Maiti, Banerjee, Kanwara Vascul Pharmacol.June 2021

Omigosh! Omicron

The COVID-19 Pandemic is a global disaster of biblical proportions. The Omicron variant is sweeping around the world, faster than a cloud of locusts. This version of the variant is definitely a game changer. We don’t know exactly which way it will bend the mortality curve, but at the rate this virus is spreading, we should soon have a clear idea.

Omicron first surfaced in South Africa in early November, and within a couple of weeks, became the top strain of the virus in that country. In October, 80% of all samples tested in South Africa were Delta. In November, 75% were Omicron. The first US case was confirmed on November 29. In the second week of December, this variant accounted for 0.4% of sequenced samples from COVID-19 infections. As of December 20, that number increased to 73 percent. Omicron has been detected in forty-six of the fifty states. Click this link to see the latest numbers.

A unique feature of this variant is its ability to evade immunity. A recent study from the Imperial College of London found that prior COVID-19 conferred very little immunity to Omicron, in the range of 19% protection. This compares very poorly to the level of protection that a prior COVID-19 infection confers against other variants. Two doses of vaccine also provided only very weak protection from infection with Omicron. However, a booster increased protection to as high as 80%. These data are preliminary but offer strong support for the importance of a third dose of vaccine.

Omicron’s ability to evade immunity can be attributed to alterations its spike, which is the structure that binds to a human cell and allows the virus to enter. The illustration above depicts an original SARS CoV-2 spike interacting with an H2 receptor. Antibodies, which are our first line of protection against any virus, recognize the shape of this spike. Omicron carries thirty-four different mutations in the RNA that codes for its spike, resulting a profound change in the shape of the spike. This makes it much more difficult for our immune system to detect.

Mutations come from mistakes in copying RNA during replication of the virus. A “mistake” that confer a selective advantage becomes more common in subsequent “generations” of the virus. Omicron has fifty total mutations that differentiate it from the original virus, far more mutations than any other variant. By comparison, Delta has only seven. The cause of such a quantum leap in evolution is the subject of much speculation. One theory is that the virus spread to animals, where it mutated, and then back to humans. Another possibility is that it arose during the prolonged infection of someone who was immune compromised, so that virus replication, unchecked, was massive. But Omicron also contains a unique mutation that is difficult to explain on the basis of a series of small mistakes. It has a chain of RNA that has not been found in any other variant. Other corona viruses have segments similar to that one. This suggests that Omicron may have occurred in a patient who also had another respiratory infection, and that the RNA got mixed up during replication. In other words, Omicron could be a cross between COVID-19 and the common cold.

Contagion on the level of measles and resistance to immunity make for a formidable combination. My recent article discussed the possibility that there could be one saving grace: if the illness conferred by Omicron is milder. Perhaps a virus that swept through a population with mild disease could function like a vaccine.

Reports from the South African experience were very encouraging about that possibility. Most patients had mild disease. In fact, two thirds of the patients in the hospital with a diagnosis of COVID-19 in during November had been admitted to the hospital for an unrelated problem. The surge in cases associated with Omicron was not accompanied by a spike in deaths.

Recent laboratory research provides possible clues to both increased infectivity and lower incidence of severe disease with the Omicron variant. Researchers studied the virus in human tissue culture, and found that in bronchial tissue, Omicron replicates seventy times faster than Delta. This means that a cough from a person with Omicron would carry a much greater viral load. In contrast, Omicron was ten times slower in peripheral lung cells, the site of severe COVID-19 disease. Lung damage is a leading cause of mortality in COVID-19 illness, so less involvement of the lungs by Omicron could be a game changer.

Data from Denmark and the UK do not support the notion that Omicron illness is any less severe. A Denmark study did not find any evidence that Omicron infection was any less severe. However, that study included 3400 cases and only 37 of those people required hospitalization. Differences in observed severity of illness among countries could occur due to differences in the level of existing immunity in the populations. It may be that the South African population had a higher incidence of some level of immunity in the population, whether from vaccination or prior illness, which was insufficient to prevent infection, but enough to mitigate disease severity. It is too early to draw a definitive conclusion about the relative virulence of Omicron.

But there is no doubt that Omicron has taken over. We are in for a huge wave of infections. Let’s hope it is not a tsunami that overwhelms our health system. Severe disease will predominantly occur in people who are not vaccinated.

The tools for prevention are the same as before: masking, hand washing, social distancing, and vaccination.



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Gayle Woodson is a semi-retired surgeon/educator. Her award winning novel, After Kilimanjaro, was inspired by her work in Tanzania.