On Aug. 15, the man returned to Hong Kong from a recent trip to Spain and the U.K., areas that have recently seen a resurgence of COVID-19 cases. At the airport, he was screened for COVID-19 using a test that checks saliva for the virus. He tested positive, but this time, had no symptoms. He was taken to the hospital for monitoring. His viral load — the amount of virus he had in his body — went down over time, suggesting that his immune system was taking care of the intrusion on its own.
The special thing about his case is that each time he was hospitalized, doctors sequenced the genome of the virus that infected him. It was slightly different from one infection to the next, suggesting that the virus had mutated — or changed — in the 4 months between his infections. It also proves that it’s possible for this coronavirus to infect the same person twice.
Experts with the World Health Organization responded to the case at a news briefing Monday.
“What we are learning about infection is that people do develop an immune response. What is not completely clear yet is how strong that immune response is and for how long that immune response lasts,” said Maria Van Kerkhove, PhD, an infectious disease epidemiologist with the World Health Organization in Geneva, Switzerland.
A study on the man’s case is being prepared for publication in the journal Clinical Infectious Diseases. Experts say the finding shouldn’t cause alarm, but it does have important implications for the development of herd immunity and efforts to come up with vaccines and treatments.
“This appears to be pretty clear-cut evidence of reinfection because of sequencing and isolation of two different viruses,” says Gregory Poland, MD, an expert on vaccine development and immunology at the Mayo Clinic in Rochester, MN. “The big unknown is how often is this happening,” he says. More studies are needed to learn whether this was a rare case or something that is happening often.
Past Experience Guides Present
Until we know more, Poland says the possibility of getting COVID-19 twice shouldn’t make anyone worry.
This also happens with other kinds of coronaviruses — the ones that cause common colds. Those coronaviruses change slightly each year as they circle the globe, which allows them to keep spreading and causing their more run-of-the-mill kind of misery.
It also happens with seasonal flu. It is the reason people have to get vaccinated against the flu year after year, and why the flu vaccine has to change slightly each year in an effort to keep up with the ever-evolving influenza virus.
“We’ve been making flu vaccines for 80 years, and there are clinical trials happening as we speak to find new and better influenza vaccines,” Poland says.
There has been other evidence the virus that causes COVID-19 can change this way, too. Researchers at Howard Hughes Medical Center, at Rockefeller University in New York, recently used a key piece of the SARS-CoV-2 virus — the genetic instructions for its spike protein — to repeatedly infect human cells. Scientists watched as each new generation of the virus went on to infect a new batch of cells. Over time, as it copied itself, some of the copies changed their genes to allow them to survive after scientists attacked them with neutralizing antibodies. Those antibodies are one of the main weapons used by the immune system to recognize and disable a virus.
Though that study is still a preprint, which means it hasn’t yet been reviewed by outside experts, the authors wrote that their findings suggest the virus can change in ways that help it evade our immune system. If true, they wrote in mid-July, it means reinfection is possible, especially in people who have a weak immune response to the virus the first time they encounter it.
That seems to be true in the case of the man from Hong Kong. When doctors tested his blood to look for antibodies to the virus, they didn’t find any. That could mean that he either had a weak immune response to the virus the first time around, or that the antibodies he made during his first infection diminished over time. But during his second infection, he quickly developed more antibodies, suggesting that the second infection acted a little bit like a booster to fire up his immune system. That’s probably the reason he didn’t have any symptoms the second time, too.
“I’m a little surprised at 4½ months,” Poland says, referencing the time between the Hong Kong man’s infections. “I’m not surprised by, you know, I got infected last winter and I got infected again this winter,” he says.
It also suggests that immune-based therapies such as convalescent plasma and monoclonal antibodies may be of limited help over time, since the virus might be changing in ways that help it outsmart those treatments.
Convalescent plasma is essentially a concentrated dose of antibodies from people who have recovered from a COVID-19 infection. As the virus changes, the antibodies in that plasma may not work as well for future infections.
Drug companies have learned to harness the power of monoclonal antibodies as powerful treatments against cancer and other diseases. Monoclonal antibodies, which are mass-produced in a lab, mimic the body’s natural defenses against a pathogen. Just like the virus can become resistant to natural immunity, it can change in ways that help it outsmart lab-created treatments. Some drug companies that are developing monoclonal antibodies to fight COVID-19 have already prepared for that possibility by making antibody cocktails that are designed to disable the virus by locking onto it in different places, which may help prevent it from developing resistance to those therapies.
“We have a lot to learn,” Poland says. “Now that the proof of principle has been established, and I would say it has with this man, and with our knowledge of seasonal coronaviruses, we need to look more aggressively to define how often this occurs.”