Genetically increased risk of COVID-19 death in South Asians

The LTZFL1 gene, found in over 60% of South Asians, raises health and social concerns for the South Asian community and reinforces the necessity of vaccinations and following appropriate health measures. This important study contributes to the ongoing efforts to understand and better treat COVID-19. 

What is LTZFL1 and how does it work?

A study was recently published in Nature Genetics in which scientists reported on the use of molecular technology and artificial intelligence to identify a gene, LTZFL1, which leads to a “twofold increased risk of respiratory failure from COVID-19 and an over twofold increased risk of mortality for individuals under 60”. While the exact mechanism is still unclear, it appears that LTZFL1 changes the way the lung responds to the coronavirus. Previously only studied within the context of cancers, this gene was found to be strongly expressed in the lungs. It is present in the respiratory cells that come in first contact with particles, and therefore viruses, from the air we breathe. It is known to regulate key inflammatory pathways which act as a defence, protecting the lungs from invading Covid-19 viruses. Expression of the higher-risk gene has now been shown to delay the lung’s positive defence response. This drives cellular dysfunction and respiratory failure, leading to poorer disease outcomes for those with the higher-risk gene who are infected with the COVID-19 virus. 

What makes LTZFL1 dangerous? 

What is particularly concerning is that the higher-risk LTZFL1 gene is found to be carried by over 60% of individuals from South Asian ancestry compared to 15% of populations from European ancestry. Some experts, such as geneticist Professor James Davies, believe that this could offer a partial explanation for the devastating impact of COVID-19 in the Indian subcontinent and perhaps also the ongoing higher death rate in some populations in the UK. 

How does the news of this genetic contributor impact the South Asian community?

In the UK, once socioeconomic factors were taken into account, ONS data revealed a risk of death which was 3 to 4 times higher for people of Bangladeshi backgrounds, 2.5 to 3 times higher for those of Pakistani backgrounds and 1.5 to 2 times higher for those of Indian backgrounds compared to the rest of the population during the second wave of the pandemic. According to Professor Davies, “[genetic factors] would account for a large proportion of that.”

That said, the effect that the LTZFL1 has on COVID-19 outcomes in South Asian communities must still be assessed in conjunction with a range of other relevant factors. India is notably one of the countries that has been hit hardest by the COVID-19 pandemic, with over 34 million cases and 460,268 deaths recorded to date, representing a mortality rate of 1%. In comparison the USA has recorded over 47 million cases and a 2% mortality rate based on 773,747 deaths to date. This suggests that despite a genetic predisposition for a more severe COVID-19 response, disease outcomes for South Asians may still be influenced by a range of other factors. More research into LTZFL1 and its impact on the disease progression of COVID-19 compared to other risk factors is therefore required. Furthermore, Nazrul Islam, from the Oxford University’s Nuffield Department of Population Health, cautioned that the prevalence of this gene in people of South Asian backgrounds may not be accurate because some ethnicities are not well represented in large genetic databases. Islam said that “it provides an easy gateway for policymakers to say ‘it’s genetic, we can’t do anything”.  

Importantly, Islam also emphasised that the data should be carefully analysed and questioned repeatedly due to the negative implications that the finding may, ironically, have for people of South Asian backgrounds. There are concerns that the reportedly higher prevalence of this gene in people with South Asian backgrounds may spark and intensify discrimination against South Asian communities. Professor of Sociology at Columbia University, Yao Lu, conducted a study in the United States which demonstrated that prejudice against East and South Asians and Hispanic people has increased over the past two years, fuelled by the COVID-19 pandemic. Lu’s study showed that when participants read a short informational paragraph about COVID-19 which included data on how many people were infected and died from the disease, they would demonstrate aggravated prejudices against South Asians and Hispanic people. It was believed that these ethnic groups were “likely to be perceived by the treatment group as extremely culturally incompatible”. Increased prevalence of the LTZFL1 gene in people of South Asian background and its association with increased severity of COVID-19 may trigger Anti-South Asian sentiments in the wider community. 

