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3.
Sci Rep ; 11(1): 16039, 2021 08 06.
Article in English | MEDLINE | ID: covidwho-1345587

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) induces lung injury of varying severity, potentially causing severe acute respiratory distress syndrome (ARDS). Pulmonary injury patterns in COVID-19 patients differ from those in patients with other causes of ARDS. We aimed to explore the frequency and pathogenesis of cavitary lung lesions in critically ill patients with COVID-19. Retrospective study in 39 critically ill adult patients hospitalized with severe acute respiratory syndrome coronavirus 2 including lung injury of varying severity in a tertiary care referral center during March and May 2020, Berlin/Germany. We observed lung cavitations in an unusually large proportion of 22/39 (56%) COVID-19 patients treated on intensive care units (ICU), including 3/5 patients without mechanical ventilation. Median interquartile range (IQR) time between onset of symptoms and ICU admission was 11.5 (6.25-17.75) days. In 15 patients, lung cavitations were already present on the first CT scan, performed after ICU admission; in seven patients they developed during a subsequent median (IQR) observation period of 48 (35-58) days. In seven patients we found at least one cavitation with a diameter > 2 cm (maximum 10 cm). Patients who developed cavitations were older and had a higher body mass index. Autopsy findings in three patients revealed that the cavitations reflected lung infarcts undergoing liquefaction, secondary to thrombotic pulmonary artery branch occlusions. Lung cavitations appear to be a frequent complication of severely ill COVID-19 patients, probably related to the prothrombotic state associated with COVID-19.


Subject(s)
COVID-19/pathology , Lung/pathology , Pulmonary Embolism/pathology , Aged , COVID-19/complications , Critical Illness , Female , Humans , Intensive Care Units , Male , Middle Aged , Pulmonary Embolism/etiology , Retrospective Studies , SARS-CoV-2/isolation & purification
4.
Br J Hosp Med (Lond) ; 82(7): 1-6, 2021 Jul 02.
Article in English | MEDLINE | ID: covidwho-1337825

ABSTRACT

Pulmonary embolism remains a common and potentially deadly disease, despite advances in diagnostic imaging, treatment and prevention. Managing pulmonary embolism requires a multifactorial approach involving risk stratification, determining appropriate diagnostics and selecting individualised therapy. The first part of this article reviewed the pathophysiology, risk factors, clinical presentation, diagnostic evaluation and therapeutic management and early outpatient management of pulmonary embolism. This second part summarises pulmonary embolism in the setting of pregnancy, COVID-19, recurrent disease and chronic thromboembolic pulmonary hypertension.


Subject(s)
COVID-19/epidemiology , Pulmonary Embolism/epidemiology , Pulmonary Embolism/pathology , COVID-19/pathology , Chronic Disease , Female , Humans , Hypertension, Pulmonary/epidemiology , Hypertension, Pulmonary/pathology , Male , Pregnancy , Pulmonary Embolism/diagnostic imaging , Radiography, Thoracic , Recurrence , Risk Factors , SARS-CoV-2 , Ultrasonography, Doppler , Venous Thromboembolism/epidemiology , Venous Thromboembolism/pathology
5.
Br J Hosp Med (Lond) ; 82(7): 1-16, 2021 Jul 02.
Article in English | MEDLINE | ID: covidwho-1337824

ABSTRACT

Pulmonary embolism remains a common and potentially deadly disease, despite advances in diagnostic imaging, treatment and prevention. Managing pulmonary embolism requires a multifactorial approach involving risk stratification, determining appropriate diagnostics and selecting individualised therapy. This article reviews the pathophysiology, risk factors, clinical presentation, diagnostic evaluation and therapeutic management and early outpatient management of pulmonary embolism. The second part summarises pulmonary embolism in the setting of pregnancy, COVID-19, recurrent disease and chronic thromboembolic pulmonary hypertension.


