Is Omicron becoming a second SARS-CoV-2 pandemic?

On Dec. 14, an international group of renowned researchers posted a manuscript on bioRxiv titled, “Broadly neutralizing antibodies overcome Omicron antigenic shift.” They state:

“The staggering number of substitutions present in Omicron S marks a dramatic shift in antigenicity and is associated with immune evasion of unprecedented magnitude for SARS-CoV-2 and a putative broadening of tropism. While influenza antigenic shift is defined as genetic reassortment of the RNA genome segments, the mechanism of accumulation of a large number of mutations in SARS-CoV-2 Omicron S remains to be established.”

Of note, these authors do not propose that Omicron will become a second pandemic, despite their use of the term “Omicron antigenic shift.”

With influenza, an antigenic shift is a hallmark of a new influenza pandemic. Mutations in the immunodominant hemagglutinin (H) protein of influenza cause major antigenic changes termed “antigenic shift” (rather than lesser, more frequent changes termed “antigenic drift”). Influenza A virus antigenic shifts require new pandemic influenza-specific vaccines.

In my opinion, this concept that the SARS-CoV-2 Omicron variant of concern is already becoming the second SARS-CoV-2 pandemic, a “COVID-21,” is crucial because it means we will need to reexamine our responses to Omicron.

In addition, Omicron as a “COVID-21” pandemic means we should reconsider the future of SARS-CoV-2 in terms of what to anticipate and how to recognize what actions to take.

To carry the approximate analogy with influenza further, the immunodominant spike (S) protein of SARS-CoV-2 is like the immunodominant hemagglutinin (H) protein of influenza A.  

Before Omicron, variants of SARS-CoV-2/COVID-19 were analogous to “antigenic drift,” e.g., D614G and the four previous WHO-designated variants of concern: Alpha, Beta, Gamma and Delta. With Omicron comes the first “antigenic shift” and a new pandemic virus.

The most important implication of seeing Omicron becoming a new SARS-CoV-2 pandemic, due to its numerous functional mutations that confer antigenic shift, is the essential need for new SARS-CoV-2 Omicron-specific vaccines.