1-2Google Scholar Accordingly, we propose the hypothesis that the apoE4 genotype may identify children at increased risk of developing MIS-C from SARS-CoV-2 infection. Classically, the apoE4 genotype has been associated with cardiovascular disease and Alzheimer's disease5Mahley R.W. Weisgraber K.H. Huang Y. Apolipoprotein E: structure determines function, from atherosclerosis to Alzheimer’s disease to AIDS.J Lipid Res. 2009; 50: S183-S188Abstract Full Text Full Text PDF PubMed Scopus (342) Google Scholar; however, it has also been associated with an enhanced in vivo innate immune response.6Gale S.C. Gao L. Mikacenic C. Coyle S.M. Rafaels N. Dudenkov T.M. et al.APOε4 is associated with enhanced in vivo innate immune responses in human subjects.J Allergy Clin Immunol. 2014; 134: 127-134Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar Notably, individuals of African descent may have twice the frequency of the ε4 allele (30%-40%) compared with those of European or Asian descent,7Corbo R.M. Scacchi R. Apolipoprotein E (APOE) allele distribution in the world. Is APOE∗4 a ‘thrifty’ allele?.Ann Hum Genet. 1999; 63: 301-310Crossref PubMed Google Scholar and therefore, they may be more likely to exhibit a stronger innate immune response to the SARS-CoV-2 infection. In the series presented by Carter et al, the children who were SARS-CoV-2 seropositive exhibited more severe disease; 8 of 9 black children compared with 5 of 10 white children in the series were SARS-CoV-2 seropositive.2Carter M.J. Fish M. Jennings A. Doores K.J. Wellman P. Seow J. et al.Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection.Nat Med. 2020; 26: 1701-1707Crossref PubMed Scopus (205) Google Scholar Of 21 patients with a depressed systolic ventricular function in the report by Kaushik et al, 11 were black and 1 white (Table 4).1Kaushik S. Aydin S.I. Derespina K.R. Bansal P.B. Kowalsky S. Trachtman R. et al.Multisystem inflammatory syndrome in children associated with severe acute respiratory syndrome coronavirus 2 infection (MIS-C): a multi-institutional study from New York City.J Pediatr. 2020; 224: 24-29Abstract Full Text Full Text PDF PubMed Scopus (232) Google Scholar This suggests an overrepresentation of black children diagnosed with MIS-C from severe SARS-CoV-2 infection. Therefore, as seen with adults, the apoE4 genotype may identify children at a greater risk of severe SARS-CoV-2 infection; and in particular, MIS-C. Multisystem Inflammatory Syndrome in Children Associated with Severe Acute Respiratory Syndrome Coronavirus 2 Infection (MIS-C): A Multi-institutional Study from New York CityThe Journal of PediatricsVol. 224PreviewTo assess clinical characteristics and outcomes of severe acute respiratory syndrome coronavirus 2-associated multisystem inflammatory syndrome in children (MIS-C). Full-Text PDF