Although most of the Covid-19 cases are mild, about 15 percent of patients are developing acute distress syndrome associated with systemic inflammation, responsible for more than 2.8 million deaths worldwide. This is partly due to our immune system acting as a double-edged sword to fight against the SARS-CoV-2 virus. On one side, the patient's body tries to destroy the virus right after infection with a controlled immune response. But in the case of patients who are getting more severely sick, the body loses control over the same immune system that is fighting the infection and initiates aggressive systemic inflammation, which may even cause death in some cases. One of the crucial questions related to the Covid-19 pandemic is whether we can identify the population with the highest possibility of becoming severely sick if infected. As of today, over 200 published and peer-reviewed studies are trying to answer this critical question and so far, have identified 21 genes that contribute to the severity of Covid-19; this number is also growing by the day.
A pair of recent research studies showed that two specific pieces of DNA in our genome (both inherited from Neanderthals) are associated with the severe and mild outcomes of Covid-19, depending on which is present in the patient's DNA. The first research at the Max Planck Institute identified a piece of Neanderthals' DNA in our (Homo sapiens') chromosome 3, that is associated with a higher risk of severe Covid-19 illness. Individuals with one copy of this archaic DNA have double the chances of getting severely sick from Covid-19 and therefore are more likely to need intensive care. The biology behind how the Neanderthal DNA can influence the clinical outcome with Covid-19 is an active area of investigation, and scientists are getting closer to the answer. It is theorised that one of the genes in this genomic area is a chemokine receptor 9 (CCR9), which is reported to regulate the inflammatory conditions in Homo sapiens. Thus, it is conceivable that this receptor may play a role in promoting an aggressive immune response during a coronavirus infection.
Analysis of the 23andMe data, which is a DNA testing service that I used to decode my DNA, revealed that I had inherited at least one of these Covid-19 risk variants from Neanderthals, located on my chromosome 3. According to a recent report, this is not surprising because around 63 percent of Bangladeshis carry at least one copy of this archaic DNA in their chromosome 3, compared to only 15 percent of Europeans—thus possessing a higher risk of disease severity during a coronavirus infection. It is far too early to conclude how such genetic risk factors may influence the disease outcome of Covid-19 at the level of a larger population, as additional risk factors (including age, sex, and pre-existing health conditions) may also play an equally critical role. However, a study from the United Kingdom (preprint) showed that people with South Asian backgrounds (this includes people from India, Pakistan, and Bangladesh) had a mortality rate that was approximately 20 percent higher than that of Caucasians after hospitalisation, which may indicate the possibility of this archaic DNA influencing the relatively more severe Covid-19 outcome. By carefully investigating these genetic risks at the population level, scientists believe that they can shed light on why some countries or some sub-populations within a country are more severely affected by Covid-19 than others.
Another intriguing fact associated with the high-risk Neanderthal variant in chromosome 3 is the drastic difference in its frequency being found in the South Asian (approximately 30 percent) vs East Asian population (almost nonexistent). Scientists speculate that such a difference could be due to positive selection (it is how new and advantageous genetic variants get enriched in a population) of this variant within the South Asian population by another disease or pathogenic infection in the past. Indeed, the chemokine receptor gene located within the Neanderthal variant in chromosome 3 within our genome has been reported to play a role in the fight against cholera. This disease has been a serious long-term problem for Bangladesh and India. It is conceivable that the high-risk Neanderthal variant may also be helping the population within these regions to battle diseases like cholera and thus enriched over time, as individuals without this genetic variant may have struggled to survive during a cholera pandemic in the past. However, during the current pandemic, such a variant may be functioning as a double-edged sword in the fight against Covid-19 and could be responsible for the disease's severity.
On the other hand, a second report published in the Proceeding of the National Academy of Science identified another Neanderthal variant in our chromosome 12 which has protective features against Covid-19. Having one copy of this variant in our genome reportedly reduces the chance of becoming severely sick with Covid-19 by about 22 percent. The 23andMe analysis revealed that my DNA carries at least one such variant. A gene located in this area of our genome can destroy the genetic material of coronavirus family pathogens. Thus, having this variant may be advantageous in the battle against Covid-19. The frequency of such protective variants could also be a reason why, despite a large percentage of the population carrying the Covid-19 risk variant from Neanderthal in chromosome 3, the death rate in Bangladesh (63 deaths per million) is significantly lower than in other countries where the population is not carrying the Neanderthal risk variant in their chromosome 3. More research is needed to completely understand how the archaic DNA is whittling the severity of Covid-19 outcomes.
One of the puzzling aspects of Covid-19 is how some people are becoming severely sick and losing the battle to it, while others are recovering quickly/with more ease. Recent research has established that the information carried in a patient's DNA may be critical for determining their Covid-19 outcome. As technological advancement reduces the cost of DNA analysis at an unprecedented speed, we can confidently speculate that, in the not-so-far future, physicians will be able to proactively identify high-risk populations just by looking at a patient's DNA. Although our genetics is a starting point over which we have no control, the code of life passed down to us from our ancestors is carrying the weight of their struggles, triumphs, and survivorship, inaudibly swaying our life with authority. The age of genetic revolution is upon us and is offering us an unprecedented opportunity to decode the untold story of our DNA. These stories are a gift from our ancestors, pleading us to learn from them, endowing us with the power to make necessary adjustments to our lifestyle, allowing us to amend both individual and social habits, encouraging us to write and pass policies, and implement new medical practices to rewrite our future. The codes we inherit in individual DNA may be the dawn of our life, but our responsibility is not to let them be the dusk.
Part one of this article was published yesterday.
Atique U Ahmed, PhD is Associate Professor of Neurological Surgery at Northwestern University Feinberg School of Medicine. His Twitter handle is @atiqueahmedphd.