Four COVID test kits, ordered Jan. 18 on COVIDTests.gov and received Feb. 3.

There has been increased reliance on at-home rapid COVID-19 testing in recent months, allowing individuals to learn in real-time whether they contracted the virus rather than having to wait to learn via PCR tesing.

The rapid tests can regularly be obtained at the local pharmacy and households around the country are eligible to receive up to 16 tests from the federal government. The presence has not only been convenient, but it’s proven reliable enough that schools and many companies aren’t requiring PCR testing to prove their health status.

The effectiveness of at-home COVID-19 testing begs the question of whether similar rapid tests are possible in the future for diseases ranging from flu to even cancer. Some experts say that kind of at-home test could be a “game changer,” but there are plenty of hurdles to overcome.

“At-home tests will change diagnostics, and they make a lot of sense for public health,” Yale researcher Nathan Grubaugh said. “I think that this will be especially helpful for school-age kids to know if that cough is flu/COVID/RSV or something else.”

It’s not only school-based pathogens. UConn researcher Changchun Liu’s lab has been developing both point-of-care and at-home tests for cancer.

“Oral cancer patients, you can collect your saliva sample by yourself and then you put the saliva into the diagnostic device,” he said. “After the device processes the samples, maybe it takes 15 or 30 minutes, they will tell you whether or not there are cancer biomarkers detected by this device.”

David Peaper is a clinical pathologist and medical microbiologist by training and director of Yale New Haven Hospital’s microbiology lab and a faculty member in the Department of Laboratory Medicine at the Yale School of Medicine.

Peaper agreed that widespread, free diagnostic testing “is a game changer,” though there are some caveats to that.

Diagnostic tests, for COVID or any disease, are only as good as they are accurate, however.

“My training, my job, is testing in general,” Peaper said. “COVID testing, microbiology testing. There is no perfect test ever.”

That’s why confirmatory tests are so important, Peaper said. The more tests you administer, the likelier you are to have a false positive or a false negative.

That becomes less of a problem when there is a reason to test. We are in the midst of a coronavirus pandemic, so, if you test positive for COVID you’re likely COVID-positive. If it’s flu season and you test positive for flu, there’s a good reason to think you’ve got the flu.

“That's a pretty big deal,” Peaper said. “For things like sexually transmitted infections, if, depending on the risk factors of whatever population you're in, or whatever population you're in a relationship with, even if it's just for one night, if you can have a home STI test, there's actually tremendous information that could be gathered there and cut out potential chains of transmission.”

Sheldon Campbell is an expert on diagnostic testing, a professor of Laboratory Medicine at Yale School of Medicine and the director of clinical labs at VA Connecticut Healthcare.

He said rapid antigen testing is nothing new.

“In principle, COVID home tests are very similar to pregnancy tests. The technology is really old, actually,” he said. “We've been using these tests for flu, this class of tests, these rapid antigen tests for flu for 20 years.”

But unlike COVID antigen tests, similar flu tests have never been approved for home use. When asked why, Campbell said it was for two reasons: “One was that they kind of suck.”

“The test for flu was like 40 to 60 percent sensitive,” he said. “If you've really got flu, the rapid antigen test will say you've got flu 40 to 60 percent of the time.”

The insensitivity of at-home flu tests raised an important question for regulators: What would a patient do after they take a test? A negative test might not mean much.

“So, if you get a negative, you may still have flu,” Campbell said.

At-home COVID testing has been valuable because it has been administered in such huge numbers. Even if the tests are not 100 percent accurate, every person who gets a positive test and isolates is a COVID patient who does not transmit the disease onward.

“What's driven COVID testing at home is not as much diagnosis as it is infection prevention,” Campbell said. “We're diagnosing COVID at home primarily to try and limit spread.”

At-home, rapid testing has applications, but it matters how you use it, Campbell said. Rapid testing for HIV exists but it’s relatively expensive. Rapid testing for malaria exists worldwide, but it’s only valuable if you have access to treatment for malaria.

“Do we know that pregnancy tests get women into prenatal care sooner? I don't think we do, actually,” he said. “The potential of widely available rapid tests to improve health care, improve health, depends on the right ecosystem.”

So it matters not only how sensitive a test might be, but how accessible it is, how it’s deployed and then what happens after you get the results.

“You have to get the test into the hands of the people who need it, who can benefit from it,” Campbell said. “Then once you have the results, you have to be able to use them to change something to change what you do.”

