Background In December 2019, unexplained cases of pneumonia emerged in Wuhan, China, which were found to be secondary to the novel coronavirus SARS-CoV-2. On March 11, 2020, the WHO declared the Coronavirus Disease 2019 (COVID-2019) outbreak, a pandemic. Objective To clarify the neurological complications of SARS-CoV-2 infection including the potential mechanisms and therapeutic options. Methods We conducted a systematic literature search from December 01, 2019 to May 14, 2020 using multiple combinations of keywords from PubMed and Ovid Medline databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included articles with cases of COVID-19 where neurological involvement was evident. Results We were able to identify 82 cases of COVID-19 with neurological complications. The mean age was 62.3 years. 37.8% of the patients were women (n = 31). 48.8% of the patients (n = 40) had cerebrovascular insults, 28% (n = 23) had neuromuscular disorders, and 23% of the patients (n = 19) had encephalitis or encephalopathy. Conclusions Neurological manifestations of COVID-19 are not rare, especially large vessel stroke, Guillain-Barre syndrome, and meningoencephalitis. Moving forward, further studies are needed to clarify the prevalence of the neurological complications of SARS-CoV-2 infection, investigate their biological backgrounds, and test treatment options. Physicians should be cautious not to overlook other neurological diagnoses that can mimic COVID-19 during the pandemic.

In patients with cystic fibrosis (CF) and asthma, elevated levels of interleukin-8 (IL-8) are found in the airways. IL-8 is a CXC chemokine that is a chemoattractant for neutrophils through CXCR1 and CXCR2 G protein-coupled receptors. We hypothesized that IL-8 acts directly on airway smooth muscle cells (ASMC) in a way that may contribute to the enhanced airway responsiveness and airway remodeling observed in CF and asthma. The aim of this study was to determine whether human ASMC (HASMC) express functional IL-8 receptors (CXCR1 and CXCR2) linked to cell contraction and migration. Experiments were conducted on cells harvested from human lung specimens. Real-time PCR and fluorescence-activated cell sorting analysis showed that HASMC expressed mRNA and protein for both CXCR1 and CXCR2. Intracellular Ca(2+) concentration ([Ca(2+)](i)) increased from 115 to 170 nM in response to IL-8 (100 nM) and decreased after inhibition of phospholipase C (PLC) with U-73122. On blocking the receptors with specific neutralizing antibodies, changes in [Ca(2+)](i) were abrogated. IL-8 also contracted the HASMC, decreasing the length of cells by 15%, and induced a 2.5-fold increase in migration. These results indicate that HASMC constitutively express functional CXCR1 and CXCR2 that mediate IL-8-triggered Ca(2+) release, contraction, and migration. These data suggest a potential role for IL-8 in causing abnormal airway structure and function in asthma and CF.

Background: In December 2019, unexplained cases of pneumonia emerged in Wuhan, China, which were found to be secondary to the novel coronavirus SARS-CoV-2. On March 11, 2020, the WHO declared the Coronavirus Disease 2019 (COVID-2019) outbreak, a pandemic. Although the most common presentations of COVID-19 are fever, cough and shortness of breath, several clinical observations indicate that COVID-19 does affect the central and peripheral nervous system. Methods: We conducted a systematic literature search from December 01, 2019 to May 14, 2020 using multiple combinations of keywords from PubMed and Ovid Medline databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included articles with cases of COVID-19 that were evident for neurological involvement. Results: We were able to identify 82 cases of COVID-19 with neurological complications. The mean age was 62.28 years. 37.8% of the patients were women (n = 31). 48.8% of the patients (n=40) had cerebrovascular insults, 28% (n=23) had neuromuscular disorders, 18.3% of the patients (n=15) had encephalitis or encephalopathy, and 2.4% (n=2) presented with status epilepticus. Conclusions: Neurological manifestations of COVID-19 infection are not rare, especially large vessel stroke, Guillain barre syndrome and meningoencephalitis. Moving forward, further studies are needed to clarify the prevalence of the neurological complications of COVID-19, investigate their biological backgrounds, and test treatment options. Physicians should be cautious not to overlook other neurological diagnoses that can mimic COVID-19 during the pandemic.

Phosphoinositide 3-kinase (PI3K) may potentially influence intracellular [Ca 2ϩ ] i concentration by several mechanisms. We have investigated the effects of phosphoinositide 3-kinase (PI3K) inhibitors wortmannin and LY-294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one] on Ca 2ϩ signaling in rat airway smooth muscle (ASM) cells using fura-2 and imaging methodology. Wortmannin (1 M) and LY-294002 (1 and 10 M) had opposite effects: wortmannin caused a small increase, whereas LY-294002 caused a significant decrease of peak Ca 2ϩ responses to serotonin (5-HT). LY-294002 (10 M) diminished 5-HT-induced ASM cell contraction, measured as a change in cell surface area, and inositol phosphate formation, measured by anion exchange chromatography. Thin layer chromatography revealed that the levels of phospholipase C (PLC) substrate phosphatidylinositol 4,5-bisphosphate were not affected. SDS polyacrylamide gel electrophoresis and Western blotting have shown that both wortmannin and LY-294002 inhibited plateletderived growth factor-induced PI3K activation. However, PI3K activation could not be detected after 5-HT stimulation. The specific casein kinase-2 (CK2) inhibitor 5,6-dichloro-1-␤-D-ribofuranosyl-benzimidazole (10 -40 M) reduced 5-HT-triggered responses to a similar extent as LY-294002. We conclude that LY-294002 modulates Ca 2ϩ signaling in rat ASM independently of its action on PI3K by acting on, or upstream of, PLC, possibly by inhibiting CK2.

Introduction: Multiple risk factors of mortality have been identified in patients with COVID-19. Here, we sought to determine the effect of a history of neurological disorder and development of neurological manifestations on mortality in hospitalized patients with COVID-19.Methods: From March 20 to May 20, 2020, hospitalized patients with laboratory confirmed or highly suspected COVID-19 were identified at four hospitals in Ohio. Previous history of neurological disease was classified by severity (major or minor). Neurological manifestations during disease course were also grouped into major and minor manifestations. Encephalopathy, ischemic or hemorrhagic stroke, and seizures were defined as major manifestations, whereas minor neurological manifestations included headache, anosmia, dysgeusia, dizziness or vertigo, and myalgias. Multivariate logistic regression models were used to determine significant predictors of mortality in patients with COVID-19 infection.Results: 574/626 hospitalized patients were eligible for inclusion. Mean age of the 574 patients included in the analysis was 62.8 (SD 17.6), with 298 (51.9%) women. Of the cohort, 240(41.8%) patients had a prior history of neurological disease (HND), of which 204 (35.5%) had a major history of neurological disease (HND). Mortality rates were higher in patients with a major HND (30.9 vs. 15.4%; p = 0.00002), although this was not a significant predictor of death. Major neurological manifestations were recorded in 203/574 (35.4%) patients during disease course. The mortality rate in patients who had major neurological manifestations was 37.4% compared to 11.9% (p = 2 × 10 −12 ) in those who did not. In multivariate analysis, major neurological manifestation (OR 2.1,; p = 0.002) was a predictor of death. Conclusions: In this retrospective study, history of pre-existing neurological disease in hospitalized COVID-19 patients did not impact mortality; however, development of major neurological manifestations during disease course was found to be an independent predictor of death. Larger studies are needed to validate our findings.