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Pathological features of COVID-19-associated lung injury: a preliminary proteomics report based on clinical samples.

ABSTRACT: The COVID-19 pandemic has emerged as a global health emergency due to its association with severe pneumonia and relative high mortality. However, the molecular characteristics and pathological features underlying COVID-19 pneumonia remain largely unknown. To characterize molecular mechanisms underlying COVID-19 pathogenesis in the lung tissue using a proteomic approach, fresh lung tissues were obtained from newly deceased patients with COVID-19 pneumonia. After virus inactivation, a quantitative proteomic approach combined with bioinformatics analysis was used to detect proteomic changes in the SARS-CoV-2-infected lung tissues. We identified significant differentially expressed proteins involved in a variety of fundamental biological processes including cellular metabolism, blood coagulation, immune response, angiogenesis, and cell microenvironment regulation. Several inflammatory factors were upregulated, which was possibly caused by the activation of NF-?B signaling. Extensive dysregulation of the lung proteome in response to SARS-CoV-2 infection was discovered. Our results systematically outlined the molecular pathological features in terms of the lung response to SARS-CoV-2 infection, and provided the scientific basis for the therapeutic target that is urgently needed to control the COVID-19 pandemic.

SUBMITTER: Leng L

PROVIDER: S-EPMC7557250 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Pathological features of COVID-19-associated lung injury: a preliminary proteomics report based on clinical samples.

Leng Ling L Cao Ruiyuan R Ma Jie J Mou Danlei D Zhu Yunping Y Li Wei W Lv Luye L Gao Dunqin D Zhang Shikun S Gong Feng F Zhao Lei L Qiu Bintao B Xiang Haiping H Hu Zhongjie Z Feng Yingmei Y Dai Yan Y Zhao Jiang J Wu Zhihong Z Li Hongjun H Zhong Wu W

Signal transduction and targeted therapy 20201015 1

The COVID-19 pandemic has emerged as a global health emergency due to its association with severe pneumonia and relative high mortality. However, the molecular characteristics and pathological features underlying COVID-19 pneumonia remain largely unknown. To characterize molecular mechanisms underlying COVID-19 pathogenesis in the lung tissue using a proteomic approach, fresh lung tissues were obtained from newly deceased patients with COVID-19 pneumonia. After virus inactivation, a quantitative ...[more]

PMID: 33060566

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Project description:BackgroundPulmonary involvement in COVID-19 is characterized pathologically by diffuse alveolar damage (DAD) and thrombosis, leading to the clinical picture of Acute Respiratory Distress Syndrome. The direct action of SARS-CoV-2 in lung cells and the dysregulated immuno-coagulative pathways activated in ARDS influence pulmonary involvement in severe COVID, that might be modulated by disease duration and individual factors. In this study we assessed the proportions of different lung pathology patterns in severe COVID-19 patients along the disease evolution and individual characteristics.MethodsWe analysed lung tissue from 41 COVID-19 patients that died in the period March-June 2020 and were submitted to a minimally invasive autopsy. Eight pulmonary regions were sampled. Pulmonary pathologists analysed the H&E stained slides, performing semiquantitative scores on the following parameters: exudative, intermediate or advanced DAD, bronchopneumonia, alveolar haemorrhage, infarct (%), arteriolar (number) or capillary thrombosis (yes/no). Histopathological data were correlated with demographic-clinical variables and periods of symptoms-hospital stay.ResultsPatient´s age varied from 22 to 88 years (18f/23 m), with hospital admission varying from 0 to 40 days. All patients had different proportions of DAD in their biopsies. Ninety percent of the patients presented pulmonary microthrombosis. The proportion of exudative DAD was higher in the period 0-8 days of hospital admission till death, whereas advanced DAD was higher after 17 days of hospital admission. In the group of patients that died within eight days of hospital admission, elderly patients had less proportion of the exudative pattern and increased proportions of the intermediate patterns. Obese patients had lower proportion of advanced DAD pattern in their biopsies, and lower than patients with overweight. Clustering analysis showed that patterns of vascular lesions (microthrombosis, infarction) clustered together, but not the other patterns. The vascular pattern was not influenced by demographic or clinical parameters, including time of disease progression.ConclusionPatients with severe COVID-19 present different proportions of DAD patterns over time, with advanced DAD being more prevalent after 17 days, which seems to be influenced by age and weight. Vascular involvement is present in a large proportion of patients, occurs early in disease progression, and does not change over time.

