University of Birmingham scientists beginning to unlock secrets of Covid

A University of Birmingham-led study funded by the UK Coronavirus Immunology Consortium has found that many patients with coronavirus produce immune responses that attack their body’s own tissues or organs.

Covid-19 has been associated with a variety of unexpected symptoms, both at the time of infection and for many months afterwards.

It is not fully understand what causes these symptoms, but one of the possibilities is that Covid-19 is triggering an autoimmune process. In effect, the immune system goes haywire and is misdirected to attack itself. That may explain why some go on to suffer long-term effects of the illness while others recover far quicker.

The study, published today in the journal Clinical & Experimental Immunology, investigated the frequency and types of common autoantibodies produced in 84 individuals who either had severe Covid-19 at the time of testing or in the recovery period following both severe Covid-19 and those with milder disease that did not need to attend hospital. These results were compared to a control group of 32 patients who were in intensive care for another reason other than Covid-19.

An autoantibody is an antibody – a type of protein – produced by the immune system that is directed against one or more of the individual’s own proteins and can cause autoimmune diseases. Infection can, in some circumstances, lead to autoimmune disease. Early data suggests Covid infection can trigger long-term autoimmune complications and there are reports of it being associated with a number of autoimmune disorders including Guillain-Barre Syndrome.

Supported by UK Research and Innovation and the National Institute for Health Research, the study found higher numbers of autoantibodies in the Covid-19 patients than the control group and that these antibodies lasted up to six months.

Non-Covid patients displayed a diverse pattern of autoantibodies. But in contrast, the Covid-19 groups had a more restricted panel of autoantibodies including skin, skeletal muscle and cardiac antibodies.

The authors also find that those with more severe Covid-19 were more likely to have an autoantibody in their blood.

First author Professor Alex Richter, of the University of Birmingham, explained: “The antibodies we identified are similar to those that cause a number of skin, muscle and heart autoimmune diseases.

“We don’t yet know whether these autoantibodies are definitely causing symptoms in patients and whether this is a common phenomenon after lots of infections or just following Covid-19. These questions will be addressed in the next part of our study.”

The study participants were separated into four cohorts. Group one was of 32 individuals sampled during their stay in intensive care for reasons other than Covid-19. Of those 41 per cent had autoantibodies. In this group, there were many different causes of their illness and autoantibodies were found against nearly all of the different autoantigens examined, indicating a more random distribution.

Group two had 25 individuals who were sampled during their stay in intensive care following a diagnosis of severe Covid-19. Six in 10 had autoantibodies. Of those who tested positive for autoantibodies, 41 per cent had skin antibodies, while 17 per cent had skeletal antibodies.

Group three included 35 individuals who had been admitted to intensive care with Covid-19, survived and were sampled three to six months later during routine outpatient follow up. Of those, 77 per cent had autoantibodies. Of those who tested positive for autoantibodies, 19 per cent had skin antibodies, 19 per cent had skeletal antibodies, 28 per cent had cardiac muscle antibodies; and 31 per cent had smooth muscle antibodies.

Finally, group four was made up of 24 healthcare workers sampled one to three months after mild to moderate Covid-19 that did not require hospitalisation. Of those, 54 per cent had autoantibodies. In those who tested positive for autoantibodies, 25 per cent had skin antibodies; 17 per cent smooth muscle antibodies; eight per cent anti-neutrophil cytoplasm antibodies that target a type of human white blood cells; and four per cent gastric parietal antibodies which are associated with autoimmune gastritis and anaemia.

Senior Author Professor David Wraith, of the University of Birmingham, said: “In this detailed study of a range of different tissues, we showed for the first time that Covid-19 infection is linked to production of selective autoantibodies. More work is needed to define whether these antibodies contribute to the long-term consequences of SARS-CoV-2 infection and hence could be targeted for treatment.”

Professor Paul Moss, Principal Investigator of the UK Coronavirus Immunology Consortium and Professor of Haematology at the University of Birmingham added: “This is an interesting study that reveals new insights into a potential autoimmune component to the effects of Covid-19.Research like this has been made possible by the huge collaborative efforts made by those that are a part of the UK Coronavirus Immunology Consortium. This study is another important step towards delivering real improvements in prevention, diagnosis, and treatment of Covid-19 to patients.”