August 26, 2020

What does 'immunity' to Covid-19 really mean? Here are 4 possibilities.

Daily Briefing

    Amid this week's news that a man in Hong Kong was reinfected with the novel coronavirus, STAT News Hellen Branswell asked health experts to predict how different types of immunity to the novel coronavirus, or a lack thereof, could dictate what a future with the virus would look like.

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    Researchers have been working to understand whether exposure to the novel coronavirus could protect people from future infection. Questions regarding immunity to the coronavirus haven't yet been answered definitively, but researchers have pointed to some preliminary evidence suggesting that people infected with the virus develop antibodies and other immune responses that could protect them against reinfection for at least several months to potentially a few years.

    However, some health care providers have reported cases in which patients appeared to become reinfected with the virus. And on Monday, researchers in Hong Kong confirmed the first documented case of novel coronavirus reinfection. According to the researchers, a 33-year-old man who was first diagnosed with a novel coronavirus in March, and who had recovered from that infection, was later infected with a different strain of the virus that had been spreading throughout Europe in July and August.

    That case has spurred even more questions about the type of immunity people may develop to the novel coronavirus, Branswell reports. Recently, she asked health experts to predict how different types of immunity to the virus, or a lack thereof, could dictate what a future with the virus would look like, and Vineet Menachery, a coronavirus researcher at the University of Texas Medical Branch, came up with four different scenarios that are quite "hopeful," Branswell writes. However, she cautions that the scenarios described are merely "educated guesses, based on what's known about the way the immune system works in general, and how it responds to other coronaviruses."

    The 4 immunity scenarios

    1. Sterilizing immunity

      The best-case scenario, Branswell writes, would be so-called "sterilizing immunity," which can fight off a virus "before infection can take hold."

      According to Branswell, this type of immunity usually occurs when the body incurs a pathogen that induces strong and durable immune responses during initial infection, such as measles. But unfortunately for the current crisis, respiratory viruses that infect the mucus membranes in the nose and throat—such as the novel coronavirus—don't usually result in sterilizing immunity.

      "Sterilizing [immunity] in my view is out of the question, as with any respiratory virus," said Marion Koopmans, head of virology at Erasmus Medical Center in the Netherlands.

      Stanley Perlman, a researcher at the University of Iowa, seemingly agreed, noting it was "not so likely" the novel coronavirus will induce sterilizing immunity.

      The low likelihood that infection from the coronavirus can induce sterilizing immunity has raised concerns that a vaccine against the virus wouldn't be able to generate sterilizing immunity, either, Branswell writes. It's also sparked concerns that a vaccine wouldn't prevent the virus' spread—even though it might reduce the severity of Covid-19, the disease caused by the virus.

      "[W]e'd all like … immunity that protects the individual—protects from infection and protects from transmission," said Malik Peiris, a coronavirus expert at Hong Kong University, but "[w]e may not achieve that, because protecting from infection of the upper respiratory tract and then transmission is quite a challenge."

    2. Functional immunity

      However, one type of immune response that may be "within reach," according to Branswell, is "functional immunity," which occurs when a body recognizes a pathogen, either due to a previous infection or vaccination. While people who develop this type of immunity could become reinfected with the pathogen at a later date, they would experience a milder, shorter infection.immunity, immunity, people who

      "It may be possible to become infected again, without any change in the virus," said Christian Drosten, director of the Institute of Virology at Berlin’s Charité University Hospital. But "[t]he resulting infection will be mild or asymptomatic, with significantly lower levels of virus replication and onward transmission."

      So ultimately, even though there would still be cases of coronavirus infection and Covid-19, the disease "won't have the impact it has now" under this immunity scenario, Peiris said. "It becomes manageable."

      And, according to the experts, the immune responses we've seen so far to the novel coronavirus are in line with what they'd expect to see under this scenario—including in the recent Hong Kong case. While the man in that case experienced symptoms of Covid-19 during his first infection, he reportedly didn't experience Covid-19 symptoms during the second infection.

      For his part, Menachery said he thinks it's likely that most people will develop functional immunity to the novel coronavirus.

      "The idea there is that, yes, your antibodies might wane, but your memory responses aren't absent," he said. "I'm a believer that if you've gotten Covid-19, then your likelihood of dying from a second Covid-19 case is very low, if you maintain immunity."

      And if people who are reinfected experience a lesser infection, they might also generate lower levels of the virus, meaning they could be less likely to pass it on, Branswell reports. "It may become a rare infection, although that is difficult to foresee given the size of the global population," Koopmans said.

       In addition, children, who appear less likely to develop severe cases of Covid-19 than adults, might never experience a severe case of the disease after developing functional immunity over their lifetimes. "I think that's kind of how, in the long run, it would play out without the intervention of vaccines," Krammer said. "I think with vaccines, we just basically speed up that process."

      However, experts warned of one big question regarding this type of immunity: Whether and to what extent people whose first infections did not result in symptoms of Covid-19, or who had very mild cases, would develop this longer-lasting immune response. Perlman was cautiously hopeful, saying he would hypothesize that such individuals would have sufficient protection against severe cases of the disease.

    3. Waning immunity

      The third scenario involves a variant of functional immunity called "waning immunity," Branswell writes, in which people who have been infected with or vaccinated against the novel coronavirus could experience a decreased level of protection over time. According to Branswell, this type of immune response is seen with four coronaviruses that cause common colds and can reinfect people "after a relatively short period of time."

      For example, one Dutch study, which has not yet been peer reviewed, measured antibody levels for those four coronaviruses in 10 people for decades and "saw frequent reinfections at 12 months post‐infection and substantial reduction in antibody levels as soon as six months post‐infection," the researchers wrote.

      Lia van der Hoek from Amsterdam University Medical Center, a senior author of the study, said she thinks waning immunity is the most likely immune response for people infected with the novel coronavirus.

      But, she added, "It is completely unknown what the symptoms will be when reinfection occurs. This could be less, or worse, or equal. We scientists cannot make a prediction on that."

      For his part, Menachery said he believes that, even if immunity faded over time, the reinfections would still be less severe. "You will never get as sick as you were the first time," Menachery said.

    4. Lost immunity

      A more dire scenario, according to Branswell, would be so-called "lost immunity," in which people who have previously been infected with the coronavirus lose immunity against the virus within a certain timeframe—after which point, any reinfection could be as severe as the first.

      However, Branswell writes that "[n]one of the experts … felt this was a possibility."

      Menachery said people who "generate a response to clear the virus" will likely "maintain that immunity long term." However, he added that, for "people with mild or asymptomatic infection, it may not be lost immunity, but rather no immunity generated."

      And overall, Branswell writes, if lost immunity is unlikely, then we will probably see the threat of Covid-19 decrease over time. "Our immune systems will know how to deal with" the novel coronavirus, she writes. "It could become the fifth human coronavirus to cause common colds."

      But Dan Barouch, director of the Center for Virology and Vaccine Research at Boston's Beth Israel Deaconess Medical Center, warned that it might take a long time to reach such a point. According to Barouch, the majority of the world's population has yet to be exposed to the novel coronavirus—and vaccinating everyone in the world could take years.

      Further, Barouch added that it's unlikely only one of these immunity scenarios would occur. He explained that immunity often depends on a person's immune system, as well as the nature of their exposure to a pathogen. "The short answer is we don't know. So, anyone who gives you a scenario is providing a hypothesis," he said (Branswell, STAT News, 8/25).

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