Altered immune signature linked to Long-Covid

University of Manchester scientists have discovered a persistent alteration in the immune system of patients, six months after they have been hospitalised for Covid-19, which could be associated with poorer health outcomes.

The study, published in the journal Med, examines the impact of a SARS-CoV-2 infection on the immune system of hospitalised patients in the period after a Covid-19 infection, once they have been discharged.

The team – based at the University’s Lydia Becker Institute of Immunology and Inflammation and supported by the UK Coronavirus Immunology Consortium (UK-CIC)- identified an immunological signature occurring in some of the patients that was associated with unresolved chest x-rays, indicating those patients had a poorer clinical outcome.

The researchers therefore identified immune characteristics in convalescent COVID-19 patients are associated with negative impacts on subsequent health.

The team compiled the immune cell characteristics of over 80 convalescent patients recruited from Manchester hospitals between July and October 2020.

"Our study details persistent immune alterations in previously hospitalised COVID-19 patients up to 6 months after hospital discharge. Significantly, we outline an immune signature associated with poorer clinical outcomes in convalescent patients."

Dr Joanne Konkel

They found that changes to B cells – a type of lymphocyte – that occur during the peak of COVID-19 hospitalisation were largely restored by 6 months of convalescence. However, changes to T cells, another lymphocyte, persisted into COVID-19 convalescence.

Study author Dr Joanne Konkel from The University of Manchester said: “Our study details persistent immune alterations in previously hospitalised COVID-19 patients up to 6 months after hospital discharge. Significantly, we outline an immune signature associated with poorer clinical outcomes in convalescent patients.

“Association, however, is not a causation, and what we now want to understand is what other long COVID symptoms this signature could be associated with and whether it could be used to identify the patients that should be most closely followed after hospital discharge.”

The signature present in the group of patients with the poorer clinical outcome was characterised by the team as having high levels of cytotoxic T cells – which can destroy other cells – as well as elevated production of special types of proteins called type-1 cytokines.

Study author Dr Madhvi Menon from The University of Manchester said: “It remains to be established if these immune alterations are unique to COVID-19, or whether they are also observed following other severe respiratory infections.”

The team hoped the results can be fed into larger UK wide studies, such as the University of Leicester led post-hospitalisation COVID-19 study known as PHOSP-COVID

PHOSP-COVID aims to better understand the interactions between immune cell changes and long COVID symptoms, as well as examine the clinical utility of the immune signature defined.

“Follow-up studies will determine whether this signature can provide a tool to identify acute COVID-19 patients at risk of Long COVID, enabling close monitoring and improved clinical management.”, said Dr Menon.

Study author Dr John Grainger from The University of Manchester and deputy Director of the Lydia Becker Institute said: “Given the vast numbers of previously infected individuals across the globe, it is vital to understand the impact of COVID-19 on the phenotype and functional potential of all immune cells.

“This will allow for better understanding of the long-term impacts of being hospitalised with COVID-19 on subsequent anti-pathogen or auto-inflammatory responses.”

The paper Alterations in T and B cell function persist in convalescent COVID-19 patients is published in Med

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