Oxford Led Study Shows That Most Fatal COVID-19 Cases Are Due To Weak Immune Responses And Elevated MAIT Cell Activation
Source: COVID-19 Mortality Sep 20, 2021 3 years, 2 months, 3 days, 1 hour, 16 minutes ago
COVID-19 Mortality: A new research led by scientist from Oxford University-UK that also involved researchers from St. George’s University of London-UK, St. George’s Hospital NHS Trust-UK and the Massachusetts Institute of Technology-USA has found that most fatal COVID-19 cases are due to weak immune responses and elevated MAIT(elevated mucosal associated invariant) cell activation.
.jpg)
The study team examined the immune abnormalities linked to critical illness and death in COVID-19 patients on ICU, performing immunophenotyping of viral antigen-specific and unconventional T cell responses, together with studies of neutralizing antibodies, and serum proteins.
The team compared these findings to a parallel set of patients with severe influenza.
Importantly From this screen the study team identified mucosal-associated invariant T (MAIT) cell activation as an independent and significant predictor of death in COVID-19. MAIT cell activation correlated with several other mortality-associated immunologic measures including elevated levels of cytokines and chemokines, such as GM-CSF and CXCL10.
MAIT cell activation is also a predictor of disease severity in influenza. Single-cell RNA-sequencing revealed a shift from focused IFNα-driven signals in COVID-19 ICU patients who survive to broad pro-inflammatory responses in fatal COVID-19 –a feature not observed in severe influenza.
Overall the study team observed key potential biomarkers and targetable pathways in critical viral illness, many shared between influenza and COVID-19 and some unique to each infection.
The study findings were published in the peer reviewed journal: PLOS Pathogens.
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009804
To date it has been found that the mortality rate of COVID-19 patients requiring mechanical ventilation is 30-40%, however, the immunological factors associated with death in critically ill COVID-19 patients are poorly understood.
The study findings suggest an association between systemic inflammation responses and increased mortality of COVID-19 patients.
Although antibodies and T cells play a critical role in protection from viral illness, however the exact role of T cell and antibody responses in SARS-CoV-2 infection is unclear.
In order to better understand the immune abnormalities linked to critical illness and death in COVID-19 patients on ICU, the study team conducted a prospective observational study investigating the association of T cell and antibody responses with fatal outcome in severe COVID-19.
The team analyzed serum samples from 41 mechanically ventilated COVID-19 patients, performing immunophenotyping of T cell responses and a range of experiments analyzing antibody responses. They then compared their findings to a parallel set of 18 mechanically ventilated influenza patients, as well as to 12 mild COVID-19 patients and 12 healthy controls.
The study team found that fatal COVID-19 infections were correlated with poorly coordinated systemic immune responses and elevated mucosal associated invariant (MAIT) cell activation were the strongest predict
or of a fatal outcome.
Mucosal associated invariant T cells (MAIT cells) make up a subset of T cells in the immune system that display innate, effector-like qualities. In humans, MAIT cells are found in the blood, liver, lungs, and mucosa, defending against microbial activity and infection. The MHC class I-like protein, MR1, is responsible for presenting bacterially-produced vitamin B2 and B9 metabolites to MAIT cells. After the presentation of foreign antigen by MR1, MAIT cells secrete pro-inflammatory cytokines and are capable of lysing bacterially-infected cells. MAIT cells can also be activated through MR1-independent signaling. In addition to possessing innate-like functions, this T cell subset supports the adaptive immune response and has a memory-like phenotype. Furthermore, MAIT cells are thought to play a role in autoimmune diseases, such as multiple sclerosis, arthritis and inflammatory bowel disease.
The
COVID-19 Mortality study was however limited in that it only analyzed samples in a cross sectional manner and did not observe how immune responses changed over the course of the infection.
More detailed future studies are needed to explain in depth how mortality-associated immune characteristics may develop over time.
Lead author Dr Jonathan Youngs from the Institute for Infection & Immunity, St. George’s University of London told Thailand Medical News, "Our study findings yield an enhanced understanding of the differential immunopathogenic processes driving critical COVID-19 and influenza, which can translate into improved immunotherapeutic approaches in patients with severe viral pneumonitis."
He further added, "In critically ill patients on ICU with COVID-19 and influenza, an unbiased analysis of the antiviral immune response revealed activation of a specific immune subset: Mucosal-associated invariant T (MAIT) cells as a strong immunological predictor of death. Survival in critical COVID-19 is associated with focused immune responses driven mainly by one cytokine ie interferon alpha in contrast to the very broad pro-inflammatory responses seen in those with fatal disease. This cytokine pattern linked to death versus survival separates critical COVID-19 from influenza."
For more about
COVID-19 Mortality, keep on logging to Thailand Medical News.
