An autopsy-based study of 11 people who died from COVID-19 shows a mismatch between viral hotspots in the body and sites of inflammation and organ damage.

This suggests that immune responses, rather than the virus itself, are responsible for death. The survey of 37 anatomical sites, including lungs, found that some tissues harboured the virus but were not inflamed, whereas others were damaged but did not contain high levels of SARS-CoV-2.

SARS-CoV-2 was detected across a wide variety of organs, most frequently in the respiratory tract but also in numerous extra-pulmonary sites.

Minimal histological evidence of inflammation was identified in non-pulmonary organs despite frequent detection of viral RNA and protein.

At a cellular level, viral protein was identified without adjacent inflammation in the intestine, liver and kidney. Severe inflammatory change was restricted to the lung and reticuloendothelial system.

Diffuse alveolar damage, pulmonary thrombi and a monocyte myeloidpredominant vasculitis were the predominant pulmonary findings, though there was not a consistent association between viral presence and either the presence or nature of the inflammatory response within the lung.

Immunophenotyping revealed an influx of macrophages, monocytes and T cells into pulmonary parenchyma.

Bone marrow examination revealed plasmacytosis, erythroid dysplasia and iron-laden macrophages. Plasma cell excess was also present in lymph node, spleen and lung. These stereotyped reticulo-endothelial responses occurred largely independently of the presence of virus in lymphoid tissues.

Tissue inflammation and organ dysfunction in fatal Covid-19 do not map to the tissue and cellular distribution of SARS-CoV-2, demonstrating tissue-specific tolerance. Death in Covid-19 is primarily a consequence of immune-mediated, rather than pathogen-mediated, organ inflammation and injury.