COVID-19 patients are filling more beds in Main Line Health’s hospitals, but whether it’s the new omicron variant or the delta variant that put them there, doctors largely don’t know.

Genetic sequencing, the process that could tell them quickly, is in short supply in the region and nationally, public health experts, researchers, and physicians said.

“We’re sort of in the dark clinically,” said Scott Dessain, an oncologist and professor at Lankenau Institute for Medical Research, part of the Main Line Health system. “Nobody would have said two or three weeks ago that we would need variant testing within a day to make important decisions for our patients.”

Understanding how viruses are changing is critical to tracking contagion and severity patterns so, for instance, it’s clear whether vaccines are working or need to be adjusted. What’s more, certain therapies in limited supply have a better track record for earlier variants, and doctors need to know where they’ll do the most good.

There are no hard data on the ideal amount of genetic sequencing needed, but experts said about 5% to 10% of all positive test results in an area should be sequenced to quickly identify new variants in a region. Pennsylvania sequences about 2.4% of its positive test samples, according to the CDC. New Jersey sequences about 3%. Those are among the lowest sequencing rates in the country.

The Philadelphia Department of Public Health doesn’t track the percentage of positive samples that get sequenced, a spokesperson said, but a University of Pennsylvania variant tracking program reported 4,785 samples sequenced as of Dec. 12, roughly 2% of the city’s positive COVID-19 tests.

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It also takes too long to identify variants in the COVID-19 samples that are sequenced. Public health officials and doctors want that information in a matter of days, if not hours. Turnaround time from a person’s nose being swabbed to identifying the infecting variant can take up to a month.

“Now you’re talking about a month behind, and now the virus has mutated or migrated to something else,” said Bernadette Matthis, the city health department’s laboratory director.

Both Pennsylvania and Philadelphia health officials largely rely on CDC-contracted labs or universities to conduct sequencing, but Pennsylvania’s health department established an in-house sequencing lab for the first time in July. The Philadelphia Department of Public Health plans to use more than $1 million in federal grant money to establish a lab of its own, but it won’t open until June.

Not long ago, a city health department with its own sequencing capacity was a rarity, Matthis said. Now, it’s seen as necessary to manage this pandemic and any others that come along, as well as providing valuable information about perennial health threats like the flu, tuberculosis, and E. coli.

“I think the pandemic exposed a lot of holes in public health, testing, probably surveillance as well,” she said. “That’s probably a reason the federal government has thrown a lot of money to get us up to speed.”

COVID-19′s blueprint

Genetic sequencing allows scientists to know the building blocks that make up the virus’ RNA, which determines the virus’ structure and function. The more sequencing that’s done, the faster scientists will spot a new variant and begin to understand how well it spreads, infects cells, and sickens people. Sequencing is also needed to confirm how well a variant can evade the protections vaccines offer, as omicron appears more able to do than delta has.

Once a variant has been identified, though, ongoing genetic sequencing of positive COVID-19 test samples continues to be valuable. It allows public health experts to conduct surveillance on COVID-19′s presence in the area, shaping the need for policy recommendations on masking and social distancing.

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Knowing what percentage of hospitalized COVID-19 patients have omicron or delta is essential to confirming whether omicron is indeed a milder strain of the virus. Even if it is, omicron appears to spread more easily, which means even if a smaller percentage of infected people become very sick, hospitals still could be swamped.

Some of the monoclonal antibody treatments useful to prevent severe COVID-19 complications appear to be less effective against the omicron strain, Dessain said. Doctors need to know which patients are more likely to benefit from the treatment.

“Does [omicron] actually cause disease that is less bad? Does it cause disease that has better outcomes? We don’t know that,” Dessain said. “There’s so many levels of not knowing what’s going on.”

A year ago, few health authorities in the United States prioritized genetic sequencing. It appeared there weren’t significant differences among COVID-19 variants, which result from viruses adapting as they spread, largely in unvaccinated people.

“There just wasn’t a perceived value to sequencing a high portion,” said Phil Febbo, chief medical officer at San Diego’s Illumina, which develops gene-sequencing technologies.

That changed with the arrival of the alpha variant, he said, which demonstrated how COVID-19 variants could function differently in important ways. Delta remains the dominant variant in the United States and is driving the current rise in hospitalizations, as is the low rate of immunization, as 80% of the hospitalized are unvaccinated. Breakthrough cases requiring hospitalization tend to be in older people with underlying conditions like diabetes.

Delta first emerged in India late last year, and there are adequate data showing it is highly contagious and tends to cause more severe illness than the original COVID-19 strain.

Nationwide, somewhere between 5% and 10% of COVID tests are sequenced, the Associated Press reported, though rates vary widely by region, depending on budgets and political commitment, Febbo said.

Since omicron may cause less severe illness, fewer people might get tested, resulting in an undercount even where sequencing is robust, said Reynold Panettieri, a vice chancellor and science director at the Rutgers Institute for Translational Medicine.

“This season is particularly confusing because there are many common colds, GI problems with symptoms that are similar to COVID symptoms,” Panettieri said. Plus, flu rates are on the way up.

“The only way you’re going to know is if someone stays home and gets tested,” he said.

A new public health tool

Locally, labs are collaborating on variant identification. Children’s Hospital of Philadelphia and Drexel University are working together to get more test samples to the lab and adding staff to sequence them.

“Three weeks was not going to be acceptable for us,” said Paul Planet, an attending physician in the division of infectious diseases at CHOP and head of the hospital’s sequencing lab.

The city is prioritizing sequencing for cases that have led to hospitalization or death, plus pediatric and breakthrough cases.

William Moss, of the Johns Hopkins Bloomberg School of Public Health, said spotting whether omicron is driving hospitalizations is particularly critical.

“If we start seeing that, we need omicron-specific vaccines,” Moss said. “That may be the best example I can think of where the sequencing can really lead to a fairly dramatic public health response.”

Having a city-run sequencing lab to coordinate with the universities’ efforts in the region would help, Planet said. Even though the pandemic is nearing its second year, Matthis said, it’s not too late to establish better sequencing capacity.

The technology will help the department track the presence of common viruses and bacteria and could even be used to monitor wastewater. Plus, it is unlikely omicron will be the last COVID-19 variant that will need to be tracked.

“We don’t know how long,” Matthis said, “this virus is going to continue to mutate and change.”

Staff writer Aubrey Whelan contributed to this article.