Originally published on medium.com
One of the big questions on everyone’s mind these days is, can you get the novel coronavirus twice? The World Health Organization raised concerns about this on Friday when they tweeted, “There is currently no evidence that people who have recovered from COVID-19 and have antibodies are protected from a second infection.”
The organization later amended their statement, clarifying, “We expect that most people who are infected with COVID-19 will develop an antibody response that will provide some level of protection.”
On this issue hinges the potential for a successful vaccine, herd immunity, and the proposed antibody passports to ease stay-at-home orders and open the economy. With so much at stake, scientists and politicians need a clear answer about whether people can become immune, and, if so, who is immune and for how long.
The problem — as exemplified by the WHO’s back and forth — is there are no clear answers yet.
However, scientists do know some things about immunity to the novel coronavirus, and the evidence so far is both encouraging and discouraging. An important caveat: Much of the research so far has only been published on preprint servers and hasn’t yet been peer reviewed.
“There is probably an interaction between age, between gender, and between underlying diseases that determines how you respond to this virus.”
The key to immunity to any virus are antibodies — specialized immune proteins that are programmed to recognize and attack a specific invader. Antibodies are created during the second wave of the body’s immune response to an infection.
They both help fight off the immediate threat, and they provide protection against future attacks from the same pathogen. At the first sign of reinfection, antibodies detect and overwhelm the virus, fending it off before you even feel sick.
The good news is, most people who have been infected with SARS-CoV-2 create antibodies to it. In two early studies, everyone who was infected with the virus developed antibodies within two weeks of falling ill. However, another recent preprint paper from China revealed that out of 175 people who recovered from Covid-19, 10 never developed antibodies.
What’s more, 30% of people in the study had very low antibody levels, raising questions about whether they would actually be immune to the virus if they encountered it again.
“The antibody tests that are being developed tell us that the individual has had exposure to the virus, probably had an infection, either subclinical or clinical, but that does not absolutely indicate immunity,” says Mandeep Mehra, MD, a professor of medicine at Harvard Medical School and chair in advanced cardiovascular medicine at Brigham and Women’s Hospital. “This virus tends to induce different levels of antibodies in different kinds of people, and there is probably an interaction between age, between gender, and between underlying diseases that determines how you respond to this virus.”
In the Chinese study, the researchers noted that elderly and middle-aged patients had significantly higher levels of antibodies than the younger patients. Young people tend to have less severe infections than older people, and it’s possible that the strength of the antibody response depends on the strength of the infection.
If this is the case, it raises serious concerns that people with asymptomatic infections — by some estimates 40% of all SARS-CoV-2 cases — would not have immunity to the virus. Scientists don’t yet know what is different in people who have asymptomatic infections.
“Maybe their body was able to deal with it more through their innate [initial] immunity and therefore they didn’t get as strong a stimulus to their adaptive [antibody] immune response,” says Warner Greene, MD, PhD, director of the Gladstone Center for HIV Cure Research and a professor of microbiology and immunology at the University of California, San Francisco. “Maybe they’ll have lower levels of antibodies. Maybe, in fact, they were asymptomatic because they were completely able to clear the virus and so they have magnificent antibody responses. It just emphasizes how little we know about the immune side of things.”
In most cases, the antibodies do seem to be effective at killing the virus. In test tube experiments, isolated antibodies disarm the novel coronavirus so it can’t infect cells. Also, initial studies that used convalescent plasma containing antibodies to treat Covid-19 patients in serious condition are encouraging.
One study showed that 10 people hospitalized with the infection all showed dramatic signs of recovery within three days of receiving the antibody transfusion.
A preprint paper from March provided more encouraging signs: Two monkeys that had recovered from the virus did not become reinfected after scientists deliberately exposed them to the virus a second time.
However, news reports out of South Korea made a stir earlier this month when the country’s Centers for Disease Control announced that 91 people who were thought to have recovered from the virus tested positive again.
It’s unknown whether the Korean cases are reinfections with the virus, reactivation of the same infection that may have gone temporarily dormant, or a problem with the tests themselves.
An estimated 30% of viral RNA tests used to diagnose SARS-CoV-2 can result in a false negative, so it’s possible the people were given the all clear when they were still infected.
Another possibility is that the viral RNA detected the second time around were fragments of dead virus that weren’t able to replicate and cause infection but were still lingering in the cells.
“Those cases that are being discussed out of Korea, it may be that this virus was suppressed and reactivated later,” Mehra says. “I think that that’s a much more likely scenario. There are several viruses that behave like that.”
“What will determine this is looking at the sequence of the virus that they were initially infected with, and then the sequence of the virus that has come back, either through new infection or reemergence,” adds Greene. “That fingerprinting of the virus will tell you whether it’s a new infection or just the old virus that’s come to the surface again.”
“The field is evolving so fast that it’s almost impossible to put your finger on anything.”
Another question is how long the antibodies will hang around. Based on evidence from other coronaviruses, such as MERS, SARS, and the common cold, Greene predicts “that the antibody responses will last some number of years to be determined” because it’s “much more of a systemic infection.”
Just as the number of antibodies produced appears to correlate with the severity of infection, so does the length of immunity. Prior studies have shown that people who had severe MERS infections causing pneumonia produced antibodies for at least 18 months after they recovered.
However, people who had asymptomatic infections did not show any signs of antibodies just three months after they initially tested positive for the virus.
The evidence from past SARS outbreaks is more encouraging, with 90% of people showing evidence of antibodies for at least two years after infection. Antibody levels dropped off during the third year.
In the mildest coronaviruses — those that cause the common cold — people who were infected produced a low level of antibodies for up to one year after. However, some people were able to become reinfected with the virus when exposed to it a second time.
As with all things related to SARS-CoV-2, the situation will undoubtedly change as new information emerges. Cities, counties, and states are rolling out widespread antibody testing to try to understand how many people have come into contact with the virus.
And the further we get from initial infections, the more we’ll know about how antibody levels change over time and whether reinfection really is possible.
Mehra says, “The field is evolving so fast that it’s almost impossible to put your finger on anything.”