Collaborative Study Understaken By YRC AND KMC - Genomic And Ancestral Variation Underline The Severity Of Covid-19 Disease Presentation Among Individuals Of European Descent

The manifestation of COVID-19 has shown discernible variability worldwide. While some infected individuals show little or no symptoms with quicker recovery, others are more grievously affected and even succumbing to it. In a collaborative study between Yenepoya Research Centre (YRC), Yenepoya (Deemed to be University), Mangalore and Kasturba Medical College (KMC), Manipal, Manipal Academy of Higher Education (MAHE), led by Dr. Ranajit Das of YRC, reported the genetic variations that are strongly associated with increased severity of COVID-19. Recently, this study has been published in internationally reputed journal Life (MDPI, https://doi.org/10.3390/life11090921). The team used a genome-wide approach to identify specific genetic factors or variations that are associated with the severity of COVID-19. Dr Das and colleagues used the genetic information of asymptomatic/mildly affected COVID-19 patients and compared it to that of severely affected patients. They argued that COVID-19 patients who showed little to no symptoms might have genetic attributes that protected them from the severe COVID-19 disease presentation. The genetic data used in this study was provided by Ancestry DNA and corresponded largely to COVID-19 patients of European descent. Dr. Das and colleagues identified genetic variants in biological pathways linked to host immunity, such as interferon, interleukin and cytokine signalling, and known COVID-19 comorbidities, such as obesity and cholesterol metabolism are significantly different between asymptomatic and acutely symptomatic COVID-19 patients. Their study delineates that men with underlying comorbidities and certain genetic variations in their immune system are more susceptible to the severity of COVID-19, compared to the women and individuals, without such genetic variants.

Dr Das and colleagues were also the first to link the variation in the severity of COVID-19 to the ancestral past of the patients. They found that the asymptomatic and mildly symptomatic European COVID-19 patients have higher proportions of the ancient Ancestral North Eurasian (ANE) ancestry, which was introduced to Europe through Bell Beaker culture 2000-3000 years ago and lower fractions of the Western Hunter-Gatherer (WHG) ancestry that was found in people who lived in Europe in the areas ranging from British Isles to the Carpathian mountains in the Central Europe, likely till the end of Last Glacial Maximum (LGM) ~14,000 years ago. Consistent with this the severely symptomatic patients had significantly higher fractions of WHG and lower ANE ancestral components.

This study highlights the population and ethnicity specific genetic differences underlying the spectrum of severity of COVID-19 severity worldwide. It will potentially pave the way for the development of population specific therapeutics that might be more effective in combating COVID-19 than generic drugs and approaches. Understanding the genetic information of COVID-19 patients from diverse ethnicities will also help to zero down on genetic variants and biological pathways that are associated with severe COVID-19 and hence can help to develop targeted more personalized therapies. Dr. Das and his team aim to perform similar studies using the genetic data from COVID-19 patients from various parts of India.