Where is the origin of the lesions reported in the whole lung biopsy pathology of new coronary critical patients?

The pathology of new coronary pneumonia is still to be studied in depth. In addition to the autopsy of the body carried out by Liu Liang and others at Huazhong University of Science and Technology, some scientific research teams are also obtaining pathological analysis from the organization biopsy channels. Professor Wang Fusheng, a member of the Chinese Academy of Sciences and director of the National Center for Clinical Medical Research for Infectious Diseases, led the team and the team of physicians at Xiao Shuyuan, Director of Zhongnan Hospital, Wuhan University, who has also published relevant pathological findings.

On March 2, local time, the research team of Shenzhen Third People’s Hospital (the second affiliated hospital of Southern University of Science and Technology) and the National Center for Clinical Medical Research for Infectious Diseases released the “Clinical Pathology Analysis of Patients with Critical Lyo conditions of New Coronary Virus Pneumonia” (Clinical Clinical) in the pre-printed Preprints update of the website. The study has not yet been peer-reviewed, with the first edition of the case with novel coronavirus (COVID-19), first published on February 27.

The team carried out a biopsy on the entire lungs of a critically ill patient with new coronary pneumonia who underwent a lung transplant, describing pathological changes through HE staining, immunohistic chemical staining, and special staining, including Masson staining, PAS staining, and hexamine silver staining. Whole lung tissue is diffusely congestive or partially hemorrhage necrosis. Hemorrhagic necrosis is evident on the outer edge of the right lung. There are severe congestion and bleeding changes in the pulmonary cut.

For the first time, the team said, they described major pathological changes in critically ill patients with neo-coronary pneumonia. This study shows clinical pathological biopsies in critically ill patients, which may provide a basis for an in-depth understanding of the pathogenesis and severity of the disease.

One of the authors of this paper is Professor Liu Lei, President and Secretary of the Party Committee and Chief Physician of the Third People’s Hospital of Shenzhen. According to the hospital’s official website, the National Center for Clinical Medical Research for Infectious Diseases and Shenzhen Third People’s Hospital are the only designated hospitals in Shenzhen to receive confirmed patients with new coronary pneumonia, and are also the hospitals with the largest number of patients treating new coronary pneumonia patients in addition to Hubei Province. In addition, the hospital has an area of 391 square meters of P3 laboratory, with the new coronavirus pneumonia series of research clinical resources and comprehensive research conditions.

Up to now, studies on epidemiological and clinical characteristics have been accumulated. Most patients develop symptoms such as fever and cough, but a small number of patients experience serious complications such as acute respiratory failure, acute respiratory distress syndrome (ARDS), infectious shock, etc. It is worth noting that, at present, the critically ill patients with new coronary pneumonia have poor prognosis and high mortality rates.

The patient, aged 66, returned to Shenzhen from Wuhan on January 4, 2020, with symptoms of high fever and cough. In addition to 8 years of history of hypertension, there are no other basic diseases, good heart function. Chest X-ray examination can be seen around the lung brightness increased, multiple shadows. The patient was diagnosed with new coronary pneumonia (critical type) and severe ARDS, concurrent respiratory failure, and a lung transplant.

In the P3 laboratory, the research team fixed the pulmonary pathological tissue, dehydrated, paraffin buried, tissue slicing, special tissue chemical staining, etc.

Where is the origin of the lesions reported in the whole lung biopsy pathology of new coronary critical patients?

The right lung (A, B), the left lung (C, D) are in general shape, and the right lung edge is obviously bleeding necrosis.

The results showed that the whole lung surface of the case was bronzed, the diffuse congestion was visible to the naked eye, mostly spot-shaped bleeding, partial bleeding necrosis. It is worth noting that hemorrhagic necrosis occurs mainly in the outer edge of the lower right, middle, and upper lobes of the lungs. The bronchial tubes are covered with mucus and bleeding oxuding. There are severe congestion and bleeding changes in the pulmonary cut.

Histopathology is characterized by a large number of pulmonary interbrosis fibrosis with partial transparency and pulmonary haemorrhagic infarction. Small blood vessel hyperplasia, thickening of blood vessel walls, narrow and closed tube cavity. Inflammatory intercellular leaching, including lymphocytes, plasma cells, and monocytes. Pulmonary fibrosis was confirmed by Masson staining. No other bacterial or fungal infections were found.