Subject(s)
COVID-19/epidemiology , Pulmonary Embolism/epidemiology , Pulmonary Embolism/pathology , Biomarkers , COVID-19/pathology , Chronic Disease , Female , Humans , Hypertension, Pulmonary/epidemiology , Hypertension, Pulmonary/pathology , Male , Pregnancy , Pulmonary Embolism/diagnostic imaging , Recurrence , Risk Factors , SARS-CoV-2 , Venous Thromboembolism/epidemiology , Venous Thromboembolism/pathology
6.
J Intern Med ; 290(3): 655-665, 2021 09.
Article in English | MEDLINE | ID: covidwho-1297793

ABSTRACT

IMPORTANCE: Assessment of the causative association between the COVID-19 and cause of death has been hampered by limited availability of systematically performed autopsies. We aimed to present autopsy-confirmed causes of death in patients who died with COVID-19 and to assess the association between thrombosis and diffuse alveolar damage consistent with COVID-19 (DAD). METHODS: Consecutive forensic (n = 60) and clinical (n = 42) autopsies with positive post-mortem SARS-CoV-2 PCR in lungs (age 73 ± 14 years, 50% men) were included. The cause of death analysis was based on a review of medical records and histological reports. Thrombotic phenomena in lungs were defined as pulmonary thromboembolism (PE), thrombosis in pulmonary artery branches or microangiopathy in capillary vessels. RESULTS: COVID-19 caused or contributed to death in 71% of clinical and 83% of forensic autopsies, in whom significant DAD was observed. Of the patients with COVID-19 as the primary cause of death, only 19% had no thrombotic phenomena in the lungs, as opposed to 38% amongst those with COVID-19 as a contributing cause of death and 54% amongst patients whose death was not related to COVID-19 (p = 0.002). PE was observed in 5 patients. Two patients fulfilled the criteria for lymphocyte myocarditis. CONCLUSIONS: Vast majority of all PCR-positive fatalities, including out-of-hospital deaths, during the SARS-CoV-2 pandemic were related to DAD caused by COVID-19. Pulmonary artery thrombosis and microangiopathy in pulmonary tissue were common and associated with the presence of DAD, whilst venous PE was rarely observed. Histology-confirmed lymphocyte myocarditis was a rare finding.


Subject(s)
COVID-19/mortality , COVID-19/pathology , Cause of Death , Pulmonary Alveoli/pathology , Pulmonary Embolism/pathology , Thromboembolism/pathology , Aged , Autopsy , Capillaries/pathology , Female , Humans , Lymphocytes , Male , Middle Aged , Myocarditis/pathology , Pandemics , Polymerase Chain Reaction , Pulmonary Artery/pathology , SARS-CoV-2 , Thrombotic Microangiopathies/pathology
7.
Viruses ; 13(5)2021 04 26.
Article in English | MEDLINE | ID: covidwho-1201364

ABSTRACT

The incidence of pulmonary embolism (PE) is high during severe Coronavirus Disease 2019 (COVID-19). We aimed to identify predictive and prognostic factors of PE in non-ICU hospitalized COVID-19 patients. In the retrospective multicenter observational CLOTVID cohort, we enrolled patients with confirmed RT-PCR COVID-19 who were hospitalized in a medicine ward and also underwent a CT pulmonary angiography for a PE suspicion. Baseline data, laboratory biomarkers, treatments, and outcomes were collected. Predictive and prognostics factors of PE were identified by using logistic multivariate and by Cox regression models, respectively. A total of 174 patients were enrolled, among whom 86 (median [IQR] age of 66 years [55-77]) had post-admission PE suspicion, with 30/86 (34.9%) PE being confirmed. PE occurrence was independently associated with the lack of long-term anticoagulation or thromboprophylaxis (OR [95%CI], 72.3 [3.6-4384.8]) D-dimers ≥ 2000 ng/mL (26.3 [4.1-537.8]) and neutrophils ≥ 7.0 G/L (5.8 [1.4-29.5]). The presence of these two biomarkers was associated with a higher risk of PE (p = 0.0002) and death or ICU transfer (HR [95%CI], 12.9 [2.5-67.8], p < 0.01). In hospitalized non-ICU severe COVID-19 patients with clinical PE suspicion, the lack of anticoagulation, D-dimers ≥ 2000 ng/mL, neutrophils ≥ 7.0 G/L, and these two biomarkers combined might be useful predictive markers of PE and prognosis, respectively.


