Caroline Conway, Biological Sciences, Summer 2021
Figure 1: An illustration of the SARS-CoV-2 virus. When it comes to SARS-CoV-2 infections, a new study suggests that genetics may play a role in both susceptibility and severity. (Source: Wikimedia Commons, Author: We Are Covert Ltd)
In the past, genome-wide association studies have found correlations between specific forms of certain genes and individual susceptibility to infectious diseases such as hepatitis B and C, tuberculosis, dengue, malaria, and HIV-1 (Chapman & Hill, 2012). The latest disease to join this group is COVID-19, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the current pandemic. 13 genetic variants have been connected to either an increased risk of infection or an increased degree of illness severity in regards to SARS-CoV-2 (Saey, 2021). The discovery of these genetic variants brings scientists one step closer to understanding the risk factors of SARS-CoV-2. This finding is especially useful since patient variations in age, gender, and body mass index have failed to fully account for patterns of disease severity across infected individuals (COVID-19 Host Genetics Initiative, 2021).
Overall, the study determined that 9 of the 13 loci were tied to the severity of infection following the onset of COVID-19 but that these loci did not show a significant correlation with SARS-CoV-2 susceptibility. The locus with the strongest association with COVID-19 severity was 3p21.31 (COVID-19 Host Genetics Initiative, 2021). This study confirmed a previous finding that variations at the ABO locus were tied to SARS-CoV-2 susceptibility (for example, type-O blood was associated with a decreased risk of infection) and additionally identified a locus in the 3p21.31 area with a stronger correlation with susceptibility than severity (Saey, 2021).
The study also examined non-genetic lifestyle factors. Smoking was found to correlate with higher hospitalization rates, while genetically predicted higher BMI was associated with both a higher likelihood of hospitalization and increased susceptibility to SARS-CoV-2 infection. However, it is key to acknowledge that for both genetic and lifestyle factors, correlation does not constitute causation. For instance, the study also identified a puzzling association between higher genetically predicted height and increased susceptibility (COVID-19 Host Genetics Initiative, 2021).
This is not to say that all genetic variants were associated with negative consequences for individuals’ health. For instance, genetically predicted elevated red blood cell count was tied to decreased susceptibility to SARS-CoV-2 (COVID-19 Host Genetics Initiative, 2021). Previous studies have identified other health advantages to genetic variants as well. A base-pair deletion in the tail of the HIV coreceptor CCR5, for example, is associated with a slower progression of AIDS in heterozygous individuals and with a decrease in HIV-1 susceptibility in homozygous individuals (Chapman & Hill, 2012).
Overall, the identification of single-gene defects and their repercussions for SARS-CoV-2 susceptibility and severity could help answer two of the most perplexing questions of the pandemic: why is COVID-19 capable of such devastation in otherwise healthy patients, and why do patients of comparable health have COVID-19 experiences ranging from extended hospitalization to asymptomatic obliviousness? While the study of single-gene defects is a start, it by no means provides a full explanation to address these vital questions. The majority of disease-associated variants are tied to very small increases in susceptibility/severity risk. Because gene defects tend to cluster on related immune pathways, it is likely that heritability of infectious disease susceptibility/severity results from multiple gene variants (Chapman & Hill, 2012).
Disease susceptibility is partially a matter of gene expression in addition to gene sequence, as single nucleotide polymorphisms (variations at one point in a DNA/RNA sequence) in transcribed RNAs have the potential to disrupt function (Sadee, 2009). Future studies of SARS-CoV-2 susceptibility/severity might examine the role of such characteristics of gene expression. Furthermore, the COVID-19 Host Genetics Initiative (2021) used some control groups who were unaware of their SARS-CoV-2/COVID-19 status, failing to account for the potential development of an infection. Future studies might incorporate more rigorous testing of control groups. This could be made more accessible by the development of increasingly fast and accurate SARS-CoV-2/COVID-19 testing.
References
Chapman, S. J., & Hill, A. V. S. (2012). Human genetic susceptibility to infectious disease. Nature Reviews Genetics, 13(3), 175–188. https://doi.org/10.1038/nrg3114
COVID-19 Host Genetics Initiative. (2021). Mapping the human genetic architecture of COVID-19. Nature, 1–8. https://doi.org/10.1038/s41586-021-03767-x
Sadee, W. (2009). Measuring cis-acting regulatory variants genome-wide: New insights into expression genetics and disease susceptibility. Genome Medicine, 1(12), 116. https://doi.org/10.1186/gm116
Saey, T. H. (2021, July 8). How your DNA may affect whether you get COVID-19 or become gravely ill. Science News. https://www.sciencenews.org/article/coronavirus-covid-how-dna-genetic-risk-infection-severe-illness