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With more than 900,000 confirmed cases worldwide and nearly 50,000 deaths during the first 3 months of 2020, the coronavirus disease 2019 (COVID-19) pandemic has emerged as an unprecedented health care crisis. The spread of COVID-19 has been heterogeneous, resulting in some regions having sporadic transmission and relatively few hospitalized patients with COVID-19 and others having community transmission that has led to overwhelming numbers of severe

Objective:To investigate new-onset neurologic impairments associated with coronavirus disease 2019 (COVID-19).Methods:A retrospective multicenter cohort study conducted between 18 January and 20 March 2020 including people with confirmed COVID-19 from 56 hospitals officially designated in three Chinese regions; data were extracted from medical records. New-onset neurologic events as assessed by neurology consultants based on manifestations, clinical examination and investigations, in which critical events included disorders of consciousness, stroke, CNS infection, seizures and status epilepticus.Results:We enrolled 917 people with average age 48.7 years and 55% were male. The frequency of new onset critical neurologic events was 3.5% (32/917) overall and 9.4% (30/319) among those with severe or critical COVID-19. These were impaired consciousness (n=25) or/and stroke (n=10). The risk of critical neurologic events was highly associated with age above 60 years and previous history of neurological conditions. Non-critical events were seen in less than 1% (7/917), including muscle cramp, unexplained headache, occipital neuralgia, tic and tremor. Brain CT in 28 people led to new findings in nine. Findings from lumbar puncture in three with suspected CNS infection, unexplained headache or severe occipital neuralgia were unremarkable.Conclusions:People with COVID-19 aged over 60 and neurologic comorbidities were at higher risk of developing critical neurologic impairment, mainly impaired consciousness and cerebrovascular accidents. Brain CT should be considered when new-onset brain injury is suspected, especially in people under sedation or showing an unexplained decline in consciousness. Evidence of direct acute insult of SARS-COV-2 to the CNS is still lacking.

BackgroundPD-L1 is an immune inhibitory receptor ligand that leads to T cell dysfunction and apoptosis by binding to its receptor PD-1, which works in braking inflammatory response and conspiring tumor immune evasion. However, in gliomas, the cause of PD-L1 expression in the tumor microenvironment is not yet clear. Besides, auxiliary biomarkers are urgently needed for screening possible responsive glioma patients for anti-PD-1/PD-L1 therapies.MethodsThe distribution of tumor-infiltrating T cells and PD-L1 expression was analyzed via immunofluorescence in orthotopic murine glioma model. The expression of PD-L1 in immune cell populations was detected by flow cytometry. Data excavated from TCGA LGG/GBM datasets and the Ivy Glioblastoma Atlas Project was used for in silico analysis of the correlation among genes and survival.ResultsThe distribution of tumor-infiltrating T cells and PD-L1 expression, which parallels in murine orthotopic glioma model and human glioma microdissections, was interrelated. The IFN-γ level was positively correlated with PD-L1 expression in murine glioma. Further, IFN-γ induces PD-L1 expression on primary cultured microglia, bone marrow-derived macrophages, and GL261 glioma cells in vitro. Seven IFN-γ-induced genes, namely GBP5, ICAM1, CAMK2D, IRF1, SOCS3, CD44, and CCL2, were selected to calculate as substitute indicator for IFN-γ level. By combining the relative expression of the listed IFN-γ-induced genes, IFN-γ score was positively correlated with PD-L1 expression in different anatomic structures of human glioma and in glioma of different malignancies.ConclusionOur study identified the distribution of tumor-infiltrating T cells and PD-L1 expression in murine glioma model and human glioma samples. And we found that IFN-γ is an important cause of PD-L1 expression in the glioma microenvironment. Further, we proposed IFN-γ score aggregated from the expressions of the listed IFN-γ-induced genes as a complementary prognostic indicator for anti-PD-1/PD-L1 therapy.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1330-2) contains supplementary material, which is available to authorized users.

The transition to air breathing after birth requires both anatomic and biochemical maturation of the lung. Lung morphogenesis is mediated by complex paracrine interactions between respiratory epithelial cells and mesenchymal cells that direct transcriptional programs guiding patterning and cytodifferentiation of the lung. In the present study, transgenic mice were generated in which the Kruppel-like factor 5 gene (Klf5) was conditionally deleted in respiratory epithelial cells in the fetal lung. Lack of KLF5 inhibited maturation of the lung during the saccular stage of development. Klf5Δ/Δ mice died of respiratory distress immediately after birth. Abnormalities in lung maturation and morphogenesis were observed in the respiratory epithelium, the bronchiolar smooth muscle, and the pulmonary vasculature. Respiratory epithelial cells of both the conducting and peripheral airways were immature. Surfactant phospholipids were decreased and lamellar bodies, the storage form of surfactant, were rarely found. mRNA microarray analysis demonstrated that KLF5 influenced the expression of genes regulating surfactant lipid and protein homeostasis, vasculogenesis, including Vegfa, and smooth muscle cell differentiation. KLF5 regulates genes controlling paracrine interactions during lung morphogenesis, as well as those regulating the maturation of the respiratory epithelium that is required for lung function after birth.

Using TLR agonists in cancer treatment can have either beneficial or detrimental effects. Therefore, it is important to determine their effect on the tumor growth and understand the underlying mechanisms in animal tumor models. In this study, we report a general immunotherapeutic activity of a synthetic bacterial lipoprotein (BLP), a TLR1/TLR2 agonist, on established lung carcinoma, leukemia, and melanoma in mice. Systemic treatment of 3LL tumor-bearing mice with BLP, but not LPS, led to a dose-dependent tumor regression and a long-lasting protective response against tumor rechallenge. The BLP-mediated tumor remission was neither mediated by a direct tumoricidal activity nor by innate immune cells, because it lacked therapeutic effect in immunodeficient SCID mice. Instead, BLP treatment reduced the suppressive function of Foxp3+ regulatory T cells (Tregs) and enhanced the cytotoxicity of tumor-specific CTL in vitro and in vivo. Furthermore, adoptive cotransfer of BLP-pretreated but not untreated CTL and Tregs from wild-type but not from TLR2−/− mice was sufficient to restore antitumor immunity in SCID mice by reciprocally modulating Treg and CTL function. These results demonstrate that the TLR1/TLR2 agonist BLP may have a general tumor therapeutic property involving reciprocal downregulation of Treg and upregulation of CTL function. This property may play an important role in the development of novel antitumor strategies.

These recommendations for physicians who perform bronchoscopy will help to protect those patients (un)-affected by the current COVID-19 pandemic, minimize the risk of transmission, and maintain clinical care for all patients.

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