Written by Joyce Smith, BS. This study contributes to the “COVID-19 host genetics initiative”, a human genetics community that generates, shares and analyzes data on the genetic determinants of COVID-19 susceptibility, severity and outcomes which contribute to the global knowledge of COVID-19 infection and disease etiology.
Respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) discovered in Wuhan, China in late 2019 soon became a rapidly evolving global pandemic 1 with 355,000 reported deaths as of May 28, 2020. The unpredictable behavior of COVID-19 presented as many cases with mild or no symptoms 2; however, mortality rates were driven by severe acute respiratory distress syndrome 3 requiring mechanical ventilation 4. Older age, male gender, obesity, cardiovascular disease, hypertension, and diabetes are all predisposing conditions for COVID-19, while the occurrence of vascular endothelial damage and thromboembolic events suggests a systemic disease 5.
When COVID-19 reached a peak in Italy and Spain earlier in 2020, the research team of Ellinghaus and colleagues recruited 835 patients and 1,255 control participants from various hospitals across Italy and 775 patients and 950 control participants from Spain to become part of a genome-wide association study (GWAS). These studies involve testing genetic variants across the genomes of many individuals to identify possible associations between their genotypes (genetic constitution of an individual) and phenotypes (observable traits of an individual). Today the studies are growing rapidly as scientists grapple with the not yet well understood COVID-19 and its symptoms. The Ellinghaus team of researchers 6 investigated this highly infectious disease through a genomic lens to determine whether an individual’s genetics and blood group may play a potential role in COVID-19 susceptibility. Using a GWAS methodology, they were hoping that genetic variants associated with the disease would be found at a higher frequency in the COVID-19 patients than in the control groups.
The COVID-19 participants, their disease verified via viral RNA polymerase-chain-reaction (PCR), were recruited from various hospitals across Spain and Italy with 2,381 control participants recruited from either blood donor banks or previous genotyping studies that had adopted the same array method. When analyzing 8,965,091 SNPs from the Italian cohort and 9,140,716 SNPs from the Spanish cohort, the scientists discovered two independent gene variants that appear to be associated with COVID-19 induced respiratory failure: rs11385942 at locus 3p21.31 and rs657152 at locus 9q34.2, both of which were significant at the genome wide level (P<5×10−8). On chromosome 3p21, several genes for severe COVID-19 were found. Among them was SLC6A20, a gene which encodes a transporter that interacts with the angiotensin-converting enzyme 2 (the SARS-CoV-2 cell-surface receptor) 7,8. Genotypes of 3 different SNPS indicated a higher risk for blood group A-positive individuals (meta-analysis result, P=1.48×10-4) and a protective effect for blood group O (meta-analysis result, P=1.06×10-5).
The researchers noted that GWAS studies point out associations only for a specific genetic variant, and do not demonstrate a causal role. This study is a high quality GWAS regarding COVID-19 in that it was able to identify specific genes associated with COVID-19 in the greater population; however, it does not identify the mechanistic details behind the disease progression or protection from it. Also, researchers used a bare minimum of clinical data in order to obtain adequate enrollment numbers for this study; thus limiting their ability to elaborate further on their genotype-phenotype findings or to adjust for potential sources of bias such as cardiovascular disease and diabetes. While this study, as well as some others, have implicated an association between blood group and COVID-19 susceptibility, researchers suggest the necessity for additional studies to further validate these findings.
Source: Ellinghaus, David, Frauke Degenhardt, Luis Bujanda, Maria Buti, Agustin Albillos, Pietro Invernizzi, Javier Fernandez et al. “The ABO blood group locus and a chromosome 3 gene cluster associate with SARS-CoV-2 respiratory failure in an Italian-Spanish genome-wide association analysis.” medRxiv (2020).
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Posted July 6, 2020.
Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.
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- Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. Jama. 2020.
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- Ellinghaus D, Degenhardt F, Bujanda L, et al. The ABO blood group locus and a chromosome 3 gene cluster associate with SARS-CoV-2 respiratory failure in an Italian-Spanish genome-wide association analysis. medRxiv. 2020.
- Vuille-dit-Bille RN, Camargo SM, Emmenegger L, et al. Human intestine luminal ACE2 and amino acid transporter expression increased by ACE-inhibitors. Amino Acids. 2015;47(4):693-705.
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