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1.
J Bras Pneumol ; 48(3): e20210438, 2022.
Article in English, Portuguese | MEDLINE | ID: covidwho-1836602

ABSTRACT

This brief communication demonstrates the correlation of persistent respiratory symptoms with functional, tomographic, and transbronchial pulmonary biopsy findings in patients with COVID-19 who had a long follow-up period. We report a series of six COVID-19 patients with pulmonary involvement who presented with persistent dyspnea within 4-15 months of discharge. We performed transbronchial biopsies, and the histopathological pattern consistently demonstrated peribronchial remodeling with interstitial pulmonary fibrosis. Therefore, lung biopsy may be useful in the approach of patients with long COVID-19, although the type of procedure, its precise indication, and the moment to perform it are yet to be clarified. (Brazilian Registry of Clinical Trials-ReBEC; identifier: RBR-8j9kqy [http://www.ensaiosclinicos.gov.br]).


Subject(s)
COVID-19 , Lung Diseases, Interstitial , Biopsy/methods , COVID-19/complications , Humans , Lung/diagnostic imaging , Lung/pathology , Lung Diseases, Interstitial/pathology
2.
Am J Obstet Gynecol MFM ; 4(3): 100589, 2022 05.
Article in English | MEDLINE | ID: covidwho-1664617

ABSTRACT

Data on the vertical transmission rate of COVID-19 in pregnancy are limited, although data reporting mother-fetal transmission in the second trimester of pregnancy are controversial. We described a case of second-trimester twin stillbirth in a woman with SARS-CoV-2 infection in which placental and fetal markers of infection were detected, despite the absence of respiratory syndrome. The patient developed clinical chorioamnionitis and spontaneously delivered 2 stillborn infants. Placental histology and immunohistochemistry demonstrated SARS-CoV-2 infection mostly within the syncytiotrophoblast, and fetal autopsy showed the development of interstitial pneumonia. Our findings demonstrated that in utero vertical transmission is possible in asymptomatic pregnant women with SARS-CoV-2 infection and that infection can lead to severe morbidity in the second trimester of pregnancy.


Subject(s)
COVID-19 , Lung Diseases, Interstitial , Pregnancy Complications, Infectious , COVID-19/complications , COVID-19/diagnosis , Female , Humans , Lung Diseases, Interstitial/pathology , Placenta/pathology , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/pathology , Pregnancy Trimester, Second , SARS-CoV-2 , Stillbirth
3.
Sci Rep ; 11(1): 19979, 2021 10 07.
Article in English | MEDLINE | ID: covidwho-1462032

ABSTRACT

COVID-19 pandemic led to a worldwide increase of hospitalizations for interstitial pneumonia with thrombosis complications, endothelial injury and multiorgan disease. Common CT findings include lung bilateral infiltrates, bilateral ground-glass opacities and/or consolidation whilst no current laboratory parameter consents rapidly evaluation of COVID-19 risk and disease severity. In the present work we investigated the association of sFLT-1 and CA 15.3 with endothelial damage and pulmonary fibrosis. Serum sFlt-1 has been associated with endothelial injury and sepsis severity, CA 15.3 seems an alternative marker for KL-6 for fibrotic lung diseases and pulmonary interstitial damage. We analysed 262 SARS-CoV-2 patients with differing levels of clinical severity; we found an association of serum sFlt-1 (ROC AUC 0.902, decision threshold > 90.3 pg/mL, p < 0.001 Sens. 83.9% and Spec. 86.7%) with presence, extent and severity of the disease. Moreover, CA 15.3 appeared significantly increased in COVID-19 severe lung fibrosis (ICU vs NON-ICU patients 42.6 ± 3.3 vs 25.7 ± 1.5 U/mL, p < 0.0001) and was associated with lung damage severity grade (ROC AUC 0.958, decision threshold > 24.8 U/mL, p < 0.0001, Sens. 88.4% and Spec. 91.8%). In conclusion, serum levels of sFlt-1 and CA 15.3 appeared useful tools for categorizing COVID-19 clinical stage and may represent a valid aid for clinicians to better personalise treatment.


