Researchers from La Jolla Institute for Immunology (LJI), The University of Liverpool and the University of Southampton have discovered that the degree of COVID severity appears to be linked to how long-lasting and strong the subsequent immunity is.
“The data from this study suggest people with severe COVID-19 cases may have stronger long-term immunity,” said study co-leader LJI Professor Pandurangan Vijayanand, MD, PhD.
The research examines T-cells from COVID infections in unprecedently high detail.
“This study highlights the enormous variability in how human beings react to a viral challenge,” added co-leader Christian Ottensmeier, MD, PhD, FRCP, a professor at the University of Liverpool and adjunct professor at LJI.
Vijayanand and Ottensmeier have been studying how antibodies and the different subsets of T-cells control COVID disease severity. In this study, they examined CD8+ T-cells, which are the T-cells responsible for destroying virus-infected cells, and “memory” CD8+ T-cells are also important for guarding the body against reinfections of the same virus. These memory T-cells are poised to rapidly proliferate and engage their cell-destroying functions on subsequent antigen encounters. They can reside in peripheral organs and their memory can also be shaped by infection history.
Utilising a new technique called single-cell transcriptomics analysis, they were able to study expressions of individual genes of 80 000 CD8+ T-cells drawn from 39 COVID patients and from 10 non-exposed donors, whose blood samples had been taken before the pandemic. Of the COVID patients, 17 cases were mild and non-hospitalised, 13 were hospitalised and 9 had required ICU care.
Surprisingly, the researchers found that the strongest CD8+ T-cell responses were from those with the more severe form of the disease, and not the milder cases.”There is an inverse link between how poorly T cells work and how bad the infection is,” observed Ottensmeier. “I think that was quite unexpected.” A stronger response would be expected from CD8+ T-cells in mild cases due to having the resources of a better functioning immune system. However, the mild group of CD8+ T-cells showed signs of “exhaustion”, which happens when the immune system overloads the T-cells, causing them to lose effectiveness.
The researchers believe that it will be beneficial to study whether this phenomenon may hinder the ability to build long-term immunity.
“People who have severe disease are likely to end up with a good number of memory cells,” said Vijayanand. “People with milder disease have memory cells, but they seem exhausted and dysfunctional—so they might not be effective for long enough.
“What the researchers would like to look at next is to look at T-cells from lung tissue as opposed to blood samples, because that is where the infection hits hardest.
“This study is very much a first step in understanding the spectrum of immune responses against infectious agents,” said Ottensmeier. The researchers will also look at T-cells in cancer patients who are also infected with COVID.
Source: Medical Xpress
Journal information: Anthony Kusnadi et al, Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8+ T cells, Science Immunology 21 Jan 2021: Vol. 6, Issue 55, eabe4782 DOI: 10.1126/sciimmunol.abe4782
