ABSTRACT
Mucormycosis is a rare and invasive fungal disease with potentially fatal outcome. It most commonly affects patients with compromised immunity, especiallly those with poorly controlled diabetes. The incidence of mucormycosis has increased after the COVID-19 pandemic and both COVID-19 and mucormycosis are associated with an increased incidence of stroke. We present a report of two cases of COVID associated mucormycosis who had stroke. A 50-year-old patient with uncontrolled diabetes developed swelling of left eye and face ultimately leading to complete ophthalmoplegia of left eye. Imaging studies of brain revealed infarcts. MRI/MRA brain showed left internal carotid artery thrombosis, cavernous sinus thrombosis and a brain abscess in left temporal lobe. A second patient was a 65-year-old diabetic and hypertensive male who had COVID and then developed right MCA territory infarct and right sided cavernous sinus thrombosis. Diagnostic nasal endoscopy and biopsy was suggestive of mucormycosis in both the cases. Both these cases were managed with combination of tight glycemic control, antifungal therapy, and surgery. Clinicians should be aware of the association of stroke with COVID and COVID associated mucormycosis (CAM). Copyright © 2022 International Medical Sciences Academy. All rights reserved.
ABSTRACT
BACKGROUND: An epidemic of Mucorales was reported following the second wave of COVID-19 in India, and intracranial extension of the same was one of the most dreadful complications. METHODS: A total of 62 patients with cerebral mucormycosis were recruited and followed up till 12 weeks to evaluate the risk factors, incidence, clinical manifestations, management, and prognosis of cerebral mucormycosis. FINDINGS: A median age of 51.5 years with male predominance (74%) was noted. The majority of subjects reported a history of COVID infection (93.5%) and diabetes mellitus (83.87%). The first symptom of mucormycosis appeared after a mean period of 17.63 ± 8.9 days following COVID. Facial swelling and ptosis were the most common symptoms. Only 55% of patients had neurological presentations, and hemiparesis was the most common neurological sign (30.6%). Radiologically, the involvement of maxillary sinus (90.32%) and ethmoid sinus (87.10%) was commonly noted. Cerebral findings included temporal lobe (50%) and parietal lobe (30.06%) involvement, cavernous sinus thrombosis (30.06%), and internal carotid artery thrombosis (22.58%). Acute cerebral infarction was notable in 37% of subjects (p-value=0.0015, significant association with the outcome). Conventional and liposomal amphotericin B were used in 91.94% and 53.23% of patients, respectively. Retrobulbar amphotericin injections used in 11.3% of subjects significantly affected the outcome (p-value=0.03, significant). Posaconazole step-down therapy was used in 72.5% of subjects (p-value=0.0005, significant). Surgical interventions were performed in 53 (85.48%) subjects (p-value=0.004, significant). Functional endoscopic sinus surgery was the most common (in 64.52% of subjects), followed by maxillectomy (20.97% of subjects) and craniotomy (17.7% of subjects). At the end of 12 weeks, 33.87% of patients died and 59.68% were alive; the rest (6.45%) were lost to follow-up. INTERPRETATION: The absence or late presentation of neurological symptoms led to a delayed diagnosis of cerebral mucormycosis. The presence of acute cerebral infarction indicated a worse prognosis. However, there was a significant influence of step-down posaconazole therapy, retrobulbar amphotericin injections, and surgical intervention on the prognosis of cerebral mucormycosis.
