20 March 2023

The malfunctioning behaviour of an immune cell could be linked to specific symptoms of long COVID, opening the way to treatments, British researchers have reported.

Normally functioning monocytes travel through the blood to the lungs, where they surround and kill the virus and boosts the immune response. However, researchers from the University of Manchester have found that, in patients experiencing long-COVID after being hospitalised with COVID, abnormal migration of monocytes corresponds to shortness of breath.

They also found different migration profiles and changes to other functions correspond to fatigue.

The team also included colleagues from Manchester University NHS Foundation Trust, Northern Care Alliance Foundation Trust, and the National Institute for Health and Care Research Manchester Biomedical Research Centre.

The study included 71 people who were hospitalised with acute COVID-19, and 142 follow-up patients who attended outpatient clinics months after they were discharged from hospital after being treated for COVID-19. All were recruited to the study between July 2020 and January 2021.

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

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

Healthy blood samples were also obtained from frontline workers at the University of Manchester and Manchester University NHS Foundation Trust.

When they attended an outpatient review, participants completed questionnaires that assessed whether or not they had increased levels of breathlessness and/or fatigue, and if this was new since SARS-CoV-2 infection.

They found long-COVID patients with shortness of breath and unresolved lung injury had a unique monocyte profile which distinguishes them from other long-COVID patients with only ongoing fatigue, and from asymptomatic patients.

Dr Elizabeth Mann, from the 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 include 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.”


Scott NA, Pearmain L, Knight SB, Brand O, Morgan DJ, Jagger C, Harbach S, Khan S, Shuwa HA, Franklin M, Kästele V, Williams T, Prise I, McClure FA, Hackney P, Smith L, Menon M, Konkel JE, Lawless C, Wilson J, Mathioudakis AG, Stanel SC, Ustianowski A, Lindergard G, Brij S, Diar Bakerly N, Dark P, Brightling C, Rivera-Ortega P, Lord GM, Horsley A; CIRCO; Piper Hanley K, Felton T, Simpson A, Grainger JR, Hussell T, Mann ER. (2023) “Monocyte migration profiles define disease severity in acute COVID-19 and unique features of long COVID.” European Respiratory Journal, doi: 10.1183/13993003.02226-2022.

Link: https://erj.ersjournals.com/content/early/2023/02/23/13993003.02226-2022.long

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