Disease trajectories in hospitalized COVID-19 patients are predicted by clinical and peripheral blood signatures representing distinct lung pathologies

COVID-19 is characterized by a broad range of symptoms and disease trajectories. Understanding the correlation between clinical biomarkers and lung pathology over the course of acute COVID-19 is necessary to understand its diverse pathogenesis and inform more precise and effective treatments. Here, we present an integrated analysis of longitudinal clinical parameters, peripheral blood biomarkers, and lung pathology in COVID-19 patients from the Brazilian Amazon. We identified core clinical and peripheral blood signatures differentiating disease progression between recovered patients from severe disease and fatal cases. Signatures were heterogenous among fatal cases yet clustered into two patient groups: “early death” (< 15 days of disease until death) and “late death” (> 15 days). Progression to early death was characterized systemically and in lung histopathology by rapid, intense endothelial and myeloid activation/chemoattraction and presence of thrombi, associated with SARS-CoV-2+ macrophages. In contrast, progression to late death was associated with fibrosis, apoptosis and abundant SARS-CoV-2+ epithelial cells in post-mortem lung, with cytotoxicity, interferon and Th17 signatures only detectable in the peripheral blood 2 weeks into hospitalization. Progression to recovery was associated with higher lymphocyte counts, Th2 and anti-inflammatory-mediated responses. By integrating ante-mortem longitudinal systemic and spatial single-cell lung signatures, we defined an enhanced set of prognostic clinical parameters predicting disease outcome for guiding more precise and optimal treatments. Finally, this study represents a major advance in the investigation of acute respiratory infections by integrating serial clinical data and peripheral blood samples with histopathological and spatially-resolved single-cell analyses of post-mortem lung samples.

Silva-Filho, J. L. (2024). Disease trajectories in hospitalized COVID-19 patients are predicted by clinical and peripheral blood signatures representing distinct lung pathologies [Data set]. Zenodo. https://doi.org/10.5281/zenodo.10911591