Subject(s)
COVID-19/pathology , Fibrin Fibrinogen Degradation Products/metabolism , Neutrophils/pathology , Pulmonary Embolism/virology , Aged , COVID-19/blood , Computed Tomography Angiography , Female , Humans , Logistic Models , Male , Middle Aged , Prognosis , Pulmonary Embolism/blood , Pulmonary Embolism/pathology , Retrospective Studies , Risk Factors , SARS-CoV-2/genetics , Venous Thromboembolism/blood , Venous Thromboembolism/pathology , Venous Thromboembolism/virology
8.
Pediatr Infect Dis J ; 40(5): e200-e202, 2021 05 01.
Article in English | MEDLINE | ID: covidwho-1180654

ABSTRACT

The current coronavirus disease 2019 pandemic has been particularly challenging for the clinician because of the unclear nature of the underlying disease mechanisms. One of the hallmarks of the disease involves an increased risk of thrombosis and hypercoagulable state. Here, we describe 2 cases of patients admitted with submassive pulmonary embolism in the setting of positive tests for severe acute respiratory syndrome coronavirus 2.


Subject(s)
COVID-19/diagnostic imaging , Pandemics , Pulmonary Embolism/diagnostic imaging , SARS-CoV-2/isolation & purification , Adolescent , COVID-19/complications , COVID-19/pathology , COVID-19/virology , Computed Tomography Angiography , Female , Humans , Pulmonary Embolism/etiology , Pulmonary Embolism/pathology , Pulmonary Embolism/virology
9.
Am J Forensic Med Pathol ; 42(2): 118-120, 2021 Jun 01.
Article in English | MEDLINE | ID: covidwho-1174988

ABSTRACT

ABSTRACT: We assess the utility of a Centers for Disease Control and Prevention (CDC) guidelines-based coronavirus disease 2019 (COVID-19) screening checklist for postmortem severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surveillance, detailing the relationship between the histologic findings at autopsy and attribution of death to COVID-19.SARS-CoV-2 nasopharyngeal swabs were collected at the time of autopsy in all "checklist-positive" decedents. Additional "checklist-negative" decedents were randomly tested daily. Lung slides were blindly reviewed by 3 pathologists, assessing for the presence of diffuse alveolar damage (DAD) and other findings. Sixteen decedents had positive postmortem SARS-CoV-2 nasopharyngeal swabs and underwent complete autopsies. Seven decedents had positive screening checklists. Of these, 4 had DAD and 1 had COVID-19-associated thromboembolic disease. Of the 9 decedents with negative screening checklists, 2 had DAD, but only 1 was attributed to COVID-19; the other was likely drug related. Acute bronchopneumonia was the second most common finding, and aspiration was the likely etiology in cases without concomitant DAD. COVID-19-related DAD was identified more commonly in decedents who screened positive by CDC checklist, but false-negatives did occur. Medical examiner offices should maintain a low threshold for random testing of decedents even when COVID-19 is not suspected.


Subject(s)
COVID-19/diagnosis , COVID-19/mortality , Lung/pathology , Adolescent , Adult , Aged , Autopsy , Bronchopneumonia/pathology , COVID-19 Testing , Centers for Disease Control and Prevention, U.S. , Checklist , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Nasopharynx/virology , Practice Guidelines as Topic , Pulmonary Alveoli/pathology , Pulmonary Embolism/pathology , Respiratory Aspiration/pathology , Specimen Handling , United States , Young Adult
10.
Mod Pathol ; 34(8): 1456-1467, 2021 08.
Article in English | MEDLINE | ID: covidwho-1164812

