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Fatal Covid lungs show scarring where repair failed

A peer-reviewed tissue study mapped lung damage in people who died of Covid. Oxygen-exchanging cells declined as scarring spread and attempts to rebuild the air sacs remained incomplete. The spatial analysis identifies pathways for further laboratory investigation. Proposed drug targets have yet to establish a treatment benefit in patients with severe disease.

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Glass slides with tiny pink tissue stains stand in a pale carrier on a laboratory bench.

Oxygen-exchanging tissue gives way to scarring

An international team led by Manel Esteller at the Sant Pau Research Institute mapped the damaged lungs of people who died of Covid. The peer-reviewed Nature Communications study compared samples from 19 patients with healthy control tissue. Cells forming the thin air-to-blood oxygen barrier and the small vessels beside it declined as scar-forming cells spread. The investigation examines tissue from fatal cases; it supplies no trial of a treatment for the disease.[1], [2]

The researchers used spatial transcriptomics, a method that locates gene activity within intact tissue architecture. Keeping that location information allowed the team to examine which cellular changes occupied particular parts of the lung. Their map connects the distribution of damaged oxygen-exchanging structures with the growth of fibrotic tissue, the scarring that hardens the lung. The comparison concerns the sampled lungs rather than a direct observation of every stage within each living patient.[1], [2]

Repair cells increase without rebuilding the air sacs

Alveolar progenitor cells known as AT2 attempted to replenish the lost AT1 cells, which provide the oxygen-exchange surface of the air sacs. In the fatal cases, this repair remained incomplete or disrupted. The finding places attempted regeneration alongside tissue destruction: the presence of repair-associated cells did not mean that the functional oxygen-exchange surface had been restored.[1], [2]

The immune-cell population changed as well. Natural killer cells, which take part in early antiviral defence, decreased, while myeloid cells associated with chronic inflammation increased. Fibroblasts around the small airways became more prominent as normal tissue structure deteriorated. These observations describe the cellular setting in which scarring spread, alongside the loss of the structures needed for breathing.[1], [2]

Proposed drug targets await preclinical tests

The team identified molecular pathways associated with fibrosis and inflammation as possible drug targets. Esteller proposed preclinical experiments with existing antifibrotic medicines, including pirfenidone and nintedanib, as well as molecules that block the scarring pathway. Such experiments would test whether the expected tissue response occurs. Existing approval for another use does not establish benefit for severe Covid, and this observational study supplies no patient evidence that the proposed medicines reverse the damage.[1]

References

  1. News sourceEL PAÍSLung repair stalled in fatal Covid cases
    Primary paperNature CommunicationsSpatial transcriptomics unveils the in situ cellular and molecular hallmarks of the lung in fatal COVID-19
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  2. News sourceEl MundoCellular map of Covid lung damage suggests drug targets↩1↩2↩3↩4
Space and explorationEnergy transition and climate

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