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Event Review: COVID-19 – Evidence and limitations of genetics in relation to BAME groups

14 September 2020
Appeared in BioNews 1063

I was aware of the disproportionate impact of COVID-19 on black, Asian and minority ethnic (BAME) people in the UK but I did not know much about the causes. I'd often asked myself whether these were solely genetic or environmental. The search is on to find genetic vulnerabilities linked to race, but will we disregard the ethnic inequalities in health and wellbeing in the UK by explaining it all away with genetics?

'COVID-19: Evidence and limitations of genetics in relation to BAME groups', the last in the Medical Genetics webinar series by the Royal Society of Medicine, planned to tackle these questions.

Dr Melita Irving, the previous president of the Medical Genetics Section, and trustee of the Royal Society of Medicine, chaired the webinar on 24 August. She started off by introducing the panellists and I could tell from the numerous job titles that they were impressive and well-qualified to talk on the subject. Importantly, the panel was all BAME academics – I believe those affected by health inequalities and exclusion should be the ones to address the subject.

Dr Sonya Abraham, consultant and research physician in rheumatology and general medicine at the Imperial College healthcare group, started things off by distinguishing between race, ethnicity and ancestry. Ancestry provides biological markers based on genome data which can tell us about ethnic descent. Race is a social construct based around aesthetic characteristics with no biological foundation while ethnicity refers to a commonality of cultural heritage, language and social practice.

Dr Abraham is an ambassador for fair representation and pointed out that the majority of genomics and clinical research is performed in people of European descent. Genetically diverse populations are under-researched and therefore have poorer health outcomes.

Clinical trials to test the effectiveness of beta-blockers to treat heart failure are a seminal example. An original Swedish trial in 1999 with 94 percent white participants found that beta-blockers were effective in reducing mortality caused by heart failure. A later more diverse trial in Texas, with 24 percent of participants having African ancestry, found beta-blockers were ineffective for these patients. It is vital not to overlook ancestry and genetics in clinical trials. This important discovery has led to the development of drugs that are more effective for heart disease patients of African ancestry.

Accelerating to our present situation, Dr Abraham points out that only six out of 1518 COVID-19 registered trials are collecting ethnicity data. To determine whether genomics linked to race plays a role in treatment of COVID-19, it is important to gather this data.

Dr Abraham ended on a positive note, what can we do to help? Education is the first step, then a mandate in Good Clinical Practice so we can achieve research outcomes applicable to all.

I felt Dr Abraham's passion about getting more diversity in clinical research was apparent, but the discussion around the implications this might have on structural racism was lacking. Actively looking for differences linked to race may fuel the divide that was built to suppress BAME people in our society. Biological 'differences' between races backed up by genetic data is dangerous ammunition.

Next Professor Guruprasad Aithal, professor of hepatology, deputy director and theme lead at the National Institute for Health Research at Nottingham Biomedical Research Centre, asked the question: Do biological factors beyond obvious socioeconomic variations contribute to COVID-19 susceptibility? 

Data showing that a higher proportion of BAME people die from COVID-19 compared to other viral pneumonias suggests it is not only due to socioeconomic factors. 

Professor Aithal described genome-wide association studies of patients with severe COVID-19. One study, along with others, found that the ABO blood group system may be involved in susceptibility to respiratory failure during COVID-19 infection. Conflictingly, O blood type is protective which is most common in non-white groups. Another study has found a rare genetic variant that causes a loss of function of the TLR7 gene that is associated with hospitalisation with COVID-19. The TLR7 protein is activated when COVID-19 enters human cells and leads to important immune responses. However, these genetic associations cannot explain the ethnicity differences in the general population.

Dr Steven Mack, joined at 4am local time from the University of California, San Francisco. His presentation was easy to follow, taking us on a journey through the genetics of human leukocyte antigen (HLA), his primary research interest.

The HLA system is the first line of defence in the immune system, helping immune cells discriminate between cells that belong to us and cells that don't. HLA genes code for proteins that present small proteins, or peptides, on the surface on almost all cells. If patrolling immune cells determine these peptides as foreign this sets off an immune reaction which causes the destruction of the infected cell.

Dr Mack discussed HLA presentation of SARS-CoV-2 peptides. Some HLA alleles have a higher predicted potential to bind COVID-19 peptides than others and the frequency of these vary across the world. Mirroring Professor Aithal, Dr Mack agrees that more evidence is needed before we can confirm genetic susceptibilities to COVID-19. 

By now I had realised, current evidence for genetic vulnerability to COVID-19 in BAME individuals is weak. The speakers focused on ancestry and avoided the loaded concept of race. It seemed dismissive not to discuss the structural racism that leads to health inequalities in the UK, which has been under scrutiny since Public Health England concluded in a review that it was a contributing factor.

The final speaker was Dr Winston Morgan, reader in toxicology and clinical biochemistry. He is an active campaigner in social justice and equality of opportunity in higher education, something I didn’t find hard to believe by his stimulating talk.

Dr Morgan explained why the search for a genetic cause is dangerous, with the most memorable line of the webinar: 'A genetic cause linked to race would neutralise any accusations of racism, reducing the culpability of society, including the medical profession.' 

He admits the observations that COVID-19 only effects a selection of the population does point towards a genetic vulnerability, but there is no evidence this is linked to race.

The crux of his talk was about ageing. The immune and cardiovascular systems become less efficient with age, leading to worse health outcomes with COVID-19 infection. Dr Morgan's theory is that chronic stress, experienced by many BAME individuals due to everyday discriminations and micro-aggressions, could accelerate the ageing of the immune and cardiovascular systems making them more susceptible to COVID-19. The work of Professor David Williams at Harvard inspired this theory, who pioneered our current understanding of social influences on health.

Dr Morgan ended on some evidence that quality of diagnosis is poorer for black and other non-white patients in the medical setting. Further, a population-based study in Chicago, among others, has shown that 56 percent of black people experience discrimination in the hospital and this includes receiving poorer service.

Dr Morgan concluded that rather than genes linked to race, BAME patients might be more likely to die from COVID-19 due to accelerated ageing precipitated by a lifetime of discriminations, followed by poorer diagnosis, treatment and hospital care.

There were questions from the audience which sparked a fascinating panel discussion, taking us over time. The public were curious about the difference between infection in males and females, and how we can tackle the inequalities in medical care. The panel then discussed the silver linings to come out of the COVID-19 pandemic such as the collaboration of experts worldwide into consortia to streamline analysis.

Overall, I thought this webinar had a good balance of current ideas about the genetics of COVID-19 susceptibility. The panellists agreed that genetic associations are likely, but there is no evidence they are directly linked to race. It was accessible to those who don't have a strong background in genetics, I would also recommend it to those who are in the field as a good overview of the current research landscape. 

Dr Irving stressed it is important not to let the 'biological factors distract us from recognising there are existing health inequalities and structural racism' so the addition of Dr Morgan's talk was significant. This should be considered by all geneticists as they engage the public in their research. They have a responsibility to communicate that human beings are more similar than they are different and should be treated that way.

SOURCES & REFERENCES
COVID-19: Evidence and limitations of genetics in relation to BAME groups
The Royal Society of Medicine |  24 August 2020
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