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1.
Transpl Infect Dis ; 24(3): e13823, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1741506

ABSTRACT

BACKGROUND: Previous reports of coronavirus disease 2019 (COVID-19) following lung transplantation generally described a grim prognosis, but these were anecdotal case series of symptomatic patients. A systematic study of the outcomes and pathology of SARS-CoV-2 infection in a large cohort of lung transplant patients is lacking. METHODS: To determine the histopathologic evolution of COVID-19 in lung transplant recipients, we identified all patients who underwent surveillance transbronchial biopsies at our institution, tested positive for SARS-CoV-2, and had multiple pathology specimens available for evaluation. Histology was reviewed and immunofluorescence for SARS-CoV-2 nucleocapsid protein was performed. RESULTS: Ten patients met inclusion criteria. Half (5/10) had incidental diagnosis on routine respiratory pathogen testing at the time of transbronchial biopsy. Six patients were hospitalized, with three requiring intensive care unit (ICU) admission. One patient died. Two specimens showed new onset International Society for Heart and Lung Transplantation (ISHLT) Grade A2 rejection at or following diagnosis. One patient developed bronchiolitis obliterans 111 days following diagnosis and 1 year post transplant. Two patients had organizing pneumonia at diagnosis and three patients showed evolving lung injury following diagnosis. The SARS-CoV-2 nucleocapsid protein was detected in a subset of samples at diagnosis and up to 111 days following diagnosis. CONCLUSIONS: Overall, the pathology of SARS-CoV-2 infection in lung transplant patients is varied, ranging from no pathologic alterations to organizing pneumonia and lung injury. The pathology findings did not necessarily correlate with clinical acuity, as one patient admitted to the ICU had normal pathology. These findings may be generalizable to non-transplant patients and require more follow-up regarding long-term outcomes.


Subject(s)
COVID-19 , Lung Injury , Biopsy , COVID-19/diagnosis , Humans , Lung/pathology , Lung Injury/pathology , Nucleocapsid Proteins , Postoperative Complications/diagnosis , SARS-CoV-2 , Transplant Recipients
2.
Eur Rev Med Pharmacol Sci ; 26(1): 270-277, 2022 01.
Article in English | MEDLINE | ID: covidwho-1631285

ABSTRACT

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare new syndrome occurring after the ChAdOx1 nCoV-19 vaccine immunization. Patients with VITT are characterized by a variable clinical presentation, likewise also the outcome of these patients is very variable. Here we report the lung ultrastructural findings in the course of VITT of a 58-year-old male patient. Alveoli were mainly dilated, irregular in shape, and occupied by a reticular network of fibrin, while interalveolar septa appeared thickened. The proliferation of small capillaries gave rise to plexiform structures and pulmonary capillary hemangiomatosis-like features. Near the alveoli occupied by a dense fibrin network, the medium-sized arteries showed a modified wall and an intraluminal thrombus. This scenario looks quite similar to that found during COVID-19, where the lungs suffer from the attack of the antigen-antibodies complexes and the virus respectively. In both diseases, the final outcome is a severe inflammation, activation of the haemostatic system and fibrinolysis.


Subject(s)
/adverse effects , Lung Injury/etiology , Lung Injury/pathology , Purpura, Thrombocytopenic, Idiopathic/chemically induced , Vaccination/adverse effects , COVID-19/prevention & control , Fibrin , Humans , Lung Injury/diagnostic imaging , Lung Injury/immunology , Male , Microscopy, Electron, Scanning , Middle Aged , Parenchymal Tissue/pathology , Purpura, Thrombocytopenic, Idiopathic/diagnosis , Purpura, Thrombocytopenic, Idiopathic/immunology
3.
Int J Biol Macromol ; 198: 101-110, 2022 Feb 15.
Article in English | MEDLINE | ID: covidwho-1587672

