A protein deficiency found commonly in large swathes of the populations in Europe and North America could explain why these regions have been worse hit by Covid-19 than people in Asia, researchers at a Calcutta-based national institute have established.

The protein, Alpha-1-antitrypsin (AAT), prevents lung tissue damage and its deficiency reduces the body’s ability to fight off the D614G mutant of the Coronavirus (Sars-CoV-2) which is now the dominant strain globally.

This finding which could have major implications for understanding Covid-19 and how it has spread globally has emerged in a study conducted by the National Institute of Biomedical Genomics (NIBG) in Calcutta.

“We have been looking for explanations for the rapid spread. Also, we noted it was spreading better in Europe and North American than parts of Asia,” says Partha Mazumder, founder and distinguished professor, NIBG.

NIBG’s ground-breaking work throws a new light on the reasons for the different rates in the spread of Covid-19 globally. The research also “opens up possibility for considerations of AAT supplements in prevention of the 614G subtype virus,” says the study published in the Infection, Genetics and Evolution journal.

The first strain of Coronavirus was the D614D but that was rapidly superseded by the D614G variant which spread like wildfire in Europe and North America.

The protein, Alpha-1 antitrypsin (AAT), is one of the major serum proteins that fights inflammation and helps prevent lung tissue damage.

Crucially, the researchers found in the study that covers the first report of the virus from China in late December 2109 up to July 2020 that AAT deficiency is “highly prevalent” in European and North-American populations, but “much less so” in East Asia (the report uses the term East Asia but this also includes South Asia).

“This allowed the faster spread in Europe and North America,” Majumder said. “This AAT deficiency enhanced the ability of the virus to infect human cells and spread in Europe and North America,” he added. In addition, clinical studies from England and the US reported a three-fold increase in viral load for individuals infected with the 614G variant than the 614D subtype. Studies suggest that higher viral loads are associated with worse disease severity.

There has been widespread speculation about why the virus has spread at different rates across the world with some experts attributing smaller caseloads in Asia to such factors as higher temperatures. Also, Indians are thought to have higher immunity levels because we have to face illnesses like malaria and dengue.

But Majumder said his team was convinced that the reason for the “explosive spread among individuals of European and North American ancestry” and the “slower spread” among those of Asian ancestry was related to biological factors.

“This is the first time we have got an insight into the mechanics” of how this mutant type of the coronavirus (DG614G variant) spread, said Majumder.

In January 2020, the viral landscape globally was overwhelmingly dominated by 614D. But by March, 614G subtype had become the dominant subtype in Europe and in North America. However, in Asia. the spread of the 614D variant was much slower. To reach 50 per cent of cases, the 614G subtype took two months in Europe and nearly three months in North America compared to East Asia where the time lag was five-and-a-half months.

According to the paper, AAT deficiency is highest in Portugal at 75.9 individuals per 1,000. Spain has the second-highest deficiency of the AAT protein at 67.3 individuals per 1,000. Barcelona was hit very badly by the pandemic with overflowing hospital wards at the peak.

In France, the AAT deficiency stands at 51.9 per 1,000 individuals. Poland has the lowest rate of AAT deficiency at 18.7 per 1,000. Canada has 32.1 per 1,000 individuals with AAT deficiency while the US has 29 per 1,000 individuals. In Asia, the AAT deficiency rate was two per 1,000 individuals in the Philippines; 2.5 in Singapore; nearly five-and-a-half in South Korea. The study gave no AAT deficiency figures for India but Majumder said the researchers’ conclusions could be applied to this country.

The Indian study’s findings are backed up by research published in The Lancet which suggests people with AAT deficiency face increased risk of catching Covid and development of severe symptoms. “Identifying populations who are risk of severe complications is crucial” in order to develop Covid prevention and treatment strategies,” the paper says.

It notes that patients with AAT deficiency also have a higher prevalence of hypertension, kidney problems, respiratory illnesses and diabetes -- diseases already associated with higher Covid infection chances and poor prognoses. “Identifying populations who are risk of severe complications is crucial” in order to develop Covid prevention and treatment strategies, the paper says.