Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 7 de 7
Filter
1.
PLoS Genet ; 18(4): e1010137, 2022 04.
Article in English | MEDLINE | ID: covidwho-1789166

ABSTRACT

Viral infections can alter host transcriptomes by manipulating host splicing machinery. Despite intensive transcriptomic studies on SARS-CoV-2, a systematic analysis of alternative splicing (AS) in severe COVID-19 patients remains largely elusive. Here we integrated proteomic and transcriptomic sequencing data to study AS changes in COVID-19 patients. We discovered that RNA splicing is among the major down-regulated proteomic signatures in COVID-19 patients. The transcriptome analysis showed that SARS-CoV-2 infection induces widespread dysregulation of transcript usage and expression, affecting blood coagulation, neutrophil activation, and cytokine production. Notably, CD74 and LRRFIP1 had increased skipping of an exon in COVID-19 patients that disrupts a functional domain, which correlated with reduced antiviral immunity. Furthermore, the dysregulation of transcripts was strongly correlated with clinical severity of COVID-19, and splice-variants may contribute to unexpected therapeutic activity. In summary, our data highlight that a better understanding of the AS landscape may aid in COVID-19 diagnosis and therapy.


Subject(s)
COVID-19 , Alternative Splicing/genetics , COVID-19/genetics , COVID-19 Testing , Humans , Proteomics , SARS-CoV-2/genetics , Transcriptome
2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323677

ABSTRACT

Background: More and more studies showed pneumothorax is a complication of the 2019 novel coronavirus disease (COVID-19). But no autopsy findings of pneumothorax in COVID-19 decedent were reported, and direct relations between pneumothorax and lung pathology in these decedents were not discussed so far. Methods: A 62-year-old man with COVID-19 presenting with persistent hypoxemia and suddenly dead, who was treated by mechanical ventilation in the intensive care unit (ICU) for 5 days. A systemic autopsy examination of COVID-19 decedent, including histopathology study, was conducted and the medical record, chest computerized tomography (CT) image were reviewed by forensic pathologists and clinicians. Results: Severe pneumothorax, diffuse alveolar damage and airway obstruction were observed. Pneumothorax should be one of the causes of death. Conclusion: Pneumothorax, due to SARS-CoV-2 infection, is a fatal complication of COVID-19. Regular examination of chest CT or X-ray and airway management are important to clinical treatment.

3.
Allergy ; 76(2): 483-496, 2021 02.
Article in English | MEDLINE | ID: covidwho-1140084

ABSTRACT

BACKGROUND: The impacts of chronic airway diseases on coronavirus disease 2019 (COVID-19) are far from understood. OBJECTIVE: To explore the influence of asthma and chronic obstructive pulmonary disease (COPD) comorbidity on disease expression and outcomes, and the potential underlying mechanisms in COVID-19 patients. METHODS: A total of 961 hospitalized COVID-19 patients with a definite clinical outcome (death or discharge) were retrospectively enrolled. Demographic and clinical information were extracted from the medical records. Lung tissue sections from patients suffering from lung cancer were used for immunohistochemistry study of angiotensin-converting enzyme II (ACE2) expression. BEAS-2B cell line was stimulated with various cytokines. RESULTS: In this cohort, 21 subjects (2.2%) had COPD and 22 (2.3%) had asthma. After adjusting for confounding factors, COPD patients had higher risk of developing severe illness (OR: 23.433; 95% CI 1.525-360.135; P < .01) and acute respiratory distress syndrome (OR: 19.762; 95% CI 1.461-267.369; P = .025) than asthmatics. COPD patients, particularly those with severe COVID-19, had lower counts of CD4+ T and CD8+ T cells and B cells and higher levels of TNF-α, IL-2 receptor, IL-10, IL-8, and IL-6 than asthmatics. COPD patients had increased, whereas asthmatics had decreased ACE2 protein expression in lower airways, compared with that in control subjects without asthma and COPD. IL-4 and IL-13 downregulated, but TNF-α, IL-12, and IL-17A upregulated ACE2 expression in BEAS-2B cells. CONCLUSION: Patients with asthma and COPD likely have different risk of severe COVID-19, which may be associated with different ACE2 expression.


