COVID testing is the first line of defense against the virus, and the key to its effectiveness may be taking multiple.

Experts caution that one negative test may not be enough to determine if those feeling ill, particularly those who were knowingly exposed to COVID, have stayed clear of infection.

The most recent U.S. recommendations released in August have officials urging that those who were exposed to COVID take three home tests instead of two to boost accuracy.

Previously, the Food and Drug Administration had advised taking two rapid antigen tests over the course of two or three days to rule out infection. But the agency said new studies suggest that protocol can miss too many infections, and could result in people spreading the coronavirus to others, especially if they don't develop symptoms.

The new guidance applies to people without symptoms who think they may have been exposed. People with symptoms can continue using two tests spaced 48 hours apart.

Health officials have repeatedly cautioned that the tests can give false negatives if taken too early.

The Centers for Disease Control and Prevention recommends people without symptoms wait five days after an exposure. That's because it generally takes several days before the antigens reach levels detectable via testing with a nose swab.

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Chicago's top doctor said there's no clear answer for how long it could take.

"I don't have a single answer," Chicago Department of Public Health Commissioner Dr. Allison Arwady said last Tuesday. "What I can say is that if you had a known recent COVID exposure - somebody in your family just had COVID, you had a close call on contacts who had COVID - and you develop COVID symptoms in the next, you know, 10 days ... you have COVID almost certainly and you should treat it like that, even if it takes a few days for the test to turn positive."

Arwady herself recently experienced a testing delay when she contracted the virus following a vacation in August.

"When I had recently been on vacation, I started testing right away when I came back, knowing that that had been a higher-risk setting," she said earlier during a Facebook Live. "I learned that one of my travel companions tested positive for COVID. I was feeling just fine, I took a COVID test, it was negative. I was being really careful about wearing a mask, which I would have done anyway for 10 days after vacation, but I didn't quarantine at that point. I didn't stay home. I was super careful with wearing my N95 mask. But as soon as my very first symptom developed - just a little bit of feeling tired, a little bit of tickle in my throat - I was like, 'Oh boy, I probably have COVID.' I stayed home at that point. I took a COVID test - an at-home test - it was negative that night. I developed a fever... It was still negative the next morning, and then it took about my third COVID test, which was probably about 18 hours after my symptoms started, it turned positive."

Arwady noted that while negative test results may not be the most reliable, those who do test positive should "treat a positive test as a positive."

"What I tell people is a negative at-home test is probably negative, unless you're testing too early - meaning that the virus hasn't yet had a chance to build up in your body," she said. "The good news is, when the virus hasn't had a chance to build up in your body, you're less likely to be spreading COVID yet, but nevertheless, it means that the test can stay negative and this omicron variant moves so fast that we are seeing sometimes people it can take a day or two for those tests to turn positive. But I will take any positive though... we don't see false positives on the at-home test, just to be clear. So any positive is a positive. And the negative is somewhat reassuring, but if you've had an exposure or you have new symptoms, there's still a very good chance that it could be COVID."

According to the Centers for Disease Control and Prevention, "positive results from self-tests are highly reliable."

For those who are unsure, a PCR test may provide more accurate results earlier in an infection, experts say.

"The laboratory testing outside of homes, the PCR testing, is a little more sensitive," Arwady said. "Usually it will turn positive a little faster."

Those tests, however, can also indicate a positive result for infections that are no longer active.

The CDC previously said people can test positive for up to three months after contracting an infection.

For those who do test positive, the CDC recommends isolation for the first five days after symptom onset, which is when you're likely to be the most infectious. After that, a well-fitting mask should be worn through day 10.