In a new study, researchers found that the likelihood of severe and ‘long’ COVID may be established very early on the following infection.
They also found clues to why some people experience “long COVID.”
The findings provide important insights into the role of the immune system in preventing—and in some cases increasing the severity of—COVID-19 symptoms in patients.
The research was conducted by scientists at the University of Cambridge and elsewhere.
The immune response associated with COVID-19 is complex. Most people who get infected by SARS-CoV-2 mount a successful antiviral response, resulting in few if any symptoms.
In a minority of patients, however, there is evidence that 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.
In the study, the team tested individuals who test positive for SARS-CoV-2. These individuals range from asymptomatic healthcare workers in whom the virus was detected on routine screening, to patients requiring assisted ventilation.
The team take blood samples from patients over several months, as well as continuing to measure their symptoms.
They found an early, robust adaptive immune response in those infected individuals whose disease was asymptomatic or mildly symptomatic.
An adaptive immune response is where the immune system identifies an infection and then produces T cells, B cells and antibodies specific to the virus to fight back.
These individuals produced the immune components in larger numbers than patients with more severe COVID-19 managed, and within the first week of infection—after which these numbers rapidly returned to normal.
There was no evidence in these individuals of systemic inflammation that can lead to damage in multiple organs.
The team also found patients requiring admission to hospital have impaired immune responses and systemic inflammation (that is, chronic inflammation that may affect several organs) from the time of symptom onset.
In these people, the early adaptive immune response was delayed, and profound abnormalities in a number of white cells subsets were present.
Also present in the first blood sample taken from these patients was evidence of increased inflammation, something not seen in those with asymptomatic or mild disease.
This suggests that 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 the 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 researchers also found 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 SARS-CoV-2.
They 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.
Some recover as systemic inflammation itself resolves while 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 the hospital.
The findings together suggest 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.
It suggests doctors need to begin treatment to stop the immune system from causing damage very early on, and perhaps even pre-emptively in high-risk groups screened and diagnosed before symptoms develop.
One author of the study is Professor Ken Smith.
The study is published on MedRXiv.
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