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1.
Saudi J Kidney Dis Transpl ; 32(6): 1523-1544, 2021.
Article in English | MEDLINE | ID: covidwho-1975051

ABSTRACT

The major targets of coronavirus disease 2019 (COVID-19) are the respiratory and immune systems. However, a significant proportion of hospitalized patients had kidney dysfunction. The histopathological surveys have principally focused on respiratory, hematopoietic, and immune systems, whereas histopathologic data of kidney injury are lacking. Our study aimed to summarize the renal histopathological findings in COVID-19 from the published case report and case series. We conducted a systematic searching of databases such as MEDLINE, EMBASE, and Cochrane Library for published reports of COVID-19 patients with renal histopathological changes from autopsy studies and from "for cause" indication biopsies. Included in our study are case reports and case series with extractable quantitative data on patient demographics such as age, sex, ethnicity, as well as data on renal function tests, their comorbidities, and biopsy to study the histopathological changes. Data were analyzed with Microsoft Excel. To evaluate the methodological quality, we chose the framework for appraisal, synthesis, and application of evidence suggested by Murad et al. Systematic searches of literature found 31 studies that fulfilled the eligibility criteria. These studies included a total of 139 cases, where individual case details including clinical and histopathological findings were available. The median age of the cases was 62 years with a male:female ratio of 2.5:1. Associated comorbidities were noted in 78.4% of cases. The majority of the cases had renal dysfunction with proteinuria which was documented in more than two-thirds of the cases. The histopathological findings observed the frequent tubular involvement manifested by acute tubular injury. Regarding glomerular pathology, collapsing glomerulopathy emerged as a distinct lesion in these patients and was noted among 46.8% of cases with glomerular lesions. A small subset of cases (4.3%) had thrombotic microangiopathy. Collapsing glomerulopathy emerged as a hallmark of glomerular changes among COVID-19 patients. Tubular damage is common and is linked to multiple factors including ischemia, sepsis among others. In the form of thrombotic microangiopathy seen in a subset of patients, vascular damage hints toward the hyper-coagulable state associated with the infection. The demonstration of viral particles in renal tissue remains debatable and requires further study.


Subject(s)
COVID-19 , Kidney Diseases , Thrombotic Microangiopathies , Female , Humans , Kidney/pathology , Kidney/physiology , Kidney Diseases/pathology , Kidney Glomerulus/pathology , Male , Middle Aged , Proteinuria/etiology , Thrombotic Microangiopathies/complications
2.
Exp Clin Transplant ; 19(9): 990-993, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1315995

ABSTRACT

The present COVID-19 pandemic is a cause for concern among solid-organ transplant recipients, who are generally at high risk for infection and for whom infection with COVID-19 carries additional risks for complications and mortality that are higher than the COVID-19-associated risks for the general population. We report the case of a liver transplant recipient who presented with COVID-19 and multiple complications. A 39-year-old woman with a liver transplant was diagnosed with COVID-19 within the first week after transplant surgery. Mycophenolate was withheld, and interferon ß was administered for management of COVID-19. She developed thrombotic thrombocytopenic purpura, acute antibody-mediated rejection, and posterior reversible leukoencephalopathy syndrome during hospitalization. All of these complications may be related to COVID-19 or its management modalities. We considered 3 possible causes for thrombotic thrombocytopenic purpura in this patient: the COVID-19 infection itself, immunosuppression treatment with cyclosporine, and treatment with interferon ß. Immunosuppression reduction and interferon treatment may result in antibody-mediated rejection. COVID-19, thrombotic thrombocytopenic purpura, and cyclosporine may play a combined role in the development of posterior reversible leukoencephalopathy syndrome. In conclusion, thrombotic thrombocytopenic purpura, antibody-mediated rejection, and posterior reversible leukoencephalopathy syndrome may represent a continuum of 3 thrombotic microangiopathy conditions fostered by interplay between the COVID-19 infection and the treatment modalities for COVID-19 management in this patient.


