long COVID, severe
© Narongrit Sritana

Cambridge researchers have published their findings on how the immune system could be an early clue for the later development of severe or long COVID

Scientists at the University of Cambridge and Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, have been working to understand if severe and long COVID can be predicted.

The team assert that their findings are not currently peer-reviewed, but that the urgency of the ongoing pandemic led them to make their data immediately accessible.

According to their work, individuals who are asymptomatic or experience a mild COVID-19 show a powerful immune response – early on, at the initial stages of infection. However, people who need to go to hospital have impaired immune responses and systemic inflammation – something that can impact several organs.

Abnormalities in immune cells and a change in the body’s organ response can be the first clues for if long COVID will hit.

This has been a concern throughout the pandemic, a delayed organ failure that can impact individuals around six months after their first symptom, documented in a separate study at Jin Yin-tan Hospital in Wuhan.

How does the immune system react to COVID-19?

The immune response associated with COVID-19 is complex.

Most people who get COVID have a successful antiviral response, with few symptoms. Some even have no symptoms. However, a minority of patients are showing a different immune response – an overreaction, which leads to a flood of immune cells. This is known as a cytokine storm, which leads to chronic inflammation and damage to multiple organs.

This often ends in death.

Professor Ken Smith, senior co-author and Director of the Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), said: “The NIHR BioResource has allowed us to address two important questions regarding SARS-CoV-2. 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?

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

The molecular actions that could predict if a patient will die

The team 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.

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.”

Some cell populations do not recover

The team found that profound alterations in many immune cell types often persisted for weeks or even months after 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 hospital.

However, no connection was found between viral load (like the Brazilian or Kent based mutations that spread faster) and severity of the disease. This is good news for policymakers and healthcare professionals.

‘The journey to severe COVID-19 may be established immediately’

Dr Paul Lyons, senior co-author, also from 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.”

The data is available here in full.


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