This is the fourth in a series on the Omicron variants.

The current wave of Omicron-based Covid-19 infections has highlighted both the strengths and weaknesses of our current Covid-control strategy, which relies primarily on vaccines. The Omicron virus seems to infect most of those vaccinated once or twice, almost as if they were not previously vaccinated at all. Three doses provide some protection, but that protection wanes over four to six months to a very low level. The good news is that two or three doses of currently-available vaccines provide excellent protection against severe disease leading to hospitalization or death.

Initial data from the United Kingdom confirms some fears regarding the new strain. A “fully vaccinated” individual with two doses of mRNA vaccine is only protected from Omicron infection roughly 25% of the time. That percentage jumps to 50% in triple-vaccinated individuals. Protection from hospitalization and death in those with two and three doses is much greater than protection from infection. Two-dose prevention of hospitalization is roughly 57%, whereas three-dose prevention jumps to approximately 90%. This rise is mirrored in protection from death, as two doses prevent death 59% of the time, while the rate for three doses skyrockets to 95%. If anything, this data is an advertisement to immediately get a third dose of vaccine.

FIGURE 1: Vaccine effectiveness against Omicron comparing infection, hospitalization, and death contrasted by two and three-shot regiments.UK HEALTH SECURITY AGENCY

These risks are exponential in household settings. At present, children and specifically toddlers or newborns are far less likely to be fully vaccinated or boosted based on previous and existing CDC guidelines. That means they are at far greater risk of infection, hospitalization, or worse. Now picture those children in their home setting. If both parents are fully vaccinated or boosted, that child is much less likely to contract Covid-19 at home. However, suppose one is partially or unvaccinated. In that case, the do-diligence of the other is negated, and the children are at much greater risk, not to mention the risk of living with two unvaccinated parents that interact with others at work or society at large.

FIGURE 2: Visual representation of the dangers of Covid-19 infection in a household with one or more unvaccinated parents or children.HAYEK ET AL.

What accounts for the ability of omicron to infect those who have been previously vaccinated? Molecular studies show that both major Omicron sublineages, BA.1 and BA.2, are heavily mutated in the Spike protein, both in the gene’s S1 and S2 subunit portions. These mutations dramatically alter the ability of both convalescent sera and monoclonal antibodies to recognize, bind, and neutralize the Omicron variants. Although BA.1 and BA.2 share many common mutations in the Spike protein, there are several differences. Of the 42 distinct mutations found in the BA.1 and BA.2 sublineages, 21 are shared, while 13 are exclusive to BA.1 and eight are exclusive to BA.2.

It seems likely that both BA.1 and BA.2 are similar concerning their diminished sensitivity to neutralizing antibodies from vaccines, monoclonal treatments, or convalescent sera, perhaps accounting for the variant’s rapid spread. A thoroughly-vaccinated population such as Denmark and Israel seem to be highly susceptible to infection by Omicron as a consequence.

Will Omicron infection provide robust protection against other infections? If current vaccines do not provide reasonable protection against Omicron, will Omicron-specific vaccines provide good protection against previous and new variants to come? The answer is not necessarily yes. Although existing data shows that Omicron infection will protect against reinfection, Omicron sera poorly neutralizes other variants. A simple conclusion would be that Omicron infection is unlikely to protect against future variants to come. 

A recent study by Gagne et al. on monkeys tested whether Omicron-specific vaccines granted greater protection against the strain than a standard mRNA vaccine booster. Their results suggest that the rush to license variant-specific vaccines may not be justified. They tested an Omicron-specific mRNA booster against a currently-available mRNA vaccine to test the jump in neutralizing antibody titers post-inoculation. Not only did the Omicron booster provide worse protection against the D614G Triad variant than the current mRNA vaccines, but protection against Omicron itself was also worse.

FIGURE 3: Kinetics of mucosal antibody responses following mRNA-1273 immunization and boost (C-D) D614G, Delta, Beta and Omicron S-2P-ACE2 binding inhibition in the presence of mucosal fluids. All samples diluted 1:5. (caption quoted from study).GAGNE ET AL.

If the virus can infect a previously vaccinated population, the entire population is susceptible. This enables the virus to spread much faster as it has many more targets in a given population. In contrast, previous variants were somewhat limited to those that were partially or unvaccinated against SARS-CoV-2. That, alone, does not account for the rapid acceleration of the rate of transmission as compared to previous variants.

The virus is intrinsically more transmissible. Factors that affect the speed of replication may be independent of the Spike protein changes. We know that the Spike structure of the BA.1 variant is more avid to the host ACE2 receptor than the wildtype virus, but that does not entirely account for the rapid spread of Omicron not as avid as Delta. This indicates that changes throughout the genome in non-Spike proteins likely contribute to the rapid increase of transmissibility along with the Spike mutations.

The next question is pathogenicity. It is clear that vaccines vigorously protect against Omicron death compared to other variants. However, in the United States, for example, a small portion of the population has received their third dose.

FIGURE 4: Share of the US population boosted, fully vaccinated, partially vaccinated, and unvaccinated.NYTIMES

Those partially vaccinated or even wholly unvaccinated are at the most significant risk of infection, hospitalization, and death. In the state of Texas, for instance, the Texas Department of State Human Services estimates that compared to fully vaccinated Texans, those unvaccinated are at least twice as likely of becoming infected with Covid-19 and 17 times as likely to die from Covid-19-related health complications. These rates are consistent with estimations throughout the world. 

An even more dire comparison is between unvaccinated and boosted individuals. The CDC estimates that unvaccinated adults are 13 times more likely to be infected with Covid-19 and 68 times more likely to die from Covid-19 than boosted individuals. In the United States, as of early December, weekly death rates based on vaccination status were vastly different. The unvaccinated had a weekly death rate of 9.74 per 100,000, those fully vaccinated dropped to 0.71 per 100,000, and those boosted dropped even further to 0.10 per 100,000. In the United States, with a population of roughly 330 million, these rates extrapolate to about 32,000 Covid deaths per week in the unvaccinated, compared to 2,300 for fully vaccinated individuals and 330 for boosted individuals.

FIGURE 5: Rates of death in the United States among the unvaccinated, fully vaccinated, and boosted populations.OUR WORLD IN DATA

In short, if someone is reading this that has not received three doses of mRNA vaccine, we implore them to do so. It is the quickest and most reliable way to protect yourself against the most infectious virus in recent memory.

Recent data emerging from Israel suggests that a fourth dose of mRNA vaccine is more effective at preventing severe outcomes. It is very likely that doses of the mRNA Covid-19 vaccine become regular aspects of regular vaccine schedules, akin to the flu, measles, and tetanus shots. We can only hope and encourage people to receive their doses for their protection and that of those around them. Although vaccine protection against infection seems to be more transient, protection against hospitalization and death appears more robust for at least the current period of observation—about one year. It remains an open question how long such protection will last.