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Severe and long Covid risk could be established ‘very early on’

New research has suggested there are specific molecular responses found in some Covid-19 patients which could be used to determine their likelihood of suffering from severe or long Covid symptoms, very early on following infection.

Researchers, supported by NIHR Cambridge Biomedical Research Centre, had set out to increase our understanding of the relationship between the immune response and Covid-19 symptoms by recruiting individuals who tested positive for the virus into a cohort of the NIHR BioResource.

Studying 207 people who had tested positive for Covid-19 over a three-month period, taking blood samples and measuring their symptoms, then comparing to samples taken from 45 healthy people, the researchers were able to uncover a number of interesting new findings.

Their research showed that people with either an asymptomatic or mild case of Covid-19 mounted a robust immune response to the virus soon after getting infected. These individuals produced a greater number of T cells, B cells and antibodies than patients with more severe Covid-19 infections and within the first week of infection - after which these numbers rapidly returned to normal.

The study also showed there was no evidence in these patients of widespread inflammation which can lead to damage in multiple organs.

In contrast, people with severe Covid-19 who required hospitalisation showed an impaired immune response, which led to a delayed and weakened attempt to fight the virus and widespread inflammation from the time of symptom onset. In patients requiring admission to hospital, the early immune response was delayed, and profound abnormalities were present in a number of immune cells.

Also, patients with severe Covid-19 had evidence of increased inflammation in their first blood sample, something not seen in those with asymptomatic or mild disease.

It is hoped that this discovery could help medical professionals to better predict patients’ Covid-19 severity risk going forward.

The findings, published for peer-review, noted how they had found specific molecular ‘signatures’ produced in response to inflammation 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.

Dr Paul Lyons, senior co-author from the Cambridge Institute of Therapeutic Immunology & 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 we would 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.”

Researchers in the same study also looked to discover clues to the biology of long Covid - whereby Covid-19 patients reported experiencing symptoms of the disease, including fatigue, for several months after infection, even when they no longer tested positive for Covid-19.

As part of their research, the team discovered that in many immune cell types of these people, profound alterations often persisted for weeks or even months after the Covid-19 infection.

These problems resolved themselves very differently depending on the type of immune cell. Some could recover as widespread inflammation itself resolved, while others recovered in the face of persistent inflammation. However, for some cell population, they remained markedly abnormal or showed limited recovery, even after the systemic inflammation had resolved and patients were discharged from hospital.

It was theorised that these long-altered immune cells could play a role in long-term impacts of Covid-19; the long Covid symptoms which have presented in some people.

Dr Laura Bergamaschi, the study’s first author, said: “It’s these populations of immune cells, which 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 aftereffects of Covid-19.”

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