ABSTRACT

Respiratory infected by COVID-19 represents a major global health problem at moment even after recovery from virus corona. Since, the lung lesions for infected patients are still sufferings from acute respiratory distress syndrome including alveolar septal edema, pneumonia, hyperplasia, and hyaline membranes Therefore, there is an urgent need to identify additional candidates having ability to overcome inflammatory process and can enhance efficacy in the treatment of COVID-19. The polypenolic extracts were integrated into moeties of bovine serum albumin (BSA) and then were coated by chitosan as a mucoadhesion polymer. The results of interleukin-6, and c-reactive protein showed significant reduction in group treated by Encap. SIL + CUR (64 ± 0.8 Pg/µL & 6 ± 0.5 µg/µL) compared to group treated by Cham. + CUR (102 ± 0.8 Pg/µL & 7 ± 0.5 µg/µL) respectively and free capsules (with no any drug inside) (148 ± 0.6 Pg/µL & 10 ± 0.6 µg/µL) respectively. Histopathology profile was improved completely. Additionally, encapsulating silymarin showed anti-viral activity in vitro COVID-19 experiment. It can be summarized that muco-inhalable delivery system (MIDS) loaded by silymarin can be used to overcome inflammation induced by oleic acid and to overcome COVID-19.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antiviral Agents/pharmacology , COVID-19/drug therapy , Curcumin/pharmacology , Lung Injury/drug therapy , Nanoparticles/chemistry , Silymarin/pharmacology , Administration, Inhalation , Animals , Anti-Inflammatory Agents/administration & dosage , Antiviral Agents/administration & dosage , C-Reactive Protein/metabolism , Chamomile/chemistry , Chitosan/chemistry , Chlorocebus aethiops , Curcumin/administration & dosage , Drug Delivery Systems/methods , Flavonoids/analysis , Flavonoids/chemistry , Interleukin-6/metabolism , Lung Injury/blood , Lung Injury/chemically induced , Lung Injury/pathology , Male , Mice , Milk Thistle/chemistry , Nanoparticles/administration & dosage , Oleic Acid/toxicity , Silymarin/administration & dosage , Vero Cells , Viral Plaque Assay
4.
Front Immunol ; 12: 735922, 2021.
Article in English | MEDLINE | ID: covidwho-1477823

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major public health issue. COVID-19 is considered an airway/multi-systemic disease, and demise has been associated with an uncontrolled immune response and a cytokine storm in response to the virus. However, the lung pathology, immune response, and tissue damage associated with COVID-19 demise are poorly described and understood due to safety concerns. Using post-mortem lung tissues from uninfected and COVID-19 deadly cases as well as an unbiased combined analysis of histology, multi-viral and host markers staining, correlative microscopy, confocal, and image analysis, we identified three distinct phenotypes of COVID-19-induced lung damage. First, a COVID-19-induced hemorrhage characterized by minimal immune infiltration and large thrombus; Second, a COVID-19-induced immune infiltration with excessive immune cell infiltration but no hemorrhagic events. The third phenotype correspond to the combination of the two previous ones. We observed the loss of alveolar wall integrity, detachment of lung tissue pieces, fibroblast proliferation, and extensive fibrosis in all three phenotypes. Although lung tissues studied were from lethal COVID-19, a strong immune response was observed in all cases analyzed with significant B cell and poor T cell infiltrations, suggesting an exhausted or compromised immune cellular response in these patients. Overall, our data show that SARS-CoV-2-induced lung damage is highly heterogeneous. These individual differences need to be considered to understand the acute and long-term COVID-19 consequences.


Subject(s)
COVID-19/mortality , COVID-19/pathology , Lung Injury/pathology , Pulmonary Alveoli/pathology , Pulmonary Fibrosis/pathology , Aged , Aged, 80 and over , Autopsy , CD8-Positive T-Lymphocytes/immunology , Cytokine Release Syndrome/mortality , Cytokine Release Syndrome/pathology , Epithelial Cells/pathology , Female , Hemorrhage/pathology , Humans , Inflammation/pathology , Lung/pathology , Lung Injury/virology , Lymphopenia/pathology , Macrophage Activation/immunology , Macrophages/immunology , Male , Middle Aged , Myocytes, Smooth Muscle/pathology , Neutrophils/immunology , SARS-CoV-2 , Thrombosis/pathology
5.
PLoS One ; 16(10): e0254985, 2021.
Article in English | MEDLINE | ID: covidwho-1448572

ABSTRACT

BACKGROUND: The goal of this study was to determine if IL-22:Fc would Acute Respiratory Distress Syndrome (ARDS). SUMMARY BACKGROUND DATA: No therapies exist for ARDS and treatment is purely supportive. Interleukin-22 (IL-22) plays an integral component in recovery of the lung from infection. IL-22:Fc is a recombinant protein with a human FC immunoglobulin that increases the half-life of IL-22. STUDY DESIGN: ARDS was induced in C57BL/6 mice with intra-tracheal lipopolysaccharide (LPS) at a dose of 33.3 or 100 ug. In the low-dose LPS group (LDG), IL-22:FC was administered via tail vein injection at 30 minutes (n = 9) and compared to sham (n = 9). In the high-dose LPS group (HDG), IL-22:FC was administered (n = 11) then compared to sham (n = 8). Euthanasia occurred after bronchioalveolar lavage (BAL) on post-injury day 4. RESULTS: In the LDG, IL-22:FC resulted in decreased protein leak (0.15 vs. 0.25 ug/uL, p = 0.02). BAL protein in animals receiving IL-22:Fc in the HDG was not different. For the HDG, animals receiving IL-22:Fc had lower BAL cell counts (539,636 vs 3,147,556 cells/uL, p = 0.02). For the HDG, IL-6 (110.6 vs. 527.1 pg/mL, p = 0.04), TNF-α (5.87 vs. 25.41 pg/mL, p = 0.04), and G-CSF (95.14 vs. 659.6, p = 0.01) levels were lower in the BAL fluid of IL-22:Fc treated animals compared to sham. CONCLUSIONS: IL-22:Fc decreases lung inflammation and lung capillary leak in ARDS. IL-22:Fc may be a novel therapy for ARDS.


