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2.
J Thromb Haemost ; 20(4): 919-928, 2022 04.
Article in English | MEDLINE | ID: covidwho-1626880

ABSTRACT

BACKGROUND: Resistance to fibrinolysis, levels of procoagulant/antifibrinolytic neutrophil extracellular traps (NETs), and the severity of acute ischemic stroke (AIS) are increased by COVID-19. Whether NETs are components of AIS thrombi from COVID-19 patients and whether COVID-19 impacts the susceptibility of these thrombi to thrombolytic treatments remain unknown, however. OBJECTIVES: We aimed to characterize AIS thrombi from COVID-19 patients by immunohistology and to compare their response to thrombolysis to that of AIS thrombi from non-COVID-19 patients. PATIENTS/METHODS: For this monocentric cohort study, 14 thrombi from COVID-19 AIS patients and 16 thrombi from non-COVID-19 patients, all recovered by endovascular therapy, were analyzed by immunohistology or subjected to ex vivo thrombolysis by tissue-type plasminogen (tPA)/plasminogen. RESULTS: COVID-19 AIS thrombi were rich in neutrophils and contained NETs, but not spike protein. Thrombolysis assays revealed a mean resistance profile to tPA/plasminogen of COVID-19 AIS thrombi similar to that of non-COVID-19 AIS thrombi. The addition of DNase 1 successfully improved thrombolysis by potentiating fibrinolysis irrespective of COVID-19 status. Levels of neutrophil, NETs, and platelet markers in lysis supernatants were comparable between AIS thrombi from non-COVID-19 and COVID-19 patients. CONCLUSIONS: These results show that COVID-19 does not impact NETs content or worsen fibrinolysis resistance of AIS thrombi, a therapeutic hurdle that could be overcome by DNase 1 even in the context of SARS-CoV-2 infection.


Subject(s)
Brain Ischemia , COVID-19 , Ischemic Stroke , Stroke , Thrombosis , Brain Ischemia/drug therapy , COVID-19/drug therapy , Cohort Studies , Fibrinolysis , Humans , SARS-CoV-2 , Stroke/drug therapy , Stroke/metabolism , Thrombolytic Therapy , Thrombosis/metabolism , Tissue Plasminogen Activator/therapeutic use
4.
J Stroke Cerebrovasc Dis ; 31(1): 106179, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1525870

ABSTRACT

OBJECTIVES: This study aims to evaluate shortening door-to-needle time of intravenous recombinant tissue plasminogen activator of acute ischemic stroke patients by multidisciplinary collaboration and workflow optimization based on our hospital resources. MATERIALS AND METHODS: We included patients undergoing thrombolysis with intravenous recombinant tissue plasminogen activator from January 1, 2018, to September 30, 2020. Patients were divided into pre- (January 1, 2018, to December 31, 2019) and post-intervention groups (January 1, 2020, to September 31, 2020). We conducted multi-department collaboration and process optimization by implementing 16 different measures in prehospital, in-hospital, and post-acute feedback stages for acute ischemic stroke patients treated with intravenous thrombolysis. A comparison of outcomes between both groups was analyzed. RESULTS: Two hundred and sixty-three patients received intravenous recombinant tissue plasminogen activator in our hospital during the study period, with 128 and 135 patients receiving treatment in the pre-intervention and post-intervention groups, respectively. The median (interquartile range) door-to-needle time decreased significantly from 57.0 (45.3-77.8) min to 37.0 (29.0-49.0) min. Door-to-needle time was shortened to 32 min in the post-intervention period in the 3rd quarter of 2020. The door-to-needle times at the metrics of ≤ 30 min, ≤ 45 min, ≤ 60 min improved considerably, and the DNT> 60 min metric exhibited a significant reduction. CONCLUSIONS: A multidisciplinary collaboration and continuous process optimization can result in overall shortened door-to-needle despite the challenges incurred by the COVID-19 pandemic.


