The frequency of combined IFITM3 haplotype involving the reference alleles of both rs12252 and rs34481144 is in line with COVID-19 standardized mortality ratio of ethnic groups in England.

Dimitris Nikoloudis,Asimina Hiona,Dimitrios Kountouras

doi:10.7717/peerj.10402

Abstract

Evidence was brought forward in England and the USA that Black, Asian, Latino and Minority Ethnic people exhibit higher mortality risk from COVID-19 than White people. While socioeconomic factors were suggested to contribute to this trend, they arguably do not explain the range of the differences observed, allowing for possible genetic implications. Almost concurrently, the analysis of a cohort in Chinese COVID-19 patients proposed an association between the severity of the disease and the presence of the minor allele of rs12252 of the Interferon-induced transmembrane protein 3 (IFITM3) gene. This SNP, together with rs34481144, are the two most studied polymorphisms of IFITM3 and have been associated in the past with increased severity in Influenza, Dengue, Ebola, and HIV viruses. IFITM3 is an immune effector protein that is pivotal for the restriction of viral replication, but also for the regulation of cytokine production. Following up on these two developments in the ongoing SARS-CoV-2 pandemic, the present study investigates a possible association between the differences in mortality of ethnic groups in England and the combined haplotypes of rs12252 and rs34481144. The respective allele frequencies were collected for 26 populations from the 1000 Genomes Project and subgroups were pooled wherever possible to create correspondences with ethnic groups in England. A significant correlation (r = 0.9687, p = 0.0003) and a striking agreement was observed between the reported Standardized Mortality Ratios and the frequency of the combined haplotype of both reference alleles, suggesting that the combination of the reference alleles of the specific SNPs may be implicated in more severe outcomes of COVID-19. This study calls for further focus on the role of IFITM3 variants in the mechanism of cellular invasion of SARS-CoV-2, their impact in COVID-19 severity and their possible implications in vaccination efficacy.

Highlights

Very recent, emerging scientific evidence from international (Kirby, 2020) and UK (Aldridge et al, 2020) COVID -19 patient reports and death records, indicate a disproportionate effect of the novel coronavirus on ethnic minorities
In the USA (Garg et al, 2020), preliminary data compiled from hospitals in 14 US states, confirmed the UK study outcomes, showing that African Americans are disproportionately affected by COVID-19
Rankings were produced by sorting all populations by individual allele and by haplotype frequency ratios (rs12252_rs34481144: h1_ratio=A_C/(A_T+G_C), h2_ratio=G_C/(A_C+A_T), h3_ratio=A_T/(G_C+A_C), G_T haplotype not represented) and subsequently compared to the reported Standardized Mortality Ratios (SMR) of ethnic groups in England (Figure 1b)

Summary

Introduction

Very recent, emerging scientific evidence from international (Kirby, 2020) and UK (Aldridge et al, 2020) COVID -19 patient reports and death records, indicate a disproportionate effect of the novel coronavirus on ethnic minorities. According to CDC (CDC, 2020), Black, Asian and Minority Ethnic (BAME) people are at higher risk of death from COVID-19. In the USA (Garg et al, 2020), preliminary data compiled from hospitals in 14 US states, confirmed the UK study outcomes, showing that African Americans are disproportionately affected by COVID-19. Among COVID-19 deaths in New York City, for which race and ethnicity data were available, death rates from COVID-19 among black or African Americans and Hispanic or Latinos were substantially higher than that of white or Asian people (Garg et al, 2020)

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