Human Organotypic Airway and Lung Organoid Cells of Bronchiolar and Alveolar Differentiation Are Permissive to Infection by Influenza and SARS-CoV-2 Respiratory Virus.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has led to the initiation of unprecedented research efforts to understand the pathogenesis mediated by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). More knowledge is needed regarding the cell type-specific cytopathology and its impact on cellular tropism. Furthermore, the impact of novel SARS-CoV-2 mutations on cellular tropism, alternative routes of entry, the impact of co-infections, and virus replication kinetics along the respiratory tract remains to be explored in improved models. Most applied virology models are not well suited to address the remaining questions, as they do not recapitulate the histoarchitecture and cellular composition of human respiratory tissues. The overall aim of this work was to establish from single biopsy specimens, a human adult stem cell-derived organoid model representing the upper respiratory airways and lungs and explore the applicability of this model to study respiratory virus infection. First, we characterized the organoid model with respect to growth pattern and histoarchitecture, cellular composition, and functional characteristics. Next, in situ expression of viral entry receptors, including influenza virus-relevant sialic acids and SARS-CoV-2 entry receptor ACE2 and TMPRSS2, were confirmed in organoids of bronchiolar and alveolar differentiation. We further showed successful infection by pseudotype influenza A H7N1 and H5N1 virus, and the ability of the model to support viral replication of influenza A H7N1 virus. Finally, successful infection and replication of a clinical isolate of SARS-CoV-2 were confirmed in the organoids by TCID50 assay and immunostaining to detect intracellular SARS-CoV-2 specific nucleocapsid and dsRNA. The prominent syncytia formation in organoid tissues following SARS-CoV-2 infection mimics the findings from infected human tissues in situ. We conclude that the human organotypic model described here may be particularly useful for virology studies to evaluate regional differences in the host response to infection. The model contains the various cell types along the respiratory tract, expresses respiratory virus entry factors, and supports successful infection and replication of influenza virus and SARS-CoV-2. Thus, the model may serve as a relevant and reliable tool in virology and aid in pandemic preparedness, and efficient evaluation of antiviral strategies.

Assessment of emission reduction effect in Beijing, Tianjin and surrounding 26 cities from January to March in 2020 during the epidemic of COVID-19

In order to evaluate the effect of air pollutions emission reduction in Beijing, Tianjin, Hebei and its surrounding 26 cities（"2 + 26" cities） from January to March in 2020 during the epidemic of COVID-19, the air quality model of nested air quality prediction modeling system（NAQPMS） was applied to conduct a few scenarios. The characteristics of air quality from January to March 2020, and during the periods before and after the epidemic of COVID-19 were investigated. The influences of meteorology, emergency emission reduction measures and social economic activities on ambient air quality as well as the uncertainties were elucidated and discussed. The results showed that the number of days achieving good and moderate air quality standard in "2+26" cities accounted for 59.6%, on average of 10.9% increase relative to the same period last year. The mean concentration of PM10、PM2.5、SO2、NO2、O3-8 h-90 per and CO-95 per in "2 + 26" cities from January to March in 2020 were 108, 76, 14, 109, 36μg/m3, and 2.3 mg/m3, respectively. During the epidemic period from January 24 to March 31, the concentrations of PM10, NO2, PM2.5, and CO decreased significantly compared with the period prior to the epidemic from January 1 to 23. In contrast to January to March in 2019, the PM2.5 concentrations of the cities along the Yan mountain and Taihang mountain increased by 1%～8% in 2020. However, the model simulations revealed that the emergency emission reduction measures potentially avoided twice of the regional heavy air pollution events, resulting in the quarterly mean PM2.5 concentration in "2 + 26" cities reduced by 6 to 26μg/m3. Due to the influence of the Spring Festival holiday and epidemic, the traffic emissions were reduced substantially. In contrast, the emissions from the industry such as coking and thermal power did not show large variations, and the negative impact of loose coal combustion on ambient air quality may become even more severe.

Mycobacterium vaccae Nebulization in the Treatment of COVID-19: A Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Severe acute respiratory syndrome coronavirus 2 infection is associated with strong infectiousness and has no effective therapy. We aimed to explore the efficacy and safety of Mycobacterium vaccae nebulization in the treatment of Coronavirus Disease 2019 (COVID-19). Methods: In this randomized, double-blind, placebo-controlled clinical trial, we included 31 adult patients with moderate COVID-19 who were admitted to the Fourth People's Hospital of Nanning (Nanning, China) between January 22, 2020 and February 17, 2020. Patients were randomly divided into two groups: group A (standard care group) and group B (M. vaccae in combination with standard care group). The primary outcome was the time interval from admission to viral RNA negative conversion (oropharyngeal swabs were used in this study). Secondary outcomes included chest computed tomography (CT), mortality, length of hospital stay, complications during treatment, and so on. Patients were followed up to 4 weeks after discharge (reexamination of viral RNA, chest CT, etc.). Results: Nucleic acid test negative conversion time in group B was shorter than that in group A (2.9 days [2.7-8.7] vs. 6.8 days [3.3-13.8]; p = 0.045). No death and no conversion to severe or critical cases were observed in both groups. Two weeks after discharge, neither "relapse" nor "return to positive" cases were found. Four weeks after discharge, it was found that there was no case of " relapse " or "return to positive" in group B, and 1 patient in group A showed "return to positive", but there was no clinical manifestation and imaging progression. No adverse reactions related to M. vaccae were found during observation period. Conclusion:M. vaccae treatment might shorten the time interval from admission to viral RNA negative conversion, which might be beneficial to the prevention and treatment of COVID-19. Clinical Trial Registration: ChiCTR2000030016.