Malfunctioning cell behaviour could be drug target in Long COVID

A young black woman wearing a protective face mask sits in a medical clinic as her male doctor of Asian descent prepares to give her a COVID-19 vaccination injection in the upper arm.

Scientists have shown for the first time that the malfunctioning behaviour of a type of immune cell is linked to Long COVID.

Normally-functioning monocytes, made in the bone marrow, travel through the blood to the lungs where they surround and kill the virus and boost the immune response.

However, The University of Manchester scientists have discovered that in Long COVID, abnormal migration of these cells corresponds to the most commonly-reported symptom: shortness of breath. A different migration profile alongside changes to other functions correspond to fatigue.

The unique monocyte signatures defining subgroups of Long COVID patients reveal new pathways that could be targeted for novel therapeutic opportunities in Long COVID patients.

The study

The study is published today in the European Respiratory Journal.

The patients were recruited to the study between July 2020 and January 2021.

They included 71 hospitalised patients with acute COVID-19 and 142 follow up patients attending outpatient clinics months after hospital discharge from COVID-19, across Manchester University NHS Foundation Trust and the Northern Care Alliance Foundation Trust.

Using blood samples, they examined key monocyte migratory signatures in acute disease that persisted into convalescence up to nine months following hospital discharge.

The hospitalised patients were arranged into mild, moderate and severe disease based on their oxygen requirements.

Patients on acute non-invasive ventilation, invasive ventilation and admission to intensive care automatically led to classifying patients as having severe disease.

Healthy blood samples were obtained from frontline workers at The University of Manchester and Manchester University NHS Foundation Trust and examined alongside patient samples.

At outpatient review, patients undertook rigorous questionnaires which assessed whether they had increased levels of breathlessness or fatigue, and if this was new since SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection.

Unique monocyte profiles distinguished Long COVID patients with shortness of breath and unresolved lung injury from those with ongoing fatigue, and from asymptomatic patients.

Funding the study

The study was funded by:

  • the Wellcome Trust
  • the Royal Society
  • the Medical Research Council
  • The Kennedy Trust for Rheumatology Research
  • The Lister Institute
  • Biotechnology and Biological Sciences Research Council
  • UK Research and Innovation

Finding a link

Dr Elizabeth Mann, Wellcome Trust, Royal Society Sir Henry Dale Fellow at the University of Manchester’s Lydia Becker Institute said:

There is now a wealth of evidence indicating that chronic morbidity persists in many COVID-19 patients during convalescence manifesting as Long COVID which remains a global public health problem despite vaccination programmes and milder strains of SARS-CoV-2.

These debilitating symptoms including extreme fatigue, shortness of breath, myalgia, brain fog, depression, fibrotic lung disease and pulmonary vascular disease and we now know this can last for many months or even years following infection.

But treatment options for Long COVID are currently limited, since the development of targeted therapeutic strategies requires an in depth understanding of the underlying immunological pathophysiology.

Our work finding a link between monocyte function and specific Long COVID symptoms may provide an important first step on the road to possible treatments.

Top image:  Credit: Fly View Productions, E+ via Getty Images

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