Subject(s)
COVID-19/blood , Mucin-1/blood , Pulmonary Fibrosis/blood , Vascular Endothelial Growth Factor Receptor-1/blood , Aged , Biomarkers/blood , COVID-19/complications , COVID-19/pathology , Female , Humans , Lung Diseases, Interstitial/blood , Lung Diseases, Interstitial/complications , Lung Diseases, Interstitial/pathology , Male , Middle Aged , Pulmonary Fibrosis/complications , Pulmonary Fibrosis/pathology , SARS-CoV-2/isolation & purification
4.
Dis Markers ; 2021: 5536360, 2021.
Article in English | MEDLINE | ID: covidwho-1378085

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the diagnostic and prognostic value of red blood cell distribution width (RDW) in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). METHODS: We retrospectively reviewed 213 CTD-ILD patients and 97 CTD patients without ILD from February 2017 to February 2020. Hospital and office records were used as data sources. CTD-ILD patients were followed up. RESULTS: Patients with CTD-ILD had significantly higher RDW than those with CTD without ILD (p < 0.001). The area under the receiver operating characteristic curve (AUROC) of RDW for discriminating CTD-ILD from CTD without ILD was 0.64 (95% CI: 0.57-0.70, p < 0.001). The cutoff value of RDW for discriminating CTD-ILD from CTD without ILD was 13.95% with their corresponding specificity (55.9%) and sensitivity (70.1%). Correlation analyses showed that the increased RDW was significantly correlated with decreased DLCO%predicted (r = -0.211, p = 0.002). Cox multiple regression analysis indicated that RDW (HR = 1.495, p < 0.001) was an independent factor in the survival of CTD-ILD. The best cutoff value of RDW to predict the survival of patients with CTD-ILD was 14.05% (AUC = 0.78, 95% CI: 0.72-0.84, p < 0.001). The log-rank test showed a significant difference in survival between the two groups (RDW > 14.05% and RDW < 14.05%). CONCLUSION: RDW was higher in CTD-ILD patients and had a negative correlation with DLCO%predicted. RDW may be an important serum biomarker for severity and prognosis of patients with CTD-ILD.


Subject(s)
Biomarkers/blood , Connective Tissue Diseases/complications , Erythrocyte Indices , Lung Diseases, Interstitial/pathology , Case-Control Studies , Disease Progression , Female , Follow-Up Studies , Humans , Lung Diseases, Interstitial/blood , Lung Diseases, Interstitial/etiology , Male , Middle Aged , Prognosis , ROC Curve , Retrospective Studies , Survival Rate
5.
Int J Mol Sci ; 22(12)2021 Jun 09.
Article in English | MEDLINE | ID: covidwho-1264471

ABSTRACT

Interstitial lung diseases (ILDs) comprise different fibrotic lung disorders characterized by cellular proliferation, interstitial inflammation, and fibrosis. The JAK/STAT molecular pathway is activated under the interaction of a broad number of profibrotic/pro-inflammatory cytokines, such as IL-6, IL-11, and IL-13, among others, which are increased in different ILDs. Similarly, several growth factors over-expressed in ILDs, such as platelet-derived growth factor (PDGF), transforming growth factor ß1 (TGF-ß1), and fibroblast growth factor (FGF) activate JAK/STAT by canonical or non-canonical pathways, which indicates a predominant role of JAK/STAT in ILDs. Between the different JAK/STAT isoforms, it appears that JAK2/STAT3 are predominant, initiating cellular changes observed in ILDs. This review analyzes the expression and distribution of different JAK/STAT isoforms in ILDs lung tissue and different cell types related to ILDs, such as lung fibroblasts and alveolar epithelial type II cells and analyzes JAK/STAT activation. The effect of JAK/STAT phosphorylation on cellular fibrotic processes, such as proliferation, senescence, autophagy, endoplasmic reticulum stress, or epithelial/fibroblast to mesenchymal transition will be described. The small molecules directed to inhibit JAK/STAT activation were assayed in vitro and in in vivo models of pulmonary fibrosis, and different JAK inhibitors are currently approved for myeloproliferative disorders. Recent evidence indicates that JAK inhibitors or monoclonal antibodies directed to block IL-6 are used as compassionate use to attenuate the excessive inflammation and lung fibrosis related to SARS-CoV-2 virus. These altogether indicate that JAK/STAT pathway is an attractive target to be proven in future clinical trials of lung fibrotic disorders.