Subject(s)
Immunoglobulin Fc Fragments/pharmacology , Interleukins/pharmacology , Lung Injury/drug therapy , Pneumonia/drug therapy , Respiratory Distress Syndrome/drug therapy , Animals , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/cytology , Female , Lipopolysaccharides/toxicity , Lung Injury/pathology , Lymphocyte Count , Lymphocytes/immunology , Macrophages/immunology , Male , Mice , Mice, Inbred C57BL , Neutrophils/immunology , Pneumonia/pathology , Receptors, Interleukin/metabolism , Recombinant Proteins/pharmacology , Respiratory Distress Syndrome/pathology , Respiratory Mucosa/pathology
6.
Cell Rep ; 37(1): 109798, 2021 10 05.
Article in English | MEDLINE | ID: covidwho-1415262

ABSTRACT

Despite the worldwide effect of the coronavirus disease 2019 (COVID-19) pandemic, the underlying mechanisms of fatal viral pneumonia remain elusive. Here, we show that critical COVID-19 is associated with enhanced eosinophil-mediated inflammation when compared to non-critical cases. In addition, we confirm increased T helper (Th)2-biased adaptive immune responses, accompanying overt complement activation, in the critical group. Moreover, enhanced antibody responses and complement activation are associated with disease pathogenesis as evidenced by formation of immune complexes and membrane attack complexes in airways and vasculature of lung biopsies from six fatal cases, as well as by enhanced hallmark gene set signatures of Fcγ receptor (FcγR) signaling and complement activation in myeloid cells of respiratory specimens from critical COVID-19 patients. These results suggest that SARS-CoV-2 infection may drive specific innate immune responses, including eosinophil-mediated inflammation, and subsequent pulmonary pathogenesis via enhanced Th2-biased immune responses, which might be crucial drivers of critical disease in COVID-19 patients.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Complement System Proteins/immunology , Eosinophils/immunology , Inflammation/immunology , Pneumonia, Viral/immunology , SARS-CoV-2/immunology , Adaptive Immunity , Adult , Aged , Aged, 80 and over , Antigen-Antibody Complex/metabolism , COVID-19/metabolism , COVID-19/virology , Complement Activation , Complement Membrane Attack Complex/metabolism , Eosinophils/virology , Female , Humans , Inflammation/metabolism , Inflammation/virology , Lung Injury/immunology , Lung Injury/pathology , Lung Injury/virology , Male , Middle Aged , Pneumonia, Viral/metabolism , Receptors, IgG/immunology , Receptors, IgG/metabolism , Severity of Illness Index , Signal Transduction , Th2 Cells/immunology , Viral Load , Young Adult
7.
Mol Med Rep ; 24(4)2021 Oct.
Article in English | MEDLINE | ID: covidwho-1395036

ABSTRACT

Chronic alcohol abuse increases the risk of mortality and poor outcomes in patients with acute respiratory distress syndrome. However, the underlying mechanisms remain to be elucidated. The present study aimed to investigate the effects of chronic alcohol consumption on lung injury and clarify the signaling pathways involved in the inhibition of alveolar fluid clearance (AFC). In order to produce rodent models with chronic alcohol consumption, wild­type C57BL/6 mice were treated with alcohol. A2a adenosine receptor (AR) small interfering (si)RNA or A2bAR siRNA were transfected into the lung tissue of mice and primary rat alveolar type II (ATII) cells. The rate of AFC in lung tissue was measured during exposure to lipopolysaccharide (LPS). Epithelial sodium channel (ENaC) expression was determined to investigate the mechanisms underlying alcohol­induced regulation of AFC. In the present study, exposure to alcohol reduced AFC, exacerbated pulmonary edema and worsened LPS­induced lung injury. Alcohol caused a decrease in cyclic adenosine monophosphate (cAMP) levels and inhibited α­ENaC, ß­ENaC and γ­ENaC expression levels in the lung tissue of mice and ATII cells. Furthermore, alcohol decreased α­ENaC, ß­ENaC and γ­ENaC expression levels via the A2aAR or A2bAR­cAMP signaling pathways in vitro. In conclusion, the results of the present study demonstrated that chronic alcohol consumption worsened lung injury by aggravating pulmonary edema and impairing AFC. An alcohol­induced decrease of α­ENaC, ß­ENaC and γ­ENaC expression levels by the A2AR­mediated cAMP pathway may be responsible for the exacerbated effects of chronic alcohol consumption in lung injury.


