How swiftly a person’s immune system responds following infection with the coronavirus plays a crucial role in determining disease severity, a study shows.
Cambridge researchers studied 207 people who tested positive for Covid-19 over a three-month period and found those with no symptoms or mild cases mounted a robust immune response soon after getting infected.
But the people with severe cases who required hospitalisation had an impaired immune response, which led to a delayed and weakened attempt to fight the virus.
This undercooked response to the infection is characterised by inflammation of several organs, which occurs immediately after a person catches the coronavirus.
Scientists say abnormalities in immune cells may be behind the slack response to viral infection as well as the body’s inflammatory response, and may contribute to severe disease and also ‘long Covid’.
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How swiftly a person’s immune system responds following infection with the coronavirus plays a crucial role in determining disease severity, a study shows (file)
Dr Paul Lyons, senior co-author of the study from the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), said: ‘Our evidence suggests that the journey to severe Covid-19 may be established immediately after infection, or at the latest around the time that 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.’
There is no cure for Covid-19 but treatments have improved since it first emerged in China at the end of 2019.
The researchers from the University of Cambridge recruited a range of people who tested positive for the virus to see how the response of the immune system affected a person’s prognosis.
These individuals ranged from asymptomatic healthcare workers to patients requiring ventilation.
In the study, which has not yet been peer-reviewed but is available as a pre-print on medRxiv, the team analysed blood samples taken regularly over three months.
They compared the samples against those taken from 45 healthy people.
Researchers found evidence of an early, robust adaptive immune response in those infected individuals whose disease was asymptomatic or mildly symptomatic.
An adaptive immune response is when the immune system identifies an infection and then produces T cells, B cells and antibodies specific to the virus to fight back.
Cambridge researchers studied 207 people who tested positive for Covid-19 over a three month period and found those with no symptoms or a mild case mounted a robust immune response straight after getting infected (file)
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These people produced the immune components in larger numbers than patients with more severe Covid-19, and within the first week of infection.
After this the numbers rapidly returned to normal.
There was no evidence in these individuals of systemic inflammation that can lead to damage in multiple organs.
In patients who needed to be admitted to hospital, the early adaptive immune response was delayed, and profound abnormalities in a number of white cell subsets were present.
Researchers say 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.
Professor Derek Hill from UCL, who was not involved with the study, said: ‘This paper… finds that there are signatures in early blood tests that are associated with the subsequent course of the disease, from having only mild disease through to serious symptoms.
‘Furthermore, there is a hint of a signal in the blood tests about those who might get long COVID.
‘These are interesting findings, but it is important to note that a much larger study would be needed to determine whether the blood test ‘signatures’ the authors have identified are reliable predictors of course of the diseases, and whether such information could be used to help make treatment decisions.’
The team also found that key molecular signatures produced in response to inflammation were present in patients admitted to hospital.
They say that these signatures could potentially be used to predict the severity of a patient’s disease, as well as correlating with their risk of Covid-19 associated death.
The study also provides clues to the biology underlying cases of long Covid – where patients report experiencing symptoms of the disease, including fatigue, for several months after infection, even when they no longer test positive for the virus.
The team found that profound alterations in many immune cell types often persisted for weeks or even months after SARS-CoV-2 infection, and these problems resolved themselves very differently depending on the type of immune cell.
While some recover as systemic inflammation itself resolves, some others recover even in the face of persistent systemic inflammation.
However, some cell populations remain markedly abnormal, or show only limited recovery, even after systemic inflammation has resolved and patients have been discharged from hospital.
Dr Laura Bergamaschi, the study’s first author, said: ‘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.
‘For some cell types, it may be that 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.’