ABSTRACT
Background: COVID-19 is accompanied by excessive systemic thrombotic events, but the mechanism is unknown. All major COVID-19 vaccines were associated with thrombosis. Thymidine phosphorylase (TYMP) plays an important role in platelet activation, thrombosis, and inflammation. TYMP expression is significantly increased in COVID-19 patients. Aim(s): To test the hypothesis that TYMP mediates SARS-CoV-2 spike protein (SP)-enhanced thrombosis. Method(s): Transfection of plasmid encoding SP or the receptor-binding domain (RBD) with human ACE2 was conducted in COS-7 cells. BEAS-2B cells were treated with SP or RBD containing COS-7 cell lysates, and TYMP expression and activation of NF-kappaB were examined. K18-hACE2 transgenic (ACE2-TG) mice were intraperitoneally treated with SP or RBD containing COS-7 cells lysates, and thrombosis was assessed three days later using the FeCl3 injury-induced carotid artery thrombosis model. Result(s): SP and RBD led to ACE2 shedding, significantly increased TYMP expression, and NF-kappaB activation in BEAS-2B cells. In comparison to wildtype mice, ACE2-TG mice are anti-thrombotic and had significantly prolonged thrombosis time. Treating ACE2-TG mice with COS-7 cells transfected with empty plasmid did not affect the thrombosis. However, treating the ACE2-TG mice with SP-or RBD-containing COS-7 cell lysates dramatically enhanced thrombosis and significantly shortened time to occlusive thrombi formation. SP is more powerful than RBD in enhancing thrombosis. SP-enhanced thrombosis was dramatically inhibited by simultaneously feeding the mice with 1 mg/kg of tipiracil. TYMP is expressed in human type II alveolar epithelial cells and bronchial epithelium. By using the MGH Emergency Department COVID-19 Cohort with Olink Proteomics TYMP data and Receiver Operating Characteristic analysis, we found TYMP is a sensitive and specific marker in diagnosing COVID-19 (AUC 0.8721, p < 0.0001). Conclusion(s): SARS-CoV-2 SP and RBD are pro-inflammatory and pro-thrombotic. SP/RBD-induced thrombosis is inhibited by tipiracil, a TYMP inhibitor. TYMP is a sensitive marker for COVID-19 diagnosis. Targeting TYMP could be a novel effective treatment for COVID-19.
ABSTRACT
Rhinocerebral mucormycosis has emerged as a common coinfection in coronavirus disease 2019 (COVID-19) patients during the convalescence period. Frequent spread of disease from sinonasal mucosa to bone, neck spaces, orbit, and brain occurs along the perivascular/perineural routes or through direct invasion. Brain involvement represents severe manifestation and is often associated with poor functional outcomes and high mortality rates. Magnetic resonance imaging (MRI) is the modality of choice for the intracranial assessment of disease severity in mucormycosis. Early and accurate identification of intracranial extension is imperative to improve survival rates. With this pictorial essay, we aim to familiarize the readers with the cross-sectional imaging features of intracranial complications of mucormycosis. The radiological details in this essay should serve as a broad checklist for radiologists and clinicians while dealing with this fulminant infection.
ABSTRACT
Patients with severe COVID-19 may have an increased risk of venous and arterial thrombotic events, including ischemic stroke (IS). It has been hypothesized that the infection by SARS-CoV-2 alone may be a risk factor for IS, particularly in young subjects. Our objective was to compare stroke etiologies in patients with IS, with (ISCOVID+) or without (ISCOVID-) SARS-CoV-2 infection, < or 45 years. Patients ≥ 18 years with IS confirmed by computerized tomography (CT) or magnetic resonance imaging (MRI), consecutively admitted to our institution at two different periods: between April and June 2019 (ISCOVID-), and between April and August 2020 (ISCOVID+ and ISCOVID-) were included in an observational single-center cohort. Patients with molecular detection of SARS-CoV-2 before the stroke, or within 15 days after stroke or detection of serum antibodies before or within 30 days after the IS were compared with matching controls. The primary outcome was the stroke etiology according to the Causative Classification System for Ischemic Stroke (CCS) algorithm. In addition, two subgroups were determined for the category of Other uncommon Causes (OC): iatrogenic causes (OC-IC) and Other uncommon Causes excluding iatrogenic (OC-EI). A total of 212 patients were included (160 in ISCOVID+ and 42 in ISCOVID-). Cardio-aortic embolism (CE) was the most common etiology in the two groups. Two patients in the ISCOVID+ group but none in the ISCOVID-group had unexplained thrombosis of the carotid bifurcation. There were independent associations between younger age (RR 0.91, 95% CI 0.87 - 0.95) as well as COVID infection (RR 4.08;CI 95% 1.03 - 16.14) and IS due to OCEI. Classic stroke etiologies accounted for most of the cases of IS and concomitant COVID-19 infection but large-artery thrombosis was more common in infected than in non-infected patients.