Subject(s)
COVID-19/complications , Graft Rejection/complications , Liver Transplantation , Posterior Leukoencephalopathy Syndrome/complications , Thrombotic Microangiopathies/complications , Adult , Female , Humans , Transplant Recipients
3.
Blood Adv ; 4(23): 6051-6063, 2020 12 08.
Article in English | MEDLINE | ID: covidwho-962802

ABSTRACT

Most children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have mild or minimal disease, with a small proportion developing severe disease or multisystem inflammatory syndrome in children (MIS-C). Complement-mediated thrombotic microangiopathy (TMA) has been associated with SARS-CoV-2 infection in adults but has not been studied in the pediatric population. We hypothesized that complement activation plays an important role in SARS-CoV-2 infection in children and sought to understand if TMA was present in these patients. We enrolled 50 hospitalized pediatric patients with acute SARS-CoV-2 infection (n = 21, minimal coronavirus disease 2019 [COVID-19]; n = 11, severe COVID-19) or MIS-C (n = 18). As a biomarker of complement activation and TMA, soluble C5b9 (sC5b9, normal 247 ng/mL) was measured in plasma, and elevations were found in patients with minimal disease (median, 392 ng/mL; interquartile range [IQR], 244-622 ng/mL), severe disease (median, 646 ng/mL; IQR, 203-728 ng/mL), and MIS-C (median, 630 ng/mL; IQR, 359-932 ng/mL) compared with 26 healthy control subjects (median, 57 ng/mL; IQR, 9-163 ng/mL; P < .001). Higher sC5b9 levels were associated with higher serum creatinine (P = .01) but not age. Of the 19 patients for whom complete clinical criteria were available, 17 (89%) met criteria for TMA. A high proportion of tested children with SARS-CoV-2 infection had evidence of complement activation and met clinical and diagnostic criteria for TMA. Future studies are needed to determine if hospitalized children with SARS-CoV-2 should be screened for TMA, if TMA-directed management is helpful, and if there are any short- or long-term clinical consequences of complement activation and endothelial damage in children with COVID-19 or MIS-C.


Subject(s)
COVID-19/diagnosis , Thrombotic Microangiopathies/diagnosis , Acute Kidney Injury/etiology , Acute Kidney Injury/pathology , Adolescent , Antibodies, Viral/blood , Biomarkers/metabolism , COVID-19/pathology , COVID-19/virology , Child , Child, Preschool , Cluster Analysis , Complement Membrane Attack Complex/metabolism , Creatinine/blood , Female , Humans , Male , RNA, Viral/metabolism , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Severity of Illness Index , Thrombotic Microangiopathies/complications
4.
Cardiorenal Med ; 10(6): 462-469, 2020.
Article in English | MEDLINE | ID: covidwho-889976

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a pandemic that has affected >188 countries, involved >24 million people, and caused >840,000 deaths. COVID-19, in its severe form, presents as acute respiratory distress syndrome (ARDS), shock, and multiorgan failure. Thrombotic microangiopathy of the lungs and kidneys has been observed in these patients. Elevated D-dimer levels have been observed in people with serious COVID-19 illness, and this could be helpful in guiding treatment with anticoagulation in these patients. OBJECTIVE: To analyze the role of anticoagulation as a treatment modality for COVID-19. METHODS: We present the unique case of a COVID-19 patient who developed sepsis, ARDS, acute kidney injury, and deep-vein thrombosis (DVT), who was deteriorating clinically. She was treated with anticoagulation. RESULTS: There was rapid recovery after treatment with systemic anticoagulation. CONCLUSIONS: Systemic anticoagulation could prove to be essential in the treatment of CO-VID-19. Further studies are required to assess its role in improving long-term morbidity and mortality in these patients.


Subject(s)
COVID-19/complications , SARS-CoV-2/genetics , Thromboembolism/etiology , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Anticoagulants/therapeutic use , COVID-19/epidemiology , COVID-19/virology , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/etiology , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Middle Aged , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/etiology , Sepsis/diagnosis , Sepsis/etiology , Thromboembolism/diagnosis , Thromboembolism/prevention & control , Thrombotic Microangiopathies/complications , Thrombotic Microangiopathies/prevention & control , Treatment Outcome , Venous Thrombosis/diagnosis , Venous Thrombosis/etiology
5.
Rev Esp Anestesiol Reanim (Engl Ed) ; 67(9): 516-520, 2020 Nov.
Article in English, Spanish | MEDLINE | ID: covidwho-834694

