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expert reaction preprint looking at the early immune response to SARS-CoV-2 and how that may relate to severe and long-COVID

A preprint, an unpublished non-peer reviewed study, looks at early immune response to SARS-CoV-2 and likelihood of developing severe and ‘long’ COVID.


Prof Derek Hill, Professor of medical imaging science, UCL, and expert in medical devices, said:

“This paper, which has not yet undergone peer review, is an observational study that looks at the immune response from blood tests of just over 200 people who tested positive for COVID and followed up for 12 weeks.  It finds that there are signatures in those early blood tests that are associated with the subsequent course of the disease, from having only mild disease through to serious symptoms.   Furthermore, there is a hint of a signal in the blood tests about those who might get long COVID. These are interesting findings, but it is important to note that a much larger study would be needed to determine whether the blood test “signatures” the authors have identified are reliable predictors of course of the diseases, and whether such information could be used to help make treatment decisions.”


Prof Lawrence S. Young, Virologist and Professor of Molecular Oncology, University of Warwick, said:

“It appears that the early immune response to virus infection dictates the severity of COVID-19. This could mean that early intervention with therapies that target the virus and/or the immune system could prevent severe disease and even the development of ‘long covid’.

“This preprint describes an extremely thorough study examining how the early immune response to SARS-CoV-2 infection impacts the clinical course of COVID-19. It uses detailed analysis of immune cells over a 3 month period in a cohort of 207 patients ranging from those who are asymptomatic to those who required assisted ventilation as compared to 45 healthy controls. The data clearly shows that early immune changes predict the severity of the course of COVID-19. An early robust immune response with no evidence of systemic inflammation is associated with asymptomatic or mildly symptomatic disease that did not progress. More severe and progressive disease is associated with profound abnormalities in circulating immune cells and with evidence of early systemic inflammation. While evidence of immune recovery was observed in some patients, the failure to completely return to normal may be associated with long-term disease. How these immune changes relate to other risk factors (e.g. age, diabetes, chronic inflammatory disease) and are impacted by infection with virus variants remains to be determined.”


Prof Charles Bangham FRS FMedSci, Chair of Immunology, Imperial College London, said:

“This is a very important and illuminating study.  The central findings are that an early adaptive immune response to SARS-CoV-2 is associated with a lower risk of severe COVID-19, and that markers of inflammation are strongly associated with the severe disease.  In particular, an early CD8+ (cytotoxic) T lymphocyte (CTL) response was associated with a lower risk of disease.  These results are of great importance in a number of respects.  First, they imply that improving the efficacy of the early immune response by vaccination reduces the risk of severe disease.  Second, they throw light on the pathogenesis of the disease: an early adaptive (especially CTL) response restricts the replication of the virus, and so diminishes the serious secondary consequences of widespread infection, which are largely inflammatory.  Third, the longer-term tissue damage may be caused by a combination of the inflammatory response and the immune response to the widely disseminated virus that was inadequately controlled by the early T cell response.  Finally, as the authors point out, if these longer-term processes persist, they may result in the potentially disabling condition of Long Covid.  More work is urgently needed, in particular, to investigate the mechanisms that cause this sometimes devastating syndrome, as well as acute COVID-19 itself.”



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



Declared interests

Prof Derek Hill: “No conflicts of interest.”

None others received.

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