Subject(s)
Brain Ischemia/drug therapy , COVID-19/complications , Cooperative Behavior , Ischemic Stroke/drug therapy , Patient Care Team , Thrombolytic Therapy/methods , Tissue Plasminogen Activator/administration & dosage , Administration, Intravenous , Early Medical Intervention , Emergency Medical Services , Female , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/therapeutic use , Humans , Male , Pandemics , SARS-CoV-2 , Time Management , Time-to-Treatment , Tissue Plasminogen Activator/therapeutic use , Treatment Outcome , Workflow
5.
Neurologist ; 26(6): 271-273, 2021 Nov 04.
Article in English | MEDLINE | ID: covidwho-1501227

ABSTRACT

INTRODUCTION: Wake-up strokes are challenging to manage due to unknown time of onset. Recently, the wake-up trial demonstrated that recombinant tissue plasminogen activator (rtPA) could be administered based on the magnetic resonance imaging (MRI)- diffusion weighted imaging/fluid attenuated inversion recovery mismatch. Many still doubt the safety results due to the higher rate of hemorrhagic conversion reported. Although it was statistically insignificant, the study was terminated early. Furthermore, Corona virus disease-19 is associated with coagulopathy and a higher risk of hemorrhagic conversion. CASE REPORT: A 46-year-old fully functioning male presented with a wake-up right hemiparesis, right facial droop, and expressive aphasia. His National Institute of Health Stroke Scale was 4 upon arrival. Last known well state was >4.5 hours. He tested positive for SARS-CoV-2 viral infection. He had left distal-M2 occlusion. He was deemed not a candidate for rtPA. Hyperacute-MRI protocol showed diffusion weighted imaging/fluid attenuated inversion recovery mismatch. The patient received rtPA at 6.5 hours from the last knwn well state. Follow-up MRI-susceptibility weighted imaging revealed fragmented clot. The stroke burden was less than that shown on the initial computed tomography-perfusion scans implying saved penumbra. There was no hemorrhagic conversion despite low fibrinogen levels. CONCLUSION: The hyperacute-MRI protocol for wake-up COVID-19 associated strokes might be a safe option.


Subject(s)
Brain Ischemia , COVID-19 , Ischemic Stroke , Stroke , Brain Ischemia/drug therapy , Diffusion Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging , Male , Middle Aged , SARS-CoV-2 , Stroke/diagnostic imaging , Stroke/drug therapy , Thrombolytic Therapy , Tissue Plasminogen Activator/therapeutic use
6.
Acta Neurol Scand ; 145(1): 47-52, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1367290

ABSTRACT

OBJECTIVE: Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator is the core medical therapy of acute ischaemic stroke (AIS). COVID-19 infection negatively modifies acute stroke procedures and, due to its pro-coagulative effect, may potentially impact on IVT outcome. Thus, short-term efficacy and safety of IVT were compared in patients with and without evidence of SARS-CoV-2. METHODS: An observational, retrospective study included 70 patients with AIS, including 22 subjects (31%) with evidence of acute COVID-19 infection, consecutively treated with IVT in 4 stroke centres between 15 September and 30 November 2020. RESULTS: Patients infected with COVID-19 were characterized by higher median of National Institute of Health Stroke Scale (NIHSS) score (11.0 vs. 6.5; p < .01) and D-dimers (870 vs. 570; p = .03) on admission, higher presence of pneumonia (47.8% vs. 12%; p < .01) and lower percentage of 'minor stroke symptoms' (NIHSS 1-5 pts.) (2% vs., 18%; p < .01). Hospitalizations were longer in patients with COVID-19 than in those without it (17 vs. 9 days, p < .01), but impact of COVID-19 infection on patients' in-hospital mortality or functional status on dismission has been confirmed neither in uni- or multivariate analysis. CONCLUSION: SARS-CoV-2 infection prolongs length of stay in hospital after IVT, but does not influence in-hospital outcome.