ABSTRACT

Coronavirus associated severe acute respiratory syndrome (SARS-CoV-2) causes a worldwide syndrome called Covid-19 that has caused 5,940,441 infections and 362,813 deaths until May 2020. In moderate and severe stages of the infection a generalized swelling, cytokine storm and an increment of the heart damage biomarkers occur. In addition, a relation between Covid-19 and neurological symptoms have been suggested. The results of autopsies suggest thrombotic microangiopathy in multiple organs. We present 2 cases of patients infected with severe Covid-19 that were hospitalized in the Reanimation Unit that presented cerebrovascular symptoms and died afterwards. A high dose prophylaxis with antithrombotic medication is recommended in patients affected by moderate to severe Covid-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Hemorrhage/complications , Ischemia/complications , Pneumonia, Viral/complications , Stroke/etiology , Aged , COVID-19 , Fatal Outcome , Hemorrhage/diagnostic imaging , Humans , Ischemia/diagnostic imaging , Male , Middle Aged , Pandemics , SARS-CoV-2 , Stroke/diagnostic imaging , Thrombotic Microangiopathies/complications , Thrombotic Microangiopathies/diagnostic imaging , Tomography, X-Ray Computed
6.
Am J Case Rep ; 21: e927418, 2020 Sep 12.
Article in English | MEDLINE | ID: covidwho-761141

ABSTRACT

BACKGROUND Patients receiving immunosuppressive therapies might be more susceptible to COVID-19. Conversely, an exaggerated inflammatory response to the SARS-CoV-2 infection might be blunted by certain forms of immunosuppression, which could be protective. Indeed, there are data from animal models demonstrating that complement may be a part of the pathophysiology of coronavirus infections. There is also evidence from an autopsy series demonstrating complement deposition in the lungs of patients with COVID-19. This raises the question of whether patients on anti-complement therapy could be protected from COVID-19. CASE REPORT Case 1 is a 39-year-old woman with an approximately 20-year history of paroxysmal nocturnal hemoglobinuria (PNH), who had recently been switched from treatment with eculizumab to ravulizumab prior to SARS-CoV-2 infection. Case 2 is a 54-year-old woman with a cadaveric renal transplant for lupus nephritis, complicated by thrombotic microangiopathy, who was maintained on eculizumab, which she started several months before she developed the SARS-CoV-2 infection. Case 3 is a 60-year-old woman with a 14-year history of PNH, who had been treated with eculizumab since 2012, and was diagnosed with COVID-19 at the time of her scheduled infusion. All 3 patients had a relatively mild course of COVID-19. CONCLUSIONS We see no evidence of increased susceptibility to SARS-CoV-2 in these patients on anti-complement therapy, which might actually have accounted for the mild course of infection. The effect of anti-complement therapy on COVID-19 disease needs to be determined in clinical trials.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Complement C5/metabolism , Coronavirus Infections/complications , Hemoglobinuria, Paroxysmal/drug therapy , Pneumonia, Viral/complications , Thrombotic Microangiopathies/drug therapy , Adult , Betacoronavirus , COVID-19 , Complement C5/drug effects , Complement C5/immunology , Complement Inactivating Agents/therapeutic use , Coronavirus Infections/epidemiology , Female , Hemoglobinuria, Paroxysmal/complications , Hemoglobinuria, Paroxysmal/immunology , Humans , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Thrombotic Microangiopathies/complications , Thrombotic Microangiopathies/immunology
7.
Immunobiology ; 225(6): 152001, 2020 11.
Article in English | MEDLINE | ID: covidwho-696536

ABSTRACT

In COVID-19, acute respiratory distress syndrome (ARDS) and thrombotic events are frequent, life-threatening complications. Autopsies commonly show arterial thrombosis and severe endothelial damage. Endothelial damage, which can play an early and central pathogenic role in ARDS and thrombosis, activates the lectin pathway of complement. Mannan-binding lectin-associated serine protease-2 (MASP-2), the lectin pathway's effector enzyme, binds the nucleocapsid protein of severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2), resulting in complement activation and lung injury. Narsoplimab, a fully human immunoglobulin gamma 4 (IgG4) monoclonal antibody against MASP-2, inhibits lectin pathway activation and has anticoagulant effects. In this study, the first time a lectin-pathway inhibitor was used to treat COVID-19, six COVID-19 patients with ARDS requiring continuous positive airway pressure (CPAP) or intubation received narsoplimab under compassionate use. At baseline and during treatment, circulating endothelial cell (CEC) counts and serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), C-reactive protein (CRP) and lactate dehydrogenase (LDH) were assessed. Narsoplimab treatment was associated with rapid and sustained reduction of CEC and concurrent reduction of serum IL-6, IL-8, CRP and LDH. Narsoplimab was well tolerated; no adverse drug reactions were reported. Two control groups were used for retrospective comparison, both showing significantly higher mortality than the narsoplimab-treated group. All narsoplimab-treated patients recovered and survived. Narsoplimab may be an effective treatment for COVID-19 by reducing COVID-19-related endothelial cell damage and the resultant inflammation and thrombotic risk.