Subject(s)
Asthma/epidemiology , COVID-19/complications , Pulmonary Disease, Chronic Obstructive/epidemiology , Aged , Angiotensin-Converting Enzyme 2/biosynthesis , Asthma/immunology , Asthma/metabolism , COVID-19/immunology , Comorbidity , Female , Humans , Male , Middle Aged , Prevalence , Pulmonary Disease, Chronic Obstructive/immunology , Pulmonary Disease, Chronic Obstructive/metabolism , SARS-CoV-2
4.
Natl Sci Rev ; 7(12): 1868-1878, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1087785

ABSTRACT

Systematic autopsy and comprehensive pathological analyses of COVID-19 decedents should provide insights into the disease characteristics and facilitate the development of novel therapeutics. In this study, we report the autopsy findings from the lungs and lymphatic organs of 12 COVID-19 decedents-findings that evaluated histopathological changes, immune cell signature and inflammatory factor expression in the lungs, spleen and lymph nodes. Here we show that the major pulmonary alterations included diffuse alveolar damage, interstitial fibrosis and exudative inflammation featured with extensive serous and fibrin exudates, macrophage infiltration and abundant production of inflammatory factors (IL-6, IP-10, TNFα and IL-1ß). The spleen and hilar lymph nodes contained lesions with tissue structure disruption and immune cell dysregulation, including lymphopenia and macrophage accumulation. These findings provide pathological evidence that links injuries of the lungs and lymphatic organs with the fatal systematic respiratory and immune malfunction in critically ill COVID-19 patients.

5.
Proc Natl Acad Sci U S A ; 117(45): 28336-28343, 2020 11 10.
Article in English | MEDLINE | ID: covidwho-882991

ABSTRACT

Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2, has resulted thus far in greater than 933,000 deaths worldwide; yet disease pathogenesis remains unclear. Clinical and immunological features of patients with COVID-19 have highlighted a potential role for changes in immune activity in regulating disease severity. However, little is known about the responses in human lung tissue, the primary site of infection. Here we show that pathways related to neutrophil activation and pulmonary fibrosis are among the major up-regulated transcriptional signatures in lung tissue obtained from patients who died of COVID-19 in Wuhan, China. Strikingly, the viral burden was low in all samples, which suggests that the patient deaths may be related to the host response rather than an active fulminant infection. Examination of the colonic transcriptome of these patients suggested that SARS-CoV-2 impacted host responses even at a site with no obvious pathogenesis. Further proteomics analysis validated our transcriptome findings and identified several key proteins, such as the SARS-CoV-2 entry-associated protease cathepsins B and L and the inflammatory response modulator S100A8/A9, that are highly expressed in fatal cases, revealing potential drug targets for COVID-19.


Subject(s)
COVID-19/metabolism , Proteome/metabolism , Transcriptome , Aged , Aged, 80 and over , COVID-19/genetics , COVID-19/immunology , COVID-19/pathology , Colon/metabolism , Fatal Outcome , Female , Humans , Lung/metabolism , Lung/pathology , Lung/virology , Male , Middle Aged , Neutrophil Activation , Proteome/genetics , SARS-CoV-2/pathogenicity , Viral Load
6.
J Am Soc Nephrol ; 31(9): 2205-2221, 2020 09.
Article in English | MEDLINE | ID: covidwho-725838

