Written by Rebekah Penrice-Randal

COVID-19 fatality may be associated with damage caused by our immune system as opposed to direct damage from the virus. Dexamethasone, a drug that has recently proved to reduce fatality in severely ill COVID-19 patients, suggests that inflammation plays a direct role in patient outcomes.

Is the inflammation caused be the virus itself, or the body’s immune system? Currently, this is unknown.

For a quick recap on the immune system: visit our infographic here.

The ICECAP consortia have released a preprint in MedRxiv that may hold the answer to this question. Tissues from 12 individuals who have died from COVID-19 in hospital were analysed by a team of pathologists, clinicians and virologists to determine where the virus was found and whether this corresponded to where inflammation was found.

Who are ICECAP?

ICECAP: Inflammation in COVID-19-Exploration of Critical Aspects of Pathogenesis.

“ICECAP was established as a rapid response to the COVID-19 pandemic. We collect and analyse tissue samples to understand COVID-19 and other fatal diseases, contributing to finding tests and treatments for these conditions.”

Tissue-specific tolerance in fatal Covid-19 is the first research output from this consortia.

Definitions of key words:

  • Inflammation: a local immune response to cellular injury.
  • Post-mortem: the study of the deceased.
  • Immune system: a system of the body that fights off infection and disease, including white blood cells, antibodies and the organs that produce these cells.
  • Macrophage: a specialised immune cell involved in the innate immune response.
  • Plasma cell: an immune cell that produces antibodies that make up the adaptive immune response.
  • Pulmonary: relating to the lungs.

Key findings

The Coronavirus was found in multiple organs within patients who died from COVID-19.

Most commonly in the lungs but also in other parts of the body, such as the heart, muscle and the gastrointestinal tract. In some cases, virus was detected in the liver, kidney and other organs.

Inflammation was not observed in non-pulmonary organs

Interestingly, virus that was detected outside of the lung, was usually not associated with local inflammation, despite frequent detection of viral RNA and protein. This was the case for tissues such as the intestine, liver and kidney.

Inflammation was identified in lung tissue

Lung damage consisted of significant injury to the alveoli (the part of the lung involved in uptake of oxygen), the identification of blood clots and inflammation of pulmonary blood vessels. Interestingly again, there was not a consistent association between the presence of viral RNA and either the presence or nature of the inflammatory response within the lung.

Abnormalities of the blood and the immune system

Abnormalities were found in the blood and immune system; two key cell types are discussed:

  • Macrophages – an immune cell that is involved in sensing and responding to pathogens and tissue repair.
  • Plasma cells – cells involved in producing antibodies.

Abnormal macrophages and an increased number of abnormal plasma cells were identified in the organs of the immune system. Within damaged lung tissues, the researchers identified that macrophages and macrophage-like cells were in high numbers.

The consequence of these abnormalities is currently unknown; however, this finding provides a direction for COVID-19 researchers and future studies.

Conclusions

The take home message from this research is that different tissues appear to have a different tolerance to the virus. Inflammation and damage to organs are likely to be extensively mediated by the body’s own immune system, and drives outcome from disease.

A note on preprint and peer review:

This research has not gone through the peer review process yet – visit our posts on peer review here.

Interested in communicating your research to a lay audience? Get in touch at info@thesciencesocial.com

Thank you to Dr Chris Lucas, an ICECAP investigator and co-author of the original article for permission to write this blog, and for the valuable comments.