Renal vein thrombosis after COVID-19, A case report Dr. Vida Shirzadeh (Corresponding Author); Ardabil University of Medical Sciences, Faculty of medicine, Emam Khomeini hospital, Ardabil, Iran Email: vidashsh95@gmail.com (preprint)

COVID-19 can lead to pneumonia or acute respiratory distress syndrome. Non-respiratory manifestations of COVID-19 include venous and arterial thrombosis. The disease can affect kidneys and lead to renal vein thrombosis leading to symptoms such as flank pain, hematuria, or acute kidney damage.

[Carotid endarterectomy in patients with internal carotid artery thrombosis in the acutest period of ischemic stroke with COVID-19]. / Karotidnaya endarterektomiya u patsientov s trombozom vnutrennei sonnoi arterii v ostreishem periode ishemicheskogo insul'ta na fone COVID-19.

OBJECTIVE: Analysis of the results of emergency carotid endarterectomy (CEE) in internal carotid artery (ICA) thrombosis in the acute period of acute cerebrovascular accident (ACVI) in patients with COVID-19. MATERIAL AND METHODS: During the COVID-19 pandemic (April 1, 2020 - May 1, 2021), 43 patients with ICA thrombosis and a positive polymerase chain reaction (PCR) result for SARS-CoV-2 were included in this prospective study. In all cases, CEE was performed in the acutest period of ACVA. These patients were included in group 1. The comparison group was represented by 89 patients who underwent CEE in the acute period of stroke, in the period before the COVID-19 pandemic (April 1, 2019 - March 1.2020). RESULTS: In the hospital postoperative period, the groups were comparable in terms of the incidence of deaths (group 1: 2.3%, n=1; group 2: 1.1%, n=1; p=0.81; OR=2.09; 95% CI=0.12-34.3) myocardial infarction (group 1: 2.3%, n=1; group 2: 0%; p=0.7; OR=6.3; 95% CI=0.25-158.5), CVA (group 1: 2.3%, n=1; group 2: 2.2%, n=2; p=0.55; OR=1.03; 95% CI=0.09-11.,7). ICA thrombosis and hemorrhagic transformations were not recorded. However, in view of severe coagulopathy with ongoing anticoagulant/antiplatelet therapy, patients with COVID-19 more often developed bleeding in the operation area (group 1: 11.6%, n=5; group 2: 1.1%, n=1; p=0.02; OR=11.5; 95% CI=1.3-102.5). CONCLUSION: Emergency CEE in the acute period of stroke is an effective and safe method of cerebral revascularization in case of ICA thrombosis in conditions of COVID-19.

Successful Endovascular Therapy in COVID-19 Associated Pediatric Ischemic Stroke.

Cerebrovascular diseases attributed to coronavirus disease 2019 (COVID-19) are uncommon but can result in devastating outcomes. Pediatric acute ischemic strokes are themselves rare and with very few large vessel occlusion related acute ischemic strokes attributed to COVID-19 described in the literature as of date. COVID-19 pandemic has contributed to acute stroke care delays across the world and with pediatric endovascular therapy still in its infancy, it poses a great challenge in facilitating good outcomes in children presenting with acute ischemic strokes in the setting of COVID-19. We present a pediatric patient who underwent endovascular therapy for an internal carotid artery occlusion related acute ischemic stroke in the setting of active COVID-19 and had an excellent outcome thanks to a streamlined stroke pathway involving the vascular neurology, neuro-interventional, neurocritical care, and anesthesiology teams.

Experience of Danaparoid to Treat Vaccine-Induced Immune Thrombocytopenia and Thrombosis, VITT (preprint)