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated clinical syndrome COVID-19 are causing overwhelming morbidity and mortality around the globe and disproportionately affected New York City between March and May 2020. Here, we report on the first 100 COVID-19-positive autopsies performed at the Mount Sinai Hospital in New York City. Autopsies revealed large pulmonary emboli in six cases. Diffuse alveolar damage was present in over 90% of cases. We also report microthrombi in multiple organ systems including the brain, as well as hemophagocytosis. We additionally provide electron microscopic evidence of the presence of the virus in our samples. Laboratory results of our COVID-19 cohort disclose elevated inflammatory markers, abnormal coagulation values, and elevated cytokines IL-6, IL-8, and TNFα. Our autopsy series of COVID-19-positive patients reveals that this disease, often conceptualized as a primarily respiratory viral illness, has widespread effects in the body including hypercoagulability, a hyperinflammatory state, and endothelial dysfunction. Targeting of these multisystemic pathways could lead to new treatment avenues as well as combination therapies against SARS-CoV-2 infection.


Subject(s)
COVID-19/physiopathology , Lung/physiopathology , Pulmonary Embolism/physiopathology , Adult , Aged , Aged, 80 and over , Autopsy , Blood Coagulation , COVID-19/blood , COVID-19/pathology , COVID-19/virology , Cause of Death , Cytokines/blood , Female , Host-Pathogen Interactions , Humans , Inflammation Mediators/blood , Lung/pathology , Lung/virology , Male , Middle Aged , New York City , Pulmonary Embolism/blood , Pulmonary Embolism/pathology , Pulmonary Embolism/virology , SARS-CoV-2/pathogenicity
11.
Arch Pathol Lab Med ; 145(1): 11-21, 2021 01 01.
Article in English | MEDLINE | ID: covidwho-1067935

ABSTRACT

CONTEXT.­: Respiratory failure appears to be the ultimate mechanism of death in most patients with severe coronavirus disease 2019 (COVID-19) infection. Studies of postmortem COVID-19 lungs largely report diffuse alveolar damage and capillary fibrin thrombi, but we have also observed other patterns. OBJECTIVE.­: To report demographic and radiographic features along with macroscopic, microscopic, and microbiologic postmortem lung findings in patients with COVID-19 infections. DESIGN.­: Patients with confirmed COVID-19 infection and postmortem examination (March 2020-May 2020) were included. Clinical findings were abstracted from medical records. Lungs were microscopically reviewed independently by 4 thoracic pathologists. Imaging studies were reviewed by a thoracic radiologist. RESULTS.­: Eight patients (7 men, 87.5%; median age, 79 years; range, 69-96 years) died within a median of 17 days (range, 6-100 days) from onset of symptoms. The median lung weight was 1220 g (range, 960-1760 g); consolidations were found in 5 patients (62.5%) and gross thromboemboli were noted in 1 patient (12.5%). Histologically, all patients had acute bronchopneumonia; 6 patients (75%) also had diffuse alveolar damage. Two patients (25%) had aspiration pneumonia in addition. Thromboemboli, usually scattered and rare, were identified in 5 patients (62.5%) in small vessels and in 2 of these patients also in pulmonary arteries. Four patients (50%) had perivascular chronic inflammation. Postmortem bacterial lung cultures were positive in 4 patients (50%). Imaging studies (available in 4 patients) were typical (n = 2, 50%), indeterminate (n = 1, 25%), or negative (n = 1, 25%) for COVID-19 infection. CONCLUSIONS.­: Our study shows that patients infected with COVID-19 not only have diffuse alveolar damage but also commonly have acute bronchopneumonia and aspiration pneumonia. These findings are important for management of these patients.