ABSTRACT

BACKGROUND: The incidence, severity, and outcomes of AKI in COVID-19 varied in different reports. In patients critically ill with COVID-19, the clinicopathologic characteristics of AKI have not been described in detail. METHODS: This is a retrospective cohort study of 81 patients critically ill with COVID-19 in an intensive care unit. The incidence, etiologies, and outcomes of AKI were analyzed. Pathologic studies were performed in kidney tissues from ten deceased patients with AKI. RESULTS: A total of 41 (50.6%) patients experienced AKI in this study. The median time from illness to AKI was 21.0 (IQR, 9.5-26.0) days. The proportion of Kidney Disease Improving Global Outcomes (KDIGO) stage 1, stage 2, and stage 3 AKI were 26.8%, 31.7%, and 41.5%, respectively. The leading causes of AKI included septic shock (25 of 41, 61.0%), volume insufficiency (eight of 41, 19.5%), and adverse drug effects (five of 41, 12.2%). The risk factors for AKI included age (per 10 years) (HR, 1.83; 95% CI, 1.24 to 2.69; P=0.002) and serum IL-6 level (HR, 1.83; 95% CI, 1.23 to 2.73; P=0.003). KDIGO stage 3 AKI predicted death. Other potential risk factors for death included male sex, elevated D-dimer, serum IL-6 level, and higher Sequential Organ Failure Assessment score. The predominant pathologic finding was acute tubular injury. Nucleic acid tests and immunohistochemistry failed to detect the virus in kidney tissues. CONCLUSIONS: AKI was a common and multifactorial complication in patients critically ill with COVID-19 at the late stage of the disease course. The predominant pathologic finding was acute tubular injury. Older age and higher serum IL-6 level were risk factors of AKI, and KDIGO stage 3 AKI independently predicted death.


Subject(s)
Acute Kidney Injury/pathology , Betacoronavirus , Coronavirus Infections/complications , Kidney/pathology , Pneumonia, Viral/complications , Acute Kidney Injury/etiology , Aged , Aged, 80 and over , COVID-19 , Coronavirus Infections/pathology , Creatinine/blood , Critical Illness , Female , Humans , Intensive Care Units , Interleukin-6/blood , Kidney/ultrastructure , Kidney/virology , Male , Middle Aged , Pandemics , Pneumonia, Viral/pathology , Retrospective Studies , Risk Factors , SARS-CoV-2
7.
Curr Med Sci ; 40(4): 618-624, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-695581

ABSTRACT

The COVID-19 pandemic caused by SARS-CoV2 is characterized by a remarkable variation in clinical severity ranging from a mild illness to a fatal multi-organ disease. Understanding the dysregulated human immune responses in the fatal subjects is critical for management of COVID-19 patients and the pandemic. In this study, we examined the immune cell compositions in the lung tissues and hilar lymph nodes using immunohistochemistry on 6 deceased COVID-19 patients and 4 focal organizing pneumonia (FOP) patients who underwent lung surgery and served as controls. We found a dominant presence of macrophages and a general deficiency of T cells and B cells in the lung tissues from deceased COVID-19 patients. In contrast to the FOP patients, Tfh cells and germinal center formation were largely absent in the draining hilar lymph nodes in the deceased COVID-19 patients. This was correlated with reduced IgM and IgG levels compared to convalescent COVID-19 patients. In summary, our data highlight a defect of germinal center structure in deceased COVID-19 patients leading to an impaired humoral immunity. Understanding the mechanisms of this deficiency will be one of the key points for the management of this epidemic.


Subject(s)
Betacoronavirus , Coronavirus Infections/immunology , Germinal Center/immunology , Pneumonia, Viral/immunology , T-Lymphocytes, Helper-Inducer/immunology , Adaptive Immunity , Aged , Aged, 80 and over , COVID-19 , Case-Control Studies , China/epidemiology , Coronavirus Infections/mortality , Coronavirus Infections/pathology , Fatal Outcome , Female , Germinal Center/pathology , Humans , Lymphopenia/immunology , Lymphopenia/mortality , Lymphopenia/pathology , Macrophages/immunology , Macrophages/pathology , Male , Middle Aged , Pandemics , Pneumonia, Viral/mortality , Pneumonia, Viral/pathology , SARS-CoV-2 , T-Lymphocytes, Helper-Inducer/pathology
SELECTION OF CITATIONS
SEARCH DETAIL