Ischemic stroke in COVID-19-positive patients: an overview of SARS-CoV-2 and thrombotic mechanisms for the neurointerventionalist

Zakeri, Amanda; Jadhav, Ashutosh P.; Sullenger, Bruce A.; Nimjee, Shahid M

doi:10.1136/neurintsurg-2020-016794

Cited by 92 publications

(83 citation statements)

References 58 publications

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“…Therefore, the prognostic value of D-dimer in COVID-19 could differ for COVID-19 patients presenting with AIS, in whom D-dimer levels may be independently elevated. Our study confirmed that D-dimer levels at admission were elevated among COVID-19 patients [0.95 (0.56-1.83) µg/ml FEU] beyond normal range (<0.5 µg/ml FEU) and greater elevations were observed among COVID-19 patients presenting with AIS [1.42 (0.76-3.96) µg/ml FEU] (15,16).…”

Section: Discussionsupporting

confidence: 83%

Predicting In-hospital Mortality Using D-Dimer in COVID-19 Patients With Acute Ischemic Stroke

et al. 2021

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Background: Coronavirus disease 2019 (COVID-19) has been associated with coagulopathy, and D-dimer levels have been used to predict disease severity. However, the role of D-dimer in predicting mortality in COVID-19 patients with acute ischemic stroke (AIS) remains incompletely characterized.Methods: We conducted a retrospective cohort study using the Optum® de-identified COVID-19 Electronic Health Record dataset. Patients were included if they were 18 or older, had been hospitalized within 7 days of confirmed COVID-19 positivity from March 1, 2020 to November 30, 2020. We determined the optimal threshold of D-dimer to predict in-hospital mortality and compared risks of in-hospital mortality between patients with D-dimer levels below and above the cutoff. Risk ratios (RRs) were estimated adjusting for baseline characteristics and clinical variables.Results: Among 15,250 patients hospitalized with COVID-19 positivity, 285 presented with AIS at admission (2%). Patients with AIS were older [70 (60–79) vs. 64 (52–75), p < 0.001] and had greater D-dimer levels at admission [1.42 (0.76–3.96) vs. 0.94 (0.55–1.81) μg/ml FEU, p < 0.001]. Peak D-dimer level was a good predictor of in-hospital mortality among all patients [c-statistic 0.774 (95% CI 0.764–0.784)] and among patients with AIS [c-statistic 0.751 (95% CI 0.691–0.810)]. Among AIS patients, the optimum cutoff was identified at 5.15 μg/ml FEU with 73% sensitivity and 69% specificity. Elevated peak D-dimer level above this cut-off was associated with almost 3 times increased mortality [adjusted RR 2.89 (95% CI 1.87–4.47), p < 0.001].Conclusions: COVID-19 patients with AIS present with greater D-dimer levels. Thresholds for outcomes prognostication should be higher in this population.

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Section: Discussionsupporting

confidence: 83%

Predicting In-hospital Mortality Using D-Dimer in COVID-19 Patients With Acute Ischemic Stroke

et al. 2021

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“…This agrees with previous studies in which COVID-19 was identified as an independent risk factor for stroke. 18,19 The varied multisystemic manifestations of our patients may be related to the wide distribution of the preferred SARS-CoV-2 host receptor, angiotensin-converting enzyme † Based on WHO definition of severity 1 : mild, symptomatic patients with no evidence of viral pneumonia or hypoxia; moderate, SpO2 $ 90%, fever, cough, dyspnea, fast breathing (clinical signs of pneumonia) but no signs of severe pneumonia; severe, SpO2 , 90%, adolescent or adult with clinical signs of pneumonia (fever, cough, dyspnea, fast breathing), severe respiratory distress.…”

Section: Discussionmentioning

confidence: 99%

Post-Discharge Symptoms among Hospitalized COVID-19 Patients in Nigeria: A Single-Center Study

