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A variant with 50 mutations: omicron

The Body Scientific

Afew months ago, we were enjoying the reopening of civil society. But events intervened. First, the protection of two-dose vaccines started to subside. Second, unvaccinated patients, including children, were sickened by the furiously infectious omicron variant of SARS-CoV-2. More patients survive the omicron virus many experts say, but there are so many that the medical system can still be overwhelmed. Nursing and medical staff are exhausted, and patients with other diseases or conditions may not get the treatments they need.

On Jan. 6, in New York, the number of people with positive tests was 22.5%; in Connecticut, 29.1% and in Massachusetts, 21.8%. By the time you read this these numbers will be higher. Infections do not go on indefinitely — eventually there will be no uninfected or unvaccinated people.

Epidemiologists, or rather the clan of mathematical modelers among them, predict a crash in the number of infections by early February 2022. That may signal herd immunity and a change from pandemic status to endemic. The latter causes sporadic infection at low levels and tends not to overwhelm hospitals or harm the economy.

Omicron appeared in Botswana and South Africa in November 2021.  South African physicians have seen mild disease, and the infection is declining there. In the UK, some reports said severity is unaffected; others that the disease caused by omicron is milder than that caused by the Delta variant. The CDC’s Morbidity and Mortality Weekly Reports appears every Thursday and is online. It provides no conclusions yet on the severity of omicron on unvaccinated people, including children. Deaths do not seem to be increasing as rapidly as infections. In the early stage of a new infection or treatment, information comes in press reports, which can be written with more enthusiasm than data.  We will know more soon.

There are about 50 mutations in the omicron virus and a dozen in the delta variant. A virus-specific enzyme copies the RNA genome of SARS-CoV-2 but makes errors—30 have accumulated in the omicron spike protein and 20 in other omicron genes. Think of them as typos that the virus has not corrected. If the typos help the virus survive counterattack by the immune system, the typos (mutations) are retained. Each infected lung cell can make thousands of viruses, so the infection spreads fast. Since November, omicron, which makes about five times more virus than the original strain, has nearly replaced the delta variant.

You may wonder how any living thing survives viral onslaughts; the answer is that sometimes they don’t. When we do survive, it is because the human immune system is a wondrous collection of rapid defenses. Immunology is the science of engaging these defenses before a pathogen does. Think of it as an ambush. Immunity is as complicated as it is vital. I taught a course called The Cell Biology of Tissues and Organelles for beginning medical and dental students for 25 years.  Immunology flummoxed the students. It takes time to learn.

A group at Baylor College of Medicine and The Texas Children’s Hospital headed by Elena Bottazzi and Peter Hotez has fashioned a vaccine that does not employ an mRNA, but rather fragments of viral protein. The vaccine does not require refrigeration; a dose costs $1.50 and it is not patent protected. In India, the vaccine, called Corbevax, has been approved. It is an older method, but sometimes that is best.  A recent issue of Nature has a fine review on the status of COVID vaccines written for non-scientists.  Type “How COVID Vaccines Shaped 2021” into your browser to read it.

Treatments are being developed that stop infections, including immunoglobulins that can be inhaled. In the same vein, nanobodies, tiny antibodies made by Camelids (alpacas) neutralize omicron or other viruses. Think of an asthma inhaler spraying antibodies directly onto the virus in your lungs.

Drugs to inhibit viruses are a recent development — in the 1990s for HIV and now for other viruses. Pfizer has a drug called Paxlovid, which blocks the cleavage of viral proteins into functional units.  It is highly effective early after symptoms of COVID have appeared.  There are limited supplies, and the drug is tricky to make, but it will be in use shortly.

The Merck drug Molnupiravir blocks the enzyme that copies the virus genome. Molnupiravir is less effective at preventing symptoms that Paxlovid, but it interesting (to me) because it appear to inhibit other unpleasant RNA viruses. These include influenza; RSV, respiratory syncytial virus (a major cause of ER visits by children); norovirus (infections on cruise ships); Chikungunya virus (a mosquito-borne virus that causes severe joint pain); Venezuelan equine encephalitis virus); and hepatitis C. Perhaps we are at the beginning of a vast improvement in antiviral drug therapy.  Pray for it.

In the meantime, the best thing to do is get your vaccine and booster.  Let’s see if the epidemiologists are right and the peak comes soon. Watch positivity. Watch hospital admissions. Watch deaths from omicron. And hope for the best.

 

Rich Kessin is Emeritus Professor of Pathology and Cell Biology at the Columbia University Irving Medical Center.  Email Richard.Kessin@gmail.com.  See other columns on his website: Richardkessin.com.

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