How does genetics affect severe Covid-19 cases in healthy patients?

In the last week of June, doctors Tomás García (Head of the microbiology area at Health in Code Valencia) and Juan López (Head of the microbiology area at Health in Code Malaga) gave an interview to Con Salud and Intereconomía, in which they explained why during the pandemic there have been healthy individuals younger than 50 years of age with a more advanced respiratory profile, with higher morbidity and mortality after being infected with Covid-19.

“Many times we think that viral load is the answer to these exceptional cases, yet in our laboratory we have seen many patients who tested very positive and did not show the slightest symptoms and whose only relation to Covid-19 was a positive PCR result proving that they had been infected with SARS-CoV-2”, said Dr. López.

A large number of studies aimed at understanding the interaction between human DNA and the SARS-CoV2 virus have been conducted during the pandemic. On the basis of these studies, several genetic risk factors have been associated with the severity of this pathology. Blood type, T cells, and the HLA genotype, among others, are the main causes in individuals without risk factors such as smoking, cancer, or diabetes.

“It is interesting to note that, in principle, the mutations of the virus that we know of and the new strains that appear do not have to interact in a different way with our cells and our DNA”, pointed out Dr. García. “We are talking about a virus that surprises with its capacity to spread, which keeps being the most worrying issue at this point”.

Regarding the blood groups, it has been observed that individuals with groups A1 and B are the ones that have a higher predisposition to suffer a critical illness due to Covid-19. “These groups have more proteins, which is why they have a higher risk of thrombosis, which is one of the comorbidities associated with this disease”, Dr. López stated.

On the other hand, we have T cells, which are in charge of eliminating everything that is exogenous, and the genotype variants HLA-I and HLA-C, which present the antigenic peptide to T-cell receptor. Doctor López explained how some variants can lead to a cytokine storm, in other words, an overexpression of immune response. To which doctor García added, “This causes an inflammatory cascade, an immunological explosion that leads to morbimortality, whether the virus is present in its active state or not”.

Other studies linked the severity of Covid-19 in certain cases with the epigenomic profiles of those same individuals.

“Research will continue to go on and we will learn much more about this virus. In the end, its diagnosis shall be a part of standard medical practice“, concluded Dr. García.

P. de Francisco. Genetics, the culprit of severe Covid-19 in healthy individuals. 2021; Available at: https://www.consalud.es/pacientes/especial-coronavirus/genetica-culpable-covid-19-grave-personas-sanas_99083_102.html