In recent months, experts have seen an increased prevalence of "delayed positivity," where individuals test negative for the coronavirus early in their illness before testing positive several days later, Katherine Wu writes for The Atlantic.

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Experts note a possible increase in cases of 'delayed positivity

A rise in cases of "delayed positivity" has left many experts wondering why certain individuals test negative several days in a row after the onset of Covid-19 symptoms before ultimately testing positive.

Currently, no one knows how often early negatives happen, or which individuals are most at risk. But according to Amesh Adalja, an infectious disease physician at the Johns Hopkins Center for Health Security, "[i]t's become more common."

If the coronavirus is changing the course of early-infections, "that makes it really scary," said Susan Butler-Wu, a clinical microbiologist at the University of Southern California's Keck School of Medicine. "You can't test and get a negative and actually know you're negative." 

The virus is "acting differently from a symptom perspective for sure," noted Emily Martin, an infectious disease epidemiologist at the University of Michigan.

"That's worth paying attention to," Wu writes. "The start of symptoms has always been a bit of a two-step: Is it COVID, or not? If SARS-CoV-2 is re-choreographing its moves, we must too—or risk losing our footing."

Why do some people experience 'delayed positivity'?

Unfortunately, experts do not yet know exactly why these "delayed positives" happen.

Currently, experts are operating off limited evidence. "I don't even know of any data that systematically evaluates this," said Yonatan Grad, who studies the viral dynamics of SARS-CoV-2 at Harvard University's School of Public Health.

According to Wu, "several phenomena could plausibly be muddying the testing timeline" and "[i]t's likely that population immunity, viral mutations, and human behavior all have some role."

Among the experts Wu spoke with, the most popular theory was the immunity hypothesis. "Perhaps symptoms are preceding test positivity, less because the virus is peaking late, and more because illness is arriving early, thanks to the lightning-fast reflexes of people's primed immune systems," Wu writes.

Sometimes, sickness comes as the direct result of a virus. However, common symptoms of a respiratory infection, including a runny nose, muscle and joint aches, chills, fevers, fatigue can also serve as "signs that the immune system is being activated," said Aubree Gordon, an infectious disease epidemiologist at the University of Michigan. 

At the start of the pandemic, infections occurred only in people who had never been infected with the coronavirus before. As a result, illness typically took several days to manifest—and the immune system struggled to fight as the virus grew stronger.

"Once people are vaccinated, though, their immune systems kick in right away," said Emily Landon, an infectious disease physician at the University of Chicago.

Notably, prior infection could also impact testing. "If the body makes fast work of the invader, some people may never end up testing positive, especially on antigen tests," Wu writes. "Others may see positives a few days after symptoms start, as the virus briefly gains a foothold."

However, some unimmunized individuals have also experienced delayed positivity, and many who have been fully vaccinated and boosted still test positive before feeling ill.

Another theory supported by experts is the virushypothesis, which recognizes that coronavirus traits could be "flipping the sickness script," Wu writes. According to Ryan McNamara, a virologist at Massachusetts General Hospital, any strain of omicron is "just a different beast."

Several studies have suggested that "[omicron] struggles to penetrate deep into the lower airway, and may not accumulate to the densities that Delta did in the nose, which could make false negatives more likely," Wu writes.

"[I]t's really hard to separate if all of this is a property of the virus, or a property of the immune system, or both," said Roby Bhattacharyya, an infectious disease physician at Massachusetts General Hospital.

In addition, testing and symptom severity involve "just so many variables," said Ali Ellebedy, an immunologist at Washington University in St Louis. "People's vaccination status, age, genetics, even the dose of virus, can affect if, when, or how they feel ill, and whether their infection registers on a test," Wu writes.

Ultimately, if delayed positivity is becoming more and more prevalent, "you cannot trust a negative rapid test at the beginning of illness," Landon said. (Wu, The Atlantic, 6/10)