Background: Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is triggered by nCOV-19 adenovirus-vectored vaccines against SARS-CoV2. Pathogenesis has been mainly related to platelet activation via PF4-reactive antibodies that activate platelets and cross-react with heparin. Data concerning optimal anticoagulation are anecdotal, and so far, there are scattered reports of danaparoid use in VITT management. Danaparoid has good efficacy and safety in treatment of heparin-induced thrombocytopenia. We report here our experience of the administration and monitoring danaparoid in VITT. Methods: : We diagnosed six hospitalized cases of definite or probable VITT, based on the international diagnostic guidance. All VITT-related data were from the local electronic medical and laboratory record system and were analyzed with IBM SPSS Statistics. Results: : Predominately women in their late forties developed VITT on average 24 days (range 9-59) after the first ChAdOx1 dose. Clinical presentation included single or multiple venous and/or arterial thrombosis, moderate thrombocytopenia and high D-dimer levels. After detecting PF4 antibodies subcutaneous danaparoid was our first-line antithrombotic treatment with an average duration of three weeks. The median plasma anti-FXa activity was in the lower part of the therapeutic range and during the first week of danaparoid administration clinical symptoms, platelet counts and fibrin turnover resolved or significantly improved. The average duration of hospital admission was 10 days (2-18). One patient died but the other five recovered completely. Conclusions: : The clinical outcomes of our small cohort align with the earlier published reports, and support danaparoid as a rational option for the initial anticoagulation of VITT patients.

Effect of Routine Thromboprophylaxis with Low Molecular Weight Heparin in Hospitalized Covid-19 Patients (preprint)

Background: Coronavirus disease 2019 (COVID-19) is commonly complicated with coagulopathy presented with venous thromboembolism and arterial thromboses. The aim of this study was to evaluate the effect of routine thromboprophylaxis with low molecular weight heparin (LMWH) on clinical outcomes including mortality and need for intensive care unit (ICU) admission in hospitalized COVID-19 patients. Methods: All confirmed patients with COVID-19 hospitalized to COVID-19 dedicated wards, from March 15 to May 15, 2020, were included in this retrospective cohort study. Two groups of patients were established, according to the non-routine and routine application of LMWH with therapeutic, weight-based, anticoagulation dosing. Clinical, laboratory and treatment data were collected, analyzed and compared between the two groups. A logistic regression model was developed to assess the factors related to in-hospital adverse outcomes. Results: A total of 1511 patients (797 men, median age 59.0 years) were retrospectively analyzed (Group non-routine LMWH (n=828); group routine LMWH (n=683)). Multivariate logistic regression analysis showed routine use of LMWH, favipiravir administration, extreme values of WBC count, NLR, and troponin I as factors independently associated with in-hospital adverse outcomes (OR=0.25, 95% CI: 0.83-0.91; p<0.001 for routine use of LMWH). Conclusion: Routine thromboprophylaxis with LMWH reduced mortality and ICU admission in patients admitted with COVID-19 infection.

Multiple Sites of Arterial Thrombosis in A 35-Year Old Patient after ChAdOx1 (AstraZeneca) Vaccination, Requiring Emergent Femoral and Carotid Surgical Thrombectomy.

BACKGROUND: Vaccine Induced Thrombotic Thrombocytopenia (VITT) is a rare complication following ChAdOx1 (AstraZeneca) vaccination. Venous thrombosis in unusual sites such as splachnic or intracranial thrombosis, is the commonest manifestation. CASE REPORT: We report a 35-year-old male patient who presented with acute left leg ischemia and thrombocytopenia 11-days after vaccination requiring emergent thrombectomy. During work-up, a localized thrombus was detected in the left carotid bifurcation mandating carotid thrombectomy. Localized right iliac thrombus causing a non-limiting flow stenosis was treated conservatively. The platelet aggregating capacity of patient's plasma was confirmed in a functional assay, thereby establishing VITT. CONCLUSION: To the best of our knowledge this is the first case presenting multiple arterial thromboses requiring surgical treatment after ChAdOx1 vaccination.

Vascular Inflammation in Lungs of Patients with Fatal Coronavirus Disease 2019 (COVID-19): Possible Role for the NLRP3 Inflammasome (preprint)

Background: Hyperinflammation is a key event that occurs with SARS-CoV-2 infection. In the lung, hyperinflammation leads to structural damage to tissue. To date, numerous lung histological studies have shown extensive alveolar damage, but there is scarce documentation of vascular inflammation in postmortem lung tissue. Methods: : Lung sections from 8 COVID-19 affected and 11 non-COVID-19 subjects [of which 8 were acute respiratory disease syndrome (ARDS) affected and 3 were from subjects with non-respiratory diseases] were stained for H & E to ascertain histopathological features including presence of thrombi/microthrombi. Inflammation along the vessel wall was also monitored by quantification of the expression of moieties of the NLRP3 inflammasome pathway (NLRP3 and caspase-1). Results: : In lungs from “fatal COVID-19”, vascular changes in the form of microthrombi in small vessels, arterial thrombosis, and organization were extensive as compared to lungs from “non-COVID-19 non respiratory disease” affected subjects. The NLRP3 pathway components were significantly higher in lungs from COVID-19 subjects as compared to non-COVID-19 fatal cases without respiratory disease. No significant differences were observed between COVID-19 lungs and non-COVID-19 ARDS lungs. Conclusion: We posit that inflammasome formation along the vessel wall is a characteristic of lung inflammation that accompanies COVID-19. Thus, the NLRP3 inflammasome pathway seems to be probable candidate that drives amplification of inflammation post SARS-CoV-2 infection.

