Although the novel coronavirus pandemic still defies prediction, medical experts are expressing increasing optimism about the human immune system’s ability to fight the virus.
Doomsday headlines followed a recent study of recovered COVID-19 patients reporting that antibodies, the hallmark of the immune system responding to an infection, may only last a few months. But in the last month, promising vaccine results and new findings analyzing the immune response of people who survived the disease are giving scientists more encouragement. Experts caution this is only provisional given that we are still in the early months of a pandemic that has so far killed more than 600,000 people.
“We don’t want to get ahead of ourselves, but the coronavirus is starting to look a lot like other viruses that have led to good vaccines,” said immunologist Danny Altmann of Imperial College London. “It doesn’t look like one of those enormous confounders that have completely stopped us in our tracks, like HIV or tuberculosis or malaria, which have been some of the great failures in the last 10 or 20 years.”
The big problem, Altmann and other experts acknowledge, is that we are still only months into the first appearance of a highly infectious, deadly, and unpredictable virus plowing into an unprepared humanity, making long-term projections hazardous.
Here’s what we know so far about how our immune systems may protect us from the coronavirus — and what that means for a COVID-19 vaccine.
So what does the immune response look like in COVID-19?
In general, our immune systems seem to be using all the usual tools available to fight the new coronavirus, immunologist John Moore of Weill Cornell Medical College told BuzzFeed News. “I’m not completely surprised by what we are seeing,” he said.
Antibodies develop over a week or longer after exposure to viruses, most strongly in severe cases and much less in mild ones. Studies show that white blood cells, which help make antibodies and kill infected cells, drop in the bloodstream after infection, seen as a sign they are being recruited to fight the virus.
There are two types of white blood cells that coronavirus vaccine makers are closely watching right now: B cells, which make virus-specific antibodies, and T cells, which either directly or indirectly kill off infected cells. Some T cells are also called “helper” cells, because they train B cells to make those targeted antibodies. The long-term persistence of these fighters — rather than the sheer numbers of antibodies — gives the immune system its “memory” of past viruses.
A good sign in recent studies is that, in addition to antibodies, people seem to be readily producing these virus-specific B cells and T cells after getting COVID-19.
How long does immunity last?
Nobody knows for certain, since SARS-CoV-2 only jumped to infecting humans last November, according to genetic studies of the virus. Just not enough time has passed to know.
Individual antibodies have half-lives measured in days and weeks; they have to be constantly manufactured by the immune system to remain at neutralizing levels in the body. A King’s College London study of 65 people made headlines two weeks ago by suggesting that antibodies to SARS-CoV-2 faded to the point where they were detectable in only 17% of patients three months after an infection.
For a few viruses like measles, immunity comes from longer-lived immune cells continually churning out antibodies for a lifetime. That doesn’t happen with coronaviruses, as seen from measures of fading antibodies after recovery from COVID-19. It’s no surprise to see antibodies fading after a viral infection, said Moore. “That’s normal,” he said.
However, a Mount Sinai School of Medicine study of nearly 20,000 recovered COVID-19 patients released last week essentially found that patients retained antibodies above the “neutralizing” amount that halts an infection for at least three months. Somewhat counterintuitively, that study found that while severe cases saw a drop in antibodies after three months, the milder cases saw an increase by then.
Typically, T cells and B cells hang around after an infection, primed to rapidly respond to a reinvasion by making more antibodies. And there are indications that after recovery from COVID-19, they should be long-lasting: In the closest human-infecting relative to the novel coronavirus, SARS, a study of 23 people who recovered from that virus in 2003 showed they still had memory T cells for the virus 17 years later. Those T cells looked similar to ones measured from a separate group of 36 COVID-19 patients, targeting the same part of the viral shell encircling both coronaviruses.
It’s a promising sign that so far the immune response to the novel coronavirus doesn’t seem to look all that different from other viruses, said Altmann.
“The devil is in the details,” Altmann said. “We need to keep watching over several months and years.”
Does everyone produce the same immune response?
Not at all. Mild cases seem to produce fewer antibodies while more severe ones make more of them. In one Chinese study, for example, 40% of asymptomatic patients had undetectable levels of antibodies eight weeks after an infection. That same paradox, a seemingly weaker antibody response in milder cases, happened with SARS.
The T cell response in COVID-19 patients also varies in unexpected ways. Broadly speaking, a novel coronavirus infection seems to lead to more “helper” T cells that lead to more antibodies, rather than the ones that hunt down and kill infected cells.
