Thread by @MdFacep

If yet another mutation or variant of concern surges that more completely evades the antibodies people have built up, “we start all over,” ---Dr. Gregory Poland, head of the Mayo Clinic's Vaccine Research Group 1/4/2022

I stress that mutations happen during rampant surge

Omicron has an enhanced and focused affinity for the upper airways, replicating 70X more than delta and not invading the lower airway.
The resultant edema, inflammation, increased secretions are presenting as bronchiolitis, RAD, bronchospasms, and croup depending on the age group

It is predicted that the next variant of concern WILL arise before June of 2022.

The unprecedented explosive surge of new cases is the perfect petri dish for Omicron's next variant.

I keep citing basic principles in virology and immunology that so many clinicians forgot

Viruses mutate during peaks of surges

Natural selection chooses the variant most adapted to dominate and emerge. Delta was that earlier this year.

When that variant is allowed to replicated in partially protected host, the virus develops immune evasion properties.

Natural selection chose that new variant in the fall of 2021. This new variant mutated to become more infectious, faster replication, immune evasive, and that was Omicron this fall of 2021.

Omicron does not propagate well in cells expressing the TMPRSS2 ( Transmembrane Protease Serine 2) and really has a focused and high affinity for cells devoid of this membrane protein.

The lungs are rich in TMPRSS2-so we see less pneumonia

Upper airway is devoid of it

The Spike protein, used for attachment of all SARS-CoV-2 viruses have subsets (S1/S2) which are needed for viral cell entry and, once the cell is infected, multiplication and cell-to-cell fusion

Lungs' cells don't support this process
upper airway does.
biorxiv.org/content/10.110…

This process is deficient in cells expressing TMPRSS2 such as the lower airway, or lungs, and is very efficient in tissue devoid of TMPRSS2, such as the upper airway.

So I remind you that children will see the worst of this disease because of this exact pathophysiologic process

Omicron avoid NABs (neutralizing Antibodies) by staying inside infected cells and causes a cell-to-cell fusion to enter the next cell to destroy.

It turns off our INF I and INF III (Interferon 1& 3) an initial step that triggers & turn on our immune defense once we're infected.

We may NOT have 6 months before the next variant emerges, which I expect to be even more immune evasive, and more difficult to detect.

We must be nimble, think ahead, and take scientific proactive moves if we are to control this viral advantage.

@EricTopol @AlbertBourla

We need a multivalent vaccine!

One which contains the Omicron strain, a tweaked Delta strain, and other pathogenic viral segments.

In the mean time everyone needs to get the booster and please, please please, if you don't and get infected isolate 6-7 day
nature.com/articles/d4158…