Clinical characteristics of the first known cases of death caused by COVID-19 pneumonia.

Severe pneumonia caused by COVID-19 has resulted in many deaths worldwide. Here, we analyzed the clinical characteristics of the first 17 reported cases of death due to COVID-19 pneumonia in Wuhan, China. Demographics, initial symptoms, complications, chest computerized tomography (CT) images, treatments, and prognoses were collected and analyzed from the National Health Committee of China data. The first 17 reported deaths from COVID-19 were predominately in older men; 82.35% of patients were older than 65 years, and 76.47% were males. The most common initial symptoms were fever or fatigue (14 cases, 82.35%), respiratory symptoms, such as cough (12 cases, 70.59%), and neurological symptoms, such as headache (3 cases, 17.65%). The most common finding of chest CT was viral pneumonia (5 cases, 29.41%). Anti-infectives (11 cases, 64.71%) and mechanical ventilation (9 cases, 52.94%) were commonly used for treatment. Most of the patients (16 cases, 94.12%) died of acute respiratory distress syndrome (ARDS). Our findings show that advanced age and male gender are effective predictors of COVID-19 mortality, and suggest that early interventions to reduce the incidence of ARDS may improve prognosis of COVID-19 pneumonia patients.

ISO-1, a macrophage migration inhibitory factor antagonist, inhibits airway remodeling in a murine model of chronic asthma.

Airway remodeling is the process of airway structural change that occurs in patients with asthma in response to persistent inflammation and leads to increasing disease severity. Drugs that decrease this persistent inflammation play a crucial role in managing asthma episodes. Mice sensitized (by intraperitoneal administration) and then challenged (by inhalation) with ovalbumin (OVA) develop an extensive eosinophilic inflammatory response, goblet cell hyperplasia, collagen deposition, airway smooth muscle thickening, and airway wall area increase, similar to pathologies observed in human asthma. We used OVA-sensitized/challenged mice as a murine model of chronic allergic airway inflammation with subepithelial fibrosis (i.e., asthma). In this OVA mouse model, mRNA and protein of macrophage migration inhibitory factor (MIF) are upregulated, a response similar to what has been observed in the pathogenesis of acute inflammation in human asthma. We hypothesized that MIF induces transforming growth factor-ß1 (TGF-ß1) synthesis, which has been shown to play an important role in asthma and airway remodeling. To explore the role of MIF in the development of airway remodeling, we evaluated the effects of an MIF small-molecule antagonist, (S,R)3-(4-hy-droxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1), on pathologies associated with the airway-remodeling process in the OVA mouse model. We found that administration of ISO-1 significantly mitigated all symptoms caused by OVA treatment. In addition, the treatment of OVA-sensitized mice with the MIF antagonist ISO-1 significantly reduced TGF-ß1 mRNA levels in pulmonary tissue and its protein level in bronchial alveolar lavage fluid supernatants. We believe the repression of MIF in the ISO-1 treatment group led to the significant suppression observed in the inflammatory responses associated with the allergen-induced lung inflammation and fibrosis in our murine asthma (OVA) model. Our results implicate a possible function of MIF in the pathogenesis of chronic asthma and suggest that MIF might be an important therapeutic target for airway remodeling.

[Effects of dexamethasone on expression of Th17 transcription factor RORgammat mRNA in experimental asthma mice.].

AIM: To study the effects of dexamethasone (Dex) on expression of Th17 transcription factor retinoic acid-related orphan receptor gamma t(RORgammat)in asthma. METHODS: The BALB/c mice asthma model was induced by ovalbumin(OVA) with classic method.Thirty female mice were randomly divided into control group, asthmatic group and Dex treated group. The level of IL-17 in mice bronchoalveolar lavage fluid (BALF) and serum was measured by enzyme-linked immunosorbent assay(ELISA). Airway Responsiveness to acetylcholine chloride(Ach) was measured by a modified non-invasive method; The airway inflammation was evaluated by HE staining.The expression of RORgammat mRNA was measured by reverse transcription-polymerase chain reaction(RT-PCR). RESULTS: The level of RORgammat mRNA, IL-17 of asthmatic group were significantly higher than those of control group(P<0.01), which were significantly reduced by Dex compared with the asthmatic group(P<0.05). CONCLUSION: Dex can inhibit the release of IL-17, whose mechanism may be the blockade of TH17 differentiation in asthmatic models by inhibit the RORgammat expression.

[Effects of dexamethasone on intracellular expression of Th17 cytokine interleukin 17 in asthmatic mice].

OBJECTIVE: To study the effects of dexamethasone on intracellular expression of Th17 cytokine interleukin 17 and the mechanisms in asthmatic mice. METHODS: Experimental asthma was induced by ovalbumin (OVA) sensitization in 20 in female Balb/c mice with (dexamethasone group, n=10) or without dexamethasone treatment (model group, n=10), with another 10 serving as the control group. The levels of IL-17 in the bronchoalveolar lavage fluid (BALF) and serum of the mice were measured by enzyme-linked immunosorbent assay (ELISA), and the airway inflammation was evaluated by HE staining. The expressions of IL-17 and RORgammat mRNA were measured by reverse transcription-polymerase chain reaction (RT-PCR), and the expression of RORgammat protein was measured by immunohistochemical staining. RESULTS: The levels of RORgammat and IL-17 mRNA and protein in the asthmatic model group were significantly higher than those in the control group (P<0.01), and the increased expressions of RORgammat and IL-17 mRNA and protein in the asthmatic mice were significantly reduced by dexamethasone treatment (P<0.05). CONCLUSION: Dexamethasone can inhibit the release of IL-17 probably by inhibiting RORgammat expression and blocking Th17 differentiation in asthmatic mice.