Write a summary of a genetics related coronavirus article from a popular news source.

“Does Covid-19 Risk Depend On Blood Type? More Research Points To Yes”

            Forbes Magazine posted an article on their website describing recent findings between COVID-19 and genetics. The first are studies posted in Blood Advances[2,5] which suggests people with type O blood are less likely to test positive for COVID-19 and less likely to have severe symptoms. The Danish study[2] noted people with type O blood were 13% less likely to test positive and people with blood types A and AB are associated with increased risk of severe symptoms. The study compared data from 473,000 tests for COVID-19 from a 2.2 million person control group. Having such an ethnically homogenous country makes for a great control group when health care is public and data is accessible to the researchers. Blood types will vary considerably due to different ethnic groups and countries, and a control population can be hard to maintain. They found that patients with blood type A or AB were more likely to require ventilation and kidney dialysis and had longer stays in intensive care units.

Genetic testing company 23andMe[1] released data on a study with more than 750,000 people and found that people with type O blood were between 9 to 18% less likely to test positive. 23andMe has access to 12 million already sequenced people with a large test pool consenting to take part in the study. They’ve found that a gene on chromosome 3 has a specific variant that coincides with blood type. A study in Spain and Italy[4] found that those with type A blood were at increased risk for respiratory failure and type O had a “protective effect.[3]” with 35% lower risk. The study also found that many of the cases had a similar variant on the gene that codes for blood type. Studies done by Harvard Medical School[6] and Columbia Presbyterian Hospital in New York did not find an independently associated link between blood type, although they did find that people with blood type B and AB were more likely to test positive for the virus. They also found symptomatic people with blood type O were less likely to test positive.  

Though the findings are still being discussed, these studies have brought in new data about the nature of the virus and it infects cells. The link between blood type and the possibility of testing positive for COVID-19 still needs to be studied to use this information in a meaningful way. While correlation does not equal causation, the data is consistent over the span of these studies mentioned in the article. However, as stated, “[..] ABO blood typing still shouldn’t be considered predictive in patients who get Covid-19.”

Works Cited

1. 23andMe finds evidence that blood type plays a role in COVID-19. 23andMe Blog. Published June 8, 2020. Accessed October 27, 2020. https://blog.23andme.com/23andme-research/blood-type-and-covid-19/

2. Barnkob MB, Pottegård A, Støvring H, et al. Reduced prevalence of SARS-CoV-2 infection in ABO blood group O. Blood Adv. 2020;4(20):4990-4993. doi:10.1182/bloodadvances.2020002657

3. Gajewski M. Does covid-19 risk depend on blood type? More research points to yes. Forbes. Accessed October 27, 2020. https://www.forbes.com/sites/mishagajewski/2020/10/14/does-covid-19-risk-depend-on-blood-type-more-research-says-yes/

4. Group TSC-19 G. Genomewide association study of severe covid-19 with respiratory failure. New England Journal of Medicine. Published online June 17, 2020. doi:10.1056/NEJMoa2020283

5. Hoiland, RL. Fergusson, NA. Mitra, AR. Griesdale, DEG. Devine, DV. Stukas, S. Cooper, J. Thiara, S. Foster, D. Chen, LYC. Lee, AYY. Conway, E. Wellington, CL. Sekhon, MS. The association of ABO blood group with indices of disease severity and multiorgan dysfunction in COVID-19. Blood Adv. 2020;4(20):4981-4989. doi:10.1182/bloodadvances.2020002623

6. Latz CA, DeCarlo C, Boitano L, et al. Blood type and outcomes in patients with COVID-19. Ann Hematol. 2020;99(9):2113-2118. doi:10.1007/s00277-020-04169-1

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Genomic determinants of pathogenicity in SARS-CoV-2 and other human coronaviruses

            Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the members of the Coronaviridae family, along with its predecessor SARS-CoV and the Middle East respiratory syndrome coronavirus (MERS-CoV). SARS and MERS have high case fatality rates (CFR) at 9% and 36% respectively. CoV-2, (COVID-19) is more infectious tha the previously mentioned viruses, but has a much lower CFR. Th closest genetic relative to CoV-2 is to bat coronavirus. These three strains are dependent on zoonotic transmission from animals, such as camels and bats, to humans.

            It was hypothesized that high-CRF strains were more pathogenetic due to similar genomic determinants. Human coronaviruses span two genera, Alphacoronavirus and Betacoronavirus. Reduction analysis showed a clustering of SARS separately from the other coronaviruses. MERS was spread between the two clusters as an intermediate between the high-CFR and low-CFR strains. This implied that the CFR trait impacts the clustering by deletions and insertions. The high-CFR strains share a common ancestor and may have emerged from the high CFR or evolved independently in different strains.  

            Machine learning was used to detect regions that show clean separation between high- and low-CFR genomes. The results were evaluated by cross-validation and filtered to find genomic regions that distinguish high- and low-CFR. This allows automatic detection of regions that are not easily distinguished. From this method, 11 regions of nucleotide alignments that are predictive of high-CFR to be identified. These regions occurred in pp 1 ab, spike glycoprotein, membrane glycoprotein, and nucleocapsid.

            The identified regions revealed that deletions and insertions result in substantial enhancement of motifs that determine nuclear localization in high-CFR. During evolution, coronavirus had stronger nuclear localization and export signals from clades that included high-CFR viruses and strains from animals, mainly bats, shown by increased positive charge of the amino acids making up the nuclear localization signals. The increasing charge could affect the functions of genomic RNA and the M protein. Localization of the nucleocapsid protein to the nucleoli has been reported and associated with pathogenicity.

            In the study of genomic features that associate with the transmission of coronaviruses from animal to human, they identified independent insertion from the three viruses in the spike glycoprotein, mainly the receptor-binding domain. However, no sequence similarity was found between SARS, MERS, and CoV-2 strains which may indicate independent evolution. Despite this, the inserted segments in the strains contained a proline-cystine (PC) doublet. In both SARS and MERS, the insert acts directly with the respective receptors but the interactions differ. MERS has a salt bridge and hydrophobic interaction while SARS and CoV-2 have a hydrophobic interaction. The flexibility gained by the receptor-binding domain could allow the spike glycoprotein to be more malleable to bind to a receptor and allowing zoonotic transmission. MERS inserts are more rigid and may explain the virus to not fully adapt to human-to-human transmission. These features conclude that the ongoing evolution of SARS-CoV-2 can allow for more highly pathogenic strains to be transmitted to humans.

Gussow AB, Auslander N, Faure G, Wolf YI, Zhang F, Koonin EV. Genomic determinants of pathogenicity in SARS-CoV-2 and other human coronaviruses. Proc Natl Acad Sci U S A. 2020;117(26):15193-15199. doi:10.1073/pnas.2008176117

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Khailany RA, Safdar M, Ozaslan M. 2020. Genomic characterization of a novel SARS-CoV-2. Gene Rep.  doi: 10.1016/j.genrep.2020.100682.