SARS-CoV-2 and the central nervous system: Emerging insights into hemorrhage-associated neurological consequences and therapeutic considerations

Mitra, Joy; Manohar, Kodavati; Provasek, Vincent E.; Rao, Kumuda; Mitra, Sankar; Hamilton, Dale J.; Horner, Philip J.; Vahidy, Farhaan S; Britz, Gavin W.; Kent, Thomas A.; Hegde, Muralidhar L.

doi:10.1016/j.arr.2022.101687

Cited by 15 publications

(13 citation statements)

References 219 publications

(245 reference statements)

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“…However, our data uniquely demonstrate, at the national level, that comorbid COVID-19 was only associated with a higher likelihood of in-hospital mortality among patients with ICH and SAH with MM-LoF, whereas among patients with E-LoF, COVID-19 status was not a significant driver of mortality. These findings have significant clinical relevance, and though we are limited from conducting a clinically detailed exploration of the biological mechanisms driving the differences in mortality between patients who have haemorrhagic stroke with and without comorbid COVID-19, it is reasonable to surmise, from previous studies, that a heightened systematic inflammatory response to the COVID-19 virus and its directed end organ damage may be potentiating these poor outcomes 16. However, further studies are needed to elucidate the mechanisms driving poorer outcomes among patients who have haemorrhagic stroke with comorbid COVID-19.…”

Section: Discussionmentioning

confidence: 90%

“…These findings have significant clinical relevance, and though we are limited from conducting a clinically detailed exploration of the biological mechanisms driving the differences in mortality between patients who have haemorrhagic stroke with and without comorbid COVID-19, it is reasonable to surmise, from previous studies, that a heightened systematic inflammatory response to the COVID-19 virus and its directed end organ damage may be potentiating these poor outcomes. 16 However, further studies are needed to elucidate the mechanisms driving poorer outcomes among patients who have haemorrhagic stroke with comorbid COVID-19. Also, given that minority races/ethnicities are at a higher likelihood of having comorbid COVID-19, the findings of this research highlight the need to further investigate the biological and environmental factors potentially driving socioeconomic disparities in the association between COVID-19 and haemorrhagic stroke outcomes.…”

Section: Discussionmentioning

confidence: 99%

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Poor haemorrhagic stroke outcomes during the COVID-19 pandemic are driven by socioeconomic disparities: analysis of nationally representative data

Bako,

Potter,

Pan

et al. 2024

BMJ Neurol Open

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BackgroundNationally representative studies evaluating the impact of the COVID-19 pandemic on haemorrhagic stroke outcomes are lacking.MethodsIn this pooled cross-sectional analysis, we identified adults (≥18 years) with primary intracerebral haemorrhage (ICH) or subarachnoid haemorrhage (SAH) from the National Inpatient Sample (2016–2020). We evaluated differences in rates of in-hospital outcomes between the prepandemic (January 2016–February 2020) and pandemic (March–December 2020) periods using segmented logistic regression models. We used multivariable logistic regression to evaluate differences in mortality between patients admitted from April to December 2020, with and without COVID-19, and those admitted from April to December 2019. Stratified analyses were conducted among patients residing in low-income and high-income zip codes, as well as among patients with extreme loss of function (E-LoF) and those with minor to major loss of function (MM-LoF).ResultsOverall, 309 965 patients with ICH (47% female, 56% low income) and 112 210 patients with SAH (62% female, 55% low income) were analysed. Prepandemic, ICH mortality decreased by ~1% per month (adjusted OR, 95% CI: 0.99 (0.99 to 1.00); p<0.001). However, during the pandemic, the overall ICH mortality rate increased, relative to prepandemic, by ~2% per month (1.02 (1.00 to 1.04), p<0.05) and ~4% per month (1.04 (1.01 to 1.07), p<0.001) among low-income patients. There was no significant change in trend among high-income patients with ICH (1.00 (0.97 to 1.03)). Patients with comorbid COVID-19 in 2020 had higher odds of mortality (versus 2019 cohort) only among patients with MM-LoF (ICH, 2.15 (1.12 to 4.16), and SAH, 5.77 (1.57 to 21.17)), but not among patients with E-LoF.ConclusionSustained efforts are needed to address socioeconomic disparities in healthcare access, quality and outcomes during public health emergencies.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Poor haemorrhagic stroke outcomes during the COVID-19 pandemic are driven by socioeconomic disparities: analysis of nationally representative data

Bako,

Potter,

Pan

et al. 2024

BMJ Neurol Open

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“…111 Mitra et al conducted a review of the effects of SARS-CoV-2 infection on the central nervous system and proposed that PEGylated carbon-NP conjugated with the iron chelator deferoxamine and an antioxidant scavenger might be a promising therapeutic option for alleviating neurodegenerative conditions associated with COVID-19. 112 Cytokine storms are one of the crucial factors that contribute to various accompanying diseases and some individuals may develop arthritis as a long-term COVID complication. 113 Rao et al found that some immune cell membrane-coated NPs effectively inhibited the cytokine storms associated with COVID-19.…”

Section: Regulation Of Ros and Inflammatory Factorsmentioning

confidence: 99%

Development of nanozymes for promising alleviation of COVID-19-associated arthritis

Zhao

Zhuang

et al. 2023

Biomater. Sci.

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“…This coagulopathy is associated with the thrombotic and ischemic events of COVID-19 in the lungs, brain, and kidneys. However, vascular events are not purely ischemic, as viral invasion affects endothelial integrity, also leading to hemorrhagic events [7].…”

Section: Amyloid Fibrin Clotsmentioning

confidence: 99%

“…The clinical picture that is being characterized is called post-COVID-19 syndrome, or long COVID-19. These residues can involve cognitive deficits and even a greater susceptibility to cerebrovascular events (ischemic or hemorrhagic) [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2-Induced Amyloidgenesis: Not One, but Three Hypotheses for Cerebral COVID-19 Outcomes

et al. 2022

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The main neuropathological feature of Alzheimer’s disease (AD) is extracellular amyloid deposition in senile plaques, resulting from an imbalance between the production and clearance of amyloid beta peptides. Amyloid deposition is also found around cerebral blood vessels, termed cerebral amyloid angiopathy (CAA), in 90% of AD cases. Although the relationship between these two amyloid disorders is obvious, this does not make CAA a characteristic of AD, as 40% of the non-demented population presents this derangement. AD is predominantly sporadic; therefore, many factors contribute to its genesis. Herein, the starting point for discussion is the COVID-19 pandemic that we are experiencing and how SARS-CoV-2 may be able to, both directly and indirectly, contribute to CAA, with consequences for the outcome and extent of the disease. We highlight the role of astrocytes and endothelial cells in the process of amyloidgenesis, as well as the role of other amyloidgenic proteins, such as fibrinogen and serum amyloid A protein, in addition to the neuronal amyloid precursor protein. We discuss three independent hypotheses that complement each other to explain the cerebrovascular amyloidgenesis that may underlie long-term COVID-19 and new cases of dementia.

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SARS-CoV-2 and the central nervous system: Emerging insights into hemorrhage-associated neurological consequences and therapeutic considerations

Cited by 15 publications

References 219 publications

Poor haemorrhagic stroke outcomes during the COVID-19 pandemic are driven by socioeconomic disparities: analysis of nationally representative data

Poor haemorrhagic stroke outcomes during the COVID-19 pandemic are driven by socioeconomic disparities: analysis of nationally representative data

Development of nanozymes for promising alleviation of COVID-19-associated arthritis

SARS-CoV-2-Induced Amyloidgenesis: Not One, but Three Hypotheses for Cerebral COVID-19 Outcomes

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