Unpacking the Long-Term Immune Response to COVID-19

As governments around the world begin to distribute coronavirus disease 2019 (COVID-19) to high-risk populations, one key question lingers unsolved: Just how long do patients remain immune after being infected with the virus or receiving a vaccine?

While apparently rare, there are increasing numbers of reports of COVID-19 reinfection, some within the 90-day window in which recovered cases are thought to be immune.

BNO News, a Dutch website that is tracking reports of reinfections, lists just 26 officially confirmed cases of reinfection, but cites another 1,600 suspected reinfection cases.

One difficulty in tracking reinfection is that it’s not clear whether a positive test result following recovery from an initial infection is indicative of a new infection or simply lingering viral shedding from the original infection.

In an article in The Conversation, Lara Herrero, MD, PhD, and Eugene Madzokere, MS, of Griffith University, in Australia, noted that shedding of SARS-CoV-2 genetic material can continue for as long as 120 days.

“Where people have recovered and then later test positive again — or return a ‘weak positive’ result — the test has picked up viral genetic material,” they wrote. “We don’t know whether the virus is infectious at this point.”

For its part, the US Centers for Disease Control and Prevention’s recently updated guidance says “some reinfections are expected.” The agency says reinfection is unlikely within 3 months, but also cautions that little is currently known about immune response and duration of immunity.

However, the scientific literature into the question is growing. Shane Crotty, PhD, of the Center for Infectious Disease and Vaccine Research at the La Jolla Institute for Immunology, and colleagues have been investigating the question, and in November published a preprint examining immune memory in COVID-19 patients.

Crotty told Contagion that their latest research demonstrates that the body’s immune system remembers the virus for at least 8 months after the onset of symptoms, “which suggests to us that the immune system can remember the virus for years, and that, most likely, many people will be protected from a repeat case of COVID-19 for a substantial time.”

Crotty’s use of the word “most” is important. Their research also indicated significant variation between individuals; a few of whom did not have measurable robust immune memory.

“We don’t know for sure yet, but it’s possible that at least some infected with SARS-SoV-2 with a particularly low immune memory could be susceptible to re-infection relatively soon after recovering from the initial infections,” he said.

Early indications are that gender and disease severity may be factors contributing to the variability, though he said they do not yet have a full picture of all of the factors involved.

As for how their findings might impact the efficacy of the new COVID-19 vaccines. Crotty’s team has only investigated immunity following natural infections, though he suspects the immune memory response following vaccination would be similar to that following natural infection, leaving open the possibility that some patients might have a more durable immunity than others.

Asked where that leaves physicians counseling patients who may be wary of continuing to use precautions like masks and social distancing once they’ve had the virus or received a vaccine, Crotty said he would urge doctors and patients to play it safe.

“Until all the data is in, my advice is to err on the side of caution and keep wearing your mask and [keep] a safe distance,” he said.