Subject(s)
Janus Kinases/metabolism , Lung Diseases, Interstitial/pathology , STAT Transcription Factors/metabolism , Cellular Senescence , Endoplasmic Reticulum Stress , Humans , Interleukins/metabolism , Janus Kinases/antagonists & inhibitors , Janus Kinases/genetics , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/metabolism , Protein Isoforms/genetics , Protein Isoforms/metabolism , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/metabolism , Protein Kinase Inhibitors/therapeutic use , STAT Transcription Factors/antagonists & inhibitors , STAT Transcription Factors/genetics , Signal Transduction
6.
Ann Diagn Pathol ; 53: 151744, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1227970

ABSTRACT

OBJECTIVES: Assess the pathologic changes in the lungs of COVID-19 decedents and correlate these changes with demographic data, clinical course, therapies, and duration of illness. METHODS: Lungs of 12 consecutive COVID-19 decedents consented for autopsy were evaluated for gross and histopathologic abnormalities. A complete Ghon "en block" dissection was performed on all cases; lung weights and gross characteristics recorded. Immunohistochemical studies were performed to characterize lymphocytic infiltrates and to assess SARS-CoV-2 capsid protein. RESULTS: Two distinct patterns of pulmonary involvement were identified. Three of 12 cases demonstrated a predominance of acute alveolar damage (DAD) while 9 of 12 cases demonstrated a marked increase in intra-alveolar macrophages in a fashion resembling desquamative interstitial pneumonia or macrophage activation syndrome (DIP/MAS). Two patterns were correlated solely with a statistically significant difference in the duration of illness. The group exhibiting DAD had duration of illness of 5.7 days while the group with DIP/MAS had duration of illness of 21.5 days (t-test p = 0.014). CONCLUSIONS: The pulmonary pathology of COVID-19 patients demonstrates a biphasic pattern, an acute phase demonstrating DAD changes while the patients with a more prolonged course exhibit a different pattern that resembles DIP/MAS-like pattern. The potential mechanisms and clinical significance are discussed.


Subject(s)
COVID-19/pathology , Immunohistochemistry/methods , Lung Diseases, Interstitial/pathology , Lung/pathology , Macrophage Activation Syndrome/pathology , Adult , Aged , Aged, 80 and over , Autopsy , COVID-19/complications , COVID-19/diagnosis , COVID-19/virology , Capsid Proteins/metabolism , Comorbidity , Female , Humans , Lung/metabolism , Lung Diseases, Interstitial/etiology , Lung Diseases, Interstitial/virology , Lymphocytes/metabolism , Lymphocytes/pathology , Macrophage Activation Syndrome/etiology , Macrophage Activation Syndrome/virology , Macrophages/pathology , Male , Middle Aged , Pulmonary Alveoli/immunology , Pulmonary Alveoli/pathology , SARS-CoV-2/genetics , Sick Leave
7.
Pulmonology ; 27(5): 423-437, 2021.
Article in English | MEDLINE | ID: covidwho-1174466

ABSTRACT

SARS-CoV-2 is a new beta coronavirus, similar to SARS-CoV-1, that emerged at the end of 2019 in the Hubei province of China. It is responsible for coronavirus disease 2019 (COVID-19), which was declared a pandemic by the World Health Organization on March 11, 2020. The ability to gain quick control of the pandemic has been hampered by a lack of detailed knowledge about SARS-CoV-2-host interactions, mainly in relation to viral biology and host immune response. The rapid clinical course seen in COVID-19 indicates that infection control in asymptomatic patients or patients with mild disease is probably due to the innate immune response, as, considering that SARS-CoV-2 is new to humans, an effective adaptive response would not be expected to occur until approximately 2-3 weeks after contact with the virus. Antiviral innate immunity has humoral components (complement and coagulation-fibrinolysis systems, soluble proteins that recognize glycans on cell surface, interferons, chemokines, and naturally occurring antibodies) and cellular components (natural killer cells and other innate lymphocytes). Failure of this system would pave the way for uncontrolled viral replication in the airways and the mounting of an adaptive immune response, potentially amplified by an inflammatory cascade. Severe COVID-19 appears to be due not only to viral infection but also to a dysregulated immune and inflammatory response. In this paper, the authors review the most recent publications on the immunobiology of SARS-CoV-2, virus interactions with target cells, and host immune responses, and highlight possible associations between deficient innate and acquired immune responses and disease progression and mortality. Immunotherapeutic strategies targeting both the virus and dysfunctional immune responses are also addressed.


