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Another COVID Mystery: Why Some Fall Ill Twice

patient who has contracted coronavirus twice

July, 23, 2020 -- Anitra Hines thought she had beaten COVID-19. After several weeks of coughing and sleeping on her stomach to ease her breathing, she says her symptoms and overwhelming fatigue began to fade. In late April, a test for the virus came back negative.

“I definitely felt better. I was like, ‘Yeah! I survived COVID,’” she says with a sad laugh.

Hines, 33, a nurse, worked in a nursing home and rehabilitation facility near Atlanta. Staff watched a slew of their residents succumb to the infection.

Early in the pandemic, before much was known about the new coronavirus, Hines says she and her fellow nurses were discouraged from wearing masks so they wouldn’t scare their patients.

She says deaths among residents in her facility are generally rare. When COVID came, that changed.

“We had like three or four residents die in a row, and I was like, ‘OK, what's going on?’” she says.

In early April, the facility tested its staff for the virus. Hines was one of 18 workers who were positive.

She got symptoms soon after. Hines, who has asthma, told her mother that at night, it felt like an elephant was sitting on her chest. Still, she managed to take care of herself at home with Tylenol, her prescription inhaler, and regular telemedicine visits with her doctor.

About a month later, she tested negative and felt well enough to return to work. She even felt safer.

“When she went back, the thinking was 'Oh, she's had COVID, so she wouldn't get it again,’ so they put her back working with COVID patients,” says her mother, Ramonda Hines. By then, more residents at the nursing home had been infected. She was working with COVID patients full-time.

Ten days after returning to work, the fatigue came back. She would come home from work and fall into bed. She wanted to sleep all the time. Her mother got worried.

“I was very scared because she seemed so much sicker the second time, and it came on so quick,” says Ramonda Hines. On May 22, Anitra sounded so bad that her mother forced her to use the video feature on her phone so she could see her. She could see Anitra’s chest was rising and falling rapidly while she was talking. Ramonda told her daughter it was time to go to the hospital.

Anitra wanted to drive herself, but her mother called an ambulance. After she walked down two flights of steps to meet the ambulance crew, the oxygen level in her blood had dropped into the low 60s. Normally, blood oxygen is close to 100%.

At the hospital, about a month after she tested negative, she tested positive for COVID-19 a second time. The virus was back.

“I was a little bit in denial,” she says. As a nurse, she knew she had all the telltale signs, but it made no sense. “It can’t be that. I can’t get it twice.”

"There are more unknowns"

That’s exactly how Carter Wright felt, too.

“I feel like I went through all the stages of grief that night, you know, denial, anger. Why me? I cried a lot that night. It was pretty devastating,” he says.

Wright, 29, a photographer in Nashville, caught COVID in March after taking a trip to New York. He ran a low fever and felt like he had a bad case of the flu but was able to manage his symptoms at home.

Wright was feeling better. He’d gone grocery shopping -- always in a mask -- and had seen a few friends from a safe distance.

Then in early July, almost four months later, his throat became so sore that he had trouble swallowing water. An urgent care clinic tested him for strep. That test was negative. So, too, was a test for COVID-19. Two days later, his fever spiked. His mother, who is a nurse, told him to go to the emergency room. There, a second COVID test was positive.

He shared his experience on Instagram, urging people to take the virus seriously. Almost a half-million people liked his post, which got more than 9,000 comments.

“I still am trying to figure out if there are long-term effects of this, so for my body to get it twice is just super hard to wrap my brain around,” he says.

Experts are puzzling over these two-timer cases, too. There’s been no comprehensive study of cases like this, and no one knows yet whether reinfection is possible, especially so soon after someone has recovered.

“Right now, there are more unknowns than there are knowns,” says Michael Sneller, MD, a specialist in infectious diseases. He is leading a study at the National Institute of Allergy and Infectious Diseases that will follow people who have recovered from COVID-19 for at least a year. He wants to document any lingering health problems they have and study how their immune systems have responded to the infection.

He hopes to get a large group that he can follow through the fall and winter.

“Next winter, anyone who gets any kind of respiratory symptoms whatsoever, we're going to have to come back in and get tested for the virus to see if they have truly become reinfected,” he says.

Rebound or reinfection?

So far, studies have shown that the amount of virus present in the back of the nose and throat -- where most people are swabbed -- falls after the first few days of a COVID-19 infection. But it can rebound, bouncing up and down for a few weeks or even months. That may help to explain why some people test positive, then negative, then positive again, even as their symptoms fade.

“There’s pretty good evidence that’s not reinfection,” Sneller says “That’s probably lingering dead virus that’s being cleared out of the nose and other places.”

But what about cases like Hines’s and Wright’s, where symptoms return along with a second positive test? Could they have caught the virus a second time?

That’s possible, says Donna Farber, PhD, who leads the Center for Translational Immunology at Columbia University.

“There are a lot of pathogens out there that we get again,” she says. “Malaria is one case where people get it again and again and again.” She says ear infections, too, are often caused by the same kind of bacteria that keeps coming back.