Project description:BackgroundAyurvedic clinical profiling of COVID-19 is a pre-requisite to develop standalone and integrative treatment approaches. At present, Ayurvedic clinicians do not have access to COVID-19 patients in clinical settings. In these circumstances, a preliminary clinical profiling of COVID-19 based on review of modern medical and classical Ayurvedic literature with inputs from Allopathic clinicians treating COVID-19 patients assumes significance.ObjectivesThis paper aims to develop an Ayurvedic clinical profile of COVID-19 by literature review supported by analysis of clinical data of a cohort of COVID-19 patients.MethodsThe typical clinical presentation of COVID-19 was categorized based on a cluster of symptoms with reference to "Interim Clinical Guidance for Management of Patients with confirmed corona virus disease (COVID-19)" released by the US CDC. As the clinical presentation is found to vary widely, research papers reporting clinical symptoms of patient samples from different parts of the world were also reviewed to identify outliers and atypical presentations. Case records of fourteen COVID-19 patients treated at Medanta Hospital, Gurgaon were analyzed to compare symptomatology with data obtained from published literature. Further, a careful correlation was done with the data collected from selected Ayurvedic classical texts and expert views of clinical practitioners to arrive at a preliminary Ayurvedic clinical profile of COVID-19.ResultsCOVID-19 can be understood from the Ayurvedic perspective as vātakapha dominant sannipātajvara of āgantu origin with pittānubandha. The asymptomatic, presymptomatic, mild, moderate, severe and critical stages of COVID-19 with varying clinical presentations have been analysed on the basis of nidāna, doṣa, dūṣya, nidānapañcaka and ṣaṭkriyākāla to present a preliminary clinical profile of the disease.ConclusionIn this paper, we have demonstrated that a preliminary clinical profiling of COVID-19 from the Ayurvedic perspective is possible through literature review supported by discussions with Allopathic clinicians as well as examination of patient case records. The provisional diagnosis proposed can be further developed with continued review of literature, wider cooperation and teamwork with Allopathic physicians and access to clinical data as well as direct clinical assessment of COVID-19 patients.

Project description:ImportancePneumonia due to COVID-19 can lead to respiratory failure and death due to the development of the acute respiratory distress syndrome. Tocilizumab, a monoclonal antibody targeting the interleukin-6 receptor, is being administered off-label to some patients with COVID-19, and although early small studies suggested a benefit, there are no conclusive data proving its usefulness.ObjectiveTo evaluate outcomes in hospitalized patients with COVID-19 with or without treatment with Tocilizumab.Design, setting, participantsRetrospective study of 1938 patients with confirmed COVID-19 pneumonia admitted to hospitals within the Jefferson Health system in Philadelphia, Pennsylvania, between March 25, 2020 and June 17, 2020, of which 307 received Tocilizumab.ExposuresConfirmed COVID-19 pneumonia.Main outcomes and measuresOutcomes data related to length of stay, admission to intensive care unit (ICU), requirement of mechanical ventilation, and mortality were collected and analyzed.ResultsThe average age was 65.2, with 47% women; 36.4% were African-American. The average length of stay was 22 days with 26.3% of patients requiring admission to the ICU and 14.9% requiring mechanical ventilation. The overall mortality was 15.3%. Older age, admission to an ICU, and requirement for mechanical ventilation were associated with higher mortality. Treatment with Tocilizumab was also associated with higher mortality, which was mainly observed in subjects not requiring care in an ICU with estimated odds ratio (OR) of 2.9 (p = 0.0004). Tocilizumab treatment was also associated with higher likelihood of admission to an ICU (OR = 4.8, p < 0.0001), progression to requiring mechanical ventilation (OR = 6.6, p < 0.0001), and increased length of stay (OR = 16.2, p < 0.0001).Conclusion and relevanceOur retrospective analysis revealed an association between Tocilizumab administration and increased mortality, ICU admission, mechanical ventilation, and length of stay in subjects with COVID-19. Prospective trials are needed to evaluate the true effect of Tocilizumab in this condition.

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Pathological features of COVID-19-associated lung injury: a preliminary proteomics report based on clinical samples.

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Pathological features of COVID-19-associated lung injury: a preliminary proteomics report based on clinical samples.

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