The likelihood of severe and long Covid-19 may be established early on following infection, according to a new study.
The research provides insights into the role of the immune system in preventing, and in some cases increasing the severity of, coronavirus symptoms in patients.
It also suggests why some people experience long Covid.
According to the study, people who have asymptomatic or mild disease show a robust immune response early on during infection.
While those requiring admission to hospital have impaired immune responses and systemic inflammation – chronic inflammation that may affect several organs – from the time of symptom onset.
Our evidence suggests that the journey to severe Covid-19 may be established immediately after infection
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Scientists say persistent abnormalities in immune cells and a change in the body’s inflammatory response may contribute to long Covid.
Dr Paul Lyons, senior co-author, of 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.”
Successful response
Most people who get infected by coronavirus mount a successful antiviral response, resulting in few if any symptoms.
However, in a minority of patients there is evidence the immune system over-reacts, leading to a flood of immune cells (a ‘cytokine storm’) and to chronic inflammation and damage to multiple organs, often resulting in death.
Scientists at the University of Cambridge and Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, have been recruiting individuals who test positive for SARS-CoV-2 to the Covid-19 cohort of the NIHR BioResource.
These individuals range from asymptomatic healthcare workers in whom the virus was detected on routine screening, through to patients requiring assisted ventilation.
In the study, which has not yet been peer-reviewed, the team analysed samples from 207 Covid-19 patients with a range of disease severities taken at regular intervals over three months following the onset of symptoms.
They compared the samples against those taken from 45 healthy controls.
Researchers found evidence of an early, robust adaptive immune response in those infected individuals whose disease was asymptomatic or mildly symptomatic.
Systemic inflammation
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.
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.
The team also found that key molecular signatures produced in response to inflammation were present in patients admitted to hospital.
Predict
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.
Scientists found no evidence of a relationship between viral load and progression to inflammatory disease.
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.