Subject(s)
Adaptive Immunity/immunology , COVID-19/immunology , Immunity, Innate/immunology , SARS-CoV-2/immunology , Adult , Aged , Antiviral Agents/therapeutic use , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/pathology , Disease Progression , Humans , Immunotherapy/methods , Inflammation/immunology , Inflammation/physiopathology , Inflammation/virology , Lung Diseases, Interstitial/complications , Lung Diseases, Interstitial/pathology , Lung Diseases, Interstitial/virology , Middle Aged , Respiration, Artificial/methods , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/therapy , SARS-CoV-2/genetics , Severity of Illness Index
8.
Medicine (Baltimore) ; 100(14): e25310, 2021 Apr 09.
Article in English | MEDLINE | ID: covidwho-1174980

ABSTRACT

ABSTRACT: To investigate the relationship between damaged lung assessed by chest computed tomography (CT) scan and laboratory biochemical parameters with the aim of finding other diagnostic tools.Patients who underwent chest CT for suspected Corona Virus Disease-2019 (COVID-19) pneumonia at the emergency department admission in the first phase of COVID-19 epidemic in Italy were retrospectively analyzed. Patients with both negative chest CT and absence of the novel coronavirus in nasopharyngeal or oropharyngeal real-time reverse transcriptase polymerase chain reaction (RT-PCR) swabs were excluded from the study. A total of 462 patients with positive CT scans for interstitial pneumonia were included in the study (250 males and 212 females, mean age 57 ±â€Š17 years, range 18-89). Of these, 344 were positive to RT-PCR test, 118 were negative to double RT-PCR tests.CTs were analyzed for quantification of affected lung volume visually and by dedicated software. Statistical analysis to evaluate the relationship between laboratory analyses and CT patterns and amount of damaged lung related with COVID-19 pneumonia was performed in 2 groups of patients: positive RT-PCR COVID-19 group and negative RT-PCR COVID-19 group, but both with positive CT scans for interstitial pneumonia.Lymphocytopenia, C-reactive protein (CRP), lactate dehydrogenase (LDH), d-dimer, and fibrinogen increased levels occurred in most patients without statistically significant differences between the 2 groups with CT scans suggestive for COVID-19. In fact, in both groups the volume of lung damage was strongly associated with altered laboratory test results, even for patients with negative RT-PCR test.The decreased number of lymphocytes, and the increased levels of CRP, LDH, d-dimer, and fibrinogen levels are associated with SARS-CoV 2 related pneumonia. This may be useful as an additional diagnostic tool in patients with double negative RT-PCR assay and with highly suspected clinic and chest CT features for COVID-19 to isolate patients in a pandemic period.


Subject(s)
COVID-19/blood , COVID-19/diagnostic imaging , Lung Diseases, Interstitial/blood , Lung Diseases, Interstitial/diagnostic imaging , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/pathology , Female , Hematologic Tests , Humans , Italy , Lung/diagnostic imaging , Lung/pathology , Lung Diseases, Interstitial/etiology , Lung Diseases, Interstitial/pathology , Male , Middle Aged , Real-Time Polymerase Chain Reaction , Retrospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed , Young Adult
9.
PLoS One ; 16(3): e0246582, 2021.
Article in English | MEDLINE | ID: covidwho-1125432

ABSTRACT

PURPOSE: To evaluate the discrimination of parenchymal lesions between COVID-19 and other atypical pneumonia (AP) by using only radiomics features. METHODS: In this retrospective study, 301 pneumonic lesions (150 ground-glass opacity [GGO], 52 crazy paving [CP], 99 consolidation) obtained from nonenhanced thorax CT scans of 74 AP (46 male and 28 female; 48.25±13.67 years) and 60 COVID-19 (39 male and 21 female; 48.01±20.38 years) patients were segmented manually by two independent radiologists, and Location, Size, Shape, and First- and Second-order radiomics features were calculated. RESULTS: Multiple parameters showed significant differences between AP and COVID-19-related GGOs and consolidations, although only the Range parameter was significantly different for CPs. Models developed by using the Bayesian information criterion (BIC) for the whole group of GGO and consolidation lesions predicted COVID-19 consolidation and AP GGO lesions with low accuracy (46.1% and 60.8%, respectively). Thus, instead of subjective classification, lesions were reclassified according to their skewness into positive skewness group (PSG, 78 AP and 71 COVID-19 lesions) and negative skewness group (NSG, 56 AP and 44 COVID-19 lesions), and group-specific models were created. The best AUC, accuracy, sensitivity, and specificity were respectively 0.774, 75.8%, 74.6%, and 76.9% among the PSG models and 0.907, 83%, 79.5%, and 85.7% for the NSG models. The best PSG model was also better at predicting NSG lesions smaller than 3 mL. Using an algorithm, 80% of COVID-19 and 81.1% of AP patients were correctly predicted. CONCLUSION: During periods of increasing AP, radiomics parameters may provide valuable data for the differential diagnosis of COVID-19.


