ABSTRACT
BACKGROUND: Acute lung injury (ALI) or its most advanced form, acute respiratory distress syndrome (ARDS) is a severe inflammatory pulmonary process triggered by a variety of insults including sepsis, viral or bacterial pneumonia, and mechanical ventilator-induced trauma. Currently, there are no effective therapies available for ARDS. We have recently reported that a novel small molecule AVR-25 derived from chitin molecule (a long-chain polymer of N-acetylglucosamine) showed anti-inflammatory effects in the lungs. The goal of this study was to determine the efficacy of two chitin-derived compounds, AVR-25 and AVR-48, in multiple mouse models of ALI/ARDS. We further determined the safety and pharmacokinetic (PK) profile of the lead compound AVR-48 in rats. METHODS: ALI in mice was induced by intratracheal instillation of a single dose of lipopolysaccharide (LPS; 100 µg) for 24 h or exposed to hyperoxia (100% oxygen) for 48 h or undergoing cecal ligation and puncture (CLP) procedure and observation for 10 days. RESULTS: Both chitin derivatives, AVR-25 and AVR-48, showed decreased neutrophil recruitment and reduced inflammation in the lungs of ALI mice. Further, AVR-25 and AVR-48 mediated diminished lung inflammation was associated with reduced expression of lung adhesion molecules with improvement in pulmonary endothelial barrier function, pulmonary edema, and lung injury. Consistent with these results, CLP-induced sepsis mice treated with AVR-48 showed a significant increase in survival of the mice (80%) and improved lung histopathology in the treated CLP group. AVR-48, the lead chitin derivative compound, demonstrated a good safety profile. CONCLUSION: Both AVR-25 and AVR-48 demonstrate the potential to be developed as therapeutic agents to treat ALI/ARDS.
Subject(s)
Acute Lung Injury/drug therapy , Immunologic Factors/pharmacology , Respiratory Distress Syndrome/drug therapy , Small Molecule Libraries/pharmacology , Animals , Chitin/pharmacology , Disease Models, Animal , Female , Lipopolysaccharides/pharmacology , Lung/drug effects , Male , Mice , Mice, Inbred C57BL , Pneumonia/drug therapy , Pulmonary Edema/drug therapy , Rats , Rats, Sprague-Dawley , Sepsis/drug therapyABSTRACT
OBJECTIVE: Novel coronavirus disease 2019 (COVID-19) seems to affect adults and pediatric patients differently. While neonates are a special population, little is known about the neonatal outcomes. This study aimed to investigate the outcomes in COVID-19 positive neonates and incidence of vertical transmission of the virus by reviewing available literature. STUDY DESIGN: This study is a narrative review of available literature on "COVID-19 in neonates," for which PubMed and Google Scholar were used to search the published articles. RESULTS: We summarized the data from 39 published studies that are comprised of 326 COVID-19 positive peripartum mothers with respective neonatal outcomes. Twenty-three neonates have been reported to be COVID-19 positive. Male neonates were affected significantly more (79%) than female neonates. Approximately 3% neonates acquired infection through suspected vertical transmission. Strict infection prevention measures during the perinatal time can significantly reduce the chance of horizontal transmission of the virus. Overall, neonates were asymptomatic or mildly symptomatic regardless of gestational age at birth and required only supportive measures. There was 0% mortality in COVID-19 positive neonates. CONCLUSION: From available published data to date, we can conclude that the prognosis of COVID-19 positive neonates is good with no mortality. There appears to be minimal vertical transmission of the infection. KEY POINTS: · Majority of COVID-19 positive neonates showed mild clinical signs and symptoms with no mortality.. · Most COVID-19 positive neonates require only supportive measures.. · Possibility of viral vertical transmission is very low..