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

To the Editor:

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). 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. 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. , 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 disease; however, it has also been associated with an enhanced in vivo innate immune response. Notably, individuals of African descent may have twice the frequency of the ε4 allele (30%-40%) compared with those of European or Asian descent, 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. Of 21 patients with a depressed systolic ventricular function in the report by Kaushik et al, 11 were black and 1 white (Table 4). 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.