Subject(s)
Brain Ischemia , COVID-19 , Ischemic Stroke , Stroke , Brain Ischemia/complications , Brain Ischemia/drug therapy , Fibrinolytic Agents/therapeutic use , Humans , Retrospective Studies , SARS-CoV-2 , Stroke/complications , Stroke/drug therapy , Thrombolytic Therapy , Tissue Plasminogen Activator/therapeutic use , Treatment Outcome
7.
BMJ Case Rep ; 14(8)2021 Aug 03.
Article in English | MEDLINE | ID: covidwho-1341318

ABSTRACT

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.


Subject(s)
Brain Ischemia , COVID-19 , Carotid Artery Thrombosis , Ischemic Stroke , Stroke , Brain Ischemia/diagnostic imaging , Brain Ischemia/etiology , Carotid Artery Thrombosis/complications , Carotid Artery Thrombosis/diagnostic imaging , Carotid Artery Thrombosis/drug therapy , Female , Humans , SARS-CoV-2 , Stroke/drug therapy , Stroke/etiology , Tissue Plasminogen Activator/therapeutic use
8.
Telemed J E Health ; 28(4): 481-485, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1310889

ABSTRACT

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted acute stroke care globally. Decreased stroke presentations and concern for delays in acute stroke care have been identified. This study evaluated the impact of COVID-19 on the timely treatment of patients with thrombolytics at hospitals utilizing telestroke acute stroke services. Methods: Acute stroke consultations seen in 171 hospitals (19 states) via telestroke from December 1, 2019, to June 27, 2020, were extracted from the TeleCare™ database. The consults were divided into pre-COVID and COVID groups (March 15, 2020, start of COVID group). The consults were reviewed for age, sex, hospital, state, date seen, last known normal, arrival time, consult call time, needle time, thrombolytic candidate, and National Institutes of Health Stroke Scale (NIHSS) score. The total number of consults, median door to needle (DTN) time for emergency department (ED) patients, and call to needle (CTN) time for inpatients were calculated. Results: Pre-COVID, 15,226 stroke consults were evaluated compared with 11,105 in the COVID group, a 27% decrease. Pre-COVID, 1,071 ED patients (7.9%) received thrombolytics and 66 inpatients (4.0%), while COVID, 813 ED patients (8.2%) and 70 inpatients (5.7%). The median DTN time for ED patients pre-COVID was 42 (32, 55) versus 40 (31, 52) in the COVID group, with no statistically significant difference between groups. CTN time pre-COVID was 53 (35, 67) versus 46 (35, 61) in the COVID group, with no statistically significant difference between groups. Conclusions: Telestroke assessments allowed for uninterrupted acute stroke care and treatment stability despite nursing and other resource realignments triggered by the COVID-19 pandemic.


Subject(s)
COVID-19 , Stroke , Telemedicine , Fibrinolytic Agents/therapeutic use , Humans , Pandemics , Retrospective Studies , Stroke/drug therapy , Stroke/therapy , Thrombolytic Therapy , Time Factors , Time-to-Treatment , Tissue Plasminogen Activator/therapeutic use , Treatment Outcome
9.
BMJ Case Rep ; 14(4)2021 Apr 19.
Article in English | MEDLINE | ID: covidwho-1194192

ABSTRACT

Emerging evidence suggests that novel COVID-19 is associated with increased prothrombotic state and risk of thromboembolic complications, particularly in severe disease. COVID-19 is known to predispose to both venous and arterial thrombotic disease. We describe a case of a 61-year-old woman with history of type II diabetes, hypertension and hyperlipidaemia who presented with dry cough and acute abdominal pain. She was found to have a significantly elevated D-dimer, prompting imaging that showed thrombi in her right ventricle and aorta. She had rapid clinical deterioration and eventually required tissue plasminogen activator with subsequent durable clinical improvement. This case highlights a rare co-occurrence of venous and arterial thrombi in a patient with severe COVID-19. Further studies are needed to clarify the molecular mechanism of COVID-19 coagulopathy, the utility of D-dimer to predict and stratify risk of thrombosis in COVID-19, and the use of fibrinolytic therapy in patients with COVID-19.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Thrombosis , Aorta/pathology , COVID-19/complications , Diabetes Mellitus, Type 2/complications , Female , Fibrin Fibrinogen Degradation Products/analysis , Heart Ventricles/diagnostic imaging , Heart Ventricles/pathology , Humans , Middle Aged , Thrombosis/complications , Thrombosis/diagnostic imaging , Thrombosis/drug therapy , Tissue Plasminogen Activator/therapeutic use
12.
Cerebrovasc Dis ; 50(3): 317-325, 2021.
Article in English | MEDLINE | ID: covidwho-1063099

