Feasibility Studies of Nebulized SARS-CoV-2 Neutralizing Antibody in Mice and Cynomolgus Monkeys.

PURPOSE: Neutralizing antibodies, administrated through intravenous infusion, have shown to be highly efficacious in treating mild and moderate COVID-19 caused by SARS-CoV-2 infection in the lung. However, antibodies do not transport across the plasma-lung barrier efficiently, and up to 100 mg/kg dose was used in human causing significant supply and cost burdens. This study was to explore the feasibility of nebulized antibodies inhalation delivery as an alternative route. METHODS: HB27, a potent RBD-specific humanized monoclonal antibody (Zhu et al. in National Sci Rev. 8:nwaa297, 2020), showed excellent protection against SARS-CoV-2 in animal model and good safety profile in clinical studies. The pharmacokinetics and preliminary safety of HB27 administrated through the respiratory tract were studied in mice and cynomolgus monkeys here. RESULTS: At a single 5 mg/kg dose, the peak HB27 concentration in mice pulmonary epithelial lining fluid (ELF) reached 857.8 µg/mL, 670-fold higher than the PRNT90 value of 1.28 µg/mL, and maintained above PRNT90 over 240 h. In contrast, when administrated by intravenous injection at a 5 mg/kg dose, the antibody concentrations in mice ELF were below PRNT90 value throughout, and were about 50-fold lower than that in the serum. In cynomolgus monkeys administrated with a single dose through inhalation, the antibody concentration in ELF remained high within 3 days. No drug-related safety concerns were observed in the studies. CONCLUSIONS: The study demonstrated that nebulized neutralizing antibody delivery though inhalation could be a more efficient and efficacious alternative approach for treating COVID-19 and other respiratory infectious diseases, and warrants further evaluation in clinical studies.

Long-Term Impacts of COVID-19 Lockdown on the NO2 Concentrations and Urban Thermal Environment: Evidence from the Five Largest Urban Agglomerations in China

Under the threat of COVID-19, many regions around the world implemented lockdown policies to control the spread of the virus. This restriction on both social and economic activities has improved the quality of the environment in certain aspects. However, most previous studies have only focused on the short-term impact of lockdown policies on the urban environment. The long-term effects of lockdown require a more focused exploration and analysis. Thus, five major urban agglomerations in China were selected as the research area;changes in the numerical and spatial distribution of NO2 concentration and surface temperature during four different lockdown stages in 2019, 2020, and 2021 were investigated to analyze the long-term effects of lockdown policies on the urban environment. The results indicated that the impact of shorter lockdowns was short-term and unsustainable;the NO2 concentrations increased again with the resumption of production. Compared with air pollutants, thermal environmental problems are more complex. The effect of the lockdown policy was not reflected in the decrease in the area proportions of the high- and sub-high-temperature regions but rather in the spatial distribution of the high-temperature area, which was manifested as a fragmentation and dispersion of heat source patches. In addition to the severity of the lockdown, the impact of the lockdown policy was also closely related to the level of development and industrial structure of each city. Among the urban environments of the five agglomerations, the most affected were the Yangtze River Delta and Yangtze River Middle-Reach urban agglomerations, which had the largest decline in NO2 concentrations and the most notable fragmentation of heat source patches.

Single-cell RNA analysis on ACE2 expression provides insights into SARS-CoV-2 potential entry into the bloodstream and heart injury.

Coronavirus disease-2019 (COVID-19) is a global pandemic with high infectivity and pathogenicity, accounting for tens of thousands of deaths worldwide. Recent studies have found that the pathogen of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), shares the same cell receptor angiotensin converting enzyme II (ACE2) as SARS-CoV. The pathological investigation of COVID-19 deaths showed that the lungs had characteristics of pulmonary fibrosis. However, how SARS-CoV-2 spreads from the lungs to other organs has not yet been determined. Here, we performed an unbiased evaluation of cell-type-specific expression of ACE2 in healthy and fibrotic lungs, as well as in normal and failed adult human hearts, using published single-cell RNA-seq data. We found that ACE2 expression in fibrotic lungs mainly locates in arterial vascular cells, which might provide a route for bloodstream spreading of SARS-CoV-2. Failed human hearts have a higher percentage of ACE2-expressing cardiomyocytes, and SARS-CoV-2 might attack cardiomyocytes through the bloodstream in patients with heart failure. Moreover, ACE2 was highly expressed in cells infected by respiratory syncytial virus or Middle East respiratory syndrome coronavirus and in mice treated by lipopolysaccharide. Our findings indicate that patients with pulmonary fibrosis, heart failure, and virus infection have a higher risk and are more susceptible to SARS-CoV-2 infection. The SARS-CoV-2 might attack other organs by getting into the bloodstream. This study provides new insights into SARS-CoV-2 blood entry and heart injury and might propose a therapeutic strategy to prevent patients from developing severe complications.