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expert reaction to study looking at ‘immune signatures’ and long COVID

A study published in Nature Communications looks at ‘immune signatures’ and risk of post-acute COVID-19 syndrome.


Dr Claire Steves, Senior Clinical Lecturer, Kings College London, said:

“The press release is a good summary and accurate represents the science. This is a well described, good quality study. The data backs up conclusions.

“It continues to be important to predict who is at risk of Long COVID early on in the disease.  Over a year ago we published the first prediction model for Long-COVID which has been replicated in this paper.  This study builds on this model adding two immune markers taken early in the disease which appear to increase the prediction of the model, especially in people who are more severely affected to start with.  This is important for two reasons – it adds precision in terms of who could be identified for trials to prevent or curtail Long COVID after infection, and second it gives another pointer that aberrations in the immune response to infection may be important in the development of long term symptoms.

“This is a small study which is undertaken in a selected population, and so particularly the immune findings do need to be replicated elsewhere.  One key limitation is that they have defined long covid as more than 4 weeks, whereas there is an international consensus developing that we should focus on individuals with more than 12 weeks.  The authors state that their findings did extrapolate to 12 weeks, but the signal was not as clear.

Secondly, we need to point out that the study participants were recruited in the wild-type alpha and delta periods in Switzerland.  Also we don’t know anything about the vaccination status of these participants.  It would be important to look to see whether these markers are still predictive in vaccinated people as more of the world is vaccinated or has prior infection.

“With cases high still, more people are at risk of developing long term symptoms.  We urgently need to scale up research on how to prevent this happening.  Tools such as these predictive models could be used to identify people at higher risk for enrolment into research trials for therapeutics. 

“Since the model uses these measures early in the disease, the interpretation is that this predicts long COVID.  However, this is meant in statistical terms. We cannot be sure from this study that these immune markers are causally related to long COVID. It could be that they are a marker, or indeed reflect something about the person’s immune system even before infection.”



‘Immunoglobulin signature predicts risk of postacute COVID-19 syndrome’ by Cervia et al. was published in Nature Communications at 16:00 UK time on Thursday 25th January 2022.

DOI: 10.1038/s41467-021-27797-1



All our previous output on this subject can be seen at this weblink:



Declared interests

Dr Claire Steves: “I have a consultancy contract with ZOE Ltd the health science company who run the app, although the app is NFP.  This is due to my work designing the app.”

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