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1.
Cell Rep ; 39(11): 110955, 2022 Jun 14.
Article in English | MEDLINE | ID: covidwho-1866959

ABSTRACT

Direct myocardial and vascular injuries due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-driven inflammation is the leading cause of acute cardiac injury associated with coronavirus disease 2019 (COVID-19). However, in-depth knowledge of the injury characteristics of the heart affected by inflammation is lacking. In this study, using a quantitative spatial proteomics strategy that combines comparative anatomy, laser-capture microdissection, and histological examination, we establish a region-resolved proteome map of the myocardia and microvessels with obvious inflammatory cells from hearts of patients with COVID-19. A series of molecular dysfunctions of myocardia and microvessels is observed in different cardiac regions. The myocardia and microvessels of the left atrial are the most susceptible to virus infection and inflammatory storm, suggesting more attention should be paid to the lesion and treatment of these two parts. These results can guide in improving clinical treatments for cardiovascular diseases associated with COVID-19.


Subject(s)
COVID-19 , Heart Injuries , COVID-19/complications , Humans , Inflammation , Proteome , SARS-CoV-2
3.
Adv Sci (Weinh) ; 9(7): e2104192, 2022 03.
Article in English | MEDLINE | ID: covidwho-1589262

ABSTRACT

Coronavirus disease 2019 (COVID-19) patients with impact on skin and hair loss are reported. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is detected in the skin of some patients; however, the detailed pathological features of skin tissues from patients infected with SARS-CoV-2 at a molecular level are limited. Especially, the ability of SARS-CoV-2 to infect skin cells and impact their function is not well understood. A proteome map of COVID-19 skin is established here and the susceptibility of human-induced pluripotent stem cell (hiPSC)-derived skin organoids with hair follicles and nervous system is investigated, to SARS-CoV-2 infection. It is shown that KRT17+ hair follicles can be infected by SARS-CoV-2 and are associated with the impaired development of hair follicles and epidermis. Different types of nervous system cells are also found to be infected, which can lead to neuron death. Findings from the present work provide evidence for the association between COVID-19 and hair loss. hiPSC-derived skin organoids are also presented as an experimental model which can be used to investigate the susceptibility of skin cells to SARS-CoV-2 infection and can help identify various pathological mechanisms and drug screening strategies.


Subject(s)
COVID-19/physiopathology , Induced Pluripotent Stem Cells/cytology , Models, Biological , Organoids/cytology , Skin/cytology , COVID-19/virology , Hair Follicle/virology , Humans , Nervous System/virology , Proteomics , SARS-CoV-2/isolation & purification
6.
Signal Transduct Target Ther ; 5(1): 240, 2020 10 15.
Article in English | MEDLINE | ID: covidwho-872677

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-κB 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.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/genetics , Lung Injury/genetics , Pneumonia, Viral/genetics , Proteome/genetics , Proteomics/methods , Severe Acute Respiratory Syndrome/genetics , Aged , Autopsy , COVID-19 , Coronavirus Infections/metabolism , Coronavirus Infections/pathology , Coronavirus Infections/virology , Cytokines/genetics , Cytokines/metabolism , Female , Gene Expression Profiling , Gene Expression Regulation , Gene Ontology , Humans , Lung/metabolism , Lung/pathology , Lung/virology , Lung Injury/metabolism , Lung Injury/pathology , Lung Injury/virology , Male , Metabolic Networks and Pathways , Molecular Sequence Annotation , NF-kappa B/genetics , NF-kappa B/metabolism , Pandemics , Pneumonia, Viral/metabolism , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Proteome/metabolism , SARS-CoV-2 , Severe Acute Respiratory Syndrome/metabolism , Severe Acute Respiratory Syndrome/pathology , Severe Acute Respiratory Syndrome/virology , Severity of Illness Index , Signal Transduction
7.
Int J Med Sci ; 17(14): 2187-2193, 2020.
Article in English | MEDLINE | ID: covidwho-719844

ABSTRACT

Background: The number of asymptomatic infected patients with coronavirus disease 2019 (COVID-2019) is rampaging around the world but limited information aimed on risk factors of asymptomatic infections. The purpose of this study is to investigate the risk factors of symptoms onset and clinical features in asymptomatic COVID-19 infected patients. Methods: A retrospective study was performed in 70 asymptomatic COVID-2019 infected patients confirmed by nucleic acid tests in Hunan province, China between 28 January 2020 and 18 February, 2020. The epidemiological, clinical features and laboratory data were reviewed and analyzed. Presence or absence at the onset of symptoms was taken as the outcome. A Cox regression model was performed to evaluate the potential predictors of the onset of symptoms. Results: The study included 36 males and 34 females with a mean age of 33.24±20.40 years (range, 0.5-84 years). There were 22 asymptomatic carriers developed symptoms during hospitalization isolated observation, and diagnosed as confirmed cases, while 48 cases remained asymptomatic throughout the course of disease. Of 70 asymptomatic patients, 14 (14/70, 20%) had underlying diseases, 3 (3/70, 4.3%) had drinking history, and 11 (11/70, 15.7%) had smoking history. 22 patients developed symptoms onset of fever (4/22, 18.2%), cough (13/22, 59.1%), chest discomfort (2/22, 9.1%), fatigue (1/22, 4.5%), pharyngalgia (1/22, 4.5%) during hospitalization; only one (1/22, 4.5%) patient developed signs of both cough and pharyngalgia. Abnormalities on chest CT were detected among 35 of the 69 patients (50.7%) after admission, except for one pregnant woman had not been examined. 4 (4/70, 5.7%) and 8 (8/70, 11.4%) cases showed leucopenia and lymphopenia. With the effective antiviral treatment, all the 70 asymptomatic infections had been discharged, none cases developed severe pneumonia, admission to intensive care unit, or died. The mean time from nucleic acid positive to negative was 13.2±6.84 days. Cox regression analysis showed that smoking history (P=0.028, hazard ratio=4.49, 95% CI 1.18-17.08) and existence of pulmonary disease (P=0.038, hazard ratio=7.09, 95% CI 1.12-44.90) were risk factors of the onset of symptoms in asymptomatic carries. Conclusion: The initially asymptomatic patients can develop mild symptoms and have a good prognosis. History of smoking and pulmonary disease was prone to illness onset in asymptomatic patients, and it is necessary to be highly vigilant to those patients.


Subject(s)
Asymptomatic Infections/epidemiology , Coronavirus Infections/diagnosis , Lung Diseases/epidemiology , Pneumonia, Viral/diagnosis , Smoking/epidemiology , Symptom Flare Up , Adolescent , Adult , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , COVID-19 , Child , Child, Preschool , China/epidemiology , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Female , Humans , Infant , Lung/diagnostic imaging , Lung Diseases/complications , Male , Middle Aged , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Pregnancy , Prognosis , Retrospective Studies , Risk Assessment , Risk Factors , Severity of Illness Index , Smoking/adverse effects , Tomography, X-Ray Computed , Treatment Outcome , Young Adult
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