The spatio-temporal landscape of lung pathology in SARS-CoV-2 infection
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Abstract
Recent studies have provided insights into the pathology and immune response to coronavirus disease 2019 (COVID-19) 1–8 . However thorough interrogation of the interplay between infected cells and the immune system at sites of infection is lacking. We use high parameter imaging mass cytometry 9 targeting the expression of 36 proteins, to investigate at single cell resolution, the cellular composition and spatial architecture of human acute lung injury including SARS-CoV-2. This spatially resolved, single-cell data unravels the disordered structure of the infected and injured lung alongside the distribution of extensive immune infiltration. Neutrophil and macrophage infiltration are hallmarks of bacterial pneumonia and COVID-19, respectively. We provide evidence that SARS-CoV-2 infects predominantly alveolar epithelial cells and induces a localized hyper-inflammatory cell state associated with lung damage. By leveraging the temporal range of COVID-19 severe fatal disease in relation to the time of symptom onset, we observe increased macrophage extravasation, mesenchymal cells, and fibroblasts abundance concomitant with increased proximity between these cell types as the disease progresses, possibly as an attempt to repair the damaged lung tissue. This spatially resolved single-cell data allowed us to develop a biologically interpretable landscape of lung pathology from a structural, immunological and clinical standpoint. This spatial single-cell landscape enabled the pathophysiological characterization of the human lung from its macroscopic presentation to the single-cell, providing an important basis for the understanding of COVID-19, and lung pathology in general.
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SciScore for 10.1101/2020.10.26.20219584: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources Slides were cooled to room temperature (RT), washed twice in TBS and blocked for 1.5 hours in SuperBlock Solution (ThermoFischer), followed by overnight incubation at 4°C with the prepared antibody cocktail containing all 36 metal-labeled antibodies (Supplementary Table 2). ThermoFischersuggested: NoneIlastik uses the labeled pixels to train a Random Forest classifier using features derived from the image and its derivatives. Ilastiksuggested: (Ilastik, RRID:SCR_015246)Images were thresholded with Otsu’s method (skimage.filters.threshold_otsu), successively dilated and closed … SciScore for 10.1101/2020.10.26.20219584: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources Slides were cooled to room temperature (RT), washed twice in TBS and blocked for 1.5 hours in SuperBlock Solution (ThermoFischer), followed by overnight incubation at 4°C with the prepared antibody cocktail containing all 36 metal-labeled antibodies (Supplementary Table 2). ThermoFischersuggested: NoneIlastik uses the labeled pixels to train a Random Forest classifier using features derived from the image and its derivatives. Ilastiksuggested: (Ilastik, RRID:SCR_015246)Images were thresholded with Otsu’s method (skimage.filters.threshold_otsu), successively dilated and closed (ski.morphology.binary_dilation/ski.morphology.closing) with a disk of 5 um diameter in order to remove objects without holes, and for the objects with holes, objects within the hole were removed on the negative image (scipy.ndimage.binary_fill_holes) and, only objects with area larger than 625 pixels (25 ** 2) were kept (skimage.morphology.remove_small_objects). scipysuggested: (SciPy, RRID:SCR_008058)Additional software versions used: Python version 3.8.2 Pythonsuggested: (IPython, RRID:SCR_001658)Results from OddPub: Thank you for sharing your code and data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on pages 3, 5 and 7. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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