ABSTRACT
The oral cavity is thought to be one of the portals for SARS-CoV-2 entry. Because there is limited evidence of active oral infection by SARS-CoV-2 viruses, we assessed the capacity of SARS-CoV-2 to infect and replicate in oral epithelial cells. Oral gingival epithelial cells (hTERT TIGKs), salivary gland epithelial cells (A-253), and oral buccal epithelial cells (TR146), which occupy different regions of the oral cavity, were challenged with replication competent SARS-CoV-2 viruses and with pseudo-typed viruses expressing SARS-CoV-2 spike proteins. All oral epithelial cells expressing undetectable or low levels of human angiotensin-converting enzyme 2 (hACE2) but high levels of the alternative receptor CD147 were susceptible to SARS-CoV-2 infection. Viral dynamics in hTERT TIGKs were different from those in A-253 and TR146 cells. For example, levels of viral transcripts were sustained in hTERT TIGKs but were significantly decreased in A-253 and TR146 cells at day 3 after infection. Analysis of oral epithelial cells infected by replication competent SARS-CoV-2 viruses expressing GFP showed that the signals of GFP and SARS-CoV-2 mRNAs were not evenly distributed. Taken together, our results demonstrated oral epithelial cells were susceptible to SARS-CoV-2 viruses despite of low or undetectable levels of hACE2, suggesting that alternative receptors contribute to SARS-CoV-2 infection and may be considered for development of future vaccines and therapeutics.
Subject(s)
Severe Acute Respiratory Syndrome , COVID-19ABSTRACT
Building a strong public health system has become an urgent task in the new era. Based on more than eight years of systematic research, we believe that five aspects need to be prioritized for a strong system. First, we should change the perspective on public health, using the word "gonggong jiankang" to replace "gonggong weisheng" and the word "gonggong jiankang tixi" to replace "gonggong weisheng tixi", to lead the public health system development. Second, we should develop a suitable public health system and continuously improve the health capacity for governance. Third, we should make it clear that the goal of building a strong system is not far-fetched, and we need to consolidate the existing institutional advantages of China's public health system: when encountering major problems, we can maintain a unified goal and mobilize the whole society to cooperate effectively to accomplish the goal. However, we need to make up for shortcomings one by one, especially to solve the key problem of lacking a strong coordination mechanism in daily work. Fourth, we should pursue excellence and consolidate the "suitable" mechanism proven in the process of coping with the COVID-19, so that efficient mechanisms to deal with major issues can be used in routine work, and efforts should be made to consolidate the advantages of prevention and control of infectious diseases and emergency response, so as to achieve the balanced development of regions categories and units. Finally, it is necessary to strengthen the coordination of government and research institutions, in the aspects of technological innovation, talent team building and accurate consulting services, and work together to pursue a suitable and strong system to realize the modernization of the health system and capacity for governance.
ABSTRACT
To (re)define tissue architecture of the lung and airways at the cellular and molecular level, we profiled five proximal-to-distal locations of healthy human lungs in depth using multi-omic single cell/nuclei and Visium Spatial Transcriptomics. Using computational data integration and analysis, we extend beyond the suspension cell paradigm of lung atlases to date, to define and discover macro and micro-anatomical tissue compartments. We describe novel cell types and states in vascular, stromal and nerve bundle microenvironments. From our spatial transcriptomics, we discover and validate a novel survival niche for IgA plasma cells in the airway submucosal glands (SMG). In this niche we define a supporting role for SMG epithelial cells in mucosal immunity through recruitment and maintenance of IgA plasma, B and CD4 T cells locally at the airway SMG. We identify an immune-supporting role for SMG duct and serous cells with distinct signalling circuits to recruit B cells and IgA plasma cells, promoting longevity and antibody secretion through expression of CCL28, APRIL and IL6. We find high expression of MHC-II in SMG duct and serous cells, which are localised closely with memory CD4 T cells, suggesting local modulation of antigen specific immune responses locally at the glands. This new tissue microenvironment, which we term the “gland-associated immune niche” (GAIN) has major implications for respiratory immunity and infection response. Our single cell and spatial data is available for download and query at lungcellatlas.org.
ABSTRACT
SARS-CoV-2 is detectable in saliva from asymptomatic individuals, suggesting the potential necessity for the use of mouth rinses to suppress viral load to reduce virus spread. Published studies on anti-SARS-CoV-2 activities of antiseptics determined by virus-induced cytotoxic effects cannot exclude antiseptic-associated cytotoxicity. Here, we determined the effect of commercially available mouth rinses and antiseptic povidone-iodine on the infectivity of pseudotyped SARS-CoV-2 virus. We first determined the effect of mouth rinses on cell viability to ensure that antiviral activity was not a consequence of mouth rinse-induced cytotoxicity. Colgate Peroxyl (hydrogen peroxide) exhibited the most cytotoxicity, followed by povidone-iodine-10% solution, chlorhexidine gluconate-0.12% (CHG), and Listerine (essential oils and alcohol). Analysis of the anti-viral activity of mouth rinses at non-cytotoxic concentrations showed that 1.5% (v/v) diluted CHG was a potent inhibitor when present in cells during infection, but the potency was reduced when CHG was removed after viral attachment, suggesting that the prolonged effect of mouth rinses on cells impacts the anti-viral activity. To minimalize mouth rinse-associated cytotoxicity, we pelleted treated-viruses to remove most of the mouth rinse prior to infection of cells. Colgate Peroxyl or povidone-iodine at 5% (v/v) completely blocked the viral infectivity. Listerine or CHG at 5% (v/v) had a moderate suppressive effect on the virus, and 50% (v/v) Listerine or CHG blocked the viral infectivity completely. Prolonged incubation of virus with mouth rinses was not required to block viral infectivity. Our results indicate that mouth rinses can significantly reduce virus infectivity, suggesting their potential use to reduce SARS-CoV-2 spread.