Data availabilitySummary statistics generated by COVID-19 Host Genetics Initiative are available online (https://www.covid19hg.org/results/r6/). The analyses described here use the freeze 6 data. The COVID-19 Host Genetics Initiative continues to regularly release new data freezes. Summary statistics for samples from individuals of non-European ancestry are not currently available owing to the small individual sample sizes of these groups, but the results for 23 loci lead variants are reported in Supplementary Table 3. Individual-level data can be requested directly from the authors of the contributing studies, listed in Supplementary Table 1.

Interferon-induced membrane proteins (IFITM) 3 gene variants are known risk factor for severe viral diseases. We examined whether IFITM3 variant may underlie the heterogeneous clinical outcomes of SARS-CoV-2 infection-induced COVID-19 in large Arab population . We genotyped 880 Saudi patients; 93.8% were PCR-confirmed SARS-CoV-2 infection, encompassing most COVID-19 phenotypes. Mortality at 90 days was 9.1%. IFITM3-SNP, rs12252-G allele was associated with hospital admission (OR = 1.65 [95% CI; 1.01–2.70], P = 0.04]) and mortality (OR = 2.2 [95% CI; 1.16–4.20], P = 0.01). Patients less than 60 years old had a lower survival probability if they harbor this allele (log-rank test P = 0.002). Plasma levels of IFNγ were significantly lower in a subset of patients with AG/GG genotypes than patients with AA genotype ( P = 0.00016). Early identification of these individuals at higher risk of death may inform precision public health response.

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In 1874, the German scientist Johann Ludwig Wilhelm Thudichum identified sphingolipids, as a class of lipids highly enriched in the central nervous system (CNS). Sphingolipids are the second most abundant membrane lipids after phospholipids (Merrill et al., 1997). This class of lipids shows great diversity and complexity, and has been implicated in CNS development and function. Indeed, sphingolipids are not only structural components of the cell membrane, they play important roles in cellular processes such as endocytosis, intracellular trafficking, and signal transduction (Hannun & Obeid, 2008).