ABSTRACT

BACKGROUND: The COVID-19 pandemic lockdown (CPL) lead to a significant decrease in emergency admissions worldwide. We performed a timely analysis of ischemic stroke (IS) and related consultations using the telestroke TEMPiS "working diagnosis" database prior (PL), within (WL), and after easing (EL) of CPL. METHODS: Twelve hospitals were selected and data analyzed regarding IS (including intravenous thrombolysis [intravenous recombinant tissue plasminogen; IV rtPA] and endovascular thrombectomy [EVT]) and related events from February 1 to June 15 during 2017-2020. In addition, we aimed to correlate events to various mobile phone mobility data. RESULTS: Following the significant reduction of IS, IV rtPA, and EVT cases during WL compared to PL in 2020 longitudinally (p values <0.048), we observed increasing numbers of consultations, IS, recommendations for EVT, and IV rtPA with the network in EL over WL not reaching PL levels yet. Absolute numbers of all consultations paralleled best to mobility data of public transportation over walking and driving mobility. CONCLUSIONS: While the decrease in emergency admissions including stroke during CPL can only be in part attributed by patients not seeking medical attention, stroke awareness in the pandemic, and direct COVID-19 triggered stroke remains of high importance. The number of consultations in TEMPiS during the lockdown parallels best with mobility of public transportation. As a consequence, exposure to common viruses, well-known triggers for acute cerebrovascular events and other diseases, are reduced and may add to the decline in stroke consultations. Further studies comparing national responses toward the course of the COVID-19 pandemic and stroke incidences are needed.


Subject(s)
COVID-19/complications , SARS-CoV-2/pathogenicity , Stroke/drug therapy , Stroke/virology , COVID-19/therapy , Communicable Disease Control , Humans , Thrombolytic Therapy/methods , Time-to-Treatment , Tissue Plasminogen Activator/therapeutic use
13.
PLoS One ; 16(1): e0243603, 2021.
Article in English | MEDLINE | ID: covidwho-1033061

ABSTRACT

Most clinical research stopped during COVID due to possible impact on data quality and personnel safety. We aimed to assess the impact of COVID on acute stroke clinical trial conduct at sites that continued to enroll patients during the pandemic. BEST-MSU is an ongoing study of Mobile Stroke Units (MSU) vs standard management of tPA-eligible acute stroke patients in the pre-hospital setting. MSU personnel include a vascular neurologist via telemedicine, and a nurse, CT technologist, paramedics and emergency medicine technicians on-board. During COVID, consent, 90-day modified Rankin Scale (mRS) and EQ5D were obtained by phone instead of in-person, but other aspects of management were similar to the pre-COVID period. We compared patient demographics, study metrics, and infection of study personnel during intra- vs pre-COVID eras. Five of 6 BEST-MSU sites continued to enroll during COVID. There were no differences in intra- (n = 57) vs pre- (n = 869) COVID enrolled tPA eligible patients' age, sex, race (38.6% vs 38.0% Black), ethnicity (15.8% vs 18.6% Hispanic), or NIHSS (median 11 vs 9). The percent of screened patients enrolled and adjudicated tPA eligible declined from 13.6% to 6.6% (p < .001); study enrollment correlated with local stay-at-home and reopening orders. There were no differences in alert to MSU arrival or arrival to tPA times, but MSU on-scene time was 5 min longer (p = .01). There were no differences in ED door to CT, tPA treatment or thrombectomy puncture times, hospital length of stay, discharge disposition, or remote vs in-person 90-day mRS or EQ5D. One MSU nurse tested positive but did not require hospitalization. Clinical research in the pre-hospital setting can be carried out accurately and safely during a pandemic. tPA eligibility rates declined, but otherwise there were no differences in patient demographics, deterioration of study processes, or serious infection of study staff. Trial registration: NCT02190500.


