T Cells a More Precise Immune Indicator in COVID-19?

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Immune system memory T-cell levels accurately corresponded with SARS-CoV-2 severity in the first study to evaluate a wide range of responses, from persons who were healthy to those who were severely ill. The researchers also evaluated responses of exposed family members.

Furthermore, the T-cell response persisted in convalescent COVID-19 patients, suggesting that such responses offer a more precise measure of potential long-term immune protection compared with antibody assays.

“The most important [take-home message] is that CoV-2 generates in most individuals a strong and very typical memory T-cell response against a respiratory viral infection,” study author Marcus Buggert, PhD, of the Center for Infectious Medicine in the Department of Medicine Huddinge at the Karolinska Institute in Stockholm, Sweden, told Medscape Medical News.

“We speculate that this type of response should provide some type of protection from recurrent episodes of severe COVID-19,” he said.

The study was published online August 14 in Cell.

Measuring memory T cells could help to identify people with asymptomatic or mild COVID-19 illness “who likely act inadvertently as the major transmitters,” the researchers note.

Furthermore, many study participants exhibited a robust memory T-cell response for months even in the absence of circulating antibodies. This finding suggests a longer window for detecting an immune response. In contrast, the ideal time to detect antibodies to SARS-CoV-2 appears to be 3 to 4 weeks post exposure, as previously reported.

Buggert’s and colleagues’ cross-sectional study, which involved 206 people, focused in particular on SARS-CoV-2–specific CD4+ and CD8+ T cells.

The study included 17 people with acute severe COVID-19 and 11 others with acute moderate disease. The 66 convalescent participants included 26 who had recovered from severe COVID-19 and 40 who had had mild illness.

The investigators measured immune response in 30 family members exposed to patients with mild or severe COVID-19. They also assessed T cells and other immune components from 55 people who donated blood during the pandemic and from 28 other blood donors from 2019.

Measuring Immunity to a T

The investigators measured T-cell responses to three specific SARS-CoV-2 proteins — one internal, one on the spike of the virus, and another on the cell membrane. The proportion of each cohort of patients who demonstrated a response to these proteins correlated with clinical severity or exposure to the virus.

For example, 100% of participants who were convalescing after having had severe COVID-19 showed “robust” T-cell responses to any of these proteins, as did 87% of those who were convalescing after mild illness, 67% of exposed family members, and 46% of healthy individuals who donated blood during the pandemic.

Furthermore, 99% of the participants who tested positive for antibodies also demonstrated SARS-CoV-2–specific CD4+ and CD8+ T-cell responses. Among those without measurable antibodies, 41% demonstrated T-cell responses to the virus.

Clinical Implications

When asked whether he was surprised by the results, Buggert said, “Yes and no. At first glance, it was surprising. However, we know that antibodies typically wane with time and in some people with milder symptoms, [they wane] to undetectable levels fairly rapidly.”

He added that the “data made sense,” because immune cells with a memory – such as B and T cells – “can persist for many years after an infection.”

Limitations of the study include its cross-sectional design and limited 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,” the researchers note.

They add, “none of the convalescent individuals in this study, including those with previous mild disease, have experienced further episodes of COVID-19.”

Answering ‘an Important Question’

“The study is very well done and has garnered a lot of interest because it dives into the details of T-cell and antibody responses across the whole range of disease severity,” Alessandro Sette, PhD, told Medscape Medical News when asked to comment.

The findings, he added, are “starting to provide answers to an important question: Do individuals with mild or asymptomatic manifestations of COVID-19 generate T-cell and antibody responses?”

It was interesting, Sette said, that some participants demonstrated T-cell responses despite a lack of detectable antibodies. “The study also confirmed that some unexposed people have cross-reactive T-cell memory to SARS2, which several studies, including ours, had shown before.” He was lead author of a May 14, 2020 study that also evaluated T-cell responses in convalescent and unexposed individuals.

Broader and more in-depth studies are needed, said Sette, of the La Jolla Institute for Immunology, in La Jolla, California.

Goals include determining how frequently people mount T-cell immune responses without detectable antibody responses, how to distinguish those T cells from preexisting T cells against common cold coronaviruses, and the level of protection against future infection, if any, that these T cells provide, he said.

Pointing to Viral Protection

These are “nice and important data showing that not only COVID-19–recovered but also asymptomatic [people] can elicit a SARS-CoV-2 T-cell response,” Antonio Bertoletti, MD, who was also unaffiliated with the current research, told Medscape Medical News.

“It is clear that at the moment we still don’t know what is the level of antibodies and T cells that can provide protection,” said Bertoletti, who is affiliated with the Emerging Infectious Diseases Program at Duke-NUS Medical School in Singapore and is the lead author of a recent study on SARS-CoV-2–specific T-cell immunity.

“It is important to show that every single subject infected by SARS-CoV-2, irrespective of their symptoms, can elicit a virus-specific T-cell response that can, if not protect from reinfection, likely contain the spread of the virus within the infected host,” he added.

Buggert, Sette, and Bertoletti have disclosed no relevant financial relationships.

Cell. Published online August 14, 2020. Abstract

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