COVID-19-associated ischaemic stroke due to underlying carotid artery thrombosis in a healthy young woman.

SARS-CoV-2 has proven its versatility in host presentations; one such presentation is a hypercoagulable state causing large-vessel thrombosis. We report a case on a previously asymptomatic COVID-19-positive patient presenting with an acute ischaemic stroke and an incidental left internal carotid artery thrombus. The patient's medical, social and family history and hypercoagulability screening excluded any other explanation for the left carotid thrombus or stroke, except for testing positive for the COVID-19. This case explores the known hypercoagulable state associated with COVID-19 and the effect of the virus on the host's immune response. It also questions whether administration of recombinant tissue plasminogen activator (t-PA), according to the American Heart Association guidelines, following a negative head CT for haemorrhagic stroke is safe without prior extended imaging in this patient population. We recommend, in addition to obtaining a non-contrast CT scan of the brain, a CT angiogram or carotid duplex of the neck be obtained routinely in patients with COVID-19 exhibiting stroke symptoms before t-PA administration as the effects may be detrimental. This recommendation will likely prevent fragmentation and embolisation of an undetected carotid thrombus.

Simultaneous Arterial and Venous Brain Infarctions in a Patient with COVID-19. (preprint)

Introduction: Stroke is one of the manifestations of COVID-19 associated coagulopathy. Arterial infarcts are the most common presentation, however involvement of both arterial and venous irrigation is possible but rare. We report, what is, to our knowledge, the second case of concomitant arterial and venous brain thrombosis evidenced in magnetic resonance. Case presentation: A 62-year-old man presented with acute weakness of the left hand and lack of coordination in the left arm. Nine days earlier, he was positive for SARS-CoV-2 RT-PCR. The brain images revealed two subacute infarcts, one corresponding to the territory of the right middle cerebral artery, and the other in the right frontal cortical vein. Conclusion: The existence of both venous and arterial brain infarcts due to COVID-19 infection, has been previously reported once. Most of the cases of stroke are due to only arterial thrombosis, therefore this could be the starting point to start collecting data about simultaneous compromise in order to assess and compare outcomes, severity of the disease, among other variables.

Simultaneous bilateral mechanical thrombectomy in a patient with COVID-19.

Owing to systemic inflammation and widespread vessel endotheliopathy, SARS-CoV-2 has been shown to confer an increased risk of cryptogenic stroke, particularly in patients without any traditional risk factors. In this report, we present a case of a 67-year-old female who presented with acute stroke from bilateral anterior circulation large vessel occlusions, and was incidentally found to be COVID-positive on routine hospital admission screening. The patient had a large area of penumbra bilaterally, and the decision was made to pursue bilateral simultaneous thrombectomy, with two endovascular neurosurgeons working on each side to achieve a faster time to recanalization. Our study highlights the utility and efficacy of simultaneous bilateral thrombectomy, and this treatment paradigm should be considered for use in patients who present with multifocal large vessel occlusions.

Intraluminal carotid thrombosis and acute ischemic stroke associated with COVID-19.

COVID-19 (Coronavirus disease 2019) caused by SARS-CoV-2 has a diverse constellation of neurological manifestations that include encephalopathy, stroke, Guillain-Barré syndrome, myelitis, and encephalitis. Intraluminal carotid thrombi (ILT) are infrequent lesions seen in only 1.6% of patients with acute ischemic stroke. Underlying atherosclerosis is the most common lesion associated with ILT formation. However, with COVID-19, we have encountered ILT in patients without significant atherosclerotic disease. The endothelial inflammation and hypercoagulable state associated with COVID-19 pose a risk of arterial and venous thromboembolism and could have contributed to this presentation although the exact pathophysiology and optimal treatment of ILT in COVID-19 remain elusive. Herein, we present a series of ischemic stroke patients with carotid ILT in the setting of a recent SARS-CoV-2 infection.

