COVID-19 Pathophysiology Predicts That Ischemic Stroke Occurrence Is an Expectation, Not an Exception—A Systematic Review

Abstract

Clinical reports of neurological manifestations associated with severe coronavirus disease 2019 (COVID-19), such as acute ischemic stroke (AIS), encephalopathy, seizures, headaches, acute necrotizing encephalitis, cerebral microbleeds, posterior reversible leukoencephalopathy syndrome, hemophagocytic lymphohistiocytosis, peripheral neuropathy, cranial nerve palsies, transverse myelitis, and demyelinating disorders, are increasing rapidly. However, there are comparatively few studies investigating the potential impact of immunological responses secondary to hypoxia, oxidative stress, and excessive platelet-induced aggregation on the brain. This scoping review has focused on the pathophysiological mechanisms associated with peripheral and consequential neural (central) inflammation leading to COVID-19-related ischemic strokes. It also highlights the common biological processes shared between AIS and COVID-19 infection and the importance of the recognition that severe respiratory dysfunction and neurological impairments associated with COVID and chronic inflammation [post-COVID-19 neurological syndrome (PCNS)] may significantly impact recovery and ability to benefit from neurorehabilitation. This study provides a comprehensive review of the pathobiology of COVID-19 and ischemic stroke. It also affirms that the immunological contribution to the pathophysiology of COVID-19 is predictive of the neurological sequelae particularly ischemic stroke, which makes it the expectation rather than the exception. This work is of fundamental significance to the neurorehabilitation community given the increasing number of COVID-related ischemic strokes, the current limited knowledge regarding the risk of reinfection, and recent reports of a PCNS. It further highlights the need for global collaboration and research into new pathobiology-based neurorehabilitation treatment strategies and more integrated evidence-based care.

Post-COVID-19 Syndrome: The Persistent Symptoms at the Post-viral Stage of the Disease. A Systematic Review of the Current Data

“…In addition to these studies, all the others found in this review analyzed heterogenic populations of patients with COVID-19, from mild to severe. In this context, a recent editorial and a systematic review provided a detailed overview into the spectrum of mental disorders that can occur during the intermediate and long-term phases of COVID-19 in mild-to-critical patients (114,115). The most frequent neurological long-term symptoms in these patients were myalgia, arthralgia, sleeping troubles, and headache (46,50,61,116).…”

Neurological Complications of COVID-19: Underlying Mechanisms and Management

“…The increased risk of these events is believed to be due to a hyperinflammatory/hypercoagulable state, and altered endothelial cell function resulting from the SARS-CoV-2 infection (Figure 2) [77][78][79][80][81]. Several studies have reported a significant increase in neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), and serum ferritin in COVID-19 patients with ischemic stroke, which could predict mortality in these patients [82][83][84][85][86][87]. Neutrophilia (increase in neutrophils) described in these patients results in the overproduction of neutrophil extracellular traps (NETs), which has been shown to increase thrombi formation [88][89][90].…”

COVID-19 and long-term neurological problems: Challenges ahead with Post-COVID-19 Neurological Syndrome

“…Similar transcription factors are activated and remain so during the first months as oedema subsides, thus inducing chronic inflammation and suppressing immunological recovery. 23,24 ) 4. Prolonged alterations in the balance between the renin-angiotensin-aldosterone system and the downregulated ACE2 pathways are likely to promote end-organ dysfunction in the setting of acute COVID-19.…”