Here in New York, the Omicron Variant Is Getting Weird

The infected have the “wrong” symptoms. Many are sick and yet test negative. Whether it’s mild is still unproven. Sequences posted by NYU have a possibly worrisome mutation.

My recent fears about Omicron came true much faster than I expected: it took less than two weeks for it to blitz past Delta and become the country’s dominant variant.

Here in New York, case counts are setting records. Testing centers have block-long lines, pharmacies are out of home-testing kits, hospitals are banning visitors. An extraordinary number of people I know are either sick or quarantining themselves because they were just exposed to someone sick. None that I know are seriously ill, but all are terrified about Christmas — especially for elderly relatives.

As the surge progresses here, we are seeing some unexpected developments. They include:

  1. Lots of people have symptoms — but they’re atypical ones. And some repeatedly test negative.

Weird Thing One: Many people are feeling sick and showing symptoms but repeatedly testing negative.

That is surprising because a hallmark of this virus has been “pre-symptomatic transmission.” That is, people have high viral loads in their nasopharynx and infect others before they themselves fall ill. Now we’re seeing the opposite: people feel sick, but have no detectable virus in their nose.

The same phenomenon was reported in India during its big April wave and in Britain during its October wave. A recent Times opinion piece suggests it is common among the author’s New York friends. It has happened to several people I know.

Negative rapid tests

One explanation could be that they actually don’t have Covid, they have flu or a cold or an allergy. But that seems unlikely. We’re in the middle of a huge Omicron wave. As the old medical school axiom goes: “If you hear hoofbeats, think horses first, not zebras.” (ie, the obvious explanation is the most likely one.)

So why do their tests come up negative? One possible explanation is this:

Omicron replicates so fast that its incubation period — the time from exposure to symptoms — may be as little as three days instead of six, as Katherine Wu notes in the Atlantic. You get sick fast.

But there is an important difference: most sick people now have typical cold or flu symptoms: moderate fever, aches, runny nose, etc. That’s quite different from the symptoms of the spring 2020 New York wave: high fever, cough, loss of smell, red eyes, and if things got serious, pneumonia with “ground glass opacities” on CT scans and high levels of D-dimer and C-reactive protein, which are markers of blood clotting and inflammation. Runny noses were distinctly not common, except in children.

Norway saw this too: researchers interviewed 111 of 117 people who attended a November 26 party that turned into a superspreader event. Their most common symptoms were cough, runny nose, fatigue, sore throat, headache, muscle aches, fever and sneezing — i.e., cold symptoms, not classic Covid symptoms.

On this Twitter thread, Michael J. Mina, who was formerly at Harvard and long a proponent of rapid tests, explains what he believes is happening:

The fever and runny noses, he argues, are not caused by the virus, but by the immune response. (It’s well-known that fevers are the body’s defense; viruses don’t like heat. Sniffles are caused by the immune system flooding nasal tissues with inflammatory molecules and white blood cells. It’s a mini-version of the “cytokine storms” that fill the lungs with fluid.)

Why? Probably because most Omicron victims in New York and Norway were vaccinated or previously infected. Their immune systems are primed to mount a fast response. So they may get fever and sniffles before enough virus builds up in their nose to make a rapid test or even a PCR test turn positive. And even then, their viral load may be high for only two days, not seven, so any test is more likely to miss it.

Nonetheless, Dr. Mina says, we still don’t know when a symptomatic person is most infectious, so we must be careful.

Therefore, if you feel ill, you should assume it’s Covid and isolate yourself.

(However, if you’re vaxxed or boosted, you may not have to isolate for 10 days. Britain lets sick people isolate for only 7 days if they get negative rapid tests on both Day 6 and Day 7. The U.S. just let health-care workers do the same. You may be next.)

Weird Thing Two: Yes, Omicron may be milder, but it’s too early to count on it. Small studies from England, Scotland and South Africa do suggest that it hospitalizes fewer people than Delta did. A Hong Kong study suggests it targets upper airway cells, not lung cells.

