A new study suggests that T cells might provide individuals who had a mild or asymptomatic case of COVID-19 with lasting immunity against future infection, even if their blood contains no neutralizing antibodies.
Most people who are exposed to SARS-CoV-2, the coronavirus that causes COVID-19, only experience mild symptoms or none at all.
However, the infection can still pass from them to other people, and the overall case fatality rate appears to be converging on 0.5–1.0%.
It is, therefore, important to establish whether individuals who have contracted the virus once can contract it again and become contagious, or whether they are immune to future infection.
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“In the absence of a protective vaccine, it is critical to determine if exposed or infected people, especially those with asymptomatic or very mild forms of the disease who likely act inadvertently as the major transmitters, develop robust adaptive immune responses against SARS-CoV-2,” says Marcus Buggert, an immunologist at the Karolinska Institutet in Solna, Sweden.
Research suggests that not all individuals who have contracted SARS-CoV-2 in the past produce antibodies capable of neutralizing the virus, particularly if they only experienced a mild infection.
Studies have also found that immune cells known as memory B cells, which produce antibodies against previously encountered infections, tend to be short-lived after infection with the closely related coronavirus SARS-CoV, which causes severe acute respiratory syndrome (SARS).
In contrast, another type of immune cell called a memory T cell, which can recognize a previously encountered pathogen and initiate an immune response to it, may persist for years after the initial infection.
In a new study, memory T cells protected against SARS-CoV-2 infection, even in the absence of antibodies against the virus.
The new research features in the journal Cell.
Five categories of exposure
In the new research, Buggert and his colleagues investigated the immune status of 206 individuals in Sweden, where measures to control the spread of SARS-CoV-2 have been less strict than in other European countries.
Their participants fell into five categories:
- people with ongoing moderate or severe COVID-19
- individuals convalescing after a mild or severe infection
- asymptomatic family members exposed to the infection
- healthy individuals who donated blood during the pandemic
- healthy individuals who donated blood in 2019, before the pandemic
As expected, the team found strong memory T-cell responses and high levels of antibodies specific to the virus in all 23 people who had recovered from severe COVID-19.
More surprisingly, 30 of the 31 people who recovered from a mild infection had memory T-cell responses to the virus, and 27 had antibodies against it.
Out of 28 family members exposed to an infected individual, 26 were able to mount T-cell responses to the virus, and 17 had antibodies against it.
Even after a very mild infection, memory T-cell responses were often detectable months later, sometimes even in the absence of SARS-CoV-2 antibodies.
“Our findings suggest that the reliance on antibody responses may underestimate the extent of population-level immunity against SARS-CoV-2,” says Buggert, the senior author of the study. “The obvious next step is to determine whether robust memory T-cell responses in the absence of detectable antibodies can protect against COVID-19 in the long term.”
“Our collective dataset shows that SARS-CoV-2 elicits robust, broad, and highly functional memory T-cell responses, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19.”
– The study authors
General coronavirus immunity
Remarkably, in 28% of those who had donated blood samples in 2019, before the current pandemic, the researchers detected T cells that reacted to SARS-CoV-2. The researchers believe that this reflects immunity induced by exposure to other coronaviruses that have protein sequences in common with SARS-CoV-2.
They speculate that these responses may provide some protection against the new coronavirus, though direct evidence for this is currently lacking.
The authors acknowledge that their study was limited by the small numbers in each group and lack of clinical follow-up. “It, therefore, remains to be determined if robust memory T-cell responses in the absence of detectable circulating antibodies can protect against severe forms of COVID-19,” they write.
Thus far, however, none of the individuals in their study who recovered from the infection have experienced further episodes of COVID-19.
In addition, the authors cite research showing that rhesus macaques infected with SARS-CoV-2 develop almost complete immunity against future infections with the virus.
There are also no confirmed cases of humans who have had COVID-19 contracting the infection again at a later date.
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