SARS-CoV-2, recurrent ischemic strokes and carotid macrothrombosis: the other face of the cytokine storm (a case report).

Since December 2019, the world has experienced the emergence in China of a new infection called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This infection quickly has progressed to a global pandemic since March 2020, with very high human-to-human transmission rate. Besides lung injury, COVID-19 is also associated with cardio and neurovascular complications. Herein, we report the case of a 77-year-old female who presented with non-severe COVID-19 and multiple ischemic strokes secondary to an extensive carotid thrombosis. The ischemic stroke was supposed to have been caused by the cytokine storm related to COVID-19. The possibility of hemorrhagic transformation, based on the assessment of bleeding score, limited the use of anticoagulation, and probably explained the stroke recurrence and poor outcome in our patient. The pathogenic mechanism and the management of this complex situation are still lacking and further studies are needed.

Pulmonary venous thrombosis in a patient with COVID-19 infection.

OBJECTIVES: Infection with the SARS-COV2 virus (COVID-19) may be complicated by thrombotic diathesis. This complication often involves the pulmonary microcirculation. While macrovascular thrombotic complications of the lung may include pulmonary artery embolism, pulmonary artery thrombus in situ has also been hypothesized. Pulmonary vein thrombosis has not been described in this context. METHODS/RESULTS: Herein, we provide a case of an otherwise healthy male who developed an ischemic stroke with left internal carotid thrombus. Further imaging revealed pulmonary emboli with propagation through the pulmonary veins into the left atrium. This left atrial thrombus provides a source of atypical "paradoxic arterial embolism". CONCLUSIONS: Thrombotic outcomes in the setting of severe COVID 19 pneumonia may include macrovascular venous thromboembolism, microvascular pulmonary vascular thrombosis and arterial thromboembolism. Pulmonary vein, herein described, provides further mechanistic pathway for potential arterial embolic phenomenon.

Internal carotid artery thrombosis in COVID 19.

CASE DESCRIPTION: 37-year-old female with PCR-RT swab for COVID-19 positive, with neurological manifestation as a result of internal carotid artery occlusion. CLINICAL FINDINGS: Nasal congestion and sneezing of 5 days duration; pulsatile headache in the left hemicranium 3 days prior to admission, with intensity 6/10 according to the visual analogue scale, accompanied by phosphenes, photophobia and diplopia; with subsequent developing right hemiparesis over a 26-hour period. TREATMENT AND RESULT: She was given medical management with oral antiplatelet agents and anticoagulants (subcutaneous and oral) during his hospitalization, it was not possible to perform thrombolysis and thrombectomy due to the high risk of complications. He was discharged at 14 days, without functional limitation, symmetrical strength in upper and lower limbs, bilateral visual acuity 20/20, denying headache. CLINICAL RELEVANCE: The case presented here describes a pattern in how data supporting an association between COVID-19 and stroke in young populations with or without typical vascular risk factors, sometimes with only mild respiratory symptoms, is increasing. Prospective studies are required to further evaluate this association, as well as anticoagulation studies to prevent these potentially life-threatening events.

DESCRIPCIÓN DEL CASO: Mujer de 37 años con hisopado PCR-RT para COVID-19 positivo, con manifestación neurológica por oclusión de la arteria carótida interna. HALLAZGOS CLÍNICOS: Congestión nasal y estornudos de 5 días de duración; cefalea pulsátil en hemicráneo izquierdo 3 días antes del ingreso, con intensidad 6/10 según la escala visual analógica, acompañada de fosfenos, fotofobia y diplopía; con posterior desarrollo de hemiparesia derecha durante un período de 26 horas. TRATAMIENTO Y RESULTADO: Se le brindó manejo médico con antiagregantes plaquetarios orales y anticoagulantes (subcutáneos y orales) durante su internación, no fue posible realizar trombólisis y trombectomía por alto riesgo de complicaciones. Fue dado de alta a los 14 días, sin limitación funcional, fuerza simétrica en miembros superiores e inferiores, agudeza visual bilateral 20/20, negando cefalea. RELEVANCIA CLÍNICA: Se describe un patrón que indica cómo están aumentando los datos que apoyan una asociación entre COVID-19 y el accidente cerebrovascular en poblaciones jóvenes con o sin factores de riesgo vascular típicos, a veces con solo síntomas respiratorios leves. Se requieren estudios prospectivos para evaluar más a fondo esta asociación, así como estudios de anticoagulación para prevenir estos eventos potencialmente mortales.

