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. A study published in PLOS Pathogens by Jonathan Youngs at St. George’s University of London, United Kingdom and colleagues suggests an association between systemic inflammation responses and increased mortality of COVID-19 patients.
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. To better understand the immune abnormalities linked to critical illness and death in COVID-19 patients on ICU, researchers conducted a prospective observational study investigating the association of T cell and antibody responses with fatal outcome in severe COVID-19. They 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 researchers 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 predictor of a fatal outcome. However, the study was 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. Future studies are needed to explain in depth how mortality-associated immune characteristics may develop over time.
According to the authors, “Our study yields 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.”
“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,” the authors add. “Survival in critical COVID-19 is associated with focused immune responses driven mainly by one cytokine - 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.”
In your coverage please use this URL to provide access to the freely available article in PLOS Pathogens: http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009804
Citation: Youngs J, Provine NM, Lim N, Sharpe HR, Amini A, Chen Y-L, et al. (2021) Identification of immune correlates of fatal outcomes in critically ill COVID-19 patients. PLoS Pathog 17(9): e1009804. https://doi.org/10.1371/journal.ppat.1009804
Funding: A.A. is supported by a Wellcome Clinical Training Fellowship [216417/Z/19/Z]. H.R.S. is supported by a Wellcome four-year PhD studentship through the IITM Programme [203805/Z/16/Z]. O.S. is supported by a Wellcome four-year PhD studentship through the IITM Programme [108869/Z/15/Z]. D.T.S. is supported by the NIHR Academic Clinical Fellow programme in Oxford. E.B. is supported through the UK Coronavirus Immunology Consortium (UK-CIC; https://www.uk-cic.org), an NIHR Senior Fellowship (https://www.nihr.ac.uk), the NIHR Biomedical Research Centre (Oxford; oxfordbrc.nihr.ac.uk). S.D. is supported by an NIHR Global Research Professorship (nihr.ac.uk). P.K. has support from the Wellcome [WT109965MA], the UK Coronavirus Immunology Consortium (UK-CIC; https://www.uk-cic.org), the NIHR Biomedical Research Centre (Oxford; https://www.oxfordbrc.nihr.ac.uk) and NIHR (UKRIDHSC COVID-19 Rapid Response Rolling Call, Grant Reference Number COV19-RECPLAS. The Healthcare worker cohort at University of Oxford was supported by the UK Department of Health and Social Care as part of the PITCH (Protective Immunity from T cells to Covid-19 in Health workers) Consortium (https://www.pitch-study.org), the UK Coronavirus Immunology Consortium (UK-CIC; https://www.uk-cic.org), the Huo Family Foundation (https://www.huofamilyfoundation.org), and the National Core Study: Immunity (NCSi4P programme) “Optimal cellular assays for SARS-CoV-2 T cell, B cell and innate immunity” (https://www.hdruk.ac.uk/covid-19/covid-19-national-core-studies/). J.Y. and T.B. are supported by the AspiFlu study, funded through a Gilead UK and Ireland Fellowship (Grant ID 07512). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Competing interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests:WH reports lecture fees from Gilead.