Two years into the pandemic, figuring out Covid immunity is more muddled than ever before.
Just about any community has some combination of the following: people who were infected early on but have since been vaccinated; people who were vaccinated and then got Covid; people who have received booster shots; people who haven’t; people who are refusing the Covid vaccines altogether, among them some who have been infected once, if not multiple times, while others haven’t. That’s also the tip of the iceberg, considering the differences the variants introduce.
Each of those scenarios produces a particular level of immunity that also varies based on a person’s immune system, making it increasingly difficult for scientists to predict immunity, both from person to person and within communities, cities and countries.
But understanding how the different branches of the immune system respond to Covid and what protections have been built up through vaccination and several waves of infection is key to figuring out how — and when — the world could emerge from the pandemic.
“How long we’re stuck with this virus is really defined by the durability of our immunity,” said Fikadu Tafesse, an assistant professor of molecular microbiology and immunology at Oregon Health & Science University’s School of Medicine. “That’s what makes the immunity question so important.”
It’s an active area of research, and while studying how the immune system behaves over time takes patience, scientists like Tafesse are already uncovering key insights into the body’s defense mechanisms against Covid.
What’s known is that the human immune system has a diverse arsenal of tools to fight infections, including neutralizing antibodies and T cells. Antibodies, produced either through infection or from vaccines, in essence function as the body’s first line of defense. Neutralizing antibodies, as their name suggests, can destroy the virus before it invades cells.
But antibody levels wane over time. And as was the case with the omicron variant, pathogens can mutate and evolve in such a way that they are better able to evade protective antibodies.
Yet scientists have found that even as antibody levels drop after vaccination or infection, the immune system can still recognize the virus. So-called T-cells, the cornerstone of the immune system’s long-term memory, can spot bits of the virus that get around antibodies, said Alessandro Sette, an immunologist at the La Jolla Institute for Immunology, a California-based research center.
In other words, T-cells won’t stop an infection from happening, but they can halt further spread to other cells, which could prevent a patient from becoming severely ill.
Measuring the sophisticated immune responses is tricky, however, because they can vary hugely from person to person.
Whether through vaccination or infection, T-cells are primed to “remember” various fragments of a virus, Sette said. After a pathogen invades the body and starts reproducing, pieces of the virus end up decorating the surfaces of infected cells.
It’s these markers that T-cells are designed to zero in on. They’re also different for every person, which means that even as a virus mutates and produces new variants, it’s much harder for it to completely dodge T-cells.
The variability in people’s T-cell targets makes it challenging to make sweeping generalizations about Covid immunity, but that very defense has helped humans outrun pathogens throughout history.
“T-cells recognize a much broader repertoire of virus fragments, so the virus can’t very readily mutate all of them,” Sette said. “Even if the virus mutated the 10 fragments that I generate for killer T-cells, then it would go to the next person and have to start all over again, because the fragments for that person would be different.”
There’s much still to learn about T-cell responses to Covid, but early research has been promising.
In a study published Jan. 23 in the journal Cell, Sette and his colleagues at the La Jolla Institute found that the Covid-19 vaccines made by Pfizer-BioNTech, Moderna, Johnson & Johnson and Novavax prompt the body to make effective T-cells against the coronavirus. The researchers also found that T-cells can recognize all the known variants of concern, including omicron.
What still remains to be seen, however, is how strong the protection will remain over time and what effect different combinations of infection and vaccinations will have on the immune system.
Tafesse and his colleagues at Oregon Health & Science University are trying to answer some of those questions. In a study published Jan. 25 in the journal Science Immunology, the researchers followed 104 employees at the university who received two doses of the Pfizer-BioNTech vaccine. Of those, 42 were vaccinated with no infections, 31 were vaccinated after infections, and 31 recovered from infections following vaccination.
The scientists observed that people who recovered from infections and were subsequently vaccinated and those who were infected despite being vaccinated had developed heightened levels of immunity compared to people who were vaccinated and had never tested positive for the virus.
“There was an up to tenfold — and sometimes up to twentyfold — increase in antibody levels compared to vaccine-only groups,” Tafesse said.
The study was conducted before the emergence of the highly contagious omicron variant, but Tafesse said he expects the “super immunity” to hold true through the current wave.
The omicron variant’s ability to evade some protective antibodies meant that more vaccinated people were infected in this wave than at any other time in the pandemic. But the vast majority of those cases were mild, particularly for those who had also received booster shots.
Tafesse said the results of the study shouldn’t be misinterpreted to suggest that people should risk exposing themselves to the virus to gain better immunity. Rather, he said, the findings show how important the vaccines are to reduce the severity of illness if someone does become infected, which, in turn, offers a path to emerge from the pandemic.
If wide swaths of the population are protected by the vaccines and others have built up heightened immunity from a combination of vaccination and infection, then perhaps the ensuing waves might not be so devastating, Tafesse said.
“Even if the next variant comes along, we may end up having milder cases, there’ll be less virus in the communities, and the spikes and waves will get smaller and smaller,” he said.
Yet, that rosy scenario can play out only once infections subside, said Dr. Stuart Ray, a professor of medicine at Johns Hopkins University. If left to spread unchecked, the virus will have more opportunities to mutate, which risks the emergence of yet another variant.
Some countries, including the U.S., have already reported cases of an omicron subvariant, known as BA.2, that may be even more contagious than its predecessor. The prospect of a new variant popping up that can evade the Covid immunity that has been built up so far is a situation that scientists aren’t eager to study.
“Everybody’s thinking: Well, now that we’ve had so much omicron, maybe we’re going to be set for something like herd immunity,” Ray said. “That only works if the virus doesn’t get around that immunity.”