Peaper said COVID testing has whetted the appetite of researchers and developers for widespread testing for other diseases, but it may not be right around the corner.

“For COVID, we're in a public health emergency and the FDA pathway for authorization of tests under an emergency are different than regular business,” Peaper said. “But I think that people have seen a lot of the promise and potential of home testing like this, that I think it probably has created a market and an interest in exploring that much further.”

The first thing to understand about Bahram Javidi’s research is that when you have a disease, it actually changes the appearance and movement of your red blood cells.

“Our hypothesis, and this was confirmed later on, was that when people get sick, at a very, very small scale, it leaves a signature inside of these red blood cells,” he said. “We can't see it with the naked eye. But if you have a system that's powerful enough, it can extract information from these red blood cells.”

Javidi is a distinguished professor at the University of Connecticut, with appointments not only in the electrical and computer engineering departments but also with the biomedical engineering department.

Beginning with the hypothesis that a COVID infection could be visibly detected by changes in the red blood cells, Javidi and his colleagues have developed a simple, cheap system that detects those changes.

“For a particular disease infection, it changes not just the morphology, but the behavior of these red blood cells,” he said. “That's what the system is trying to do. The system is like a very miniaturized holographic system.”

You start with a laser source. It could be a simple laser pointer. You shine that laser pointer through a drop of a patient’s blood and into an inexpensive, 3D-printed image sensor, a mechanism that records “the diffraction of light through these cells,” Javidi said. That image is then captured by a digital camera, attached to any computer which interprets the image.

The result is a COVID diagnosis.

“COVID-infected red blood cells become much stiffer, and they look jagged,” he said. “Healthy red blood cells look nice and tubular and smooth and have a strong reading,”

It’s not just COVID. “I designed the system not for COVID. Initially, my concern was malaria,” Javidi said, but it could be applied to many, if not every viral or bacteriological disease. “Malaria consistently, on an annual basis, has killed millions. Particularly troubling was that most of the fatalities are in children.”

The system is cheap and replicable, so that it can be implemented in poorer countries that might lack access to widespread diagnostic testing. All you need is a computer, a cheap laser printer, a 3D printer, and a digital camera. “The light source can be a laser pointer. It doesn't have to be anything fancy,” Javidi said. “The camera can be the camera on your laptop, can be a camera on a phone.”

“I designed this to be very low cost, very simple, very compact, something that I can send a 3D print to some contact in Africa and Asia, they can put it together quickly,” he said.

There are limitations. Javidi said his system cannot yet detect different COVID variants. But that is probably a surmountable problem. All Javidi lacks is data. His system can definitively say, yes, a patient has COVID or malaria or sickle cell disease, but he can’t get more specific than that -- yet.

“I'm working on getting more data,” he said. “I'm working on improving the reliability, fine tuning the algorithms. So we are, you know, we are continuing to work on it, maybe optimize the design, to find ways to make the system more reliable, more cost effective, more stable. But having more data will be really helpful.”

Changchun Liu’s lab at UConn is solely devoted to developing low-cost, point-of-care screening for infectious diseases and cancer.

Though he’s been focused on this work long before the COVID pandemic, it began because of a different pandemic.

“We developed a point-of-care diagnostics device for Zika virus detections because of that pandemic,” he said.

His research has some widespread applications. Liu has shown that the presence of HPV can indicate oral and cervical cancer, and that HPV can be tested at home.

“HPV virus is a reliable biomarker for these cancers,” he said. “We can tell whether or not these patients have a high risk for cervical cancer.”

But Liu acknowledged that there are different applications when it comes to infectious disease screenings, as opposed to tests for cancer.

“For the infectious disease like the COVID-19, this is very clear. You can run the test at home, you can get the result as soon as possible, maybe 30 minutes,” he said. “In this case you can control yourself and don't spread the virus to other people.”

“For the pandemic, for infectious diseases, to add home-based tests, it's clear and really urgent,” he said.

But even though cancer is not transmissible, cheap, at-home or point-of-care testing can also have a huge impact.

“Think about developing countries or resource-limited areas. They do not have the access to expensive equipment like the U.S.,” he said. “So, if there's some rapid or point-of-care cancer or screen technology, it will save a lot of life.”

Jordan Fenster is an award-winning reporter, podcaster and children's book author.  He serves as digital products editor at Hearst Connecticut Media and lives in Stamford with his dog, cat and three daughters.