A Genetic Component to Severe COVID-19 Infection

Patrick Forcier

A Genetic Component to Severe COVID-19 Infection

European researchers were able to find evidence of several loci throughout the human genome

and variations within these loci that correlate with a more severe COVID-19 infection and respiratory

failure. This discovery was accomplished through genotyping individuals with confirmed COVID-19

infection who developed respiratory failure – defined as needing supplemental oxygen – and comparison

to genomes of healthy individuals as well as those who had mild to no symptoms during COVID-19

infection. Through the comparisons of these genomes, the researchers found two loci and variations in

these loci that correlate with the development of respiratory failure during infection. One of these loci is

found on chromosome 3 and the other can be found on chromosome 9 and exhibits type A blood.
 A Genetic Component to Severe COVID-19 Infection

In their publication, Genomewide Association Study of Severe Covid-19 with Respiratory Failure,

David Ellinghaus, Frauke Degenhardt, and many others were attempting to answer the question of; why

do some individuals develop severe symptoms and respiratory failure when infected with SARS-CoV-2

while others only ever experience mild symptoms? They sought to answer whether there is a link between

the severity of infection and the genotype of a patient. Answering this question would not only provide

context as to why some cases are so much more severe than others, but also allow for new treatment

methods and sanction earlier treatment on individuals known to be at greater risk of developing

respiratory failure. To answer this question, researchers collected blood samples from patients with

respiratory failure with confirmed Covid-19 and those with minor symptoms in Italy and Spain. They

examined about nine million base pairs to assess statistical association between the severity of a patient’s

condition and the significant presence of common loci between all severe patients.

Based on the question of whether there is a genetic component contributing to developing

respiratory failure with Covid-19, the researchers hypothesized that there is in fact a genotype shared

amongst patients with respiratory failure that is significantly associated with their development of severe

Covid-19. Reasoning used to support this hypothesis can be found in the fact that increased rates of

mortality and severe infection are associated with other comorbidities, which implies that there is a large

number of contributing factors. So, it is likely that genetics will have a role in determining the severity of

infection. If the hypothesis is correct, then genotyping should reveal one or more common marker loci in

all severe patients that is significantly associated with their development of respiratory failure (Figure 1).

Under the null hypothesis, there will be no significantly common locations in the genotypes of severe

patients with no significance in association to developing respiratory failure (Figure 2).

Considering the results of the study, the hypothesis is supported. As evident in a comparison

between Figure 1 which outlines predicted results and Figure 3 (Ellinghaus et. al 2020), there are in fact

loci within the genome that are significantly present throughout severe patients and not in healthy

patients. Further, these loci are significant in their association to developing respiratory failure with
 A Genetic Component to Severe COVID-19 Infection

Covid-19. As seen with Figure 3, the researchers have plotted their data in terms of chromosome position

on the X-axis with the p-value on the Y-axis to illustrate the various marker loci present in respiratory

failure patient’s and the significance of those locations in their association to Covid-19. With the loci on

chromosome 3 and chromosome 9, we can see that their p-values lead to rejection of the null hypothesis

and acceptance of the hypothesis that there are in fact variations in the genome which lead to respiratory

failure with Covid-19 (Ellinghaus et. al 2020). However, considering that six genes are present in the loci

on chromosome 3, a question that remains is: which of these genes most influences the course of the

SARS-CoV-2 infection and contributes to developing respiratory failure? This could be answered in a

future study which genotypes a new population of severe individuals for these genes specifically and

analyzes their respective association to Covid-19 and respiratory failure.

Carl Zimmer, the author of the secondary article, did an overall great job of describing the

research performed and outlining why this work is important. Zimmer clearly defined how the researchers

performed this study and defines terms related to what the investigators were doing to obtain their data.

However, while Zimmer does capture the question of why some people develop severe symptoms and

others do not, he does not elaborate on the hypothesis and predictions these researchers put forth in

regards to answering this question. Continuing with his article, Zimmer does explain the results of the

study in a way that can be understood by the general population by defining terms and elaborating on

functions. The problem with his explanation of the results is simply that he transitions from results to

other discussion and then back again seemingly randomly; which makes the article rather confusing when

first reading it. Overall, the problems listed are outweighed by the strengths of the article’s review of the

study and he goes beyond the scope of the study to connect it to current and past research to further

highlight just how significant the work of these scientists is. Thus, while there are some flaws with

Zimmer’s writing, these are largely outweighed by the capturing of key elements and placing the study in

context of its significance which make it a great accompaniment to the original publication.
 A Genetic Component to Severe COVID-19 Infection

Figures as Referenced in Text

Figure 1:
 A Genetic Component to Severe COVID-19 Infection

Figure 2:
 A Genetic Component to Severe COVID-19 Infection

Figure 3:

Figure 3 is taken from the original publication (Ellinghause et. al 2020) and depicts the actual results that

were obtained from this study. It demonstrated the marker loci that are statistically significant in their

presence among those who developed respiratory failure with Covid-19 as well as being significant in

their association to the infection of Covid-19 itself. It illustrates peaks on chromosome 3 and chromosome

9 to be significant in both these manners.

 A Genetic Component to Severe COVID-19 Infection

Works Cited

Ellinghaus, D., Degenhardt, F., Valenti, L., Fanke, A., & Karlsen, T. H. (2020). Genomewide

Association Study of Severe Covid-19 with Respiratory Failure. The New England Journal

of Medicine, 1522–1534. https://doi.org/10.1056/NEJMoa2020283

Zimmer, C. (2020, June 3). Genes May Leave Some People More Vulnerable to Severe Covid-

19. The New York Times.