Subject(s)
Antibodies, Monoclonal/therapeutic use , COVID-19/immunology , Complement Pathway, Mannose-Binding Lectin/drug effects , Endothelium, Vascular/drug effects , SARS-CoV-2/immunology , Thrombotic Microangiopathies/drug therapy , Antibodies, Monoclonal/immunology , C-Reactive Protein/immunology , C-Reactive Protein/metabolism , COVID-19/complications , COVID-19/virology , Complement Pathway, Mannose-Binding Lectin/immunology , Endothelium, Vascular/immunology , Endothelium, Vascular/pathology , Female , Humans , Immunoglobulin G/immunology , Immunoglobulin G/therapeutic use , Inflammation/complications , Inflammation/immunology , Inflammation/prevention & control , Interleukin-6/blood , Interleukin-6/immunology , Male , Mannose-Binding Protein-Associated Serine Proteases/antagonists & inhibitors , Mannose-Binding Protein-Associated Serine Proteases/immunology , Mannose-Binding Protein-Associated Serine Proteases/metabolism , Middle Aged , Outcome Assessment, Health Care/methods , Outcome Assessment, Health Care/statistics & numerical data , Retrospective Studies , SARS-CoV-2/physiology , Thrombotic Microangiopathies/complications , Thrombotic Microangiopathies/immunology
8.
Adv Chronic Kidney Dis ; 27(5): 397-403, 2020 09.
Article in English | MEDLINE | ID: covidwho-695253

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a rapidly spreading pandemic. Owing to changes in the immune system and respiratory physiology, pregnant women are vulnerable to severe viral pneumonia. We review the clinical course, pregnancy outcomes, and management of women with COVID-19 in pregnancy with a focus on those with kidney involvement. Current evidence does not show an increased risk of acquiring SARS-CoV-2 during pregnancy and the maternal course appears to be similar to nonpregnant patients. However, severe maternal disease can lead to complex management challenges and has shown to be associated with higher incidence of preterm and caesarean births. The risk of congenital infection with SARS-CoV-2 is not known. All neonates must be considered as high-risk contacts and should be screened at birth and isolated. Pregnant women should follow all measures to prevent SARS-CoV-2 exposure and this fear should not compromise antenatal care. Use of telemedicine, videoconferencing, and noninvasive fetal and maternal home monitoring devices should be encouraged. High-risk pregnant patients with comorbidities and COVID-19 require hospitalization and close monitoring. Pregnant women with COVID-19 and kidney disease are a high-risk group and should be managed by a multidisciplinary team approach including a nephrologist and neonatologist.


Subject(s)
Acute Kidney Injury/therapy , COVID-19/therapy , Kidney Transplantation , Pregnancy Complications, Infectious/therapy , Pregnancy Complications/therapy , Renal Insufficiency, Chronic/therapy , Acute Kidney Injury/etiology , COVID-19/complications , COVID-19/prevention & control , COVID-19/transmission , Cesarean Section/statistics & numerical data , Diagnosis, Differential , Disease Management , Female , Humans , Infectious Disease Transmission, Vertical , Kidney Cortex Necrosis/complications , Kidney Cortex Necrosis/diagnosis , Patient Care Team , Pre-Eclampsia/diagnosis , Pregnancy , Premature Birth/epidemiology , Prenatal Care/methods , Pyelonephritis/complications , Pyelonephritis/diagnosis , Renal Insufficiency, Chronic/complications , SARS-CoV-2 , Telemedicine/methods , Thrombotic Microangiopathies/complications , Thrombotic Microangiopathies/diagnosis
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