IP-10 and MCP-1 as biomarkers associated with disease severity of COVID-19 (preprint)

Background: COVID-19 is a viral respiratory disease caused by the severe acute respiratory syndrome-Coronavirus type 2 (SARS-CoV-2). Patients with this disease may be more prone to venous or arterial thrombosis because of the activation of many factors involved in it, including inflammation, platelet activation and endothelial dysfunction. Interferon gamma inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein 1-alpha (MIP1α) are cytokines related to thrombosis. Therefore, this study focused on these three indicators in COVID-19, with the hope to find biomarkers that are associated with patients’ outcome. Methods: This is a retrospective single-center study involving 74 severe and critically ill COVID-19 patients recruited from the ICU department of the Tongji Hospital in Wuhan, China. The patients were divided into two groups: severe patients and critically ill patients. The serum IP-10, MCP-1 and MIP1α level in both groups was detected using the enzyme-linked immunosorbent assay (ELISA) kit. The clinical symptoms, laboratory test results, and the outcome of COVID-19 patients were retrospectively analyzed. Results: The serum IP-10 and MCP-1 level in critically ill patients was significantly higher than that in severe patients ( P <0.001). However, no statistical difference in MIP1α between the two groups was found. The analysis of dynamic changes showed that these indicators remarkably increased in patients with poor prognosis. Since the selected patients were severe or critically ill, no significant difference was observed between survival and death. Conclusions: IP-10 and MCP-1 are biomarkers associated with the severity of COVID-19 disease and can be related to the risk of death in COVID-19 patients.

Common Carotid Artery Occlusion in a Young Patient: Can Large-Vessel Stroke Be the Initial Clinical Manifestation of Coronavirus Disease 2019?

BACKGROUND: The occurrence of large-vessel occlusion in young patients with coronavirus disease 2019 (COVID-19) infection has been exceedingly rare. An extensive review of reported studies revealed a few reported cases. In the present report, we have described the clinical presentation, radiological findings, and outcome of large-vessel occlusion in a young patient with COVID-19 and reviewed the pertinent reported data on this condition. CASE DESCRIPTION: A 31-year-old woman was in her usual state of health until she had presented with a 3-day history of right-sided weakness, slurred speech, and decreased vision. The patient had been taken to several hospitals where she had been treated conservatively with analgesics and discharged. Shortly thereafter, her weakness had become progressive. She had become severely dysarthric and unresponsive. On arrival to the emergency department, her physical examination revealed that she was stuporous, with a Glasgow coma scale of 10 (eye response, 3; verbal response, 2; motor response, 5). The National Institutes of Health Stroke Scale score was 19 on presentation. Brain computed tomography and computed tomography venography revealed an occluded left internal carotid artery and left middle cerebral artery with subacute left middle cerebral artery territory infarction and midline shift. Computed tomography angiography revealed complete occlusion of the left common carotid artery. An emergent decompressive craniectomy was successfully performed. The patient was shifted to the intensive care unit. She was later found to be positive for COVID-19. CONCLUSIONS: Although rare, patients with COVID-19 can present with large-vessel occlusion. Prompt identification of COVID-19-related coagulopathy is essential to assess young patients with clinical manifestations of infarction.

COVID-19-Associated Carotid Atherothrombosis and Stroke.

We present a radiology-pathology case series of 3 patients with coronavirus disease 2019 (COVID-19) with acute ischemic stroke due to fulminant carotid thrombosis overlying mild atherosclerotic plaque and propose a novel stroke mechanism: COVID-associated carotid atherothrombosis.

Rare presentations of COVID-19: PRES-like leukoencephalopathy and carotid thrombosis.

Coronavirus disease 2019 (COVID-19) is a global pandemic, and it is increasingly important that physicians recognize and understand its atypical presentations. Neurological symptoms such as anosmia, altered mental status, headache, and myalgias may arise due to direct injury to the nervous system or by indirectly precipitating coagulopathies. We present the first COVID-19 related cases of carotid artery thrombosis and acute PRES-like leukoencephalopathy with multifocal hemorrhage.