For many who fell ill with the coronavirus in the early days of the pandemic in the United States, there were hopes of a silver lining: Perhaps, they'd be protected against future infections.
But emerging evidence, along with anecdotal reports, are calling that hoped-for lasting protection into question.
"Most everyone I know in the scientific community has been raising that question since the beginning," Dr. Michael Saag, associate dean for global health at the University of Alabama, Birmingham, said.
The body's immune system is designed to fight infections by producing antibodies to viruses. It's been suspected that people who have had the virus, and therefore developed COVID-19 antibodies, have some level of protection from a second infection. But it's never been clear how long that immunity lasts.
Sherry Wellman, 56, of Youngstown, Ohio, and her doctors had assumed it would last longer than two months.
After an initial positive test for the virus in March, two additional COVID-19 tests in April were negative. It was welcome news to Wellman, whose job as a nurse required her to have two negative tests before returning to work.
But a month later, she had to go to the hospital for chest pains, and was tested again.
The physicians "ended up testing me for COVID just for the heck of it," Wellman said. "Sure enough, it came back positive. They were stunned."
"The nightmare of this is based on how much we don't know," Saag said. "COVID is brand new. We're discovering as we go." A growing pool of data, he said, suggests COVID-19 antibodies wane about 60 to 90 days after infection.
The nightmare of this is based on how much we don't know.
"That's certainly consistent with other coronaviruses," Derek Cummings, an infectious disease epidemiologist at the University of Florida, said. Other coronaviruses include the viruses that cause SARS and MERS, as well as several that cause common colds.
But because coronavirus infections can often occur without symptoms, "it really takes careful follow-up of individuals to detect that second infection," Cummings said.
There are three possible explanations for Wellman's second round of positive COVID-19 results. Either her negative tests were faulty; the virus remained hidden in her system undetectable by tests before flaring up again; or she really was infected a second time.
Shelby Hedgecock, 29, a wellness coach in Los Angeles, has had a similar experience: positive COVID-19 tests in April, followed by two negative tests in May, and then another positive test.
The thought of a secondary COVID-19 infection is devastating to Hedgecock, whose illness has resulted in weeks of intense headaches, body aches, shortness of breath, fatigue and a racing heartbeat.
"I cannot get this again," she said. "I'm absolutely terrified."
Dr. Daniel Kuritzkes, head of the division of infectious diseases at Brigham and Women's Hospital in Boston, said it's too soon and there's not enough data yet to know if reinfections are happening. Inconsistent testing in the United States, combined with the fact that some patients can test positive for the coronavirus up to two months after the initial infection, make it difficult to track whether the secondary positive results are lingering infections or new ones altogether.
If, indeed, people can become infected with COVID-19 twice within a period of weeks or months, it poses two major stumbling blocks in getting the pandemic under control.
The first would be the concept of herd immunity. "Just throw it out the window," Saag said. "Because not enough people could sustain an immune response that would protect against reinfection long enough for the virus to extinguish."
The second involves vaccine development. If natural infection cannot provide lasting protection against the virus, experts said, a vaccine produced in the lab may not either.
"Will people need vaccine boosters to maintain a protective level of immunity in the population? How frequent might that be?" Kuritzkes said. These are "important issues that we'll have to keep in mind as we move forward with vaccine trials," he said.
But antibodies may not be the only keys in finding an effective COVID-19 vaccine. B cells and T cells may also be essential.
B cells are cells that have been tipped off previously to invading viruses, and are constantly patrolling the body looking for them. When they detect a virus known to be potentially harmful, they start cranking out antibodies to that virus in an effort to stop it.
Also important are T cells, which do one of two things: either they find viruses and tattle on them — telling B cells to produce antibodies — or they take matters into their own hands, killing the virus.
Experts say any effective vaccine for COVID-19 may need to harness the power of all three immune system components: antibodies, B cells and T cells.
"That coordination is really important," said Dr. Buddy Creech, an infectious disease expert and the director of the Vanderbilt Vaccine Research Program at the Vanderbilt University Medical Center in Nashville.
"Some of the vaccine technologies that we're using really do seem, at least in the laboratory and in animals, to do a good job of calling into action those different parts simultaneously," Creech said. He and his team at Vanderbilt are involved in ongoing COVID-19 vaccine research.
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For Saag and Creech, the ramifications of waning immunity are personal. Both previously became severely ill with COVID-19.
Creech's entire family was infected early in the pandemic, giving them a "sense of relief that we were protected for a period of time," Creech said. Now, "we realize that we don't have that same degree of safety."
Saag continues to wear personal protective equipment while treating patients. "I don't know that I'm protected against infection," Saag said. "It's been a concern from the get-go."