Subject(s)
Acute Lung Injury/metabolism , Alveolar Epithelial Cells/metabolism , Epithelial Sodium Channels/drug effects , Epithelial Sodium Channels/metabolism , Ethanol/pharmacology , Receptors, Adenosine A2/metabolism , Acute Lung Injury/chemically induced , Acute Lung Injury/pathology , Alveolar Epithelial Cells/pathology , Animals , Cyclic AMP/metabolism , Cytokines , Lipopolysaccharides/adverse effects , Lung/metabolism , Lung Injury/chemically induced , Lung Injury/metabolism , Lung Injury/pathology , Mice , Mice, Inbred C57BL , Pulmonary Alveoli/metabolism , Pulmonary Edema/chemically induced , Pulmonary Edema/metabolism , Pulmonary Edema/pathology , RNA Splicing Factors/genetics , RNA Splicing Factors/metabolism , Rats , Receptor, Adenosine A2A/genetics , Receptor, Adenosine A2A/metabolism , Signal Transduction
8.
Dis Markers ; 2021: 5566826, 2021.
Article in English | MEDLINE | ID: covidwho-1341351

ABSTRACT

An excess formation of neutrophil extracellular traps (NETs), previously shown to be strongly associated with cytokine storm and acute respiratory distress syndrome (ARDS) with prevalent endothelial dysfunction and thrombosis, has been postulated to be a central factor influencing the pathophysiology and clinical presentation of severe COVID-19. A growing number of serological and morphological evidence has added to this assumption, also in regard to potential treatment options. In this study, we used immunohistochemistry and histochemistry to trace NETs and their molecular markers in autopsy lung tissue from seven COVID-19 patients. Quantification of key immunomorphological features enabled comparison with non-COVID-19 diffuse alveolar damage. Our results strengthen and extend recent findings, confirming that NETs are abundantly present in seriously damaged COVID-19 lung tissue, especially in association with microthrombi of the alveolar capillaries. In addition, we provide evidence that low-density neutrophils (LDNs), which are especially prone to NETosis, contribute substantially to COVID-19-associated lung damage in general and vascular blockages in particular.


Subject(s)
COVID-19/pathology , Extracellular Traps , Lung Injury/pathology , Neutrophils/pathology , Aged , Aged, 80 and over , Antigens, CD/metabolism , Autopsy , Cell Adhesion Molecules/metabolism , Extracellular Traps/virology , Female , GPI-Linked Proteins/metabolism , Humans , Immunohistochemistry , Lung/pathology , Lung/virology , Lung Injury/virology , Male , Neutrophils/metabolism , Neutrophils/virology , Peroxidase/metabolism
9.
Int J Biochem Cell Biol ; 137: 106039, 2021 08.
Article in English | MEDLINE | ID: covidwho-1318825

ABSTRACT

Following the emergence of electronic cigarette, or vaping product use associated lung injury (EVALI) in 2019 in the US, regulation of e-cigarettes has become globally tighter and the collective evidence of the detrimental effects of vaping has grown. The danger of cellular distress and altered homeostasis is heavily associated with the modifiable nature of electronic cigarette devices. An array of harmful chemicals and elevated concentrations of metals have been detected in e-cigarette aerosols which have been linked to various pathogeneses. Vaping is linked to increased inflammation, altered lipid homeostasis and mitochondrial dysfunction whilst also increasing microbial susceptibility whilst the long-term damage is yet to be observed. The scientific evidence is mounting and highlighting that, along with traditional tobacco cigarette smoking, electronic cigarette vaping is not a safe practice.


Subject(s)
Electronic Nicotine Delivery Systems/statistics & numerical data , Lung Injury/pathology , Vaping/adverse effects , Chronic Disease , Humans , Lung Injury/etiology
10.
Cells ; 10(4)2021 03 24.
Article in English | MEDLINE | ID: covidwho-1232574