Subject(s)
COVID-19/diagnostic imaging , Pneumonia, Mycoplasma/diagnostic imaging , Tomography, X-Ray Computed/methods , Adult , Aged , Aged, 80 and over , Bayes Theorem , COVID-19/pathology , Cross-Sectional Studies , Diagnosis, Differential , Disease Progression , Female , Humans , Lung/pathology , Lung Diseases, Interstitial/pathology , Male , Middle Aged , Mycoses/pathology , Parenchymal Tissue/diagnostic imaging , Pneumonia, Mycoplasma/pathology , Retrospective Studies , SARS-CoV-2/pathogenicity , Thorax , Tomography, Emission-Computed/methods
11.
Front Immunol ; 11: 587517, 2020.
Article in English | MEDLINE | ID: covidwho-887608

ABSTRACT

Background and Objectives: Understanding the pathophysiology of respiratory failure in coronavirus disease 2019 (COVID-19) is indispensable for development of therapeutic strategies. Since we observed similarities between COVID-19 and interstitial lung disease in connective tissue disease (CTD-ILD), we investigated features of autoimmunity in SARS-CoV-2-associated respiratory failure. Methods: We prospectively enrolled 22 patients with RT-PCR-confirmed SARS-CoV-2 infection and 10 patients with non-COVID-19-associated pneumonia. Full laboratory testing was performed including autoantibody (AAB; ANA/ENA) screening using indirect immunofluorescence and immunoblot. Fifteen COVID-19 patients underwent high-resolution computed tomography. Transbronchial biopsies/autopsy tissue samples for histopathology and ultrastructural analyses were obtained from 4/3 cases, respectively. Results: Thirteen (59.1%) patients developed acute respiratory distress syndrome (ARDS), and five patients (22.7%) died from the disease. ANA titers ≥1:320 and/or positive ENA immunoblots were detected in 11/13 (84.6%) COVID-19 patients with ARDS, in 1/9 (11.1%) COVID-19 patients without ARDS (p = 0.002) and in 4/10 (40%) patients with non-COVID-19-associated pneumonias (p = 0.039). Detection of AABs was significantly associated with a need for intensive care treatment (83.3 vs. 10%; p = 0.002) and occurrence of severe complications (75 vs. 20%, p = 0.03). Radiological and histopathological findings were highly heterogeneous including patterns reminiscent of exacerbating CTD-ILD, while ultrastructural analyses revealed interstitial thickening, fibroblast activation, and deposition of collagen fibrils. Conclusions: We are the first to report overlapping clinical, serological, and imaging features between severe COVID-19 and acute exacerbation of CTD-ILD. Our findings indicate that autoimmune mechanisms determine both clinical course and long-term sequelae after SARS-CoV-2 infection, and the presence of autoantibodies might predict adverse clinical course in COVID-19 patients.


Subject(s)
Connective Tissue Diseases/pathology , Coronavirus Infections/pathology , Lung Diseases, Interstitial/pathology , Pneumonia, Viral/pathology , Severe Acute Respiratory Syndrome/pathology , Adult , Aged , Aged, 80 and over , Autoantibodies/blood , Betacoronavirus/immunology , COVID-19 , Connective Tissue Diseases/immunology , Coronavirus Infections/immunology , Female , Humans , Lung/pathology , Lung Diseases, Interstitial/immunology , Male , Middle Aged , Pandemics , Pneumonia, Viral/immunology , Prospective Studies , SARS-CoV-2 , Severe Acute Respiratory Syndrome/immunology
13.
J Infect Dis ; 222(10): 1596-1600, 2020 10 13.
Article in English | MEDLINE | ID: covidwho-693639