Experts therefore caution that this preliminary research needs further confirmation and should not overshadow other significant socioeconomic risk factors and inequities faced by ethnic minorities, such as workplace exposure1. Further, care is needed to ensure that the research not be used to justify prejudice and discrimination against South Asians. 

How can we in the South Asian Australian community protect ourselves? 

While the research is still unconfirmed, it highlights the importance of us, as South Asians, taking all measures to protect ourselves and our loved ones against COVID-19. Mounting evidence consistently indicates that good hygiene practices, physical distancing and getting the COVID-19 vaccine are the best protection against getting COVID-19. 

Research based on global COVID-19 vaccine rollouts overwhelmingly demonstrates that all approved COVID-19 vaccines offer life-saving protection against the disease. In fact, Professor Davies said that “results show that the people with the higher-risk gene are likely to particularly benefit from the vaccination” and suggested that, because the LTZFL1 gene targets the lung's response to the COVID-19 virus rather than the immune system, “it means that the increased risk should be cancelled out by the vaccine.” Health advice continues to strongly suggest that all individuals who can get vaccinated should make all efforts to be fully vaccinated.

Common COVD-19 Myths Busted
Myth: I’ve already had COVID-19, I don’t need the vaccine.

Fact: The evidence overwhelmingly suggests that getting vaccinated provides greater protection since it helps reduce the spread of COVID-19. Even though previous exposure to COVID-19 provides some level of protection, we do not know how long the immunity lasts. Additionally, some evidence suggests that even after COVID-19 infection, those not vaccinated were found to be more than twice as likely to be reinfected compared to those who were fully vaccinated. 

Myth: The development of the vaccine was rushed, so its effectiveness and safety cannot be trusted.

Fact: Due to the severity of the pandemic, an abundance of resources were directed towards the development of the COVID-19 vaccinations. As such, more researchers were able to dedicate more time and finances towards vaccine development without actually skipping any important steps in the process. Furthermore, the technologies used in the development of the vaccines have been long researched and perfected for years so pharmaceutical companies could begin vaccine development early on in the pandemic rather than waiting for the appropriate technologies to be developed. Further, clinical trials were able to be completed quickly and effectively because of the fact that COVID-19 is highly contagious and symptomatic, allowing the  efficacy of the vaccine to be quickly determined 2.

Myth: The side effects of the COVID-19 vaccine are dangerous.

Fact: As with most vaccines, the COVID-19 vaccines can have side effects, which can vary in severity between individuals. The most common side effects include body aches, localised pain at the site of injection and possible headache or fever, lasting for up to 2 days. To read more about the possible side effects and get more information about how each of the COVID-19 vaccines work, visit the vaccine information page on the Centres for Disease Control and Prevention page. 

Importance of such research in our fight against COVID-19

Despite concerns that increased prevalence of the higher-risk LTZFL1 gene in South Asians may exaccerbate pre-existing discrimination issues against South Asian communities, this research provides important insights in our understanding of COVID-19 disease progression and outcome for people of South Asian background. Raghib Ali, an independent expert adviser on COVID-19 and ethnicity for the Race Disparity Unit in the Cabinet Office, highlighted the importance of this study in contributing to “ongoing efforts to understand the causes of the higher death rates from Covid in some ethnic groups and specifically as to why their outcomes or survival from Covid are worse after infection.” The study could offer a potential, highly specific therapeutic target for the treatment and prevention of COVID-19. However, further investigations into the LTZFL1 gene, its association with COVID-19 and its implications for the over 60% of South Asians who are said to express it, need to be conducted. 

This underscores the importance of everybody in the community to get vaccinated, practice good hygiene and follow the Department of Health advice on Covid related matters.  

Sadaf Zafir is a science and culture writer at SAARI. She has a background in biomedical science and is an application development analyst at Accenture. You can connect with her via LinkedIn