Prevalence of the protective OAS1 rs10774671-G allele against severe COVID-19 in Moroccans: implications for a North African Neanderthal connection.

The clinical presentation of COVID-19 shows high variability among individuals, which is partly due to genetic factors. The OAS1/2/3 cluster has been found to be strongly associated with COVID-19 severity. We examined this locus in the Moroccan population for the occurrence of the critical variant rs10774671 and its respective haplotype blocks. The frequency of single-nucleotide polymorphisms (SNPs) in the cluster of OAS immunity genes in 157 unrelated individuals of Moroccan origin was determined using an in-house exome database. OAS1 exon 6 of 71 SARS-CoV-2-positive individuals with asymptomatic/mild disease and 74 with moderate/severe disease was sequenced by the Sanger method. The genotypic, allelic, and haplotype frequencies of three SNPs were compared between these two groups. Finally, males in our COVID-19 series were genotyped for the Berber-specific marker E-M81. The prevalence of the OAS1 rs10774671-G allele in present-day Moroccans was found to be 40.4%, which is similar to that found in Europeans. However, it was found equally in both the Neanderthal GGG haplotype and the African GAC haplotype, with a frequency of 20% each. These two haplotypes, and hence the rs10774671-G allele, were significantly associated with protection against severe COVID-19 (p = 0.034, p = 0.041, and p = 0.008, respectively). Surprisingly, in men with the Berber-specific uniparental markers, the African haplotype was absent, while the prevalence of the Neanderthal haplotype was similar to that in Europeans. The protective rs10774671-G allele of OAS1 was found only in the Neanderthal haplotype in Berbers, the indigenous people of North Africa, suggesting that this region may have served as a stepping-stone for the passage of hominids to other continents.

High levels of eicosanoids and docosanoids in the lungs of intubated COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 is responsible for coronavirus disease 2019 (COVID-19). While COVID-19 is often benign, a subset of patients develops severe multilobar pneumonia that can progress to an acute respiratory distress syndrome. There is no cure for severe COVID-19 and few treatments significantly improved clinical outcome. Dexamethasone and possibly aspirin, which directly/indirectly target the biosynthesis/effects of numerous lipid mediators are among those options. Our objective was to define if severe COVID-19 patients were characterized by increased bioactive lipids modulating lung inflammation. A targeted lipidomic analysis of bronchoalveolar lavages (BALs) by tandem mass spectrometry was done on 25 healthy controls and 33 COVID-19 patients requiring mechanical ventilation. BALs from severe COVID-19 patients were characterized by increased fatty acids and inflammatory lipid mediators. There was a predominance of thromboxane and prostaglandins. Leukotrienes were also increased, notably LTB4 , LTE4 , and eoxin E4 . Monohydroxylated 15-lipoxygenase metabolites derived from linoleate, arachidonate, eicosapentaenoate, and docosahexaenoate were also increased. Finally yet importantly, specialized pro-resolving mediators, notably lipoxin A4 and the D-series resolvins, were also increased, underscoring that the lipid mediator storm occurring in severe COVID-19 involves pro- and anti-inflammatory lipids. Our data unmask the lipid mediator storm occurring in the lungs of patients afflicted with severe COVID-19. We discuss which clinically available drugs could be helpful at modulating the lipidome we observed in the hope of minimizing the deleterious effects of pro-inflammatory lipids and enhancing the effects of anti-inflammatory and/or pro-resolving lipid mediators.