ABSTRACT

Using a reliable primate model is critical for developing therapeutic advances to treat humans infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Here, we exposed macaques to high titers of SARS-CoV-2 via combined transmission routes. We observed acute interstitial pneumonia with endotheliitis in the lungs of all infected macaques. All macaques had a significant loss of total lymphocytes during infection, which were restored over time. These data show that SARS-CoV-2 causes a coronavirus disease 2019 (COVID-19)-like disease in macaques. This new model could investigate the interaction between SARS-CoV-2 and the immune system to test therapeutic strategies.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/complications , Disease Models, Animal , Lung Diseases, Interstitial/complications , Lymphopenia/complications , Monkey Diseases/virology , Pneumonia, Viral/complications , Animals , COVID-19 , Coronavirus Infections/pathology , Coronavirus Infections/virology , Female , Lung Diseases, Interstitial/pathology , Lymphopenia/pathology , Macaca fascicularis , Macaca mulatta , Male , Monkey Diseases/pathology , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2
14.
Expert Rev Clin Immunol ; 16(8): 751-770, 2020 08.
Article in English | MEDLINE | ID: covidwho-684487

ABSTRACT

INTRODUCTION: Main clinical manifestations of SARS-CoV-2 infection are characterized by fever, dyspnea, and interstitial pneumonia, frequently evolving in acute respiratory distress syndrome (ARDS). AREAS COVERED: Features of coronavirus disease 2019 (COVID-19) presents some common points with interstitial lung disease (ILD) both idiopathic and related to rheumatoid arthritis (RA), typically characterized by a chronic progression over time and possibly complicated by acute exacerbation (AE). The study of common pathogenetic mechanisms, such as the involvement of toll-like receptor 4, could contribute to the knowledge and treatment of idiopathic and RA-ILD. Moreover, hyperinflammation, mainly characterized by increase of effector T-cells and inflammatory cytokines, and activation of coagulation cascade, observed in COVID-19 related ARDS have been already shown in patients with AE of idiopathic and RA-ILD. A literature search was performed in PubMed, Embase, Scopus, and Web of Science, together with a manual search in COVID-resource centers of the main journals. EXPERT OPINION: Despite the uncertainty about pathogenetic aspects about COVID-19- pneumonia, it could be a possible model for other forms of ILD and AE. The great amount of data from studies on COVID-19 could be helpful in proposing safe therapeutic approaches for RA-ILD, in understanding pathogenesis of usual interstitial pneumonia and to develop new therapeutic strategies for AE.


Subject(s)
Arthritis, Rheumatoid/pathology , Coronavirus Infections/pathology , Lung Diseases, Interstitial/pathology , Pneumonia, Viral/pathology , Arthritis, Rheumatoid/therapy , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/therapy , Disease Progression , Humans , Idiopathic Pulmonary Fibrosis/pathology , Idiopathic Pulmonary Fibrosis/therapy , Lung/pathology , Lung Diseases, Interstitial/therapy , Pandemics , Pneumonia, Viral/therapy , SARS-CoV-2 , Symptom Flare Up , Toll-Like Receptor 4/metabolism
15.
J Crit Care ; 59: 149-155, 2020 10.
Article in English | MEDLINE | ID: covidwho-635492

ABSTRACT

PURPOSE: Pathological data of critical ill COVID-19 patients is essential in the search for optimal treatment options. MATERIAL AND METHODS: We performed postmortem needle core lung biopsies in seven patients with COVID-19 related ARDS. Clinical, radiological and microbiological characteristics are reported together with histopathological findings. MEASUREMENT AND MAIN RESULTS: Patients age ranged from 58 to 83 years, five males and two females were included. Time from hospital admission to death ranged from 12 to 36 days, with a mean of 20 ventilated days. ICU stay was complicated by pulmonary embolism in five patients and positive galactomannan on bronchoalveolar lavage fluid in six patients, suggesting COVID-19 associated pulmonary aspergillosis. Chest CT in all patients showed ground glass opacities, commonly progressing to nondependent consolidations. We observed four distinct histopathological patterns: acute fibrinous and organizing pneumonia, diffuse alveolar damage, fibrosis and, in four out of seven patients an organizing pneumonia. None of the biopsy specimens showed any signs of invasive aspergillosis. CONCLUSIONS: In this case series common late histopathology in critically ill COVID patients is not classic DAD but heterogeneous with predominant pattern of organizing pneumonia. Postmortem biopsy investigations in critically COVID-19 patients with probable COVID-19 associated pulmonary aspergillosis obtained no evidence for invasive aspergillosis.


