key: cord-0713230-0o9n4ud5
authors: Wu, Jinxiang; Yu, Jiguang; Zhou, Shengyu; Zhang, Jintao; Xu, Jiawei; Niu, Chuanzhen; Qu, Guimei; Han, Bo; Hu, Jing; Dong, Liang
title: What can we learn from a COVID-19 lung biopsy?
date: 2020-08-06
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2020.07.067
sha: 57afd5b334ad524cfab9ee1c6ebbaeef31bea001
doc_id: 713230
cord_uid: 0o9n4ud5

Abstract We reported a patient diagnosed with severe pneumonia from coronavirus disease 2019(COVID-19), and did the percutaneous lung biopsy with the guidance of ultrasound. Then we presented the patient's lung morphological, ultrastructure, and some important inflammatory biological markers changes, to help better understand the disease and make a clue for all the multidisciplinary team to save more people.

The newly emerging COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has swept nearly all over the world with stunning mortality. Even lots of researches have been investigated, few pathologies in living lung tissue has been reported due to barely accessible biopsy. Here, we investigated the pathological characteristics of a alive patient who suffered from severe infection with SARS-CoV-2. This study is in accordance with regulations issued by the National Health Commission of China. Our findings will facilitate understanding of the histopathology and the treatment of COVID-19, and improve clinical strategies against the disease.

On February 03, 2020, a 55-year-old man was admitted to a fever clinic in Yantai, China, with a 3-day history of high fever, dry cough, fatigue and shortness of breath. He disclosed that his son returned their hometown from epidemic-hit Wuhan on January 21. The patient took oral anti-fever medicine, and the fever can't be controlled. His chest computed tomography (CT) showed bilateral multifocal ground glass opacities with consolidation which suggested viral pneumonia as a differential diagnosis ( Figure 1A&B) . He was immediately admitted to the isolation ward and The patient had no special underlying disease before this onset. The physical examination revealed a body temperature of 36.8°C, blood pressure of 134/91 mmHg, pulse of 70 beats per minute, respiratory rate of 23 breaths per minute, and arterial oxygen saturation (SPO2) of 68% while the patient was breathing supplement oxygen by mask hydrogen at 5 liters per minute (L/min). The breathing sound was normal initially. The laboratory results reflected lymphopenia (6.5%).

His repeated chest CT showed significant progression of bilateral, diffuse distribution, and became "white lung" as shown ( Figure 1C ). The laboratory results reflected lymphopenia (6.5%), decreased cellular immunity (CD3+CD4+ 145/ul). A rapid screening test for influenza A and B showed negative. Some other laboratory abnormalities in our case, such as elevated SPO2, Lactate (Lac), White-cell count, absolute lymphocyte count, platelet count, Oxygen, Carbon dioxide and other routine tests were shown in Table1. Even we did our best, the illness persisted getting worse, so we did the percutaneous lung biopsy with the guidance of ultrasound on illness day 41 at 11am. Unfortunately, the patient died at night on the same day.

We fixed the specimen at the different time at an interval of 24 hours. The former biopsy showed alveolar structure collapse, occlusion and massive fibrinoid necrosis, cellulose exudate could be seen in the residual alveolar space. Alveolar epithelial hyperplasia ( Figure 2A ). The later lung biopsy showed extensive lung tissue necrosis, most of the alveolar septum were destroyed, the fibrous scaffolds disappeared, and only a few alveolar structures were preserved, accompanied by significant fibrinous exudate and hemorrhage. Necrotic and exfoliated alveolar epithelial cells and chronic inflammatory cells could be seen in the exudates, and the latter was mainly composed Figure 3G ).

So far, few accessible severe COVID-19 patient autopsies have been reported.

Here we investigated the pathological characteristics of a severe COVID-19 patient.

Our findings will facilitate understanding of the pathogenesis of COVID-19 and improve clinical strategies against the disease.

Most elderly COVID-19 patients with comorbidities, such as hypertension, diabetes and coronary heart disease are critically ill or die. But a significant part of middle-aged adults with no underlying diseases also could be infected, like the patient we report. In this case, biopsy samples were taken from lung bedside with the guidance of ultrasound. The latter lung biopsy showed extensive lung tissue necrosis; Type Ⅱ alveolar epithelial hyperplasia could be seen; No virus inclusions However, the former showed a relatively light damage. The patient's lung morphological changes were conformed to late manifestations of severe case. The findings made a clue that virus may continue to destroy the lung tissue after the virus leaves the body. To some extent, self-degradation and destruction of tissues cannot be ruled out. Even though, autopsy results cannot fully represent the patient's disease status. We also observed the virus in lung tissue by transmission electron microscopy.

Angiotensin-converting enzyme 2 (ACE2), a cell surface protein highly expressed in the lung, kidney and heart (4), SARS-CoV-2 targets the lung and other organs, leading to multiorgan damage by binding to the ACE2 receptor (5) .Inflammatory cytokines and chemokines, including interleukin-6 (IL-6) and TNF-α were significantly elevated in COVID-19 patients. Here, we could find the expression of ACE2, IL6, TNF-α in the case. MPO is a peroxidase, mainly produced by granulocytes (neutrophils and tissue monocytes)(6). The expression of MPO was Strong positive, but neutrophils could hardly be seen in the lung tissue of this patient at present, suggesting that there may be a large amount of granulocyte infiltration in lung tissue before and during the middle stage of clinic, resulting in a large amount of MPO production, and local superoxide reaction. In the later stage, granulocytes broke apart and the resulting MPO accumulated in the lung tissue, which could lead to severe tissue damage (closely related to oxidative stress response).

J o u r n a l P r e -p r o o f case presentation can not only help to identify a cause of death, but also facilitate understanding of the pathogenesis of the disease, which might help multidisciplinary team to formulate a timely therapeutic strategy for similar severe patients and reduce mortality. 

The clinical pathology of severe acute respiratory syndrome (SARS): a report from China

Clinicopathologic, Immunohistochemical, and Ultrastructural Findings of a Fatal Case of Middle East Respiratory Syndrome Coronavirus Infection in the United Arab Emirates

Overlapping and discrete aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARS-CoV, MERS-CoV, and 2019-nCoV

ACE2: from vasopeptidase to SARS virus receptor

A pneumonia outbreak associated with a new coronavirus of probable bat origin

The authors declare no conflict of interest.J o u r n a l P r e -p r o o f