But a July 15 University of Pennsylvania report found that people’s T cell responses could be divided into three very different “immunotypes.” In the first type, T cell responses were “unbalanced,” study coauthor E. John Wherry told BuzzFeed News, with an excess of helper cells and an emptying out of the ones that kill infected cells. The second type saw fewer helper cells and more killer ones. The last type largely lacked any T cell response, as if the immune system hadn’t even gotten started.
“We had patients of all three types die, even the third immunotype, but the first group was clearly the worst situation,” said Wherry. This kind of “heterogeneity” in immune system responses to a virus is unusual, he added. “We are all scratching our heads over this,” said Wherry.
Figuring out a patient’s immunotype could help doctors know which ones to treat with drugs that tamp down the immune systems, like the steroid dexamethasone, which cut the death rate by a third for patients on ventilators in a June study.
Can you get reinfected?
The specter of reinfections with the novel coronavirus have haunted health officials at least since March, spurred by reports of such cases from China.
But epidemiologists now suspect that reports of reinfections are more likely cases where people didn’t ward off infections in the first place, the New York Times recently reported. A recent Chinese team’s experiment that sought to reinfect macaques with the coronavirus, an experiment that would be unethical to conduct in people, found that the monkeys were still resistant a month later.
“Of course, macaques are not humans. Nevertheless, the findings lend hope,” National Institutes of Health Director Francis Collins wrote, noting that doctors are closely monitoring recovered patients from the New York outbreak in March and April for signs of reinfection. “By the end of this year, we should have better answers,” Collins said.
Why are old people hit harder than young people?
On July 17, the CDC eliminated age by itself as a risk factor for more severe COVID-19, offering an answer: Older people just have more of the underlying conditions, such as diabetes, cancer, obesity, heart disease, and other conditions that raise the risks of dying from the novel coronavirus. Children with heart conditions and immune system deficiencies are similarly at risk, according to the CDC, though most have mild cases. A confusing exception to this rule is that although kids under 10 comprise the smallest portion of severe cases, a few have suffered from a mysterious inflammatory syndrome afflicting many organs at once.
But despite the CDC’s revision, age might still matter when it comes to vaccines. The Chinese candidate vaccine reported this week found that people over 55 had lower antibody responses to their inoculation and might require a second dose (or it might mean they had already been exposed to the harmless virus used in that vaccine and thus shrugged it off with other antibodies).
The immune response to the coronavirus in kids is particularly puzzling, said Wherry. Typically infectious respiratory diseases, like the flu, are particularly hard on both the elderly and the very youngest patients. “I think the kids here are telling us something very interesting about the pediatric immune system,” Wherry said.
One speculative possibility raised by Altmann is that the near-constant colds of early childhood, including some from coronaviruses, may offer some degree of immunity to kids. The Singapore study that found a 17-year T cell response to SARS also found a response against SARS-CoV-2 in some people who had not been infected by either disease. “This finding suggests that other presently unknown coronaviruses, possibly of animal origin, might induce SARS-CoV-2 T cells,” the authors wrote.
What does this all mean for vaccines?
The big question is how long a vaccine would provide immunity, or even just limit symptoms of COVID-19 so that fewer people die. If the immune response to the virus only lasts about a year, as seems to happen for the much less severe coronaviruses that cause around 20% of common colds, then a SARS-CoV-2 vaccine would need to be administered yearly, like the flu shot. That could compromise efforts to contain the virus, as only around half the population gets a flu shot every year. Or it might mean the vaccine requires boosters, losing more people who’d rather skip a shot.
On the encouraging side, two candidate vaccine results released this week from both China and the UK produced both “neutralizing” antibody responses in most volunteers, as well as strong T cell responses, said Altmann. Both of those vaccines prime the immune system by inoculation with a harmless virus bearing some of the “spike” proteins of the novel coronavirus.
Two other vaccine candidates’ results published in the last month, one from the US-based Moderna and the other from Germany’s BioNTech, inject genetic instructions for making spike proteins into cells in an effort to mobilize the immune system against the novel coronavirus. These vaccines also produced virus-targeted T cells but required two shots about a month apart. And in June, Chinese pharmaceutical company Sinovac reported its candidate vaccine, an old-fashioned injection of killed viruses to trigger alarm in the immune system, produced neutralizing antibodies in 90% of volunteers in a safety trial.
“It looks like almost any vaccine approach that you can use will elicit a decent level of neutralizing activity against the virus,” said Altmann.
The ultimate answer to the question of whether those numbers will prevent infections or just help to lessen symptoms will come in the Phase 3 trials involving tens of thousands of volunteers that started this month.