Subject(s)
COVID-19/pathology , Lung/pathology , Aged , Aged, 80 and over , Autopsy , Bronchopneumonia/pathology , COVID-19/diagnostic imaging , COVID-19/mortality , Fatal Outcome , Female , Humans , Lung/diagnostic imaging , Male , Minnesota/epidemiology , Pandemics , Pneumonia, Aspiration/pathology , Pulmonary Alveoli/pathology , Pulmonary Embolism/pathology , SARS-CoV-2 , Tomography, X-Ray Computed
13.
Shock ; 55(6): 700-716, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-998566

ABSTRACT

ABSTRACT: There is increasing evidence that novel coronavirus disease 2019 (COVID-19) leads to a significant coagulopathy, a phenomenon termed "COVID-19 associated coagulopathy." COVID-19 has been associated with increased rates of both venous and arterial thromboembolic events, a source of significant morbidity and mortality in this disease. Further evidence suggests a link between the inflammatory response and coagulopathy associated with COVID-19. This presents a unique set of challenges for diagnosis, prevention, and treatment of thrombotic complications. In this review, we summarize and discuss the current literature on laboratory coagulation disruptions associated with COVID-19 and the clinical effects of thromboembolic events including pulmonary embolism, deep vein thrombosis, peripheral arterial thrombosis, and acute ischemic stroke in COVID-19. Endothelial injury and augmented innate immune response are implicated in the development of diffuse macro- and microvascular thrombosis in COVID-19. The pathophysiology of COVID-19 associated coagulopathy is an important determinant of appropriate treatment and monitoring of these complications. We highlight the importance of diagnosis and management of dysregulated coagulation in COVID-19 to improve outcomes in COVID-19 patients with thromboembolic complications.


Subject(s)
Blood Coagulation Disorders , Blood Coagulation/immunology , COVID-19 , Immunity, Innate , SARS-CoV-2/immunology , Blood Coagulation Disorders/etiology , Blood Coagulation Disorders/immunology , Blood Coagulation Disorders/pathology , Blood Coagulation Disorders/therapy , COVID-19/complications , COVID-19/pathology , COVID-19/therapy , Humans , Ischemic Stroke/complications , Ischemic Stroke/metabolism , Ischemic Stroke/pathology , Pulmonary Embolism/etiology , Pulmonary Embolism/immunology , Pulmonary Embolism/pathology , Pulmonary Embolism/therapy , Thrombosis/etiology , Thrombosis/immunology , Thrombosis/pathology , Thrombosis/therapy
14.
Clin Radiol ; 75(10): 795.e1-795.e5, 2020 10.
Article in English | MEDLINE | ID: covidwho-987413

ABSTRACT

AIM: To evaluate the incidence of pulmonary ischaemia in COVID-19 patients on extracorporeal membrane oxygenation (ECMO), and its correlation with pulmonary artery thrombosis. MATERIALS AND METHODS: Computed tomography (CT) thorax of all patients receiving ECMO with proven COVID-19 pneumonitis between March and May 2020 were analysed for the presence and extension of pulmonary thromboembolic disease. RESULTS: Fifty-one patients were reviewed. The mean (range) age of 45 (26-66) years; 38/51 (74.5%) were men. All patients had severe COVID-19 pneumonitis, and 18/51 (35.3%) had macroscopic thrombosis (15 with associated ischaemia); however, 13/51 (25.5%) patients had ischaemia without associated thrombus. CONCLUSION: The majority of patients with COVID-19 who received ECMO had areas of ischaemia within consolidated lungs, almost half of these without subtending pulmonary artery thrombosis. Although the prognostic significance of these findings is unclear, they are highly suggestive of lung ischaemia due to isolated microvascular immune thrombosis.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Coronavirus Infections/therapy , Extracorporeal Membrane Oxygenation/methods , Pneumonia, Viral/complications , Pneumonia, Viral/therapy , Pulmonary Embolism/complications , Adult , Aged , COVID-19 , Cohort Studies , Coronavirus Infections/pathology , Female , Humans , Lung/diagnostic imaging , Lung/pathology , Male , Middle Aged , Pandemics , Pneumonia, Viral/pathology , Pulmonary Embolism/pathology , SARS-CoV-2 , Tomography, X-Ray Computed
15.
Exp Biol Med (Maywood) ; 246(6): 688-694, 2021 03.
Article in English | MEDLINE | ID: covidwho-971191