However, it’s not clear if the variant itself is milder, or just appears so because it is successfully infecting so many vaccinated or previously infected people. It’s like testing a new pistol on someone who has just slipped into a bulletproof vest. Is it the pistol or the target that’s different?

Data from Scandinavia, where Omicron appeared soon after it was isolated in South Africa, are contradictory. Norway and Denmark have similar-sized populations with high rates of vaccination. Norway is having a case surge with deaths up so sharply that they have surpassed last winter’s. Denmark is having an even bigger case surge — but deaths have barely budged. On the other hand, it had six times as many deaths last winter as Norway did, so perhaps many more of its unvaccinated have survived infections.

Britain, like Denmark, is seeing a huge surge in cases but not in deaths — yet. It also had two previous big death surges and so may have relatively few completely unprotected people. But hospitalizations in London, the epicenter, are rising fast.

We can’t be sure about Omicron until its impact is gauged on a large pool of unvaccinated older people — the group most likely to suffer and die. That’s not a typical New York cohort. But it is in some red states.

Weird Thing Three: In Gauteng, the urbanized Johannesburg-Pretoria region of South Africa where Omicron was first isolated, new cases are plummeting so fast that there are already only half as many as there were at the peak. It’s not a curve, it’s an icepick, and it lasted barely a month. That suggests that, as the former F.D.A. commissioner, Dr. Scott Gottlieb, said on Sunday, it’s “going to blow its way through the population, probably very quickly.”

If that’s the case, New York, as the country’s most crowded metropolis, should set the pace. If our cases drop to near zero in January (as India’s did after their intense Delta wave last spring), we will know that the pandemic is nearing an end because everyone is immunized either by the vaccine or the virus. It will take longer for the virus to mop up less-crowded places like South Dakota and Idaho, but eventually, it will find all of us.

It’s possible that, once every 100 years or so, a new coronavirus makes the jump from animals to humans and causes a pandemic so big that resistance to it persists into future generations, said Benjamin tenOever, a virologist at NYU Langone medical school. The four coronaviruses that now cause common colds — known as 229E, NL63, OC43 and HKU1 — may all be “pandemic strains that burned out” centuries ago.

Weird Thing Four: In the last three days, an unusual mutation has cropped up more than 60 times in genetic sequences of the Omicron variant released by the NYU Langone genetics lab.

The mutation, known as P681R, inserts an “R” (for the amino acid arginine) at position 681 in the spike protein gene instead of a “P” (for proline). According to Henry L. Niman, an independent tracker of viral mutations, that change could enhance the virus’s “cleavage site” so it is better able to attack different kinds of human cells. (After attaching to a cell, the virus’s shell needs to “cleave” or split, so it can inject its RNA payload.) Being able to cleave to lung cells or heart cells instead of just to nose cells would make a virus more dangerous.)

A similar change in avian flu genes makes mild flus into bird killers, Dr. Niman said.

Whether or not this is worrisome remains to be seen.

Dr. Niman has tracked such mutations, especially in flu samples, for many years — long before science journalists routinely paid attention to them. That has made him a thorn in the side of the C.D.C., which is cautious about reacting to such changes. Sometimes his warnings prove alarmist; sometimes he’s been dead right.

In 2006, he was right that there were more cases of human-to-human transmission of H5N1 bird flu than had been acknowledged. In 2009, he was right in predicting that the H1N1 “swine flu” in Mexico would reach the United States and that Tamiflu resistance in it would spread. In 2015, he was overly worried about a circulating H5N2 bird flu. Earlier in this pandemic, he was correct to worry about the D614G mutation in the Wuhan variant and E484K mutation in the British one.

“This combines Omicron’s rapid spread with Delta’s lethality,” he said.

Dr. tenOever’s reaction was that the mutation bore watching but it was “not a foregone conclusion” that it would confer more pathogenicity. If such sequences turned up mostly in I.C.U. patients “that would be worrying,” he said.

It’s early days still but, as it did last spring, New York may prove a harbinger for the rest of the nation. What happens in New York never stays in New York.

New York Times, 1976–2021. Last beat: lead reporter on pandemic. 2020 Chancellor Award; 2021 NYT Pulitzer donaldgmcneiljr1954@gmail.com