The Immune System and Long Covid

"The journey to severe or long COVID could be established immediately after infection, or at the latest when symptoms appear, according to new research"

This is a quote from the yet to be peer-reviewed paper “Early immune pathology and persistent dysregulation characterise severe COVID-19” by Bergamaschi et al. The following is an article by UK Research and Innovation and, for those of us with Long Covid, it is starting to shed some light on why we have reacted so, so differently to SARS-CoV-2.

The immune response associated with COVID-19 is complex. Most people who are infected mount a successful anti-viral response, which results in few, if any, symptoms.

In a minority of patients, however, there is evidence that the immune system overreacts. This leads to a flood of immune cells 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 National Institute of Health Research (NIHR) BioResource to better understand the relationship between the immune response and COVID-19 symptoms.

These individuals ranged from asymptomatic healthcare workers to patients requiring assisted ventilation. They had blood samples taken over several months, and their symptoms measured.

The key findings, which have not yet been peer-reviewed, are:

  • individuals who have asymptomatic or mild disease show a robust immune response early on during infection

  • 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

  • persistent abnormalities in immune cells and a change in the body’s inflammatory response may contribute to ‘Long COVID.’

The researchers found NO evidence of a relationship between viral load and progression to inflammatory disease. However, once inflammatory disease was established, viral load was associated with subsequent outcome.

The study also provides clues to the biology underlying cases of Long COVID. In Long COVID 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.

The team found that profound alterations in many immune cell types often persisted for weeks or even months after SARS-CoV-2 infection.

These problems resolved themselves very differently depending on the type of immune cell. Some recover while some 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".

I have to be honest I am a tiny bit excited by this. It's the first research paper that I have seen that is actually proving that those of us with Long Covid have not reacted the same way to the virus and it may be what we thought all along - our immune systems.


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