Multi-organ proteomic landscape of COVID-19 autopsies

Nie, Xiu; Qian, Liujia; Sun, Rui; Huang, Bo; Dong, Xiaochuan; Xiao, Qin; Zhang, Qiushi; Tian, Li; Liang, Yue; Chen, Shuo; Li, Xiang; Sun, Yaoting; Li, Lü; Xu, Luang; Li, Yan; Yang, Ming; Xue, Zhangzhi; Liang, Shuang; Ding, Xuan; Yuan, Chunhui; Li, Peng; Liu, Wei; Yi, Xiao; Lyu, Mengge; Xiao, Guixiang; Xu, Xia; Ge, Weigang; He, Jiale; Fan, Jun; Wu, Junhua; Luo, Meng; Chang, Xiaona; Pan, Haitao; Cai, Xue; Zhou, Junjie; Yu, Jing; Gao, Huanhuan; Xie, Mingxing; Wang, Sihua; Ruan, Guan; Chen, Hao; Su, Hua; Mei, Heng; Luo, Danju; Zhao, Dashi; Xu, Fei; Zhu, Yi; Xia, Jiahong; Hu, Yu; Guo, Tiannan

doi:10.1016/j.cell.2021.01.004

Cited by 337 publications

(316 citation statements)

References 109 publications

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“…ACE2 and TMPRSS2 are expressed in a variety of tissues including the liver; however, their expression extensively varies among the different cell types, being more highly expressed in cholangiocytes than in hepatocytes, and are expressed in the endothelial cells of blood vessels but not in the sinusoidal endothelium [ 22 , 23 ]. Hepatocyte and cholangiocyte organoids have been shown to be permissive to SARS-CoV-2 infection [ 24 ], but whether SARS-CoV-2 can infect hepatocytes and/or cholangiocytes in vivo is still debated [ 25 ], and recent data on in-depth proteomic assessment of autopsy tissue revealed little evidence of viral replication in the liver [ 26 ]. Therefore, the exact pathophysiological mechanisms to explain hepatic dysfunction in COVID-19 is presently not fully understood.…”

Section: Discussionmentioning

confidence: 99%

Hepatic Failure in COVID-19: Is Iron Overload the Dangerous Trigger?

Nonno

Nardacci

Colombo

et al. 2021

Cells

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Liver injury in COVID-19 patients has progressively emerged, even in those without a history of liver disease, yet the mechanism of liver pathogenicity is still controversial. COVID-19 is frequently associated with increased serum ferritin levels, and hyperferritinemia was shown to correlate with illness severity. The liver is the major site for iron storage, and conditions of iron overload have been established to have a pathogenic role in development of liver diseases. We presented here six patients who developed severe COVID-19, with biochemical evidence of liver failure. Three cases were survived patients, who underwent liver biopsy; the other three were deceased patients, who were autopsied. None of the patients suffered underlying liver pathologies. Histopathological and ultrastructural analyses were performed. The most striking finding we demonstrated in all patients was iron accumulation into hepatocytes, associated with degenerative changes. Abundant ferritin particles were found enclosed in siderosomes, and large aggregates of hemosiderin were found, often in close contact with damaged mitochondria. Iron-caused oxidative stress may be responsible for mitochondria metabolic dysfunction. In agreement with this, association between mitochondria and lipid droplets was also found. Overall, our data suggest that hepatic iron overload could be the pathogenic trigger of liver injury associated to COVID-19.

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Section: Discussionmentioning

confidence: 99%

Hepatic Failure in COVID-19: Is Iron Overload the Dangerous Trigger?

Nonno

Nardacci

Colombo

et al. 2021

Cells

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“…Virus RNA sequencing, next-generation sequencing (NGS) [34,43,45], nested PCR [46], and proteomics [39] have been applied only in single studies. Sequenc-ing of the virus is important for genealogical determination of virus origin and detection of mutations.…”

Section: Other Methodsmentioning

confidence: 99%

“…Viral RNA detection has been established and validated as a standard method for the diagnosis of COVID-19 swabs, similarly to the RNA-based detection of SARS in 2003. Predominantly, genomic viral RNA is detected, although detection of viral transcripts or transcriptome is also possible [39]. Various genes can be used (.…”

Section: Rna Detectionmentioning

confidence: 99%

Detection methods for SARS-CoV-2 in tissue

Stillfried

2021

Pathologe

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Several methods are available for SARS-CoV-2 detection: electron microscopy, antigen detection by immunohistochemistry and immunofluorescence, and nucleic acid detection by in-situ hybridization and reverse transcriptase polymerase chain reaction (RT-PCR). Due to various factors in the preanalytical, analytical, and postanalytical phase, virus detection in pathology material presents specific diagnostic challenge. This article gives an overview of several SARS-CoV-2 detection methods and discusses existing data on specific sources of error, validity, and robustness of these methods.

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“…Binding to the receptor mediates the subsequent fusion between the virus envelope and the host cell membrane, allowing the virus to enter [ 13 , 14 ]. By examining tissue samples from seven organs, including the lungs, spleen, liver, heart, kidneys, thyroid, and the testicles of patients who died from COVID-19 in 2019, it was found that the lungs of these patients had diffuse alveolar damage, pulmonary fibrosis, and neutrophil infiltration; fatty metaplasia, and sometimes infarction in the liver; myocardial edema and interstitial lymphocyte infiltration of the heart; and acute tubular injury in the kidneys [ 15 ]. These are related to a series of excessive reactions due to SARS-CoV-2 infection, including cytokine storm, immune system disorders, and abnormal blood coagulation.…”

Section: Covid-19mentioning

confidence: 99%

The three syndromes and six Chinese patent medicine study during the recovery phase of COVID-19

Duan

Zhang

et al. 2021

Chin Med

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The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), first broke out in Wuhan, China, in 2019. SARS-CoV-2 develops many types of mutations (such as B.1.1.7), making diagnosis and treatment challenging. Although we now have a preliminary understanding of COVID-19, including pathological changes, clinical manifestations, and treatment measures, we also face new difficulties. The biggest problem is that most COVID-19 patients might face sequelae (e.g., fatigue, sleep disturbance, pulmonary fibrosis) during the recovery phase. We aimed to test six Chinese patent medicines to treat three major abnormal symptoms in COVID-19 patients during the recovery phase, including cardiopulmonary function, sleep disturbance, and digestive function. We launched the “three syndromes and six Chinese patent medicines” randomized, double-blind, placebo-controlled, multicenter clinical trial on April 10, 2020. The results showed that Jinshuibao tablets and Shengmaiyin oral liquid significantly improved the cardiopulmonary function of recovering COVID-19 patients. Shumian capsules, but not Xiaoyao capsules, significantly improved patients’ sleep disorders. This might be because the indication of Xiaoyao capsules is liver qi stagnation rather than psychological or emotional problems. Xiangsha Liujun pills and Ludangshen oral liquid significantly improved digestive function. Our research provides a guideline for treating COVID-19 sequelae in patients during the recovery period based on high-quality evidence.

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Multi-organ proteomic landscape of COVID-19 autopsies

Cited by 337 publications

References 109 publications

Hepatic Failure in COVID-19: Is Iron Overload the Dangerous Trigger?

Hepatic Failure in COVID-19: Is Iron Overload the Dangerous Trigger?

Detection methods for SARS-CoV-2 in tissue

The three syndromes and six Chinese patent medicine study during the recovery phase of COVID-19

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