They create a cellular map of the lung that reveals how the damage progresses in the most serious covid

A team of Spanish researchers has developed a detailed cellular map of the lung that allows us to observe how cells and molecular signals change as the damage caused by severe Covid-19 progresses. The work reconstructs the deterioration of lung tissue until the most advanced stages of the disease and provides new clues about the mechanisms involved in fibrosis.

The research is signed by Carlos A. García-Prieto and Eva Musulén as first authors and the study, linked to researchers from centers such as the Sant Pau Research Institute, the Josep Carreras Leukemia Research Institute and the Barcelona Supercomputing Center, appears in 2026 as a work in press in the scientific journal Nature Communications.

To prepare this atlas, scientists studied lung tissue from patients who died from Covid-19 and analyzed different stages of diffuse alveolar damage. This injury affects the alveoli, the tiny lung structures where the exchange of oxygen and carbon dioxide between the lungs and blood takes place, and constitutes one of the main alterations observed in the most serious respiratory conditions.

The key to the research is a spatial transcriptomics technique, which allows us to study which genes are active while preserving the position of the cells within the tissue. This offers a fundamental advantage over methods that require separating cells: Researchers can know not only what is changing, but also where it is happening and what other cells are around.

The map obtained shows a progressive loss of cells essential for lung function. Among them, type I pneumocytes stand out, which cover a good part of the alveoli and are essential for gas exchange. The researchers also observed a reduction in different populations of blood vessel endothelial cells and NK (natural killer) cells, members of the immune system that participate in the response to viral infections.

At the same time that certain cell populations disappear, others gain presence. The study identifies an increase in myeloid and stromal cells, including certain fibroblasts located around the bronchi. These cells are normally involved in tissue repair, but they can contribute to fibrosis when their activity and the signals they receive favor an abnormal healing response.

The scientists were also able to observe attempts at lung repair. Type II pneumocytes have the capacity to act as progenitors and generate type I pneumocytes, helping to reconstruct the epithelium of the alveoli. The analysis allowed us to follow signals related to this differentiation process, although in the most advanced phases of the damage this regenerative response fails to restore the normal architecture of the lung.

Among the molecular signals identified, the TGF-β signaling pathway stands out, closely related to fibrotic processes. The researchers also found different behaviors of SMAD3 and SMAD7, proteins that participate in this molecular pathway. The possibility of spatially locating these signals allowed us to relate them to the cell populations that appear as the damage progresses.