Ogoina

James

Ogoinja

2021

The American Journal of Tropical Medicine and Hygiene

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There is a paucity of studies on post-acute COVID-19 syndrome (PCS) among hospitalized COVID-19 survivors from Nigeria. We describe the frequency, types, and duration of post-discharge symptoms suggestive of PCS among previously hospitalized COVID-19 patients in a treatment center in Nigeria. We conducted a retrospective review of admission and post-discharge follow-up medical records of COVID-19 survivors admitted between April and December 2020. A standardized checklist was used to document post-discharge symptoms. PCS was defined as persisting or new post-discharge symptoms lasting at least 3 weeks after initial COVID-19 symptoms. The relationship between study variables and development of PCS was ascertained by univariate analysis. Thirty of 51 previously hospitalized COVID-19 patients (median age, 46 years; male, 66.7%) were studied. Seventeen (56.7%) of the 30 patients developed features suggestive of PCS. Approximately three post-discharge symptoms were reported per patient over a follow-up period of ranging from 3 weeks to 9 months after initial COVID-19 symptoms. Cough, fatigue, and dyspnea were the most common post-discharge symptoms reported. A few patients had symptoms suggestive of thrombosis and COVID-19 reinfection. Among all study variables, baseline COVID-19 severity was the only significant variable associated with the development of PCS. PCS is common in our setting and is characterized by multisystemic signs and symptoms that require vigilance by clinicians for appropriate diagnosis and treatment. Long-term multicenter prospective studies are needed to characterize fully the burden of PCS among COVID-19 survivors in Nigeria.

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“…The well-accepted mechanism of thrombosis due to COVID-19 starts with the innate immune system activation to fight against SARS-CoV-2 invasion. Several factors are involved in the activation of the contact pathway of coagulation, including, innate immune cells, platelets, endothelial cells, intravascular tissue factor, and neutrophil release of extracellular traps ( 88 ). Thus, a reduced blood/oxygen supply to the inner ear can enhance drug ototoxicity ( 89 ).…”

Section: Risk Factors That Exacerbate Ototoxicitymentioning

confidence: 99%

Detecting Novel Ototoxins and Potentiation of Ototoxicity by Disease Settings

Coffin

Boney²,

Hill

et al. 2021

Front. Neurol.

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Over 100 drugs and chemicals are associated with permanent hearing loss, tinnitus, and vestibular deficits, collectively known as ototoxicity. The ototoxic potential of drugs is rarely assessed in pre-clinical drug development or during clinical trials, so this debilitating side-effect is often discovered as patients begin to report hearing loss. Furthermore, drug-induced ototoxicity in adults, and particularly in elderly patients, may go unrecognized due to hearing loss from a variety of etiologies because of a lack of baseline assessments immediately prior to novel therapeutic treatment. During the current pandemic, there is an intense effort to identify new drugs or repurpose FDA-approved drugs to treat COVID-19. Several potential COVID-19 therapeutics are known ototoxins, including chloroquine (CQ) and lopinavir-ritonavir, demonstrating the necessity to identify ototoxic potential in existing and novel medicines. Furthermore, several factors are emerging as potentiators of ototoxicity, such as inflammation (a hallmark of COVID-19), genetic polymorphisms, and ototoxic synergy with co-therapeutics, increasing the necessity to evaluate a drug's potential to induce ototoxicity under varying conditions. Here, we review the potential of COVID-19 therapies to induce ototoxicity and factors that may compound their ototoxic effects. We then discuss two models for rapidly detecting the potential for ototoxicity: mammalian auditory cell lines and the larval zebrafish lateral line. These models offer considerable value for pre-clinical drug development, including development of COVID-19 therapies. Finally, we show the validity of in silico screening for ototoxic potential using a computational model that compares structural similarity of compounds of interest with a database of known ototoxins and non-ototoxins. Preclinical screening at in silico, in vitro, and in vivo levels can provide an earlier indication of the potential for ototoxicity and identify the subset of candidate therapeutics for treating COVID-19 that need to be monitored for ototoxicity as for other widely-used clinical therapeutics, like aminoglycosides and cisplatin.

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Ischemic stroke in COVID-19-positive patients: an overview of SARS-CoV-2 and thrombotic mechanisms for the neurointerventionalist

Cited by 92 publications

References 58 publications

Predicting In-hospital Mortality Using D-Dimer in COVID-19 Patients With Acute Ischemic Stroke

Predicting In-hospital Mortality Using D-Dimer in COVID-19 Patients With Acute Ischemic Stroke

Post-Discharge Symptoms among Hospitalized COVID-19 Patients in Nigeria: A Single-Center Study

Detecting Novel Ototoxins and Potentiation of Ototoxicity by Disease Settings

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