180 CMAAO CORONA FACTS and MYTH RTPCR
Dr K Aggarwal
With inputs from Dr Monica Vasudev
New York Times: A flurry of recent studies has revealed that a large proportion of the population — in some places, 20 to 50 percent of people — might harbor immunity assassins called T cells that recognize the new coronavirus despite having never encountered it before. It’s too early to tell how helpful they might be, but even a modest influence on immune response could make the disease milder.
Eight months ago, the new coronavirus was unknown. But to some human immune cells, it was already something of a familiar foe.
These T cells, which lurked in the bloodstreams of people long before the pandemic began, are most likely stragglers from past scuffles with other related coronaviruses, including four that frequently cause common colds. It’s a case of family resemblance: In the eyes of the immune system, germs with common roots can look alike, such that when a cousin comes to call, the body may already have an inkling of its intentions.
The presence of these T cells has intrigued experts, who say it is too soon to tell whether the cells will play a helpful, harmful or entirely negligible role against the current coronavirus.
But should these cross-reactive T cells exert even a modest influence on the body’s immune response, they might make the disease milder — and perhaps partly explain why some people who catch the germ become very sick while others are dealt only a glancing blow.
SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls
• Nina Le Bert, Anthony T. Tan, Kamini Kunasegaran et al: Nature (2020)
Memory T cells induced by previous pathogens can shape the susceptibility to, and clinical severity of, subsequent infections.
Little is known about the presence of pre-existing memory T cells in humans with the potential to recognize SARS-CoV-2.
Here, we first studied T cell responses to structural (nucleocapsid protein, NP) and non-structural (NSP-7 and NSP13 of ORF1) regions of SARS-CoV-2 in COVID-19 convalescents (n=36).
In all of them we demonstrated the presence of CD4 and CD8 T cells recognizing multiple regions of the NP protein.
We then showed that SARS-recovered patients (n=23) still possess long-lasting memory T cells reactive to SARS-NP 17 years after the 2003 outbreak, which displayed robust cross-reactivity to SARS-CoV-2 NP.
Surprisingly, we also frequently detected SARS-CoV-2 specific T cells in individuals with no history of SARS, COVID-19 or contact with SARS/COVID-19 patients (n=37).
SARS-CoV-2 T cells in uninfected donors exhibited a different pattern of immunodominance, frequently targeting the ORF-1-coded proteins NSP7 and 13 as well as the NP structural protein.
Epitope characterization of NSP7-specific T cells showed recognition of protein fragments with low homology to “common cold” human coronaviruses but conserved amongst animal betacoranaviruses.
Thus, infection with betacoronaviruses induces multispecific and long-lasting T cell immunity to the structural protein NP.
Understanding how pre-existing NP- and ORF-1-specific T cells present in the general population impact susceptibility and pathogenesis of SARS-CoV-2 infection is of paramount importance for the management of the current COVID-19 pandemic.