Wide World of Vaccines

December 2021

Omicron! “When the plague comes sweepin’ across the plains”

(adapted from Oklahoma! Rodgers & Hammerstein 1943)

Christopher Harrison, MD

Column Editor: Christopher Harrison, MD | Professor of Pediatrics, UMKC School of Medicine | Clinical Professor of Pediatrics, University of Kansas School of Medicine

Unless you have been under a rock for the last couple of weeks, you likely have been bombarded with sound bites and headlines about the Omicron variant of SARS-CoV-2 (designated B.1.1.529, clade 21K). Let’s review what we know and what we don't know and what data are evolving so we can best share with others what differences are important in Omicron compared to prior variants. Also, remember current understandings will evolve as more data become available.

What we know as of Dec. 16, 2021:

1. Mutations: Omicron has over 50 mutations with at least 15 in the spike protein (the target of the vaccine-induced immunity). Figure 1. As a result, Omicron has increased binding to the ACE2 receptor and increased efficiency in enzyme activities that facilitate infection.¹ One mutation is actually a sequence it stole from the seasonal coronavirus (HCoV-229E); note: this sequence is also present in the human genome. This sequence may make Omicron look less “foreign” and allow it to evade some first-line innate immune responses.

2. Contagion: Omicron is much more contagious than most prior variants; data suggest it is somewhere between 30% and 400% more contagious than the Delta variant. This increased contagion explains Omicron’s nearly completely supplanting Delta in many areas of South Africa within a month of its discovery. The U.K. is now in the midst of a major surge as well.

3. Geography:

a. Omicron was discovered on Nov. 11 in S. Africa during a COVID-19 outbreak mostly in young adults on a university campus.¹

b. Omicron appears to outcompete the Delta variant in the locales where the Omicron variant is emerging. Figure 2.²

c. Originally, Omicron was seen in regionally dispersed clusters in S. Africa (initially hundreds of cases/day), but it has spread rapidly (over 22,000 cases per day in the third week of December). This case rate is higher than their Delta peak in June.

d. Omicron has now been detected in over 30 states in the U.S. (including Missouri) and in Canada plus at least 60 other countries, (Figure 3) so we should assume it is here in Kansas City. That said, Delta is still the main driver of cases, hospitalizations and deaths in the U.S. due to a post-Thanksgiving surge. The surge includes children now being found in KC area schools.

4. Severity: Most Omicron infections noted to date have been mild-moderate in severity, but hospitalizations are increasing due to the surging number of cases in S. Africa and the U.K. The current estimation is that Omicron severity is no worse and perhaps a bit less than Delta.

5. Protection from “natural” or vaccine-induced immunity:

a. Infection with prior variants does not seem to protect very well against Omicron infection. Consider that 80% of the S. African population had “natural immunity,” i.e., were seropositive from prior infection. Current rates of full vaccination in S. Africa hover in the mid 30% range. That said, full vaccination with mRNA vaccine also seems to allow breakthrough but most S. African Omicron infections so far are in the unvacccinated. Preliminary data show that a booster dose of Pfizer vaccine enhances protection.

b. In the U.S., a majority of cases detected so far have been among the vaccinated (data not available about boosted population) – but the hospitalizations in the U.K. and S. Africa have been mostly among the unvaccinated.

c. In vitro neutralization testing of sera from non-boosted two-dose vaccine recipients (Moderna and Pfizer) shows lower neutralizing activity against Omicron when compared to activity vs. Delta or prior variants. However, neutralization using sera from third-dose boosted patients (Moderna and Pfizer) suggests 74%-80% protection.

6. Children: To date, children have been overrepresented even among hospitalizations in S. Africa.

7. Testing accuracy: Current PCR testing assays detect Omicron variants as well as they do other strains.

8. Treatment: In vitro data using Merck and Pfizer antiviral drugs show Omicron reference strains are susceptible to the drugs, meaning the viral targets of the drugs (which are not the spike protein) are still present in Omicron – so far.

What we don’t know:

1. Will infections in the elderly or medically vulnerable populations be as mild as those documented to date in otherwise healthy or younger populations?

2. Is this variant, while more contagious, less virulent? Could a milder virus help reduce the disease burden of the pandemic?

3. Will Omicron-specific vaccines be needed? Several companies have already begun developing Omicron-specific vaccines – the first of which should be available if needed by February 2022. At present, boosting with current vaccines seems adequate.

4. How many of us will need a fourth dose booster of current vaccines or Omicron-specific dose? My assessment is that the elderly and medically vulnerable populations will need a fourth dose in the spring of 2022. Children will be watched to see if they need even a third dose given that they are just now being immunized and will carry high titers for at least six months. That said, even healthy adults will likely need another dose by summer.

5. Will long COVID-19 be as frequent with Omicron as with other variants even if acute disease from Omicron is not severe? If so, is there protection either from prior infection with other variants or from vaccine? Finally, will early treatment with antivirals protect against long COVID-19 as well as hospitalization and/or death?

As always with SARS-CoV-2, stay tuned. Things will become clearer in the next six weeks. But my advice is, in the meantime, err on the side of caution during the holiday season (masks and distancing even if around vaccinated and boosted people inside). Happy holidays!

Figure 1. Number of mutations in the spike protein (target of natural and vaccine-induced immunity). Created based on open-source data.²

Figure 2. Proportion of cases due to differing variants in South Africa since January 2021. Note sudden rise in Omicron cases in November 2021 (red color). Generated from open-source data on Dec. 16, 2021.²

Figure 3. Global detection of Omicron variant – South Africa and the U.K. as hot spots as of Dec. 16, 2021. Adapted from open-source data.³ The darker the pink color, the more cases have been detected.

References:

Wide World of Vaccines

December 2021

Omicron! “When the plague comes sweepin’ across the plains”

(adapted from Oklahoma! Rodgers & Hammerstein 1943)

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