ABSTRACT
BACKGROUND: Ischaemic stroke may be a major complication of SARS-CoV-2 infection.Studying and characterising the different aetiological subtypes, clinical characteristics, and functional outcomes may be valuable in guiding patient selection for optimal management and treatment. METHODS: Data were collected retrospectively on consecutive patients with COVID-19 who developed acute focal brain ischaemia (between 1 March and 19 April 2020) at a tertiary university hospital in Madrid (Spain). RESULTS: During the study period, 1594 patients were diagnosed with COVID-19. We found 22 patients with ischaemic stroke (1.38%), 6 of whom did not meet the inclusion criteria. The remaining 16 patients were included in the study (15 cases of ischaemic stroke and one case of transient ischaemic attack).Median baseline National Institutes of Health Stroke Scale score was 9 (interquartile range: 16), and mean (standard deviation) age was 73 years (12.8). Twelve patients (75%) were men. Mean time from COVID-19 symptom onset to stroke onset was 13 days. Large vessel occlusion was identified in 12 patients (75%).We detected elevated levels of D-dimer in 87.5% of patients and C-reactive protein in 81.2%. The main aetiology was atherothrombotic stroke (9 patients, 56.3%), with the predominant subtype being endoluminal thrombus (5 patients, 31.2%), involving the internal carotid artery in 4 cases and the aortic arch in one. The mortality rate in our series was 44% (7 of 16 patients). CONCLUSIONS: In patients with COVID-19, the most frequent stroke aetiology was atherothrombosis, with a high proportion of endoluminal thrombus (31.2% of patients). Our clinical and laboratory data support COVID-19-associated coagulopathy as a relevant pathophysiological mechanism for ischaemic stroke in these patients.
ABSTRACT
A case of successful emergency carotid endarterectomy (CEE) in the acute period of ischemic stroke (within an hour after the onset of symptoms) in a patient with acute occlusive thrombosis of the internal carotid artery in the course of moderate-severe COVID-19 with a positive result of the polymerase chain reaction of the nasopharyngeal smear for SARS-CoV-2. The diameter of the ischemic focus in the brain according to multispiral computed tomography did not exceed 2.5 cm. The course of ischemic stroke was characterized by mild neurological deficit (score 5 according to National Institute of Health Stroke Scale). It was demonstrated that the severity of the patient’s condition was associated with bilateral, polysegmental, viral penvmonia with 65% damage to the lung tissue, a decrease in SpO2 to 93%. Laboratory noted coagulopathy with an increase in D-dimer (2837.0 ng/ml), prothrombin according to Quick (155.3%), fibrinogen (14.5 g/l) and signs of a “cytokine storm” with leukocytosis (28.4 10E9/l), an increase in C-reactive protein (183.5 mg/l), ferritin (632.8 ng/ml), interleukin-6 (176.9 pg/ml). The patient underwent glomus-sparing eversional CEE. The intervention was performed under local anesthesia due to the high risk of developing pulmonary barotrauma when using mechanical ventilation. To prevent the development of acute hematoma, a double active drainage was used into the paravasal space and subcutaneous fatty tissue (SFT). In case of thrombosis of one of the drainages, the second could serve as a spare. Also, upon receipt of hemorrhagic discharge from the drainage located in the SFT, the patient would not need to be transported to the operating room. Removal of skin sutures with revision and stitching of the bleeding source could be performed under local anesthesia in a dressing room. The postoperative period was uneventful, with complete regression of neurological symptoms. Used anticoagulant (heparin 5 thousand units 4 times a day s/c) and antiplatelet therapy (acetylsalicylic acid 125 mg at lunch). The patient was discharged from the hospital on the 12th day after CEE in satisfactory condition. © 2021 Sklifosovsky Research Institute for Emergency Medicine. All rights reserved.
ABSTRACT
Coronavirus disease 2019 (COVID-19) is a severe infectious respiratory disease caused by the novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Multiple studies in the literature highlight the association between COVID-19 and stroke. We report a case of acute ischemic stroke in a COVID-19 patient without displaying symptoms of active COVID-19 infection or risk factors for stroke with further review of the literature. The patient's recovery was complicated by hemorrhagic stroke, which resulted in death. Acute ischemic strokes are one of the challenging complications of COVID-19 infection. Initial rapid assessment and management are crucial in optimizing the outcomes on these patients. Nevertheless, wearing appropriate PPE should be instituted while providing adequate care.
ABSTRACT
Coronavirus disease 2019 (COVID-19) is a pandemic disease currently affecting millions of people worldwide. Its neurological implications are poorly understood, and further study is urgently required. A hypercoagulable state has been reported in patients with severe COVID-19, but nothing is known about coagulopathy in patients with milder disease. We describe cases of patients in New York City presenting with stroke secondary to large vessel thrombosis without occlusion, incidentally found to have COVID-19 with only mild respiratory symptoms. This is in contrast to the venous thrombosis and microangiopathy that has been reported in patients with severe COVID-19. Our cases suggest that even in the absence of severe disease, patients with COVID-19 may be at increased risk of thrombus formation leading to stroke, perhaps resulting from viral involvement of the endothelium. Further systematic study is needed because this may have implications for primary and secondary stroke prevention in patients with COVID-19.