ABSTRACT

Despite vaccination and antivirals, influenza remains a communicable disease of high burden, with limited therapeutic options available to patients that develop complications. Here, we report the development and preclinical characterization of Adipose Stromal Cell (ASC) concentrated secretome (CS), generated by process adaptable to current Good Manufacturing Practices (cGMP) standards. We demonstrate that ASC-CS limits pulmonary histopathological changes, infiltration of inflammatory cells, protein leak, water accumulation, and arterial oxygen saturation (spO2) reduction in murine model of lung infection with influenza A virus (IAV) when first administered six days post-infection. The ability to limit lung injury is sustained in ASC-CS preparations stored at -80 °C for three years. Priming of the ASC with inflammatory factors TNFα and IFNγ enhances ASC-CS ability to suppress lung injury. IAV infection is associated with dramatic increases in programmed cell death ligand (PDL1) and angiopoietin 2 (Angpt2) levels. ASC-CS application significantly reduces both PDL1 and Angpt2 levels. Neutralization of PDL1 with anti-mouse PDL1 antibody starting Day6 onward effectively ablates lung PDL1, but only non-significantly reduces Angpt2 release. Most importantly, late-phase PDL1 neutralization results in negligible suppression of protein leakage and inflammatory cell infiltration, suggesting that suppression of PDL1 does not play a critical role in ASC-CS therapeutic effects.


Subject(s)
Adipose Tissue/cytology , Influenza A virus/physiology , Lung Injury/therapy , Lung Injury/virology , Orthomyxoviridae Infections/therapy , Orthomyxoviridae Infections/virology , Angiopoietin-2/metabolism , Animals , B7-H1 Antigen/metabolism , Bronchoalveolar Lavage , Cryopreservation , Culture Media, Conditioned/pharmacology , Cytokines/metabolism , Disease Models, Animal , Female , Humans , Inflammation/complications , Inflammation/pathology , Lung Injury/complications , Lung Injury/pathology , Male , Mice , Orthomyxoviridae Infections/complications , Orthomyxoviridae Infections/pathology , Respiratory Distress Syndrome/complications , Respiratory Distress Syndrome/pathology , Respiratory Distress Syndrome/virology , Sex Characteristics , Stromal Cells/metabolism
11.
Clin Immunol ; 226: 108716, 2021 05.
Article in English | MEDLINE | ID: covidwho-1152310

ABSTRACT

Lung inflammation and damage is prominent in people infected with SARS-Cov-2 and a major determinant of morbidity and mortality. We report the deposition of complement components in the lungs of people who succumbed to COVID-19 consistent with the activation of the classical and the alternative pathways. Our study provides strong rationale for the expansion of trials involving the use of complement inhibitors to treat patients with COVID-19.


Subject(s)
COVID-19/immunology , Complement Activation/immunology , Complement Pathway, Alternative/immunology , Lung Injury/immunology , Aged , Aged, 80 and over , COVID-19/complications , Complement Inactivating Agents/pharmacology , Complement Inactivating Agents/therapeutic use , Epithelial Cells/metabolism , Epithelial Cells/pathology , Female , Humans , Immunohistochemistry , Lung/diagnostic imaging , Lung/immunology , Lung/pathology , Lung Injury/complications , Lung Injury/pathology , Lung Injury/virology , Male , Middle Aged
12.
Life Sci ; 274: 119341, 2021 Jun 01.
Article in English | MEDLINE | ID: covidwho-1126966

ABSTRACT

The COVID-19 pandemic surges on as vast research is produced to study the novel SARS-CoV-2 virus and the disease state it induces. Still, little is known about the impact of COVID-19-induced microscale damage in the lung on global lung dynamics. This review summarizes the key histological features of SARS-CoV-2 infected alveoli and links the findings to structural tissue changes and surfactant dysfunction affecting tissue mechanical behavior similar to changes seen in other lung injury. Along with typical findings of diffuse alveolar damage affecting the interstitium of the alveolar walls and blood-gas barrier in the alveolar airspace, COVID-19 can cause extensive microangiopathy in alveolar capillaries that further contribute to mechanical changes in the tissues and may differentiate it from previously studied infectious lung injury. Understanding microlevel damage impact on tissue mechanics allows for better understanding of macroscale respiratory dynamics. Knowledge gained from studies into the relationship between microscale and macroscale lung mechanics can allow for optimized treatments to improve patient outcomes in case of COVID-19 and future respiratory-spread pandemics.