ABSTRACT

Acute respiratory disease caused by a novel coronavirus (SARS-CoV-2) has spread all over the world, since its discovery in 2019, Wuhan, China. This disease is called COVID-19 and already killed over 1 million people worldwide. The clinical symptoms include fever, dry cough, dyspnea, headache, dizziness, generalized weakness, vomiting, and diarrhea. Unfortunately, so far, there is no validated vaccine, and its management consists mainly of supportive care. Venous thrombosis and pulmonary embolism are highly prevalent in patients suffering from severe COVID-19. In fact, a prothrombotic state seems to be present in most fatal cases of the disease. SARS-CoV-2 leads to the production of proinflammatory cytokines, causing immune-mediated tissue damage, disruption of the endothelial barrier, and uncontrolled thrombogenesis. Thrombin is the key regulator of coagulation and fibrin formation. In severe COVID-19, a dysfunctional of physiological anticoagulant mechanisms leads to a progressive increase of thrombin activity, which is associated with acute respiratory distress syndrome development and a poor prognosis. Protease-activated receptor type 1 (PAR1) is the main thrombin receptor and may represent an essential link between coagulation and inflammation in the pathophysiology of COVID-19. In this review, we discuss the potential role of PAR1 inhibition and regulation in COVID-19 treatment.


Subject(s)
Blood Coagulation/physiology , COVID-19/pathology , Disseminated Intravascular Coagulation/pathology , Receptor, PAR-1/metabolism , Thrombin/metabolism , Anticoagulants/therapeutic use , Blood Coagulation/drug effects , Blood Coagulation Factors/metabolism , COVID-19/drug therapy , Disseminated Intravascular Coagulation/drug therapy , Humans , Pulmonary Embolism/pathology , Pulmonary Embolism/prevention & control , Receptor, PAR-1/antagonists & inhibitors , Receptors, Cell Surface/metabolism , SARS-CoV-2 , Venous Thrombosis/pathology , Venous Thrombosis/prevention & control
16.
Biofactors ; 46(6): 927-933, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-966303

ABSTRACT

Recent articles report elevated markers of coagulation, endothelial injury, and microthromboses in lungs from deceased COVID-19 patients. However, there has been no discussion of what may induce intravascular coagulation. Platelets are critical in the formation of thrombi and their most potent trigger is platelet activating factor (PAF), first characterized by Demopoulos and colleagues in 1979. PAF is produced by cells involved in host defense and its biological actions bear similarities with COVID-19 disease manifestations. PAF can also stimulate perivascular mast cell activation, leading to inflammation implicated in severe acute respiratory syndrome (SARS). Mast cells are plentiful in the lungs and are a rich source of PAF and of inflammatory cytokines, such as IL-1ß and IL-6, which may contribute to COVID-19 and especially SARS. The histamine-1 receptor antagonist rupatadine was developed to have anti-PAF activity, and also inhibits activation of human mast cells in response to PAF. Rupatadine could be repurposed for COVID-19 prophylaxis alone or together with other PAF-inhibitors of natural origin such as the flavonoids quercetin and luteolin, which have antiviral, anti-inflammatory, and anti-PAF actions.


Subject(s)
COVID-19/prevention & control , Cyproheptadine/analogs & derivatives , Disseminated Intravascular Coagulation/prevention & control , Platelet Activating Factor/antagonists & inhibitors , Pulmonary Embolism/prevention & control , SARS-CoV-2/pathogenicity , Severe Acute Respiratory Syndrome/prevention & control , Antiviral Agents/therapeutic use , Blood Platelets/drug effects , Blood Platelets/pathology , Blood Platelets/virology , COVID-19/blood , COVID-19/pathology , COVID-19/virology , Cyproheptadine/therapeutic use , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/pathology , Disseminated Intravascular Coagulation/virology , Gene Expression Regulation , Humans , Inflammation , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Lung/drug effects , Lung/pathology , Lung/virology , Luteolin/therapeutic use , Mast Cells/drug effects , Mast Cells/pathology , Mast Cells/virology , Platelet Activating Factor/genetics , Platelet Activating Factor/metabolism , Pulmonary Embolism/blood , Pulmonary Embolism/pathology , Pulmonary Embolism/virology , Quercetin/therapeutic use , SARS-CoV-2/drug effects , Severe Acute Respiratory Syndrome/blood , Severe Acute Respiratory Syndrome/pathology , Severe Acute Respiratory Syndrome/virology
17.
Am J Respir Cell Mol Biol ; 64(4): 407-415, 2021 04.
Article in English | MEDLINE | ID: covidwho-922610

