RESUMEN
During the first and second waves of coronavirus-19 disease, Sardinia had one of the lowest hospitalization and related mortality rates in Europe. However, in contrast with this evidence, the Sardinia population showed a very high frequency of the Neanderthal risk locus variant rs35044562, considered to be a major risk factor for a severe SARS-CoV-2 disease course. We evaluated 358 patients who had tested positive for SARS-CoV-2 and 314 healthy Sardinian controls (Italy). Patients were divided according to WHO classification: 120 patients asymptomatic, 90 pauci-symptomatic, 108 with a moderate disease course and 40 severely ill. The allele frequencies of Neanderthal-derived genetic variants reported as being protective (rs1156361) or causative (rs35044562) for severe illness were calculated in patients and controls. The Thalassemia variant (rs11549407), the HLA haplotypes, the KIR genes, as well as KIRs and their HLA class I ligand combinations were also investigated. The rs35044562 and rs1156361 Neanderthal variants revealed a distribution in Hardy-Weinberg equilibrium (HWE) both in SARS-CoV-2 patients and the control population (X2HWE = 0.82, p = 0.37 and X2HWE = 0.13, p = 0.72, respectively). Our findings reported an increased risk for severe disease in Sardinian patients carrying the rs35044562 high-risk variant [OR 5.32 (95% CI 2.53-12.01), p<0.0001]. Conversely, the protective effect of the HLA-A*02:01~B*18:01~DRB1*03:01 three-loci extended haplotype in the Sardinian population was shown to efficiently contrast the high risk of a severe and devastating outcome of the infection predicted for carriers of the Neanderthal locus [OR 15.47 (95% CI 5.8 - 41.0), p<0.0001]. This result suggests that the balance between risk and protective immunogenetic factors plays an important role in the evolution of COVID-19. A better understanding of these mechanisms may well turn out to be the biggest advantage in the race for the development of more efficient drugs and vaccines.
RESUMEN
Background: According to preliminary sequences from 2010, 99.7% of the nucleotide sequences of the modern human and Neanderthal genomes are identical, compared to humans sharing around 98.8% of sequences with the chimpanzee. In contrast, the difference between chimpanzees and modern humans is approximately 1,462 mtDNA base pairs. Materials and Methods: Neanderthal-inherited genetic material is found in all non-African populations and was initially reported to comprise 1 to 4% of the genome. This fraction was later refined to 1.5 to 2.1%. We had gone through many researches of Neanderthals affected gene flow in humans. Results: It is estimated that 20% of Neanderthal DNA currently survives in modern humans. Modern human genes involved in making keratin, a protein constituent of skin, hair, and nails, have especially high levels of introgression. For example, approximately 66% of East Asians contain a POUF23L variant introgressed from Neanderthals, while 70% of Europeans possess an introgressed allele of BNC2. Our finding shines a light on an enzyme called dipeptidyl peptidase4 (DPP4). Scientists already know the protein allows another coronavirus, which causes Middle Eastern respiratory syndrome (MERS), to bind to and enter human cells. The new analysis, of DPP4 gene variants among COVID-19 patients, suggests the enzyme also provides SARS-CoV-2 with a second door into our cells, along with its usual infection route via the angiotensin-converting enzyme 2 (ACE2) receptor on cell surfaces. Conclusion: Most Europeans, Asians, and Native Americans harbor a handful of genes from Neanderthals, up 1.8% to 2.6% of their DNA. Studies of ancient DNA in Neanderthal fossils have shown the hominin's DPP4 gene subtly differs from the typical human one. Conclusion: The hominin's DPP4 gene inherited from Neanderthals plays a major role in Immune System Disorders and Lower Immune response in many diseases. This gene plays a major role in affecting humans with COVID-19 and spreading it through the world. All humans contain this gene from 1 to 4%. East Asians, Europeans, Middle and south Americans conveys more, hence, native Africans contain less amounts of hominin's DPP4 gene. Therefore, East Asians, Europeans, Middle and south Americans are prone to severe COVID-19.