Fighting the common cold may prepare the body for Covid-19

Researchers trace a source of immune "memory."

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In May, scientists curiously reported that up to half of people may possess a certain type of immune "memory" to Covid-19, without ever being exposed to the novel coronavirus.

This strange phenomenon, where people have T cells that recognize SARS-CoV-2 without previously encountering it, has been seen globally in cohorts in the United Kingdom, Netherlands, Germany, and Singapore.

Researchers have suspected this immune "memory" is linked to previously fighting the common cold, but it has been simply that — a suspicion.

In a recent study, published Tuesday in the journal Science, researchers report evidence supporting this connection.

Study of blood sampled from 25 people before the pandemic suggests that exposure to common cold viruses can induce immune "memory" and teach the immune system to recognize the Covid-19 virus. This discovery could explain, in part, why people have vastly different responses to the virus— some experiencing mild or asymptomatic courses of disease, while others experience devastating symptoms, and sometimes, death.

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"Our new study provided conclusive evidence that pre-existing immune memory can be induced by exposure to common cold viruses," study co-authors Alessandro Sette and Daniela Weiskopf, researchers at the La Jolla Institute for Immunology, tell Inverse. "SARS-CoV-2 is closely related to other human common cold coronaviruses that are widely circulating within human populations."

However, further studies are needed to determine if this immune "memory" translates to better clinical outcomes when it comes to Covid-19.

"While currently only an hypothesis, it is possible that if people already have T cells that recognize bits and piece of SARS-CoV-2 because they have been exposed to common cold viruses that contain bits and pieces that are nearly identical, their immune system could have a head start and develop a faster and stronger immune response," Sette and Weiskopf say. "They may be less likely to get Covid-19 or only develop milder symptoms."

Recognizing virus fragments— To trace the source of this "memory," researchers examined human blood samples that were collected from 25 healthy people before the Covid-19 virus was discovered in 2019.

Specifically, the team analyzed T cells within the samples. T cells are white blood cells that coordinate other immune cell and antibody responses as well as find and destroy infected cells in the body.

"T cells remember past infections, and also tend to hang around for decades," Sette and Weiskopf say. "People who had been infected during the SARS epidemic, another coronavirus, still have SARS-specific T cell activity 17 years later. These memory T cells can jump into action very quickly when needed again."

The team mapped 142 T cell epitopes across the viral genome. These are the spikes, ridges, and locations of the coronavirus which T cells might recognize and in turn, attack.

In these blood samples, researchers also discovered a range of existing T cells "trained" to remember four common cold coronaviruses: HCoV-OC43, HCoV-229E, HCoV-NL63, or HCoV-HKU1.

This isn't unexpected, because colds are indeed common. Adults have an estimated two to three colds every single year. Exposure to these colds taught T cells how to recognize the viruses.

What is surprising is that the team also found the a group of T cells that also recognized SARS-CoV-2 — the novel coronavirus these the people had never encountered. This indicates that fighting off a common cold primed T cells to fight Covid-19, inducing a type of immune "memory."

"The results of the study emphasize that T cells, the white blood cell type that orchestrates antibody responses and kills infected cells should be considered and measured both, in studies about Covid and the efficacy of vaccines," Sette and Weiskopf say.

While T cells can be more difficult to measure than antibodies, scientists pursuing effective treatments or vaccines should target T-cell "memory" in their research, they add.

But if, and how, this "memory" helps people fare better in the battle against Covid-19 remains to be seen.

"We are still missing an important piece: We don’t know whether these cross-reactive T cells indeed make a difference for disease severity or whether people with pre-existing immunity induce a stronger immune response," the researchers say. "That’s something everybody is very interested in right now."

Abstract: Many unknowns exist about human immune responses to the SARS-CoV-2 virus. SARS-CoV-2 reactive CD4+ T cells have been reported in unexposed individuals, suggesting pre-existing cross-reactive T cell memory in 20-50% of people. However, the source of those T cells has been speculative. Using human blood samples derived before the SARS-CoV-2 virus was discovered in 2019, we mapped 142 T cell epitopes across the SARS-CoV-2 genome to facilitate precise interrogation of the SARS-CoV-2-specific CD4+ T cell repertoire. We demonstrate a range of pre-existing memory CD4+ T cells that are cross-reactive with comparable affinity to SARS-CoV-2 and the common cold coronaviruses HCoV-OC43, HCoV-229E, HCoV-NL63, or HCoV-HKU1. Thus, variegated T cell memory to coronaviruses that cause the common cold may underlie at least some of the extensive heterogeneity observed in COVID-19 disease.

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