Where is the origin of the lesions reported in the whole lung biopsy pathology of new coronary critical patients?

Pathological biopsy of pulmonary interstitial tissue in critically ill patients: A, a large number of pulmonary interpulmonary fibrosis. B, pulmonary interbrosis fiber with partial transparency. C, Masson dyed pulmonary fibrosis. D, Masson chromatin fibrosis, alveolar epithelial cell dissandering. E, pulmonary hemorrhage changes. F, pulmonary hemorrhagic infarction. G, blood vessel wall thickening, narrow tube cavity. H, blocking vasculitis is surrounded by inflammatory cells. I, interlesoclins cell immersion (box indication).

It can be seen that alveolaritis with the celial epithelial cells (mainly type II) atrophy, proliferation, dandruff and scaly epithelial of various changes. The rest of the alveoli show eduns thickening, alveoli epithelial cells necrosis, dissonance. In addition, a large number of cellulose-like oozing, polynuclear macrocells and intracellular viral envelopes were observed. Necrosis bronchitis is characterized by bronchial wall necrosis, with epithelial cells visible in the tube cavity.

Where is the origin of the lesions reported in the whole lung biopsy pathology of new coronary critical patients?

COVID-19 alveoli change biopsy. A, necrotising bronchitis, necrotist bronchial epithelial cells can be seen in the cavity. B, alveoli epithelial cells atrophy. C, thin bronchial epithelial cell squamous epithelial. D, alveolar cells squamous epithelial. E, alveoli thickened. F, alveoli epithelial cells necrosis, druffles. G, intra-cavity inflammatory cells and a large number of cellulose-like oozing. H, polynuclear macrocells. I, alveoli epithelial cell cell cell plasma intraviral inclusion (box indication).

Immune histology results showed that immune cells such as CD3, CD4, CD8, CD20, CD79a, CD5 and CD38 were positive. The study found that positive expression of immune cells was concentrated near the pulmonary interstitial and blood vessels. In addition, CD31, TTF1, CK5/6, CK7, CK19, SMA, F VIII and TYPE IV collagen are also positive (some data are not shown).

Where is the origin of the lesions reported in the whole lung biopsy pathology of new coronary critical patients?

Critical coVID-19 immunohistology results. Continuous tissue slices show positive expressions of CD3 (A), CD4 (B), CD8 (C), CD20 (D), CD79a (E), CD5 (F), CD38 (G), CK7 (H), IV collagen (I).

In the discussion session, the research team pointed out that in SARS lung pathology, previously a team found local hemorrhagic necrosis, alveolaritis and bronchitis, alveoli cell druffles and other lung lesions. In fact, in this study, the results also showed pulmonary damage such as pulmonary edema, thin bronchitis, and endolaritis with epithelial cytomatitis. It is worth noting that under the microscope the team observed a large amount of pulmonary interscopic fibrosis, thickening of the tube wall, narrow tube cavity and more blocking.

The team speculates that these major changes may lead to severe respiratory failure in critically ill patients.

On the other hand, at present, general observation found that hemorrhagic necrosis is mainly present on the outer edge of the right lung. This observation suggests two things: first, this may be one of the leading causes of death in serious lyspatients;

In addition, recent studies have shown that the new coronavirus has the same cell entry receptor as SARS-CoV, known as ACE2 (angiotensin-converting enzyme II). In general, ace2 proteins are expressed in alveolar cells, bronchial epithelial and vascular endothelial cells, so binding to SARS-CoV-2 infection sepsis can lead to acute lung injury and pulmonary edema. The team also observed large amounts of pulmonary edema and bleeding, shed bronchial and alveolar epithelial cells.

Cytokine storms, on the other hand, are associated with over-immune responses and uncontrolled inflammatory reactions, which can lead to serious organ disease, including lung damage. Several representative cytokines have been identified, including IL-1 beta, IL-18, TNF-alpha, IL-6, IL-8, and IL-10, all of which are produced and regulated by various immune cells including CD8 and CD4.

It is worth noting that the team observed that lymphocytes, monocytes, and plasma cells are immersed in the pulmonary interstitial, and these types of inflammatory cells are confirmed by immunohistology methods. As mentioned earlier, pathological changes such as large-scale fibrosis of the pulmonary interstenal, stenosis of the tube cavity occurred in the lung in the case, and the team believes that these results may explain why critically ill patients have acute pulmonary dysfunction.