News Release

SARS-CoV-2 Spike protein binds to heart’s vascular cells potentially contributing to severe microvascular damage

A new study has shown how SARS-CoV-2 may contribute to severe microvascular damage seen in severely-ill COVID-19 patients by transforming human heart vascular cells into inflammatory cells, without infecting them

Peer-Reviewed Publication

University of Bristol

A new study has shown how SARS-CoV-2 may contribute to severe microvascular damage seen in severely-ill COVID-19 patients by transforming human heart vascular cells into inflammatory cells, without infecting them. The University of Bristol-led research, published in Clinical Science, indicates blocking antibodies could represent a new treatment to alleviate cardiovascular complications.

In this new study, a multidisciplinary research team from the University’s Bristol Heart Institute sought to investigate how SARS-CoV-2 interacts with heart cells causing the myocardial damage seen in COVID-19 patients. Until now, it remained unclear whether heart cells are infected by the virus or damaged because of an excess cytotoxic defence response. This response, also known as ‘the cytokine storm’, comes from our immune cells, whereby cytotoxic cells attack and kill the infected cells by releasing proteins, called cytokines. The team also sought to investigate  whether heart cells contribute to producing excess cytokines. 

A research team led by Bristol’s Professor Paolo Madeddu exposed human heart pericytes, which are cells that wrap small blood vessels in the heart, to SARS-CoV-2 Alpha and Delta variants, along with the original Wuhan virus. Surprisingly, they found the heart pericytes were not infected.  

Intrigued by this finding, in a second test-tube experiment, the researchers challenged the cardiac pericytes with the spike protein alone, without the virus. The spike protein made pericytes unable to interact with their companion endothelial cells and induced them to secrete inflammatory cytokines, suggesting the spike protein is harmful to human cardiac cells. Interestingly, the team found that antibodies blocking CD147 - a receptor for the spike protein – protected heart pericytes from damage.

Finally, the team identified the presence of the SARS-CoV-2 spike protein in blood samples obtained from COVID-19 patients, which opens the possibility that spike protein particles travelling through the circulation can reach a site distant from the respiratory system and cause systemic damage.

Dr Elisa Avolio, the study’s first author from the University’s Bristol Medical School, said: “Pericytes are essential cells of the heart, although their role in maintaining the structural integrity of the coronary vascular tree has emerged only recently. Our ongoing research on human cardiac pericytes indicates these cells co-operate with coronary endothelial cells during healing from a heart attack. This new study shows that the spike protein jeopardises this interaction and transforms pericytes into inflammatory cells. Hopefully, CD147 blocking antibodies could represent a new treatment to alleviate cardiovascular complications in COVID-19 patients.”

Professor Paolo Madeddu, cardiologist and the study lead from the University’s Bristol Medical School, added: “Microvascular complications are frequent and harmful in patients with COVID-19, with up to 11 percent of those hospitalised in intensive care units having myocardial damage or having suffered a heart attack. Furthermore, people with pre-existing cardiovascular diseases are more likely to die of COVID-19.

“Our findings newly suggest that SARS-CoV-2 can damage vascular cells without infecting them. In addition, cleaved spike protein particles could amplify the damage induced by the engagement of the full virion with vascular cells.”

“The Omicron variant has multiple mutations to its spike protein, which helps the virus to enter and infect human cells, resulting in higher transmissibility and stronger binding with human cells.”

“However, in the case of the current Omicron wave, experts say there haven't been any cardiac symptoms reported so far although it is still very early to say for sure. If confirmed, this may indicate a dissociation between infectivity and capacity of SARS-CoV-2 to cause cardiac cell damage. The multifunctional spike protein being the key determinant in these phenomena.”

The research has been supported by a pump-priming grant from the Wellcome Trust, the Elizabeth Blackwell Institute (EBI) Rapid Response COVID-19 and a British Heart Foundation grant (number PG/20/10285). The authors are members of the University of Bristol COVID19 Emergency Research Group (UNCOVER).

Paper

The SARS-CoV-2 Spike protein disrupts human cardiac pericytes function through CD147 receptor-mediated signalling: a potential non-infective mechanism of COVID-19 microvascular disease’ by Elisa Avolio et al in Clinical Science.

Ends

For further information or to arrange an interview with the researchers please contact Joanne Fryer [Mon to Wed], email joanne.fryer@bristol.ac.uk, mobile: +44 (0)7747 768805 or Caroline Clancy [Wed to Fri], email caroline.clancy@bristol.ac.uk, mobile: +44 (0)7776 170238 at the University of Bristol Press Office.

Further information

About coronavirus (SARS-CoV-2)
The surface of the coronavirus particle has proteins sticking out of it known as Spike proteins which are embedded in a membrane.  They have the appearance of tiny little crowns, giving the virus its name (corona). Inside the membrane is the viral genome wrapped up in other proteins. The genome contains all the genetic instruction to mass produce the virus. Once the virus attaches to the outside of a human cell, its membrane fuses with the human cell membrane and its genetic information into the human cell.  Next, the virus instructs the cell to start replicating its genome and produce its proteins. These are then assembled into many new copies of the virus which, upon release, can infect many more cells. The viral proteins play diverse further roles in coronavirus pathology.

Support our COVID-19 research
Bristol’s researchers are part of a global network of scientists responding urgently to the challenge of the coronavirus pandemic.

Find out how you can support their critical work.

Bristol UNCOVER Group
In response to the COVID-19 crisis, researchers at the University of Bristol formed the Bristol COVID Emergency Research Group (UNCOVER) to pool resources, capacities and research efforts to combat this infection.

Bristol UNCOVER includes clinicians, immunologists, virologists, synthetic biologists, aerosol scientists, epidemiologists and mathematical modellers and has links to behavioural and social scientists, ethicists and lawyers.

Follow Bristol UNCOVER on Twitter at: twitter.com/BristolUncover

For more information about the University of Bristol’s coronavirus (COVID-19) research priorities visit: www.bristol.ac.uk/research/impact/coronavirus/research-priorities/

Bristol UNCOVER is supported by the Elizabeth Blackwell Institute
Find out more about the Institute’s COVID-19 research looking into five key areas: virus natural history, therapeutics and diagnostics research; epidemiology; clinical management; vaccines; and ethics and social science.

About Bristol Heart Institute
Bristol Heart Institute is one of seven Specialist Research Institutes (SRIs) at the University of Bristol designed to reflect Bristol’s strength and depth in key specialisms.

The institute is a world-leading centre for translational cardiovascular research and the leading academic cardiac surgery centre in the UK. Specialising in preventing, predicting, detecting, reducing and treating cardiovascular disease, it brings together scientists and clinicians from across the University and the NHS in Bristol; training the next generation of cardiovascular scientists and clinical academics.

About Wellcome 

Wellcome supports science to solve the urgent health challenges facing everyone. We support discovery research into life, health and wellbeing, and we’re taking on three worldwide health challenges: mental health, global heating and infectious diseases. 

Issued by the University of Bristol, UK.


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