CME INDIA Presentation by Dr N K Singh, Admin.

I’ve quite frankly, never seen anything like it, where a single, well-characterized virus in individuals can have a range of manifestations, that go from being completely asymptomatic, no symptoms at all, to having a few symptoms that don’t bother you much, to having symptoms enough to keep you home, to have symptoms enough to keep you in bed really feeling poorly for a couple of weeks, to have the symptoms and signs of  having you go to a hospital, to then possibly getting intensive care, and then to dying. So it’s very very unusual to have a disease with that range of manifestation with one etiological agent Dr Anthony Fauci (Lead members of the Trump administration’s White House Coronavirus Task Force in the United States. Fauci is one of the world’s leading experts on infectious disease).

It is fascinating to think that our ancestor’s genetic legacy might be playing a part in the current pandemic. Latest research, published in Nature on 30th September reviews its possibility.

Panic Unmeasurable

  • Many instances all over world surprised us the way COVID behaved.
  • July was the month when cases in Jharkhand started peaking. Just 30 km from my place of work, six members of a family died due to COVID-19 in Katras, near Dhanbad.
  • It started with an 88-year-old woman and later her five sons who died. It happened between July 4th and July 20th.
  • The lady came from Delhi and brought the virus from Delhi. Dhanbad was till then safe and we thought that our area will not see disasters.
  • People started socialising and this lady came to attend a marriage.
  • Party happened with all the zeal but she fell ill, detected having COVID-19 and died. She was cremated by her 5 sons, but till then no one had any clue that she had contracted the deadly virus. Report came later.
  • Soon, all these five brothers contracted the virus.
  • Her eldest son (66) died at Dhanbad on July 10.
  • Next day, her second son (63) died.
  • On July 12, third son (60) succumbed to infection.
  • Four days later, on July 16, her fourth son (55) died.
  • The woman’s fifth son (50) died on July 20.
  • Panic was unmeasurable all over.

Green Recovery with multiple co-morbidities

  • We have seen cases with age group 80 to 95 recovering well.
  • Many obese, above 80-year cases with uncontrolled comorbidities recovered well.
  • Many young and healthy cases died unexpectedly.

Why this happens?

Many factors have been corelated:

  • Age.
  • Co-morbidities.
  • Viral load.
  • Male sex.
  • Immune status.
  • Genetics.
  • Etc.

Our ancestor’s genetic legacy might be playing a part

Zeberg, H., Pääbo, S. in the article titles “The major genetic risk factor for severe COVID-19 is inherited from Neanderthals”, published on 30th September 2020 raises very interesting concern that that some people who have severe reactions to the SARS-CoV-2 virus inherited certain sections of their DNA from Neanderthals as per a genetic analysis study.

(Nature (2020).

What is this Neanderthals?

  • Neanderthals existed about 40,000 years ago in the Eurasia region. They are classified as a species of archaic humans that became extinct either due to competition (with early modern humans) or due to a mix of factors including climate change.

A Neanderthal gene is the Game Changer in getting cytokine storm?

  • It is well known that 1–4% of the modern human genome comes from these ancient relatives.
  • Many of the surviving archaic genes are harmful to modern humans with an increased risk of disease.
  • Uneven global spread of a genetic risk factor for COVID-19 is associated with severe COVID-19 infection and hospitalization is derived from Neanderthals with a long sequence of DNA.
  • The sequence is unevenly distributed across modern human populations.
  • A genetic analysis has revealed that some people who have severe reactions to the SARS-CoV-2 virus if inherited certain sections of their DNA from Neanderthals.

Risk factor map
This map shows the frequency at which the risk factor is found in various populations from around the world. Courtesy: Nature Zeberg, H., Pääbo, S.

Some salient features of the Research:

  • The prevalence of the Neanderthal-derived haplotype in the modern human population has been checked. It is rare or completely absent in east Asians and Africans.
  • The risk haplotype (a group of genes within an organism inherited together from a single parent) has been found in:
    • Latin Americans – 4%.
    • Europeans – 8%.
    • Asian ancestry – 30% (reaching as high as 37% in those with Bangladeshi heritage).
    • African ancestry-Absent (Still high mortality seen, may be due to social inequality and its consequences and Neanderthal-derived DNA does not explain it.
  • It has been speculated that the Neanderthal-derived haplotype is a substantial contributor to COVID-19 risk in specific groups.
  • May be that when you get infected with COVID virus, the protective immune response mediated by these ancient genes might be overly aggressive. This might lead to the potentially fatal immune response.
  • It could be that a haplotype that at times in our past might have been beneficial for survival could now be having an adverse effect.

CME INDIA Learning Points

  • Our ancestors can’t take all the blame for how someone responds to the virus.
  • A key part of tackling COVID-19 is understanding why some people experience more-severe symptoms than others? As we still do not know the reasons, this research might be an answer.
  • This research not only sheds light on the reason that some people are more susceptible to severe disease, but also provides insights into human evolutionary biology.
  • In the beginning of the pandemic a segment of DNA 50,000 nucleotides long (corresponding to 0.002% of the human genome) was found to have a strong association with severe COVID-19 infection and hospitalization. New research simply reports that this region is inherited from Neanderthals.
  • Let us acknowledge, although genes involved in the COVID-19 response might be inherited, social factors and behaviours (such as social distancing and mask wearing) are in our control, and can effectively reduce the risk of infection.

CME INDIA Tail Piece

  • We can correlate between this risk haplotype and clinical outcomes but it should be clear that genetics alone do not determine a person’s risk of developing severe COVID-19.
  • It is true that our genes and their origins clearly influence the development and progression of COVID-19 but environmental factors also have key roles in disease outcomes.

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