In late 2021, as the omicron
variant of SARS-CoV-2 spread over the globe, it was clear that the pandemic had
entered a new phase. Having experienced a previous COVID-19 infection or being
vaccinated still left many people wondering how vulnerable they were to the
virus.
As of late February 2022, 4.9 billion people – or 63.9 % of the
world's population – had gotten at least one dose of the COVID-19 vaccine. And
more than 430 million cases of COVID-19 have been confirmed since the start of
the pandemic.
With the majority of the world's population either immunized
against COVID-19 or recovering from an infection, the question has arisen as to
how long the immunity triggered by vaccination, active infection, or a
combination of both will provide immune protection.
Because the virus is still relatively new, new variations are
continuously developing; this is a complex question. Researchers are
discovering more about how existing immunity protects against reinfection and
the onset of severe COVID-19, resulting in hospitalization and death.
We are interested in understanding the nature of such protective
immunity as immunologists studying inflammatory and infectious diseases,
including COVID-19.
The role of antibodies and 'killer' T cells
Your body produces two types of protective immune responses in
response to COVID-19 vaccination or infection. B cells are the first type, and
they produce antibodies.
Antibodies are Y-shaped proteins that serve as the body's first
line of defense against infection or a perceived invader, such as a vaccine.
Antibodies can directly bind to a virus – or the spike protein of COVID-19 in
the case of mRNA vaccines – and prevent it from entering the cells, similar to
a lock and key. On the other hand, antibiotics are no longer effective once a
virus has effectively entered the cells. Infected cells begin replicating the
virus, which then spreads to other cells.
This is when the immune system calls another type of immune cell
known as killer T cells, which act as the second line of defense.
Unlike antibodies, killer T cells cannot directly "see"
the virus and thus cannot prevent a virus from entering cells. On the other
hand, Killer T cells may recognize a virus-infected cell and destroy it before
the virus has a chance to replicate. Killer T cells can help stop a virus from
multiplying and spreading in this way.
Throughout the COVID-19 pandemic, the general public has
mistakenly believed that antibodies provide the bulk of protective immunity,
ignoring the essential importance of killer T cells. This is partly because
antibodies are easy to detect, whereas killer T-cell detection is complex and
involves advanced technology. Killer T cells prevent more severe COVID-19
outcomes, such as hospitalization and death when antibodies fail.
Memory is key to long-term protective immunity.
Then there are the immune system's real veterans, who may provide
long-lasting and strong immunity against an infection based on previous
experience.
The antibody-producing B cells and killer T cells are converted
into memory cells when they have finished clearing the infection or the virus's
spike protein. When these cells encounter the same protein from the virus, they
recognize the threat immediately and mount a robust response that helps prevent
infection.
This explains why multiple doses of COVID-19 vaccines that
increase the number of memory B cells prevent reinfection – or breakthrough
infections – are better when compared with a single dose. A similar increase in
memory killer T cells prevents hospitalization and severe disease.
Memory cells can live for a long time in the immune system,
perhaps up to 75 years. This explains why people develop lifelong protective
immunity in some cases, such as after measles vaccination or smallpox
infection.
The trick, however, is that memory cells are particular. Memory
cells may not be as effective if new strains or variants of a virus emerge, as
has happened many times during the COVID-19 pandemic.
This begs the question: When do these various immune system key
players appear following an infection, and how long do they last?
Duration and longevity of immunity against COVID-19
Antibodies begin mobilizing within the first few days following
infection with COVID-19 or after receiving the vaccine. They steadily increase
in concentration for weeks and months after that. People develop a robust
antibody response three months after infection. This is why the CDC has long
maintained that people who have had a confirmed COVID-19 infection within the
last 90 days do not need to quarantine when they come into contact with someone
who has COVID-19.
But by about six months, antibodies start declining. This is what
led researchers to discover "waning immunity" in the fall of 2021,
months after many people had been fully vaccinated.
On the other hand, immunity is far more nuanced and complex, and
antibodies only tell part of the story. Some B cells live for a long time and
develop antibodies against a virus. For this reason, antibodies against
SARS-CoV-2 have been detected even a year after infection. Following COVID-19
illness, memory B cells can be found for at least eight months, while memory
killer T cells can be detected for nearly two years.
Vaccines, in general, have been shown to generate an immune memory
similar to that of a natural illness. Despite this, a recent study that has not
yet been peer-reviewed found that a third dose of vaccine boosts memory B cell
diversity, resulting in improved protection even against variants like omicron.
On the other hand, long-term studies of the comparison are not yet available.
But the mere detection of an immune response does not translate to
complete protection against COVID-19.
It's challenging to match the levels of antibodies precisely and
killer T cells with the degree of protection they offer based on the short
amount of time and research that researchers like us have had to study
COVID-19.
While it is becoming clear that some immune responses to COVID-19
can be found for more than a year after infection, the levels of protection may
not be enough to prevent reinfection.
Immunity from vaccination versus infection
One recent study from the U.K. Health Security Agency showed that
protection against infection from two doses of vaccine might last for six
months. Another study found that while mRNA vaccines were highly protective at
two months, their effectiveness decreased by seven months, partly due to the
emergence of the delta variation. Vaccines were better at reducing
hospitalization and mortality in both studies than they were at preventing
infection over time.
There are contradictory reports on whether the protective immunity
triggered following an active infection is better than that induced by the
current vaccines. This may have resulted from the emergence of different virus
variants during the study.
However, as shown in a recent study that has not yet been
peer-reviewed, COVID-19 infection can provide protection comparable to that
offered by vaccines.
Hybrid immunity
Researchers also found that the protective immunity acquired from
a COVID-19 infection followed by vaccination – known as mixed immunity – is
highly potent and seems to last for more than a year after infection with
COVID-19.
Interestingly, hybrid immunity triggers a robust antibody response
over an extended period.
Such studies show how important it is for even people who have
been previously infected with COVID-19 to get vaccinated to ensure the most
robust protection against COVID-19.
Immunologists are now researching how to develop vaccines that can trigger a similar sustained long-term antibody response to prevent reinfections, based on the growing knowledge that both vaccines and active infections can trigger a strong and sustained killer T cell response that protects against hospitalization and death. Hybrid immunity from being vaccinated and having experienced COVID-19 disease may offer valuable clues.