Subject(s)
Coronavirus Infections/pathology , Lung Diseases, Interstitial/pathology , Lung/pathology , Pneumonia, Viral/pathology , Pulmonary Aspergillosis/pathology , Respiratory Distress Syndrome/pathology , Aged , Aged, 80 and over , Autopsy , Betacoronavirus , Biopsy , Biopsy, Large-Core Needle , Bronchoalveolar Lavage Fluid/chemistry , COVID-19 , Coinfection , Coronavirus Infections/complications , Coronavirus Infections/diagnostic imaging , Critical Illness , Female , Galactose/analogs & derivatives , Humans , Lung/diagnostic imaging , Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/etiology , Male , Mannans/metabolism , Middle Aged , Pandemics , Phenotype , Pneumonia, Viral/complications , Pneumonia, Viral/diagnostic imaging , Pulmonary Aspergillosis/complications , Pulmonary Aspergillosis/diagnostic imaging , Pulmonary Embolism/complications , Pulmonary Embolism/diagnostic imaging , Respiratory Distress Syndrome/diagnostic imaging , Respiratory Distress Syndrome/etiology , SARS-CoV-2 , Tomography, X-Ray Computed
16.
Science ; 369(6505): 818-823, 2020 08 14.
Article in English | MEDLINE | ID: covidwho-631755

ABSTRACT

Coronavirus disease 2019 (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. It is unclear whether convalescing patients have a risk of reinfection. We generated a rhesus macaque model of SARS-CoV-2 infection that was characterized by interstitial pneumonia and systemic viral dissemination mainly in the respiratory and gastrointestinal tracts. Rhesus macaques reinfected with the identical SARS-CoV-2 strain during the early recovery phase of the initial SARS-CoV-2 infection did not show detectable viral dissemination, clinical manifestations of viral disease, or histopathological changes. Comparing the humoral and cellular immunity between primary infection and rechallenge revealed notably enhanced neutralizing antibody and immune responses. Our results suggest that primary SARS-CoV-2 exposure protects against subsequent reinfection in rhesus macaques.


Subject(s)
Betacoronavirus , Coronavirus Infections/immunology , Coronavirus Infections/virology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Anal Canal/virology , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , B-Lymphocyte Subsets/immunology , Betacoronavirus/immunology , Betacoronavirus/isolation & purification , Betacoronavirus/physiology , COVID-19 , Coronavirus Infections/pathology , Coronavirus Infections/physiopathology , Disease Models, Animal , Host Microbial Interactions , Immunity, Cellular , Immunity, Humoral , Lung/diagnostic imaging , Lung/immunology , Lung/pathology , Lung/virology , Lung Diseases, Interstitial/immunology , Lung Diseases, Interstitial/pathology , Lung Diseases, Interstitial/virology , Macaca mulatta , Nasopharynx/virology , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/physiopathology , Recurrence , SARS-CoV-2 , T-Lymphocyte Subsets/immunology , Viral Load , Virus Replication
17.
Vet Q ; 40(1): 190-197, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-598972

ABSTRACT

Background: The natural MERS-CoV infection in dromedary camels is understudied. Recent experimental studies showed no obvious clinical signs in the infected dromedary camels.Aim: To study the pathological changes associated with natural MERS-CoV infection in dromedary camels.Methods: Tissues from three MERS-CoV positive animals as well as two negative animals were collected and examined for the presence of pathological changes. The screening of the animals was carried out first by the rapid agglutination test and then confirmed by the RT-PCR. The selected animals ranged from six to twelve months in age. The sensitivity of the latter technique was much higher in the detection of MERS-CoV than the Rapid test (14 out of 75 animals positive or 18% versus 31 out of 75 positive or 41%).Results: MERS-CoV induced marked desquamation of the respiratory epithelium accompanied by lamina propria and submucosal mononuclear cells infiltration, epithelial hyperplasia in the respiratory tract, and interstitial pneumonia. Ciliary cell loss was seen in the trachea and turbinate. In addition, degeneration of glomerular capillaries with the complete destruction of glomerular tufts that were replaced with fibrinous exudate in renal corpuscles in the renal cortex were noticed. Expression of the MERS-CoV-S1 and MERS-CoV-N proteins was revealed in respiratory tract, and kidneys.Conclusion: To our knowledge, this is the first study describing the pathological changes of MERS-CoV infection in dromedary camels under natural conditions. In contrast to experimental infection in case of spontaneous infection interstitial pneumonea is evident at least in some affected animals.