Subject(s)
COVID-19/complications , Lung Injury/pathology , Lung Injury/virology , Pulmonary Ventilation , SARS-CoV-2/isolation & purification , COVID-19/transmission , COVID-19/virology , Humans
13.
J Immunother Cancer ; 9(2)2021 02.
Article in English | MEDLINE | ID: covidwho-1081352

ABSTRACT

By the beginning of the global pandemic, SARS-CoV-2 infection has dramatically impacted on oncology daily practice. In the current oncological landscape, where immunotherapy has revolutionized the treatment of several malignancies, distinguishing between COVID-19 and immune-mediated pneumonitis can be hard because of shared clinical, radiological and pathological features. Indeed, their common mechanism of aberrant inflammation could lead to a mutual and amplifying interaction.We describe the case of a 65-year-old patient affected by metastatic squamous head and neck cancer and candidate to an experimental therapy including an anti-PD-L1 agent. COVID-19 ground-glass opacities under resolution were an incidental finding during screening procedures and worsened after starting immunotherapy. The diagnostic work-up was consistent with ICIs-related pneumonia and it is conceivable that lung injury by SARS-CoV-2 has acted as an inflammatory primer for the development of the immune-related adverse event.Patients recovered from COVID-19 starting ICIs could be at greater risk of recall immune-mediated pneumonitis. Nasopharyngeal swab and chest CT scan are recommended before starting immunotherapy. The awareness of the phenomenon could allow an easier interpretation of radiological changes under treatment and a faster diagnostic work-up to resume ICIs. In the presence of clinical benefit, for asymptomatic ICIs-related pneumonia a watchful-waiting approach and immunotherapy prosecution are suggested.


Subject(s)
COVID-19/diagnosis , Lung Neoplasms/diagnosis , Pneumonia/diagnosis , Squamous Cell Carcinoma of Head and Neck/diagnosis , Aged , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/immunology , COVID-19/drug therapy , COVID-19/immunology , COVID-19/virology , Diagnosis, Differential , Humans , Immune Checkpoint Inhibitors/administration & dosage , Immune Checkpoint Inhibitors/adverse effects , Immunotherapy/adverse effects , Lung Injury/diagnosis , Lung Injury/diagnostic imaging , Lung Injury/pathology , Lung Injury/virology , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Lung Neoplasms/virology , Male , Nasopharynx/metabolism , Nasopharynx/pathology , Neoplasm Metastasis , Pandemics , Pneumonia/drug therapy , Pneumonia/immunology , Pneumonia/virology , SARS-CoV-2/pathogenicity , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/immunology , Squamous Cell Carcinoma of Head and Neck/virology
14.
Respir Res ; 22(1): 32, 2021 Jan 29.
Article in English | MEDLINE | ID: covidwho-1054820

ABSTRACT

BACKGROUND: Pulmonary 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. METHODS: We 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. RESULTS: Patient´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. CONCLUSION: Patients 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.


Subject(s)
COVID-19/pathology , Lung Injury/pathology , Lung/pathology , Adult , Age Factors , Aged , Aged, 80 and over , Autopsy , COVID-19/complications , Demography , Disease Progression , Female , Humans , Infarction/epidemiology , Infarction/pathology , Lung Injury/etiology , Male , Middle Aged , Pulmonary Alveoli/pathology , Thrombosis/etiology , Thrombosis/pathology , Young Adult
15.
Viruses ; 13(2)2021 01 22.
Article in English | MEDLINE | ID: covidwho-1045367

ABSTRACT

Respiratory viruses such as influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are a constant threat to public health given their ability to cause global pandemics. Infection with either virus may lead to aberrant host responses, such as excessive immune cell recruitment and activation, dysregulated inflammation, and coagulopathy. These may contribute to the development of lung edema and respiratory failure. An increasing amount of evidence suggests that lung endothelial cells play a critical role in the pathogenesis of both viruses. In this review, we discuss how infection with influenza or SARS-CoV-2 may induce endothelial dysfunction. We compare the effects of infection of these two viruses, how they may contribute to pathogenesis, and discuss the implications for potential treatment. Understanding the differences between the effects of these two viruses on lung endothelial cells will provide important insight to guide the development of therapeutics.


Subject(s)
Endothelium/virology , Influenzavirus A/pathogenicity , Lung Injury/pathology , Lung Injury/virology , SARS-CoV-2/pathogenicity , Blood Platelets/metabolism , Cytokines/metabolism , Endothelial Cells/metabolism , Endothelial Cells/pathology , Endothelium/metabolism , Endothelium/pathology , Extracellular Traps/immunology , Humans , Intercellular Junctions/pathology , Lung Injury/therapy
16.
Int J Mol Sci ; 22(2)2021 01 19.
Article in English | MEDLINE | ID: covidwho-1038653

ABSTRACT

A complete understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) physiopathology and related histopathologic lesions is necessary to improve treatment and outcome of coronavirus disease 2019 (COVID-19) patients. Many studies have focused on autopsy findings in COVID-19-related deaths to try and define any possible specific pattern. Histopathologic alterations are principally found within lungs and blood vessels, and these abnormalities also seem to have the highest clinical impact. Nevertheless, many of the morphological data collected so far are non-specific, fickle, and possibly associated with other co-existing factors. The aim of this minireview is to describe the main histopathological features related to COVID-19 and the mechanism known as "cytokine storm".