Our immune systems, which defend us against incoming threats, are complex, relying on several lines of defense. Farber likens it to different branches of the military, akin to the Army, Navy, and Air Force. Some of these branches act quickly to thwart a threat and then fade, while others stay in place to stand guard, ready to recognize and respond if that particular invader gets into the body again.

“You can mount an immune response that clears an infection the first time. It’s really whether you develop that persisting memory that gives you protective immunity,” says Farber.

Doctors don’t know whether everyone who gets COVID-19 will have this immune memory.

Early evidence suggests that some people might not.

John Wherry, PhD, directs the Institute for Immunology at the University of Pennsylvania. He’s been studying immune responses to cancer to learn why certain drugs help some patients but fail others. He recently applied this same detailed immune study, which he calls deep immune profiling, to 125 people with COVID-19.

“We actually see patients that are responding in very different ways to this infection,” he says.

Wherry says it’s not uncommon to see a range of immune responses to an infection. But he says all of those responses are usually the same flavor, so to speak. They’re all vanilla ice cream, he says, it’s just that some people get a really big bowl of vanilla ice cream -- or a big immune response -- while others get a small bowl of vanilla ice cream. That’s what happens in an infection like the flu, he says.

With COVID-19, “there are many different flavors of ice cream,” Wherry says. “That’s what’s been a little bit different here.”

He sorted all those many-flavored responses into three groups, which he called “immunotypes.”

All of these patients were really sick. They were all hospitalized in the intensive care unit. There were patients who died in each group. But some had a very strong immune response, where certain cell types were more highly activated than others. A second group had a more balanced immune response. A third group, Wherry says, looked like they didn’t have any ice cream in their bowls at all.

“It was hard for us to tell that they were even responding to a viral infection,” he says.

A Long Recovery

Anitra Hines may have been in that category.

Early into her second bout of COVID-19, doctors tested her for antibodies. Antibodies are proteins made by the immune system. They bind to an invading virus and block it from entering cells. With a brand-new virus, like the one that causes COVID-19, it takes the body 2 to 3 weeks to make these kinds of antibodies. Hines didn’t have any.

There could be other explanations for these cases, too. Wherry notes that the tests being used to diagnose COVID-19 can be falsely positive and falsely negative. It may be that the results from one of the tests Hines or Wright took were just wrong. Perhaps their bodies never fully got rid of the virus the first time around, and it roared back later.

“There’s still way more we don’t know than we’ve learned,” he says. “We just don’t have real data to understand what’s happening.”

Hines received convalescent plasma, clear fluid that’s separated from the blood of people who have recovered from an infection. It’s rich in protective antibodies to the virus. She was also treated with the antiviral drug remdesivir.

Doctors told her that she needed to go on a ventilator. That worried her, because she knew she might not recover. Before they put a tube down her throat to help her breathe, she used the video feature on her phone to call her parents and sisters.

“She told us she was sorry that she was putting us through this,” Ramonda says.

Anitra was put in a special bed that kept her on her stomach for 16 hours a day. That position seems to help people breathe better. She remained on the ventilator, in a medically induced coma, for 9 days. The breathing tube rubbed deep sores into the sides of her cheeks, which became infected. All told, she was in the hospital for about a month.

The treatments worked, but they left her disabled. After she left the hospital, her mother brought her to Illinois so she could regain her strength. She’s had to retrain her body to walk, eat, and talk. She’s tired all the time and prone to coughing fits.

She’s also struggling with medical bills. So far, her bills for a 36-day hospital stay have totaled $421,000. That’s not counting any of the rehabilitation she will need as she recovers in Illinois. Her mother has started a GoFundMe account to help offset the costs.

Still, she believes she is lucky.

“This is a good news story,” her mother says.

Carter Wright is still recovering, too. He’s almost finished with his second quarantine. He has a lingering cough, and his energy still isn’t back, but he’s on the mend, at least physically.

“Outside of the physical aspects, which are difficult, it is mentally exhausting and taxing to have the virus that the whole world is talking about and you can't get away from it,” he says.

Wright really wants people to understand that COVID-19 is real, and it’s serious.

“Take these simple precautions of wearing a mask, washing your hands, socially distancing, take them seriously,” he says.

Wherry agrees. He says those precautions should still apply, even if you’ve recovered from the infection.

“We are all very hopeful that recovering from COVID will provide some level of protective immunity. The actual data does not exist on that.”

Wherry says that means, “Even if you’ve recovered, practice all social distancing, mask-wearing, and everything because you don’t know for sure.”

WebMD Health News Reviewed by Brunilda Nazario, MD on July 23, 2020

Sources

Anitra Hines, licensed practical nurse, Lithia Springs, GA.

Ramonda Hines, mother of Anitra Hines, Decatur, IL.

Carter Wright, photographer, Nashville.

Michael Sneller, MD, infectious disease specialist, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.

Donna Farber, PhD, George Humphreys professor of surgical sciences; chief, Division of Surgical Sciences and professor of microbiology & immunology, Columbia University, New York City.

E. John Wherry, PhD, chair, Department of Systems Pharmacology and Translational Therapeutics; director, Institute for Immunology, University of Pennsylvania, Philadelphia.

Science: “Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications.”

Nature: “Virological assessment of hospitalized patients with COVID-2019.”

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