Subject(s)
COVID-19/epidemiology , Stroke/drug therapy , Aged , COVID-19/virology , Female , Humans , Male , Middle Aged , Mobile Health Units , Pandemics , Patient Discharge , SARS-CoV-2/physiology , Time Factors , Tissue Plasminogen Activator/therapeutic use
14.
Food Chem Toxicol ; 148: 111974, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1009497

ABSTRACT

The coronavirus disease (COVID)-19 pandemic is a major challenge for the health systems worldwide. Acute respiratory distress syndrome (ARDS), is one of the most common complications of the COVID-19 infection. The activation of the coagulation system plays an important role in the pathogenesis of ARDS. The development of lung coagulopathy involves thrombin generation and fibrinolysis inhibition. Unfractionated heparin and its recently introduced counterpart low molecular weight heparin (LMWH), are widely used anticoagulants with a variety of clinical indications allowing for limited and manageable physio-toxicologic side effects while the use of protamine sulfate, heparin's effective antidote, has made their use even safer. Tissue-type plasminogen activator (tPA) is approved as intravenous thrombolytic treatment. The present narrative review discusses the use of heparin and tPA in the treatment of COVID-19-induced ARDS and their related potential physio-toxicologic side effects. The article is a quick review of articles on anticoagulation in COVID infection and the potential toxicologic reactions associated with these drugs.


Subject(s)
COVID-19/physiopathology , Hemostasis/drug effects , Heparin/therapeutic use , Thrombosis/complications , Tissue Plasminogen Activator/therapeutic use , Heparin/pharmacology , Humans , Tissue Plasminogen Activator/pharmacology
15.
Int J Infect Dis ; 104: 108-110, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-988033

ABSTRACT

Existing literature highlights the fact that patients with COVID-19 exhibit alterations in the coagulation process and are associated with respiratory and cardiovascular diseases, including acute respiratory distress syndrome and acute cor pulmonale. In this report, we describe the effects of systemic thrombolysis on acute cor pulmonale in a patient suffering from COVID-19. We demonstrated that systemic thrombolysis successfully improved the hemodynamics of our patient and resulted in a prominent reduction in hypercapnia, alveolar dead space, and ventilatory ratio.


Subject(s)
COVID-19/complications , Heart Failure/drug therapy , Respiratory Distress Syndrome/drug therapy , SARS-CoV-2/physiology , Thrombolytic Therapy , Tissue Plasminogen Activator/therapeutic use , Acute Disease , Aged , COVID-19/virology , Heart Failure/diagnostic imaging , Heart Failure/etiology , Humans , Male , Recombinant Proteins , Respiratory Distress Syndrome/diagnostic imaging , Respiratory Distress Syndrome/etiology
17.
World Neurosurg ; 145: 356-359, 2021 01.
Article in English | MEDLINE | ID: covidwho-850856

ABSTRACT

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, a rapid screening method for COVID-19 detection is needed to decide the appropriate strategy to treat stroke patients. In acute ischemic stroke treatment, the efficacy and safety of emergent carotid artery stenting (eCAS) for hyperacute ischemic stroke (hAIS) due to internal carotid artery stenosis (ICS) have not been sufficiently established. CASE DESCRIPTION: A 71-year-old man with hAIS caused by severe ICS was treated via intravenous alteplase infusion. The patient underwent screening for COVID-19 by the loop-mediated isothermal amplification (LAMP) assay shortly after arrival at our institution. The LAMP result was obtained within 90 minutes, during intravenous alteplase infusion, and turned out to be negative. The symptom of hemiplegia worsened during alteplase infusion, and he, therefore, underwent eCAS after administration of aspirin (200 mg). Recanalization was achieved successfully by eCAS, and dual antiplatelet therapy and argatroban were administrated following eCAS. Hemorrhagic complications or restenosis/occlusion of the carotid artery were not observed. He was discharged without neurologic deficits 15 days following eCAS. Because of the rapid negative diagnosis for COVID-19 using the LAMP method, eCAS could be performed following standard procedures, along with infectious defense, without delay. CONCLUSIONS: This case report suggests that eCAS for hAIS due to ICS following intravenous alteplase can be an effective treatment, along with appropriate antiplatelet medication and management in select patients. During the COVID-19 pandemic, the LAMP assay for COVID-19 detection might be a suitable diagnostic strategy preceding stroke treatment because of the rapid turnaround time.