Subject(s)
COVID-19/immunology , COVID-19/pathology , Lung Injury/immunology , Lung Injury/virology , Angiotensin-Converting Enzyme 2/metabolism , Autopsy , COVID-19/diagnostic imaging , Cytokine Release Syndrome , Cytokines/blood , Humans , Lung Injury/diagnostic imaging , Lung Injury/pathology , SARS-CoV-2/isolation & purification
17.
S Afr Med J ; 110(12): 1195-1200, 2020 10 19.
Article in English | MEDLINE | ID: covidwho-994151

ABSTRACT

BACKGROUND: An outbreak of a novel coronavirus in China in late 2019 has resulted in a global pandemic. The virus (SARS-CoV-2) causes a severe acute respiratory syndrome and had been responsible for >14 000 deaths in South Africa (SA) at the time of writing, 30 August 2020. Autopsies in our setting have not been prioritised owing to the infective risks for staff, resulting in a lack of information on the histopathology of the disease in the SA setting. Postmortem biopsies are relatively quick and easy to perform and reduce the infective risk posed by full autopsies. OBJECTIVES: To determine whether postmortem biopsies of lung tissue could be used to determine cause of death in lieu of full autopsies in patients dying from COVID-19. METHODS: We performed postmortem biopsies of lung tissue on 4 patients with SARS-CoV-2 confirmed by reverse transcriptase polymerase chain reaction who died in the Tygerberg Hospital (Cape Town, SA) intensive care unit (ICU) in June - July 2020, in order to determine their cause of death. The biopsies were performed in the ICU with the necessary personal protective equipment within 2 hours after death. Clinical information was obtained from the hospital records and the histopathology was reviewed by two consultant histopathologists. Microbiology and electron microscopy were also performed on this tissue. RESULTS: All 4 patients were aged >50 years and had multiple comorbidities. Pulmonary pathology was present in only 3 cases, and the findings were surprisingly heterogeneous. One case demonstrated several findings including diffuse alveolar damage, extensive fibrin thrombi in pulmonary arteries with pulmonary infarction, organising pneumonia and bronchopneumonia. Other findings included type 2 pneumocyte hyperplasia, intra-alveolar macrophages and squamous metaplasia. An organising pneumonia was present in 2 other cases, although these findings were not deemed to be severe enough to be the cause of death. Fibrin thrombi were present in pulmonary arteries of 3 cases. One case showed no significant acute pulmonary pathology. The cause of death could only be determined in 1 case. CONCLUSIONS: The pulmonary findings we observed are in keeping with those described in the international literature. However, the pathology was surprisingly heterogeneous between cases, and was only deemed severe enough to be the cause of death in 1 of 4 cases. While lung-targeted, standardised postmortem biopsies may be safe, easy to perform and provide useful insights into the disease, they are not suitable to replace full autopsies in determining cause of death.


Subject(s)
Biopsy , COVID-19/pathology , Lung Injury/pathology , Lung/pathology , Pulmonary Artery/pathology , Pulmonary Edema/pathology , Pulmonary Infarction/pathology , Thrombosis/pathology , Aged , Alveolar Epithelial Cells/pathology , Autopsy , C-Reactive Protein/metabolism , COVID-19/blood , COVID-19/mortality , Cause of Death , Comorbidity , Diabetes Mellitus, Type 2/epidemiology , Female , Fibrin Fibrinogen Degradation Products/metabolism , Giant Cells/pathology , Humans , Hypertension/epidemiology , Lymphocytes/pathology , Macrophages, Alveolar/pathology , Male , Middle Aged , Obesity/epidemiology , Procalcitonin/blood , SARS-CoV-2 , South Africa , Tertiary Care Centers
18.
Biofactors ; 47(1): 6-18, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-950385

