No abstract

Objectives To identify clinical characteristics of severe patients with COVID-19. Methods The WHO database of publications on COVID-19 and PubMed were searched from inception to March 20, 2020 and all valuable studies were analyzed using Stata 15.0. Results We selected forty-four studies with 13,497 patients. In the comparison of severe and non-severe groups, age over 50 (OR = 4.090; 95% CI = 2.422–6.907, P = 0.000) and underlying disease (OR = 3.992; 95% CI = 2.631–6.507, P = 0.000) are risk factors. Female gender (OR = 0.740; 95% CI = 0.622–0.881, P = 0.001) is a protective factor. Characteristics like dyspnea (OR = 4.914; 95% CI = 3.069–7.867, P = 0.000), lymphopenia (OR = 5.528; 95% CI = 3.484–8.772, P = 0.000), thrombocytopenia (OR = 3.623; 95% CI = 1.034–12.691, P = 0.044), elevated C-reactive protein (OR = 5.217; 95% CI = 2.459–11.070, P = 0.000) and D-dimer (OR = 3.780; 95% CI = 1.481–9.648, P = 0.005) were more frequently in severe cases. Diffuse lesions and consolidation (OR = 4.680; 95% CI = 3.183–6.881, P = 0.000) in imaging was considered reliable. Conclusions Men older than 50 with underlying disease are susceptible to develop severe pneumonia while female gender is protective. The typical symptom of severe pneumonia was dyspnea, but high fever, headache and diarrhea were not significantly different among patients with varying degrees of severity. Lymphopenia, thrombocytopenia, elevated C-reactive protein and D-dimer occurred more frequently in severe patients and yet leukopenia is not a characteristic laboratory indicator. Diffuse lesions and consolidation are important imaging features to distinguish severe pneumonia.

Intracerebral hemorrhage (ICH), the most lethal type of stroke, often leads to poor outcomes in the clinic. Due to the complex mechanisms and cell-cell crosstalk during ICH, the neurovascular unit (NVU) was proposed to serve as a promising therapeutic target for ICH research. This review aims to summarize the development of pathophysiological shifts in the NVU and neural-glia networks after ICH. In addition, potential targets for ICH therapy are discussed in this review. Beyond cerebral blood flow, the NVU also plays an important role in protecting neurons, maintaining central nervous system (CNS) homeostasis, coordinating neuronal activity among supporting cells, forming and maintaining the blood-brain barrier (BBB), and regulating neuroimmune responses. During ICH, NVU dysfunction is induced, along with neuronal cell death, microglia and astrocyte activation, endothelial cell (EC) and tight junction (TJ) protein damage, and BBB disruption. In addition, it has been shown that certain targets and candidates can improve ICH-induced secondary brain injury based on an NVU and neural-glia framework. Moreover, therapeutic approaches and strategies for ICH are discussed.

Neuronal mitochondrial dynamics are disturbed after ischemic stroke. Optic atrophy 1 (OPA1) and its GTPase activity are involved in maintaining mitochondrial cristae and inner membrane fusion. This study aimed to explore the role of OMA1-mediated OPA1 cleavage (S1-OPA1) in neurons exposed to cerebral ischemia and reperfusion. After oxygen-glucose deprivation (OGD) for 60 min, we found that mitochondrial fragmentation occurred successively in the axon and soma of neurons, accompanied by an increase in S1-OPA1. In addition, S1-OPA1 overexpression significantly aggravated mitochondrial damage in neurons exposed to OGD for 60 min and 24 h after OGD/R, characterized by mitochondrial fragmentation, decreased mitochondrial membrane potential, mitochondrial cristae ultrastructural damage, increased superoxide production, decreased ATP production and increased mitochondrial apoptosis, which was inhibited by the lysine 301 to alanine mutation (K301A). Furthermore, we performed neuron-specific overexpression of S1-OPA1 in the cerebral cortex around ischemia of middle cerebral artery occlusion/reperfusion (MCAO/R) mice. The results further demonstrated in vivo that S1-OPA1 exacerbated neuronal mitochondrial ultrastructural destruction and injury induced by cerebral ischemia-reperfusion, while S1-OPA1-K301 overexpression had no effect. In conclusion, ischemia induced neuronal OMA1-mediated cleavage of OPA1 at the S1 site. S1-OPA1 aggravated neuronal mitochondrial fragmentation and damage in a GTPase-dependent manner, and participated in neuronal ischemia-reperfusion injury.