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Immunity to COVID-19 may be higher than tests have shown — Karolinska Institutet

Research from Karolinska Institutet and Karolinska University Hospital shows that many people with mild or asymptomatic COVID-19 demonstrate so-called T-cell-mediated immunity to the new coronavirus, even if they have not tested positively for antibodies. According to the researchers, this means that public immunity is probably higher than antibody tests suggest. The research has been submitted for publication in a scientific journal.

“T cells are a type of white blood cells that are specialised in recognising virus-infected cells, and are an essential part of the immune system,” says Marcus Buggert, assistant professor at the Centre for Infectious Medicine, Karolinska Institutet, and one of the paper’s main authors. “Advanced analyses have now enabled us to map in detail the T-cell response during and after a COVID-19 infection. Our results indicate that roughly twice as many people have developed T-cell immunity compared with those who we can detect antibodies in.”

In the present study, the researchers performed immunological analyses of samples from over 200 people, many of whom had mild or no symptoms of COVID-19. The study included inpatients at Karolinska University Hospital and other patients and their exposed asymptomatic family members who returned to Stockholm after holidaying in the Alps in March. Healthy blood donors who gave blood during 2020 and 2019 (control group) were also included.

Consultant Soo Aleman and her colleagues at Karolinska University Hospital’s infection clinic have monitored and tested patients and their families since the disease period. “One interesting observation was that it wasn’t just individuals with verified COVID-19 who showed T-cell immunity but also many of their exposed asymptomatic family members,” says Soo Aleman. “Moreover, roughly 30 per cent of the blood donors who’d given blood in May 2020 had COVID-19-specific T cells, a figure that’s much higher than previous antibody tests have shown.”

The T-cell response was consistent with measurements taken after vaccination with approved vaccines for other viruses. Patients with severe COVID-19 often developed a strong T-cell response and an antibody response; in those with milder symptoms it was not always possible to detect an antibody response, but despite this many still showed a marked T-cell response.

“Our results indicate that public immunity to COVID-19 is probably significantly higher than antibody tests have suggested,” says Professor Hans-Gustaf Ljunggren at the Centre for Infectious Medicine, Karolinska Institutet, and co-senior author. “If this is the case, it is of course very good news from a public health perspective.”

T-cell analyses are more complicated to perform than antibody tests and at present are therefore only done in specialised laboratories, such as that at the Centre for Infectious Medicine at Karolinska Institutet.

“Larger and more longitudinal studies must now be done on both T cells and antibodies to understand how long-lasting the immunity is and how these different components of COVID-19 immunity are related,” says Marcus Buggert.

The study was financed by the Knut and Alice Wallenberg Foundation, Nordstjernan AB, the Swedish Research Council, Karolinska Institutet, the Swedish Society for Medical Research, the Jeansson Foundations, the Åke Wiberg Foundation, the Swedish Society of Medicine, the Swedish Cancer Society, the Swedish Childhood Cancer Foundation, the Magnus Bergvall Foundation, the Hedlund Foundation, the Lars Hierta Foundation, the Swedish Physicians against AIDS foundation, the Jonas Söderquist Foundation, the Clas Groschinsky Memorial Foundation, and the Wellcome Trust.

The authors report no conflicts of interest or patents associated with the results of the study.

Abstract
SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. We systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in a large cohort of unexposed individuals as well as exposed family members and individuals with acute or convalescent COVID-19. Acute phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative family members and individuals with a history of asymptomatic or mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits robust memory T cell responses akin to those observed in the context of successful vaccines, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19 also in seronegative individuals.

Authors
Takuya Sekine, André Perez-Potti, Olga Rivera-Ballesteros, Jean-Baptiste Gorin, Annika Olsson, Habiba Kamal, Sian Llewellyn-Lacey, David Wulliman, Tobias Kamann, Gordana Bogdanovic, Sandra Muschiol, Elin Folkesson, Olav Rooyackers, Lars I Eriksson, Anders Sönnerborg, Tobias Allander, Jan Albert, Morten Nielsen, Kristoffer Strålin, Sara Gredmark-Russ, Niklas K Björkström, Johan K Sandberg, David A Price, Hans-Gustaf Ljunggren, Soo Aleman, Marcus Buggert, Karolinska COVID-19 Study Group

[link url="https://news.ki.se/immunity-to-covid-19-is-probably-higher-than-tests-have-shown?_ga=2.251817039.772117132.1593776425-506776609.1593776425"]Karolinska Institutet material[/link]
[link url="https://www.biorxiv.org/content/10.1101/2020.06.29.174888v1"]bioRxiv abstract[/link]

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