Study shows major differences in mild versus severe COVID-19 infection

These days, a crucial question on people’s minds is how long does SARS-CoV-2 immunity last after infection?

Severely ill patients who required hospitalization or ICU support had the strongest T cell responses. Image Credit: La Jolla Institute for Immunology.

A team of researchers from the La Jolla Institute for Immunology (LJI), The University of Liverpool, and the University of Southampton has now revealed an exciting clue. According to their new study, patients who have severe COVID-19 infection could have more numbers of the protective “memory” T cells required to combat reinfection.

The data from this study suggest people with severe COVID-19 cases may have stronger long-term immunity.”

Pandurangan Vijayanand, MD, PhD, Study Co-Leader and Professor, La Jolla Institute for Immunology

Published in the Science Immunology journal on January 22^nd, 2021, the study is the first to explain the T cells that combat the SARS-CoV-2 virus in “high resolution” detail.

This study highlights the enormous variability in how human beings react to a viral challenge.”

Christian H Ottensmeier, MD, PhD, FRCP, Study Co-Leader and Professor, University of Liverpool

Dr Ottensmeier is also an adjunct professor at La Jolla Institute for Immunology.

Ever since the initial stages of the COVID-19 pandemic, the LJI team has studied which T cells and antibodies are crucial for combating SARS-CoV-2. Vijayanand and Ottensmeier, who are both experts in genomics, have employed sequencing tools to reveal the types of T cell subsets that may regulate severity of the disease. Then in October, the researchers published the first comprehensive study of how CD4+ T cells react to the SARS-CoV-2 virus.

In the latest study, the team employed a method known as single-cell transcriptomics analysis to examine the expression of individual gene of over 80,000 CD8+ T cells obtained from both non-exposed donors and COVID-19 patients.

CD8+ T cells are essentially the cells that are responsible for killing virus-infected host cells. Also, “memory” CD8+ T cells are significant for protecting the body from reinfection against several viruses.

The researchers analyzed CD8+ T cells from a total of 39 COVID-19 patients as well as 10 subjects who were never been subjected to the virus (their blood samples were collected prior to the pandemic). Among the COVID-19 patients, 17 individuals had a milder case that did not warrant hospitalization, 13 individuals were hospitalized, and 9 others needed more ICU support.

To their amazement, the researchers observed weaker CD8+ T cell responses in patients who had milder cases of COVID-19 infection. They also observed the strongest CD8+ T cell responses in the extremely ill patients who needed ICU support or hospitalization.

There is an inverse link between how poorly T cells work and how bad the infection is. I think that was quite unexpected.”

Christian H Ottensmeier, MD, PhD, FRCP, Study Co-Leader and Professor, University of Liverpool

In the mild cases, one may expect to observe a stronger CD8+ T cell response because these are the cases where the immune system had the ability to combat serious infections; however, the study showed the reverse.

As a matter of fact, in milder cases, CD8+ T cells exhibited the molecular signs of a phenomenon known as T cell “exhaustion.” In the cases of the exhaustion of T cells, cells receive extreme immune system stimulation during a viral attack such that they become less effective in performing their tasks.

Although more studies are required, Vijayanand and Ottensmeier believe that it is worth investigating whether T cell exhaustion in the case of mild COVID-19 infection may suppress an individual’s capability to build long-term immunity.

According to Vijayanand, “People who have the severe disease are likely to end up with a good number of memory cells. People with milder disease have memory cells, but they seem exhausted and dysfunctional—so they might not be effective for long enough.”

The latest study offers a valuable window into CD8+ T cell responses; however, it is still restricted because it depends on the CD8+ T cells present in blood samples. As a subsequent step, the team hopes to shed new light on how T cells in tissues hit hardest by the SARS-CoV-2 virus, for example, the lungs, respond to the pathogen. Such a step will be significant because the memory T cells that offer long-term immunity had to survive in the tissues.

Ottensmeier added, “This study is very much a first step in understanding the spectrum of immune responses against infectious agents.”

In the future, the team is hoping to use single-cell sequencing methods to observe CD8+ T cells in cancer patients infected with COVID-19.

“This research highlights the power of these new tools to understand human immunology,” Vijayanand concluded.