SARS-CoV-2 infection can manifest as a wide range of respiratory and systemic symptoms well after the acute phase of infection in over 50% of patients. Key questions remain on the long-term effects of infection on tissue pathology in recovered COVID-19 patients. To address these questions we performed multiplexed imaging of post-mortem lung tissue from 12 individuals who died post-acute COVID-19 (PC) and compare them to lung tissue from patients who died during the acute phase of COVID-19, or patients who died with idiopathic pulmonary fibrosis (IPF), and otherwise healthy lung tissue. We find evidence of viral presence in the lung up to 359 days after the acute phase of disease, including in patients with negative nasopharyngeal swab tests. The lung of PC patients are characterized by the accumulation of senescent alveolar type 2 cells, fibrosis with hypervascularization of peribronchial areas and alveolar septa, as the most pronounced pathophysiological features. At the cellular level, lung disease of PC patients, while distinct, shares pathological features with the chronic pulmonary disease of IPF. which may help rationalize interventions for PC patients. Altogether, this study provides an important foundation for the understanding of the long-term effects of SARS-CoV-2 pulmonary infection at the microanatomical, cellular, and molecular level.
### Competing Interest Statement
R.E.S. is on the scientific advisory board of Miromatrix Inc and Lime Therapeutics and is a paid consultant and speaker for Alnylam Inc. O.E. is scientific advisor and equity holder in Freenome, Owkin, Volastra Therapeutics and OneThree Biotech. The remaining authors declare no competing financial interests.
### Funding Statement
This work was partially supported by the WorldQuant Initiative for Quantitative Prediction. A.F.R. was supported by a NCI T32CA203702 grant. O.E. is supported by Volastra, Janssen and Eli Lilly research grants, NIH grants UL1TR002384 and R01CA194547, and Leukemia and Lymphoma Society SCOR 7012-16, SCOR 7021-20 and SCOR 180078-02 grants. R.E.S. is supported by NIH grants NIAID 2R01AI107301 and NIDDK R01DK121072 and the American Heart Association. R.E.S. is supported as Irma Hirschl Trust Research Award Scholar.
### Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
Tissue samples were provided by the Weill Cornell Medicine Department of Pathology using protocols approved by the Tissue Procurement Facility of Weill Cornell Medicine. Experiments using samples from human subjects were conducted in accordance with local regulations and with the approval of the IRB at the Weill Cornell Medicine. The autopsy samples were collected under protocol 20-04021814.
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Multiplexed imaging data are available at the following publicly available repository: https://doi.org/10.5281/zenodo.7060271. Source code used in data analysis is available at the following publicly available repository: https://github.com/ElementoLab/post-covid-imc
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