COVID-19: Evidence continues to mount on immunity in unexposed & seronegative individuals

In May, I wrote about a number of studies which showed T-cell reactivity to SARS-CoV-2 in individuals who were not previously exposed to the virus (eg in samples obtained in 2015). The past several weeks have seen mounting evidence from independent researchers bolstering the case that a substantial proportion of the population already possess some degree of immunity to SARS-CoV-2. Partly because of this, it’s also becoming increasingly clear that seroprevalence studies may be drastically underestimating the number of individuals who’ve been infected. As I’d mentioned, previous exposure to circulating coronaviruses that contribute to the common cold seems to be facilitating this nascent T-cell response.

If a person’s T-cells are reactive to SARS-CoV-2, they may not produce detectable antibodies, may have mild symptoms (or none at all), and might possess long-term protection against COVID-19. These are all big “ifs” right now, but a clearer picture of the population’s underlying susceptibility to COVID-19 is finally starting to emerge.

Two recently published studies bolster the case. From the abstract of a June 17 paper by Nelde et al.:

“SARS-CoV-2-specific T-cell epitopes enabled detection of post-infectious T-cell immunity, even in seronegative convalescents. Cross-reactive SARS-CoV-2 T-cell epitopes revealed preexisting T-cell responses in 81% of unexposed individuals, and validation of similarity to common cold human coronaviruses provided a functional basis for postulated heterologous immunity in SARS-CoV-2 infection. Intensity of T-cell responses and recognition rate of T-cell epitopes was significantly higher in the convalescent donors compared to unexposed individuals, suggesting that not only expansion, but also diversity spread of SARS-CoV-2 T-cell responses occur upon active infection. Whereas anti-SARS-CoV-2 antibody levels were associated with severity of symptoms in our SARS-CoV-2 donors, intensity of T-cell responses did not negatively affect COVID-19 severity.”

Meanwhile, from a group at Karolinska Institutet (from which I’ve previously taken a MOOC):

“Importantly, SARS-CoV2-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.”

An article with comments from the study authors is available here:

“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 Center 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.”