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a new strain of a Coronaviridae virus that presents 79% genetic similarity to the severe acute respiratory syndrome coronavirus, has been recently recognized as the cause of a global pandemic by the World Health Organization, implying a major threat to world public health. SARS-CoV-2 infects host human cells by binding through the viral spike proteins to the ACE-2 (angiotensin-converting enzyme 2) receptor, fuses with the cell membrane, enters, and starts its replication process to multiply its viral load. Coronavirus disease (COVID-19) was initially considered a respiratory infection that could cause pneumonia. However, in severe cases, it extends beyond the respiratory system and becomes a multiorgan disease. This transition from localized respiratory infection to multiorgan disease is due to two main complications of COVID-19. On the one hand, it is due to the so-called cytokine storm: an uncontrolled inflammatory reaction of the immune system in which defensive molecules become aggressive for the body itself. On the other hand, it is due to the formation of a large number of thrombi that can cause myocardial infarction, stroke, and pulmonary embolism. The pulmonary endothelium actively participates in these two processes, becoming the last barrier before the virus spreads throughout the body. In this review, we examine the role of the pulmonary endothelium in response to COVID-19, the existence of potential biomarkers, and the development of novel therapies to restore vascular homeostasis and to protect and/or treat coagulation, thrombosis patients. In addition, we review the thrombotic complications recently observed in patients with COVID-19 and its potential threatening sequelae.


Subject(s)
COVID-19/metabolism , Endothelium/metabolism , Pulmonary Embolism/metabolism , SARS-CoV-2/metabolism , Thrombosis/metabolism , Angiotensin-Converting Enzyme 2/metabolism , Biomarkers/metabolism , COVID-19/pathology , COVID-19/therapy , Endothelium/pathology , Endothelium/virology , Humans , Membrane Fusion , Pulmonary Embolism/pathology , Pulmonary Embolism/therapy , Pulmonary Embolism/virology , Spike Glycoprotein, Coronavirus/metabolism , Thrombosis/pathology , Thrombosis/therapy , Thrombosis/virology
18.
J Pathol Clin Res ; 7(2): 135-143, 2021 03.
Article in English | MEDLINE | ID: covidwho-921715

ABSTRACT

Similar to the influenza A pandemic in 1918/1919, the new Coronavirus disease 2019 (COVID-19) has spread globally. The causes of death in COVID-19 are frequently compared to a seasonal influenza outbreak. Complete COVID-19 autopsy studies were almost non-existent in the first months of the outbreak and are still rare with respect to the number of deaths. It has been recently reported that capillary microthrombi are significantly more prevalent in patients with COVID-19 than in patients with influenza A. To date, the contribution of macrothrombi, i.e. visible thrombi in pulmonary arteries, to the death of patients with influenza A in comparison to COVID-19 remains unaddressed. Here, we report autopsy findings in 411 patients who died from the 'Spanish' influenza A pandemic between May 1918 and April 1919 at the University Hospital Zurich, Switzerland. We compare these results with influenza A autopsies from 2009 to 2020, other influenza A autopsy series and all COVID-19 autopsies published to date. No descriptions of any macroscopic thromboembolic events were mentioned in influenza A autopsy reports. In 75 published COVID-19 autopsies, pulmonary artery thrombosis/embolism was reported in 36%. The direct comparison of macroscopic autopsy findings suggests a significantly greater degree of grossly visible pulmonary macrothrombi in patients with COVID-19 in comparison to influenza A autopsies even though most patients received empiric thromboprophylaxis. This is consistent with the concept of a SARS-related de novo coagulopathy with generalised in situ clot formation, which could explain the high incidence of pulmonary thrombosis/embolism with or without underlying deep vein thrombosis and in the absence of a history of venous thromboembolic events.


