COVID-19: WHY OMICRON BEHAVES DIFFERENTLY

STOP PRESS:  A paper just published by Glasgow University shows the evidence for Omicron infecting human cells by a different mechanism from Delta and earlier variants. 

In an earlier blogpost, we noted that the spike proteins of the COVID-19 virus (SARS-COV-2) bind to a receptor on human cells, which allows the virus to infect the host cell.  The receptor is called ACE2 "Angiotensin-converting enzyme 2" We also noted that other coronaviruses bind through a different mechanism.

The Omicron variant has a substantial number of changes to the spike protein, especially in the area known to bind to human cells.  

The work by Glasgow University shows that is enough to change how it binds to human cells:

SO WHAT IS HAPPENING?

The report says, in technical language:

"Entry of SARS-CoV-2, and related coronaviruses, can proceed via two routes 

• Cell surface fusion following proteolysis by TMPRSS2,or
• By the endosomal proteases Cathepsin B or L

The ability of SARS-CoV-2 to achieve cell surface fusion is dependent on its S1/S2 polybasic cleavage site; this is absent from most closely related sarbecoviruses, which are confined to endosomal fusion Given the reduced fusogenicity and replication kinetics of Omicron, we used HIV pseudotypes to evaluate entry route preference. We evaluated Wuhan D614G, Alpha, Delta and Omicron spike and as a control we included Pangolin CoV (Guangdong isolate) spike, which exhibits high affinity interactions with human ACE2 but lacks a polybasic cleavage site and, therefore, enters via the endosome only."

The key results show how Omicron closely matches Pangolin CoV, whereas Delta is entirely different:

WHAT DOES THAT MEAN?

Although the Delta and Omicron variants are clearly related, there are clear differences:

• The difference in the way they bind to human cells, as above.  
• Consequently Omicron causing different symptoms more like mild flu, but with the possibility of serious disease, much like flu
  
• Omicron escapes natural and vaccination immunity for Delta and previous variants
• Other differences set out in an earlier blogpost
• Differences in how we should respond to Omicron, including the UK Government's response.  Arguably the danger of hospitalisation is being eclipsed by the risk of closure of key organisations in society, even serious disruption to food supply.  As written over a week ago. 

The Government is now asking each public sector organisation to prepare contingency plans for staff absenteeism rates of up to 25%.  Private sector organisations need to plan likewise.  But what if that means you simply don't have the staff to provide a full service? What should be the priorities at that level of absence?  How can you keep the organisation open? 

It would have been better to prevent Omicron spreading at such high rate, as this blog has been advocating in several posts in the last couple of week.

The differences suggests Omicron should be regarded as a different disease.  The response from individuals, organisations and the Government being specific to Omicron.  Call the disease from Omicron  "COVID-21" ?  Maybe naming the virus "SARS-COV-3", rather than "-2".

Will the World Health Organisation do this?  When they do, you heard it here first !