Imagine attending a Christmas or New Year’s party, learning the next day that someone there had COVID, then waking up the day after that with a sore throat, sniffles, and achiness. It wouldn’t take a genius to piece together what happened. But you’d want to be sure, so you’d reach for that rapid test you wisely purchased last month after the news about Omicron first broke, knowing that the new variant would soon be on your doorstep.

Result: Negative.

Huh. At that point you’d wonder if you had caught the flu or a bad cold instead, but the coincidence would nag at you. Seemingly half the country has Omicron at the moment and all of your symptoms line up with the symptoms Omicron patients are reporting and yet … you don’t have Omicron? What are the odds of that?

It’s happening to people across America, including a few whom I follow on Twitter.

So to follow up on this: I most definitely have this from the person in question now, am plenty symptomatic, yet tested negative today. Apparently, a recurring anecdotal story right now, https://t.co/YKrKJBPwAe

— Benjy Sarlin (@BenjySarlin) December 27, 2021

But almost all of us agree that this cold is worse than we had Covid.

— Marcus (@MarcusHUSA) December 27, 2021

Maybe you know someone (or are someone) who’s experienced the same thing. In the middle of a local Omicron outbreak, they have all the hallmarks of a case of Omicron — yet test negative. What gives?

Epidemiologist Michael Mina anticipated that 10 days ago. It’s no surprise at this stage of the pandemic that people with some form of prior immunity would begin experiencing symptoms before they test positive, he argued. The point of the immune system is to mount a rapid response to an invading pathogen; if it’s seen that pathogen (or aspects of it) before, as those who’ve been vaccinated or had COVID previously have, it will react especially quickly. The sore throat and sniffles that accompany an immune response might even occur before there’s enough live virus in their noses to be detectable by a rapid antigen test. And so they’ll end up testing negative despite the fact that they clearly have the virus.

IMPORTANT:

RAPID TESTS DO WORK WITH OMICRON

"But why are some people staying negative in the first days they have symptoms??"

This is expected. Symptoms don't = contagious virus
This is literally a reflection of the fact that vaccines are doing their job!

PLEASE READ pic.twitter.com/YBJvNovQXL

— Michael Mina (@michaelmina_lab) December 18, 2021

At the start of the pandemic in March 2020, when no one had encountered the virus before, it would have taken longer for symptoms to develop as the body slowly identified and then began to react to the new germ. In December 2021, when most of us have already encountered the virus or its spike protein, it happens in no time because our systems have been primed to respond.

There may be another reason for the negative tests, Mina went on to say. If it’s true that Omicron doesn’t replicate well in the lungs, as at least two studies have shown, it would stand to reason that some people who are infected might not have a high viral load in their nostrils. Which in turn might mean there’s not enough virus on the swab for the rapid test to pick it up, at least early in the course of the illness.

If Omicron is able to more efficiently replicate in bronchus (not measured in nasal swab), lyse & release from cells much more efficiently, then we may be in a situation where the amount of virus measured in the nose on any test may not correlate as well with exhaled virus.

5/

— Michael Mina (@michaelmina_lab) December 19, 2021

Where that leaves us with respect to Biden’s new initiative to produce 500 million rapid tests, I don’t know. Rapid tests aren’t as accurate as PCR tests even under the best circumstances but now it appears that some meaningful number of people who get them and use them will get a false negative simply because of the vagaries of immunity at this stage of COVID. We could tell people “don’t test yourself until you’ve had symptoms for three days, as that’s enough time to build up the virus in your nose,” but that would defeat the purpose of rapid testing. The optimal guidance, it seems, is to assume you have Omicron if you have any sort of flu/cold symptoms and to isolate for five days at a minimum.

The bad news is that the new variant is spreading at a crazy rate, with New York City alone recording more cases yesterday than the entire country did in late June. The good news is that data showing that Omicron is considerably milder than previous strains continues to pile up, to the point where even hyper-cautious scientists are starting to feel relief at what they’re seeing. For the past month, the caveat about Omicron has been that it’s too early to tell whether it’ll cause a wave of hospitalizations. But at this point, said one expert in NYC’s health department, it’s really not too early:

1/ We are all seeing the massive wave of Omicron sweep through our communities

Severity will make the difference between a bad winter and a horrific one

We keep saying "hospitalizations are still low, but it's early"

When is it time?

In NYC, it should be showing now. pic.twitter.com/6YkWJZYd0I

— Farzad Mostashari (@Farzad_MD) December 24, 2021

If Omicron were hospitalizing people at the same rate as Delta, New York should be seeing something like 2,000 admissions right now, Mostashari estimated. Instead it’s seen fewer than 800. And in all probability, Omicron is much milder than even those numbers would suggest. There are surely many, many infections that aren’t being recorded as official cases right now, partly due to demand for testing overwhelming supply and partly due to the false negatives Mina described above. Meanwhile, some share of patients who have been hospitalized were admitted for reasons unrelated to COVID and then tested positive in the ER, the sort of “incidental” hospitalization that was also common in South Africa this month. And of course, as Mostashari also notes, some hospitalizations for COVID in New York (maybe most?) are due to Delta, not Omicron. The older, more dangerous variant is still circulating.

It’s the same story in San Francisco. Cases are taking off, hospitalizations aren’t:

Similar to the SF argument, if case-to-hospitalization ratios were mirroring those of Delta, I’d expect at least 2-3x those hospitalizations by now. And even more impressive: we only have 4 non-ICU patients, down from ~10 last week. When we surge, it’s usually the…(19/25)

— Bob Wachter (@Bob_Wachter) December 24, 2021

Hospitalization numbers could still reach unmanageable levels if Omicron spreads far enough and for long enough. But that’s the other good news about the variant: It might blow through quickly before receding rapidly, as it seems to have done in South Africa, limiting the number of people it infects. If it’s inherently very mild and has a shorter reach than we expect then we’ll have dodged a bullet.

Still, you know how it is with COVID. There’s always bad news somewhere on the horizon:

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.)…

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

Hoo boy. I’ll leave you with Dr. Ashish Jha arguing that cases are no longer the most useful metric for measuring COVID. If everyone’s destined to catch Omicron and only a few will need medical treatment, hospitalizations will tell us more about the true state of the pandemic than cases will.

“For two years, infections always proceeded hospitalizations which proceeded deaths…Omicron changes that. This is the shift we’ve been waiting for in many ways."@ashishkjha tells @jonkarl number of new cases should no longer be major pandemic metric. https://t.co/J7RmT8QvS9 pic.twitter.com/XETOWOnzif

— This Week (@ThisWeekABC) December 26, 2021