Subject(s)
COVID-19/epidemiology , COVID-19/pathology , Influenza, Human/epidemiology , Influenza, Human/pathology , Pulmonary Embolism/epidemiology , Pulmonary Embolism/etiology , SARS-CoV-2/pathogenicity , Adolescent , Adult , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , Autopsy , COVID-19/complications , COVID-19/mortality , Cause of Death , Child , Child, Preschool , Female , Humans , Infant , Influenza, Human/mortality , Lung/pathology , Lung/virology , Male , Middle Aged , Prevalence , Pulmonary Embolism/pathology , Thrombosis/pathology , Thrombosis/virology , Young Adult
19.
Mol Med ; 26(1): 95, 2020 10 14.
Article in English | MEDLINE | ID: covidwho-873932

ABSTRACT

Pulmonary fibrosis arises from the repeated epithelial mild injuries and insufficient repair lead to over activation of fibroblasts and excessive deposition of extracellular matrix, which result in a mechanical stretched niche. However, increasing mechanical stress likely exists before the establishment of fibrosis since early micro injuries increase local vascular permeability and prompt cytoskeletal remodeling which alter cellular mechanical forces. It is noteworthy that COVID-19 patients with severe hypoxemia will receive mechanical ventilation as supportive treatment and subsequent pathology studies indicate lung fibrosis pattern. At advanced stages, mechanical stress originates mainly from the stiff matrix since boundaries between stiff and compliant parts of the tissue could generate mechanical stress. Therefore, mechanical stress has a significant role in the whole development process of pulmonary fibrosis. The alveoli are covered by abundant capillaries and function as the main gas exchange unit. Constantly subject to variety of damages, the alveolar epithelium injuries were recently recognized to play a vital role in the onset and development of idiopathic pulmonary fibrosis. In this review, we summarize the literature regarding the effects of mechanical stress on the fundamental cells constituting the alveoli in the process of pulmonary fibrosis, particularly on epithelial cells, capillary endothelial cells, fibroblasts, mast cells, macrophages and stem cells. Finally, we briefly review this issue from a more comprehensive perspective: the metabolic and epigenetic regulation.


Subject(s)
Coronavirus Infections/immunology , Epigenesis, Genetic/immunology , Idiopathic Pulmonary Fibrosis/immunology , Mechanotransduction, Cellular/immunology , Pneumonia, Viral/immunology , Pulmonary Embolism/immunology , Respiratory Insufficiency/immunology , Alveolar Epithelial Cells/immunology , Alveolar Epithelial Cells/pathology , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , Biomechanical Phenomena , COVID-19 , Coronavirus Infections/genetics , Coronavirus Infections/pathology , Coronavirus Infections/virology , Cytokines/genetics , Cytokines/immunology , Endothelial Cells/immunology , Endothelial Cells/pathology , Fibroblasts/immunology , Fibroblasts/pathology , Humans , Idiopathic Pulmonary Fibrosis/genetics , Idiopathic Pulmonary Fibrosis/pathology , Idiopathic Pulmonary Fibrosis/virology , Lung/blood supply , Lung/immunology , Lung/pathology , Macrophages/immunology , Macrophages/pathology , Mechanotransduction, Cellular/genetics , Pandemics , Pneumonia, Viral/genetics , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Pulmonary Embolism/genetics , Pulmonary Embolism/pathology , Pulmonary Embolism/virology , Respiratory Insufficiency/genetics , Respiratory Insufficiency/pathology , Respiratory Insufficiency/virology , SARS-CoV-2 , Stress, Mechanical
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