Omicron Out'chere Freeballing No Matter What You Call Yourself Doing

The data from figure 4 shows that fully-vaccinated sera with the Moderna vaccine saw a 33-fold drop in neutralization against Omicron, Pfizer a 44-fold drop, and AstraZeneca a 36-fold drop. Notably, recently released data shows that sera from people who received the third dose lost almost ninety percent of its potency against Omicron after two weeks. After three months, most third-dose sera failed to neutralize at all. This data confirms the epidemiological observations that most fully doubly-vaccinated and triply-vaccinated individuals, including those with prior infection, are susceptible to infection by Omicron within weeks of the last boost.

Forbes  | In a few short weeks, the COVID-19 virus variant Omicron has spread around the world. The incidence of new infections is rising rapidly, even in well-vaccinated populations and those previously infected by earlier variants of SARS-CoV-2. The epidemiologic evidence strongly points to a variant that is resistant to most if not all extant vaccines, and possibly many monoclonal antibodies treatments. Here we explore these concerns. This is the third in our series that outlines what we know about Omicron. We summarize the finding of recent experiments by Cameroni et al. in a bioRxiv preprint from December 14th.

Omicron ACE2 Binding

The first question asked was how tightly the Omicron Spike (S) protein binds to the ACE2 receptor. The data is summarized in Figure 1. Cameroni et al. show that Omicron’s affinity for the ACE2 receptor is 2.5 times as great as that of the S protein from the original Wuhan isolate. Omicron binds to the receptor as well as the Beta variant, but not as well as Alpha, which binds ACE2 almost six times more tightly. The N501Y mutation in Omicron is universally observed to increase affinity roughly 6-fold, yet other mutations in key sites like K417N, Q493R, and G496S were shown by deep mutational scanning to decrease affinity. Increased affinity for the receptor may account, in part, for increased transmissibility, but that is clearly not the whole story as Omicron is much more transmissible than any previously isolates, including Alpha, Beta, Gamma, and Delta.

Many seem surprised at the ability of SARS-CoV-2 to mutate to increase resistance against convalescent sera, most vaccines, and most monoclonal antibodies. However, the surprise was unwarranted for those who realized that coronaviruses have evolved over many millions of years to reinfect hosts over time. Those previously infected with earlier strains of the virus, contrary to our assumptions earlier in the pandemic, are able to be reinfected with Omicron and strains to come.

We previously predicted that SARS-CoV-2 would persist, continue to vary, and evade our natural and adaptive immune responses. We have also learned that SARS-CoV-2 has the potential to become far more lethal than it is today. We reiterate that the sister of this virus, SARS-CoV, and its cousin, MERS-CoV, ranged between 10% and 30% lethality. This is presumably due to slight variations in the structural, nonstructural, and accessory proteins. We must be ever alert now and for many years in the future of the possibility of such changes and their consequences.