Subject(s)
Camelus/virology , Coronavirus Infections/veterinary , Lung Diseases, Interstitial/veterinary , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Animals , Coronavirus Infections/pathology , Coronavirus Infections/virology , Female , Kidney Diseases/pathology , Kidney Diseases/veterinary , Kidney Diseases/virology , Lung Diseases, Interstitial/pathology , Lung Diseases, Interstitial/virology , Male , Saudi Arabia , Viral Proteins/analysis
19.
Cell Host Microbe ; 28(1): 124-133.e4, 2020 07 08.
Article in English | MEDLINE | ID: covidwho-378130

ABSTRACT

Since December 2019, a novel coronavirus SARS-CoV-2 has emerged and rapidly spread throughout the world, resulting in a global public health emergency. The lack of vaccine and antivirals has brought an urgent need for an animal model. Human angiotensin-converting enzyme II (ACE2) has been identified as a functional receptor for SARS-CoV-2. In this study, we generated a mouse model expressing human ACE2 (hACE2) by using CRISPR/Cas9 knockin technology. In comparison with wild-type C57BL/6 mice, both young and aged hACE2 mice sustained high viral loads in lung, trachea, and brain upon intranasal infection. Although fatalities were not observed, interstitial pneumonia and elevated cytokines were seen in SARS-CoV-2 infected-aged hACE2 mice. Interestingly, intragastric inoculation of SARS-CoV-2 was seen to cause productive infection and lead to pulmonary pathological changes in hACE2 mice. Overall, this animal model described here provides a useful tool for studying SARS-CoV-2 transmission and pathogenesis and evaluating COVID-19 vaccines and therapeutics.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections , Disease Models, Animal , Mice, Inbred C57BL , Pandemics , Pneumonia, Viral , Aging , Angiotensin-Converting Enzyme 2 , Animals , Brain/virology , COVID-19 , CRISPR-Cas Systems , Coronavirus Infections/pathology , Coronavirus Infections/virology , Cytokines/blood , Gene Knock-In Techniques , Lung/pathology , Lung/virology , Lung Diseases, Interstitial/pathology , Nose/virology , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , RNA, Viral/analysis , SARS-CoV-2 , Stomach/virology , Trachea/virology , Viral Load , Virus Replication
20.
Cell ; 182(1): 50-58.e8, 2020 07 09.
Article in English | MEDLINE | ID: covidwho-343611

ABSTRACT

COVID-19 has spread worldwide since 2019 and is now a severe threat to public health. We previously identified the causative agent as a novel SARS-related coronavirus (SARS-CoV-2) that uses human angiotensin-converting enzyme 2 (hACE2) as the entry receptor. Here, we successfully developed a SARS-CoV-2 hACE2 transgenic mouse (HFH4-hACE2 in C3B6 mice) infection model. The infected mice generated typical interstitial pneumonia and pathology that were similar to those of COVID-19 patients. Viral quantification revealed the lungs as the major site of infection, although viral RNA could also be found in the eye, heart, and brain in some mice. Virus identical to SARS-CoV-2 in full-genome sequences was isolated from the infected lung and brain tissues. Last, we showed that pre-exposure to SARS-CoV-2 could protect mice from severe pneumonia. Our results show that the hACE2 mouse would be a valuable tool for testing potential vaccines and therapeutics.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/pathology , Disease Models, Animal , Mice, Transgenic , Pneumonia, Viral/pathology , Angiotensin-Converting Enzyme 2 , Animals , COVID-19 , Female , Humans , Lung Diseases, Interstitial/pathology , Lung Diseases, Interstitial/virology , Male , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, Transgenic/genetics , Pandemics , Peptidyl-Dipeptidase A/genetics , SARS-CoV-2 , Viral Tropism , Weight Loss
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