ABSTRACT

Specialized proresolving mediators (SPMs) are endogenous lipid metabolites of long-chain polyunsaturated fatty acids that are involved in promoting the resolution of inflammation. Many disease conditions characterized by excessive inflammation have impaired or altered SPM biosynthesis, which may lead to chronic, unresolved inflammation. Exogenous administration of SPMs in infectious conditions has been shown to be effective at improving infection clearance and survival in preclinical models. SPMs have also shown tremendous promise in the context of inflammatory lung conditions, such as acute respiratory distress syndrome and chronic obstructive pulmonary disease, mostly in preclinical settings. To date, SPMs have not been studied in the context of the novel Coronavirus, severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), however their preclinical efficacy in combatting infections and improving acute respiratory distress suggest they may be a valuable resource in the fight against Coronavirus disease-19 (COVID-19). Overall, while the research on SPMs is still evolving, they may offer a novel therapeutic option for inflammatory conditions.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , Docosahexaenoic Acids/therapeutic use , Lipoxins/therapeutic use , Lung Injury/drug therapy , Pulmonary Disease, Chronic Obstructive/drug therapy , Respiratory Distress Syndrome/drug therapy , COVID-19/metabolism , COVID-19/pathology , COVID-19/virology , Herpes Simplex/drug therapy , Herpes Simplex/metabolism , Herpes Simplex/pathology , Humans , Influenza, Human/drug therapy , Influenza, Human/metabolism , Influenza, Human/pathology , Lung/drug effects , Lung/metabolism , Lung/pathology , Lung Injury/metabolism , Lung Injury/pathology , Lung Injury/virology , Periodontitis/drug therapy , Periodontitis/metabolism , Periodontitis/pathology , Pulmonary Disease, Chronic Obstructive/metabolism , Pulmonary Disease, Chronic Obstructive/pathology , Pulmonary Disease, Chronic Obstructive/virology , Respiratory Distress Syndrome/metabolism , Respiratory Distress Syndrome/pathology , Respiratory Distress Syndrome/virology , SARS-CoV-2/pathogenicity , Sepsis/drug therapy , Sepsis/metabolism , Sepsis/pathology , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/metabolism , Tuberculosis, Pulmonary/pathology
19.
Transl Res ; 231: 55-63, 2021 05.
Article in English | MEDLINE | ID: covidwho-939331

ABSTRACT

Although some evidence showed the activation of complement systems in COVID-19 patients, proinflammatory status and lectin pathway remain unclear. Thus, the present study aimed to demonstrate the role of MBL and ficolin-3 in the complement system activation and compared to pandemic Influenza A virus H1N1 subtype infection (H1N1pdm09) and control patients. A total of 27 lungs formalin-fixed paraffin-embedded samples (10 from H1N1 group, 6 from the COVID-19 group, and 11 from the control group) were analyzed by immunohistochemistry using anti-IL-6, TNF-alfa, CD163, MBL e FCN3 antibodies. Genotyping of target polymorphisms in the MBL2 gene was performed by real-time PCR. Proinflammatory cytokines such as IL-6 and TNF-alpha presented higher tissue expression in the COVID-19 group compared to H1N1 and control groups. The same results were observed for ICAM-1 tissue expression. Increased expression of the FCN3 was observed in the COVID-19 group and H1N1 group compared to the control group. The MBL tissue expression was higher in the COVID-19 group compared to H1N1 and control groups. The genotypes AA for rs180040 (G/A), GG for rs1800451 (G/A) and CC for rs5030737 (T/C) showed a higher prevalence in the COVID-19 group. The intense activation of the lectin pathway, with particular emphasis on the MBL pathway, together with endothelial dysfunction and a massive proinflammatory cytokines production, possibly lead to a worse outcome in patients infected with SARS-Cov-2. Moreover, 3 SNPs of our study presented genotypes that might be correlated with high MBL tissue expression in the COVID-19 pulmonary samples.


Subject(s)
COVID-19/pathology , Lectins/metabolism , Lung Injury/metabolism , Lung Injury/pathology , SARS-CoV-2 , Adult , Aged , Aged, 80 and over , Autopsy , Case-Control Studies , Complement Activation/physiology , Cytokines/genetics , Cytokines/metabolism , Female , Genotype , Humans , Immunohistochemistry , Influenza A Virus, H1N1 Subtype , Influenza, Human/metabolism , Influenza, Human/pathology , Lung/pathology , Lung/virology , Lung Injury/virology , Male , Middle Aged , Polymorphism, Single Nucleotide , Young Adult
20.
Biomed Res Int ; 2020: 5608382, 2020.
Article in English | MEDLINE | ID: covidwho-886830

ABSTRACT

Lung injury and inflammation are complex pathological processes. The influence and crosstalk between various cells form a characteristic microenvironment. Extracellular vesicles from different cell sources in the microenvironment carry multiple cargo molecules, which affect the pathological process through different pathways. Here, we mainly discussed the mechanism of crosstalk between alveolar epithelial cells and different immune cells through extracellular vesicles in lung inflammation and reviewed the mechanism of extracellular vesicles released by blood and airways on lung inflammation. Finally, the role of extracellular vesicles in viral infection of the lung was also described.


Subject(s)
Cellular Microenvironment , Extracellular Vesicles/metabolism , Inflammation/pathology , Lung Injury/pathology , Alveolar Epithelial Cells/pathology , Animals , Humans , Inflammation/complications , Inflammation/virology , Lung Injury/complications , Lung Injury/virology , Models, Biological
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