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Tissue-specific tolerance in fatal COVID-19

COVID-19 fatality: invader vs the immune system.

Our new blog provides a breakdown of a paper in preprint from the ICECAP consortium.

A team of pathologists, virologists and clinicians found that the virus was detectable in multiple organs and that there was a mismatch between virus presence and inflammation. This suggests that different tissues in the body have a different tolerance for the virus.

The study is a post-mortem study, where those who have died in hospital from COVID-19 were examined to determine mechanisms of the disease. Post-mortem examinations provide an opportunity to study the whole body in a way which is not possible during life, providing insight into disease and clinical characteristics of disease.

This research reveals how immune mediated organ inflammation and injury may be a key driver of fatality.

The study concludes that:

  • There is a mismatch between the presence of SARS-CoV-2, tissue inflammation and organ dysfunction
  • There is a tissue specific tolerance to SARS-CoV-2
  • Death is a consequence of immune mediated organ inflammation and injury

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.

Note: this article is still awaiting peer review.

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