Abstract
Whereas the COVID-19 disease pathophysiology is under investigation, it is important to identify the pathways of viral transmission and inflammation from the pre-illness to the disease-onset stages. We analyzed five lung lobes from a patient with COVID-19 who finally died after prolonged lung protective ventilation. Pathological examination revealed moderate inflammation in upper lung lobes and uneven yet severe inflammation and diffuse alveolar damage in lower lung lobes. SARS-CoV-2 was detected at higher levels not in severely, but rather moderately inflamed middle lung lobes, and immunohistochemistry and bulk RNA-sequencing results showed that immune cells were detected at higher levels in lower lung lobes. The mRNA expression of cytokine families varied. We found an increase in keratin 5- or aquaporin 3-expressing basal cells in the severely inflamed lower lung lobes, and the alveolar stromal tissues were filled with them. Thus, this analysis of lung samples from a patient helps to determine the COVID-19 pathophysiology at a specific time point, and the virus localization and inflammatory responses at each site of the lungs provide various important indications.
Highlights
The coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health crisis, but there is still limited understanding of the disease pathophysiology
We further found that the damaged lung lobes were filled with keratin 5- and/or aquaporin 3-expressing basal cells
The H&E-stained slides showed that barring the upper side of the left upper lobe (LUL), the other lobes showed diffuse alveolar damage (DAD) with the presence of a hyaline membrane (Figure 1A)
Summary
The coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health crisis, but there is still limited understanding of the disease pathophysiology. Various organ tissues obtained from biopsy samples or peripheral blood samples from patients with COVID-19 have been analyzed using the innovative single-cell RNA sequencing method [1,2,3,4]. These studies have investigated the systematic immune defense mechanism against SARS-CoV-2 at the single-cell level, and a comprehensive analysis has helped to obtain valuable information. We performed an exhaustive pathophysiological analysis of samples from a patient with COVID-19 who died after prolonged lung-protective ventilation This comprehensive analysis indicated the distribution of SARS-CoV-2 and the cellular and molecular differences among mild-to-severely inflamed microenvironments in different lung lobes from a patient. We further found that the damaged lung lobes were filled with keratin 5- and/or aquaporin 3-expressing basal cells
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