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People 'blighted by' long COVID may receive 'better treatment' after scientists get a grasp on phenomenon's cause

Alexandra Thompson
·6-min read
Upset depressed young woman lying on couch feeling strong headache migraine, sad tired drowsy teenager exhausted girl resting trying to sleep after nervous tension and stress, somnolence concept
Long COVID occurs when a former coronavirus patient endures lingering symptoms despite testing negative for the infection. (Posed by a model, Getty Images)

A new study may help medics understand the phenomenon of “long COVID”.

Early research suggests four out of five coronavirus cases are mild, however, it can trigger a disease called COVID-19.

While most return to a clean bill of health, more than 150,000 former coronavirus patients in the UK alone are said to be enduring long COVID, defined as complications like fatigue, palpitations and even organ damage that linger after the individual has tested negative for the infection.

To learn more, scientists from the University of Cambridge analysed blood samples from patients with and without complications over several months.

Results suggest persistent abnormalities to a patient’s immune cells and a change in the body’s inflammatory response may contribute to long COVID.

Read more: Coronavirus vaccines are safe despite public hesitancy

With the condition somewhat of a mystery, medics were initially stumped when it came to treating the debilitating symptoms, with official guidance still recommending patients join online support forums and set realistic goals.

The scientists hope their results will enable healthcare workers to “better treat patients whose lives continue to be blighted by the after effects of COVID-19”.

Watch: What is long COVID?

The preliminary results are yet to be published in a peer-reviewed journal, but appear on the pre-print website MedRXiv.

As many as one in three coronavirus patients is said to be asymptomatic, while many others endure just a mild cough, fever, or loss of taste or smell.

In severe cases, however, the immune system is thought to over-react to the infection, triggering a flood of immune cells that leads to chronic inflammation, organ damage and even death.

To better understand how a patient’s immune response relates to the complications they endure, the Cambridge scientists analysed the blood samples of 207 people with the infection, taken over three months after the onset of any symptoms.

Read more: Stay motivated with social distancing as pandemic continues

The patients ranged from asymptomatic healthcare workers whose virus was detected via routine screening to people who required ventilation to breathe.

The blood samples were compared against those of 45 healthy controls, in research the scientists believe helps “address two important questions”.

“Firstly, how does the very early immune response in patients who recovered from disease with few or no symptoms, compare with those who experienced severe disease?,” said study author Professor Ken Smith.

“Secondly, for those patients who experience severe disease, how rapidly does their immune system recover and how might this relate to long COVID?”

The results suggest the coronavirus patients whose infection turned out to be asymptomatic or mild launched “an early, robust adaptive immune response”.

This is defined as the immune system identifying the infection, before producing immune-fighting T cells, B cells and antibodies against the virus.

Immune cells were released in “larger numbers” among the asymptomatic or mild patients, compared to those who were more severely unwell, the results show.

The cells were also released within the first week of infection, before rapidly returning to normal levels.

“There was no evidence in these individuals of systemic inflammation that can lead to damage in multiple organs,” wrote the scientists.

Read more: Nearly half ICU staff ‘meet threshold’ for severe mental health issues

In the patients who required hospital care, the early adaptive immune response was delayed, with there also being “profound abnormalities” in the number of immune cells present.

The first blood sample from these patients also revealed markers of increased inflammation, which did not arise in those with asymptomatic or mild symptoms.

“This suggests an abnormal inflammatory component to the immune response is present even around the time of diagnosis in individuals who progress to severe disease,” wrote the scientists.

Co-author Dr Paul Lyons added: “Our evidence suggests the journey to severe COVID-19 may be established immediately after infection, or at the latest around the time they begin to show symptoms.

“This finding could have major implications as to how the disease needs to be managed, as it suggests we need to begin treatment to stop the immune system causing damage very early on, and perhaps even pre-emptively in high risk groups screened and diagnosed before symptoms develop.”

No evidence was found between a patient’s viral load and the progression to inflammatory disease.

Once inflammatory disease was established, however, viral load was associated with negative outcomes.

A patient’s viral load, or dose, is defined as the quantity of viral particles they are exposed to. For example, a frontline worker with insufficient personal protective equipment will likely have a higher viral load.

Unable to marshal the right cells and molecules to fight off the invader, the bodies of the infected instead launch an entire arsenal of weapons — a misguided barrage that can wreak havoc on healthy tissues, experts said. (Getty Images)
The severity of the coronavirus may depend on how a person's immune system reacts to the infection. (Stock, Getty Images)

When it comes to long COVID, the scientists revealed the profound alterations to many immune cells often persisted for weeks or even months after the coronavirus’ onset, with these resolving very differently depending on the type of immune cell.

Some patients recovered as the inflammation eased, while others improved while continuing to endure persistent inflammation.

For some, the immune cell populations remained markedly abnormal, or showed only limited recovery, even after the inflammation had resolved and the patient was discharged from hospital.

“It’s these populations of immune cells that still show abnormalities even when everything else seems to have resolved itself that might be of importance in long COVID,” said co-author Dr Laura Bergamaschi.

“For some cell types, it may be they are just slow to regenerate, but for others, including some types of T and B cells, it appears something is continuing to drive their activity.

“The more we understand about this, the more likely we will be able to better treat patients whose lives continue to be blighted by the after effects of COVID-19.”

Read more: Why severe coronavirus causes more damage than typical pneumonia

Other experts have hailed the study “illuminating”, “very important” and “extremely thorough”.

Professor Derek Hill from University College London added, however: “These are interesting findings, but it is important to note a much larger study would be needed to determine whether blood test ‘signatures’ are reliable predictors of course of the diseases, and whether such information could be used to help make treatment decisions.”

It is also unclear how a patient’s immune cells and inflammatory response are influenced by other coronavirus risk factors, like old age and pre-existing health conditions.

Watch: Can you catch coronavirus twice?