Researchers investigate genetic factors behind resistance or susceptibility to COVID-19

A study is being conducted by a research center supported by FAPESP to determine whether people who develop severe forms of the disease have risk genes and whether asymptomatic people or patients with only mild symptoms have protective genes.

By Elton Alisson  |  Agência FAPESP – To date, over 2.5 million people have recovered from COVID-19 in Brazil. They include older people, with some in their nineties or even aged 100 or older. Many had comorbidities, such as diabetes and high blood pressure, yet survived the disease without major complications despite these risk factors. On the other hand, more than a few of the people who did die from the disease were young and had no record of chronic disease.

Researchers believe genetics may have contributed to the surprising pattern of the disease in these two groups. “People who develop severe forms of the disease may have what we call risk genes, while others who are infected but don’t develop the disease may have protective genes,” said Brazilian researchers Mayana Zatz, a professor in the University of São Paulo’s Institute of Biosciences (IB-USP) and principal investigator for the Human Genome and Stem Cell Research Center (HUG-CELL).

HUG-CELL is one of the Research, Innovation and Dissemination Centers (RIDCs) supported by FAPESP.

To confirm or refute this hypothesis, HUG-CELL researchers are studying the genomes of people in these two groups: superresistant and susceptible. They also analyzed samples of blood cells from elderly patients who showed resistance to COVID-19, especially those aged 90 and above.

Adult cells from superresistant patients will be reprogrammed in the laboratory so that they become induced pluripotent stem cells (IPSCs) that can differentiate into lung, kidney and heart cells. The cells will be exposed to the virus in an effort to see how they respond. “We plan to determine whether the virus infects these cells and how they behave when exposed to it,” Zatz said.

To evaluate the genetic response of young patients who died from severe forms of COVID-19, the researchers are partnering with colleagues at the university’s Medical School (FM-USP).

The latter are using a minimally invasive procedure to perform autopsies on the bodies of patients diagnosed with COVID-19 who die at the institution’s general and teaching hospital (Hospital das Clínicas). The research is part of a project also supported by FAPESP.

The project has resulted in a biorepository of tissue samples that are being used by several research groups in studies of the viral mechanisms involved in infection, with the aim of refining diagnostic techniques, among others (read more at: agencia.fapesp.br/32955).

“These patients, especially the younger ones, must have had some genetic mutation that led to the development of more severe forms of the disease and unfortunately to their deaths,” Zatz said.

Differences between men and women

The HUG-CELL researchers are also studying the asymptomatic group, i.e., people who are in direct contact with COVID-19 patients but do not become infected or are infected but are not experiencing any symptoms. This group consists mainly of patients’ spouses, particularly women.

“We know of many cases in which men diagnosed with the disease by molecular and serological tests have been hospitalized or isolated at home and cared for by their wives or female partners, who remain uninfected,” Zatz said. “When they test positive for the presence of antibodies, these women are considered asymptomatic. When the serological test is negative, they’re classified as disease resistant.”

The international data show that men are more affected by the virus than are women, she added. Severe forms of the disease are also more frequent in men.

The different responses in men and women and in symptomatic and asymptomatic subjects have been analyzed in studies published by scientists in several countries. “A project has been proposed in the United Kingdom to sequence the genomes of 20,000 people. Similar initiatives are being discussed in the United States,” Zatz said.

The results of these projects could change the way patients are treated and help medical teams predict which patients are likely to develop complications.