Administration route governs the therapeutic efficacy, biodistribution and macrophage targeting of anti-inflammatory nanoparticles in the lung.

BACKGROUND: Uncontrolled inflammation is a central problem for many respiratory diseases. The development of potent, targeted anti-inflammatory therapies to reduce lung inflammation and re-establish the homeostasis in the respiratory tract is still a challenge. Previously, we developed a unique anti-inflammatory nanodrug, P12 (made of hexapeptides and gold nanoparticles), which can attenuate Toll-like receptor-mediated inflammatory responses in macrophages. However, the effect of the administration route on its therapeutic efficacy and tissue distribution remained to be defined. RESULTS: In this study, we systematically compared the effects of three different administration routes [the intratracheal (i.t.), intravenous (i.v.) and intraperitoneal (i.p.)] on the therapeutic activity, biodistribution and pulmonary cell targeting features of P12. Using the LPS-induced ALI mouse model, we found that the local administration route via i.t. instillation was superior in reducing lung inflammation than the other two routes even treated with a lower concentration of P12. Further studies on nanoparticle biodistribution showed that the i.t. administration led to more accumulation of P12 in the lungs but less in the liver and other organs; however, the i.v. and i.p. administration resulted in more nanoparticle accumulation in the liver and lymph nodes, respectively, but less in the lungs. Such a lung favorable distribution was also determined by the unique surface chemistry of P12. Furthermore, the inflammatory condition in the lung could decrease the accumulation of nanoparticles in the lung and liver, while increasing their distribution in the spleen and heart. Interestingly, the i.t. administration route helped the nanoparticles specifically target the lung macrophages, whereas the other two administration routes did not. CONCLUSION: The i.t. administration is better for treating ALI using nanodevices as it enhances the bioavailability and efficacy of the nanodrugs in the target cells of the lung and reduces the potential systematic side effects.

Clinical features in coronavirus disease 2019 (COVID-19) patients with early clearance and prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA.

BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19), the pattern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding has not been well characterized. METHODS: In our study, 652 patients in Wuhan Designated Hospital were recruited, and their clinical and laboratory findings were extracted and analyzed. RESULTS: The median duration of SARS-CoV-2 RNA detection was 23 days [interquartile range (IQR), 18 days] from symptom onset. Compared to patients with early viral RNA clearance (<23 days after illness onset), we found that patients with late viral RNA clearance (≥23 days) had a higher proportion of clinical features, as follows: symptoms, including fever, dry cough, and sputum production; comorbidities, including hypertension, chronic kidney disease, uremia, chronic liver disease, anemia, hyperlipidemia, and bilateral lung involvement; complications, such as liver injury; delayed admission to hospital; laboratory parameters at baseline, including higher eosinophils, uric acid, cholesterol, triglycerides, and lower hemoglobin; and less treatment with arbidol, chloroquine, or any antivirals. After generalized linear regression, prolonged SARS-CoV-2 RNA shedding was independently associated with younger age; delayed admission to hospital; symptoms including fever, shivering, and sputum production; comorbidities including hypertension, diabetes, cardiovascular disease, anemia, hyperlipidemia, uremia, and lung involvement; and higher alanine aminotransferase (ALT), uric acid, and cholesterol levels at baseline. CONCLUSIONS: In conclusion, the factors mentioned above are associated with the negative conversion of SARS-CoV-2 RNA. A deeper insight into virological dynamics will be helpful for establishing patient discharge and quarantine release criteria.

Lung Ultrasound Score in Evaluating the Severity of Coronavirus Disease 2019 (COVID-19) Pneumonia.

The purpose of this study is to observe the potential of lung ultrasound in evaluating the severity of coronavirus disease 2019 (COVID-19) pneumonia. Lung ultrasound was performed in ten zones of the patients' chest walls. The features of the ultrasound images were observed, and a lung ultrasound score (LUS) was recorded. The ultrasound features and scores were compared between the refractory group (PaO2/FiO2 ≤ 100 mm Hg or on extracorporeal membrane oxygenation) and the non-refractory group. The prediction value of the LUS was studied by receiver operating characteristic (ROC) curve analysis. In total, 7 patients were enrolled in the refractory group and 28 in the non-refractory group. B-line patterns and shred signs were the most common signs in all patients. Patients in the refractory group had significantly more ground-glass signs (median 6 [interquartile range {IQR}, 2.5-6.5] vs. median 0 [IQR, 0-3]), consolidation signs (median 1 [IQR, 1-1.5] vs. median 0 [IQR, 0-3]) and pleural effusions (median 5 [IQR, 1.5-6] vs. median 0 [IQR, 0-0.25]). The LUS was significantly higher in the refractory group (33.00 [IQR 27.50-34.00] vs. 25.50 [IQR 22.75-30.00]). The ROC of the LUS showed a cutoff score of 32 with a specificity of 0.893 and a sensitivity of 0.571 in diagnosing refractory respiratory failure among patients. In COVID-19 patients, lung ultrasound is a promising diagnostic tool in diagnosing patients with refractory pneumonia.