Two studies show why the Omicron variant has low fatality and high infectivity

“Out of life’s school of war—what doesn’t kill me, makes me stronger.” –  Friedrich Nietzsche, Twilight of the Idols, 

The mutations in the omicron variant allow it to escape the immune response, but its entry into the lung cells becomes impaired. This explains the higher transmission but lower mortality rates in South Africa.

The higher number of COVID-19 cases but no change in death rates. The South African omicron experience.

That is the gist of the study by scientists from the University of Cambridge, University of Tokyo, CSIR Institute of Genomics and Integrative Biology in India, University of Miyazaki, Kumamoto University, and Kyoto University.

Their work, SARS-CoV-2 Omicron spike mediated immune escape, infectivity, and cell-cell fusion, is a preprint at bioRxiv.

Before we dive into the study, let’s have a bit of a background on what is essential for the SARS-CoV-2 to spread successfully and be deadly.

What does it take for a SARS-CoV-2 to be infectious? 

The spike proteins are protrusions coming out of a coronavirus, and the virus uses them to attach to human cells that bear the ACE2 receptors. The spike protein is like an umbrella, and it needs to be open before use, and the spike protein does that by moving a “hinge.”

The figure below is a spike protein. The orange and cyan are the hinges that open the spike protein.

Source: 5-HT2AR – Wikipedia

The SARS-CoV-2 uses an enzyme from human cells, the TMPRSS2, to open the hinge in the spike protein before it enters into cells. After entry, the virus enters the cells and begins replication and infection. The viruses produced in infected cells use the TMPRSS2 again to spread from cell to cell and spread the disease.

The immune response to stop the infection.

The body tries to stop the virus from attachment to cells with antibodies to block the RBD. Once an antibody attaches to the receptor-binding domain (RBD), it prevents viral attachment, entry, and replication. Those antibodies are neutralizing antibodies. In the image above, the RBD is magenta.

Previous infections and immunization can produce neutralizing antibodies. But the problem is, neutralizing antibodies from the COVID shots is short-lived. (See related articles below).

Omicron mutations escape neutralization.

Antibodies have to fit correctly like a lock and key mechanism for antibodies to be effective—the mutations in the omicron change how the proteins fold in the Omicron and thus its shape.

The spike protein changes make it unrecognizable to the pre-existing neutralizing antibodies. The study tested the antibodies formed after Pfizer, AstraZeneca, Moderna, and Coronavac shots and found that they have reduced to no effectiveness against the omicron variant.

As it escapes the immune system, the Omicron can start to infect. The resulting symptoms will be sore throat, loss of taste or smell, and a stuffy nose. The patient will quickly expel any fluid or phlegm build-up by coughing or sneezing with the viruses and spread to others. That is why the omicron variant has higher infectiousness.

Study findings

The study showed the Omicron spike binds ACE2 receptors with enhanced affinity and can escape from monoclonal antibody therapy REGN-2, remdesivir, and the active metabolite of molnupiravir.

Furthermore, the Omicron escapes antibody neutralization from the Johnson and Johnson vaccine ChAdox-1 and two shots of BNT162b2  (Pfizer)mRNA vaccines; however, a third dose effectively neutralizes the antibodies.

How does the SARS-CoV-2 produce severe disease?

If the SARS-CoV-2 viruses reach the lungs, they cause inflammation, and fluid builds up in the alveolar spaces where oxygen-carbon dioxide exchange happens, leaving no room for air exchange.

The results are low oxygen levels, shortness of breath, and altered mental status, prompting anyone to seek medical attention. Low oxygen levels are one indication for hospital admission, and if the low oxygen is not corrected, the patient can die.

Omicron mutations decrease entry to the lung cells

The study showed that mutations In the Omicron prevented the Omicron from using the TMPRSS2 enzyme and stopped omicron fusion with the ACE2 receptors in the lungs. If there is no cell entry, there can be no lung infection.[1]

Moreover, inhibition of the TMPRSS2 enzyme also prevents syncytium formation or cell to cell spread of the Omicron in the lungs if an infection happens. Thus a severe disease is prevented.

Another study from the Erasmus Medical Center in the Netherlands confirmed that the Omicron variant replicates efficiently in the upper airways but cannot effectively multiply in the lung cells. [2]

We report that Omicron replicates more rapidly in the airways and has an increased fitness compared to the early 614G variant and Delta. 

In contrast, Omicron did not replicate productively in human alveolar type 2 cells.

Significance of the study

Many people, including those vaccinated, will get infected by the omicron variant; however, the overwhelming majority will get better and develop natural immunity to SARS-CoV-2 viruses with many mutations.

The immune memory that will develop includes neutralizing antibodies, T-cells, and plasma B cells specific to those mutants. In the end, the resulting immune response will be more robust and ready to counter future SARS-CoV-2 variants.

In summary, the Omicron variant evades neutralizing antibodies from vaccination, approved monoclonal antibodies, remdesivir, and molnupiravir. A booster shot can produce neutralizing antibodies against the Omicron.

The Omicron cannot enter the alveolar cells in the lungs and therefore cannot produce lung inflammation resulting in a milder COVID-19.

A few days after this article is published, new research shows that Omicron infections elicit neutralizing antibodies against variants like the Alpha, Beta, Gamma, Delta, Omicron, and 15 other variants. At around nine to twelve days, cross-reactive spike- and nucleocapsid-specific CD4 and CD8 T cell responses are produced from the infection. [3]

Omicron infections elicit neutralizing antibodies against other variants of concern.

A Christmas gift from God

In an interview at the Ingraham Angle, Dr. Robert Malone, the founder of the mRNA gene therapy, said,

If you believe in God, this looks awfully like a Christmas present. The last count of deaths from omicron worldwide is less than ten.

The good news is omicron is a very low disease, highly infectious.

It looks a lot to experienced vaccinologists like a live-attenuated vaccine that will elicit a strong mucosal response. This is about as good as we can possibly want right now in terms of outcomes

 

 

While that is undoubtedly great news, especially when people get together, we should remain vigilant and observe precautions. The elderly, immune-compromised, and those with comorbidities can still be at risk, and that’s why safeguards should continue while keeping the Holydays.

16 Ways to Avoid COVID-19 During the Holidays

 

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Related:

  1. USA study: Adults and children with the Omicron variant have milder COVID-19
  2. COVID-19 in children under five years old with Omicron is mild compared to the Delta variant
  3. Omicron can evade antibodies from vaccinated and COVID convalescent people
  4. Study shows the absence of omicron neutralization with the Pfizer and AstraZeneca shots
  5. A higher number of COVID-19 cases but no change in death rates. The South African omicron experience
  6. Omicron can evade antibodies from vaccinated and COVID convalescent people
  7. Study shows the absence of omicron neutralization with the Pfizer and AstraZeneca shots
  8. Durable Immunity from Pfizer COVID-19 Vaccine Lasts only Six Months
  9. Update to the I-MASK+ Prevention & Early Outpatient Treatment Protocol for COVID-19
  10. What should the household do if someone has an Early COVID-19?
  11. The I-MASK+ for the Prophylaxis and Early Treatment Protocol of COVID-19

Reference:

  1. Meng et al. SARS-CoV-2 Omicron spike mediated immune escape and tropism shift.
  2. Zhou et al. Vaccine-breakthrough infection by the SARS-CoV-2 Omicron variant elicits broadly cross-reactive immune responses. bioRxiv