Subject(s)
COVID-19/diagnosis , Carotid Stenosis/surgery , Fibrinolytic Agents/therapeutic use , Ischemic Stroke/drug therapy , Ischemic Stroke/surgery , Molecular Diagnostic Techniques , Nucleic Acid Amplification Techniques , Stents , Tissue Plasminogen Activator/therapeutic use , Aged , Arginine/analogs & derivatives , Arginine/therapeutic use , Carotid Stenosis/complications , Carotid Stenosis/diagnostic imaging , Combined Modality Therapy , Hemiplegia/etiology , Humans , Ischemic Stroke/etiology , Magnetic Resonance Imaging , Male , Pipecolic Acids/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Sulfonamides/therapeutic use , Tomography, X-Ray Computed , Treatment Outcome
18.
BMJ Case Rep ; 13(9)2020 Sep 18.
Article in English | MEDLINE | ID: covidwho-781114

ABSTRACT

We are reporting a middle-aged male patient with polycythaemia vera comorbidity. The patient was exhibiting symptoms including fever, cough and shortness of breath and was found to have acute pulmonary embolism. He was diagnosed with SARS-CoV-2. This case suggests that a high index of suspicion should be taken into consideration for thromboembolic events, when treating patients with COVID-19 with breathing difficulty and low oxygen saturation levels, especially in those who have underlying predisposing conditions for coagulopathy.


Subject(s)
Coronavirus Infections/complications , Pneumonia, Viral/complications , Polycythemia Vera/complications , Pulmonary Embolism/etiology , Betacoronavirus , COVID-19 , Computed Tomography Angiography , Coronavirus Infections/blood , Diabetes Mellitus, Type 2/complications , Echocardiography , Fibrinolytic Agents/therapeutic use , Heparin/therapeutic use , Humans , Hypertension/complications , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Polycythemia Vera/blood , Pulmonary Artery/diagnostic imaging , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/drug therapy , SARS-CoV-2 , Thrombolytic Therapy , Tissue Plasminogen Activator/therapeutic use , Tomography, X-Ray Computed , Ventricular Dysfunction, Right/diagnostic imaging , Ventricular Dysfunction, Right/etiology
19.
BMJ Case Rep ; 13(9)2020 Sep 08.
Article in English | MEDLINE | ID: covidwho-751540

ABSTRACT

A 71-year-old man presented to the emergency department (ED) with low oxygen saturations and symptoms consistent with COVID-19 infection. Apart from a small left-sided ischaemic stroke 10 years prior with very minor residual deficit, he had been well and in full-time employment until development of symptoms. Within minutes of commencing non-invasive ventilation (NIV) in the ED, he developed a complete left-sided paralysis and hemineglect. This case highlights the significance of the prothrombotic complications associated with COVID-19 infection. It also raises the question whether pressure changes upon commencing NIV could lead to clot migration.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Noninvasive Ventilation/methods , Pneumonia, Viral/complications , Stroke/diagnostic imaging , Stroke/etiology , Acute Disease , Aged , COVID-19 , Coronavirus Infections/therapy , Fatal Outcome , Fibrinolytic Agents/therapeutic use , Humans , Male , Pandemics , Pneumonia, Viral/therapy , Positive-Pressure Respiration/methods , SARS-CoV-2 , Stroke/drug therapy , Thrombolytic Therapy/methods , Tissue Plasminogen Activator/therapeutic use , Tomography, X-Ray Computed/methods
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