ABSTRACT
The Coronavirus disease 19 (COVID-19) pandemic has accumulated over 550 million confirmed cases and more than 6.34 million deaths worldwide. Although vaccinations has largely protected the population through the last two years, the effect of vaccination has been increasingly challenged by the emerging SARS-CoV-2 variants. Although several therapeutics including both monoclonal antibodies and small molecule drugs have been used clinically, high cost, viral escape mutations, and potential side effects have reduced their efficacy. There is an urgent need to develop a low cost treatment with wide-spectrum effect against the novel variants of SARS-CoV-2. Here we report a product of equine polyclonal antibodies that showed potential broad spectrum neutralization effect against the major variants of SARS-CoV-2. The equine polyclonal antibodies were generated by horse immunization with the receptor binding domain (RBD) of SARS-CoV-2 spike protein and purified from equine serum. A high binding affinity between the generated equine antibodies and the RBD was observed. Although designed against the RBD of the early wild type strain sequenced in 2020, the equine antibodies also showed a highly efficient neutralization capacity against the major variants of SARS-CoV-2, including the recent BA.2 Omicron variant (IC50 =1.867g/ml) in viral neutralization assay in Vero E6 cells using live virus cultured. The broad-spectrum neutralization capacity of the equine antibodies was further confirmed using pseudovirus neutralization assay covering the major SARS-CoV-2 variants including wild type, alpha, beta, delta, and omicron, showing effective neutralization against all the tested strains. Ex vivo reconstructed human respiratory organoids representing nasal, bronchial, and lung epitheliums were employed to test the treatment efficacy of the equine antibodies. Antibody treatment protected the human nasal, bronchial, and lung epithelial organoids against infection of the novel SARS-CoV-2 variants challenging public health, the Delta and Omicron BA.2 isolates, by reducing >95% of the viral load. The equine antibodies were further tested for potential side effects in a mouse model by inhalation and no significant pathological feature was observed. Equine antibodies, as a mature medical product, have been widely applied in the treatment of infectious diseases for more than a century, which limits the potential side effects and are capable of large scale production at a low cost. A cost-effective, wide-spectrum equine antibody therapy effective against the major SARS-CoV-2 variants can contribute as an affordable therapy to cover a large portion of the world population, and thus potentially reduce the transmission and mutation of SARS-CoV-2.
Subject(s)
Communicable Diseases , COVID-19ABSTRACT
Coal is an important basic energy source, widely distributed throughout the world, but resource abundance is uneven. Despite the need to develop and form new energy sources, coal energy maintains its dominant position. However, due to the uneven distribution and non-renewable nature of coal resources, the relationship between the supply and demand of coal resources is tight. The rational exploitation of coal and reducing resource mining wastes are particularly important at the present stage. The original mining method of the Zhangjiamao coal mine resulted in a large waste of coal resources. After replacing the “110 construction method”, the original advanced end-support was canceled, which saved a lot of process time and engineering costs and greatly improved the mine production efficiency. With an average mining depth of +300 m, the working face is in a safe and stable state, and the 110-mining process has little impact on surface subsidence. Its successful application provides a reference experience for other mines to promote resource-saving and efficient mining.
ABSTRACT
Background: An increasing number of children with severe coronavirus disease 2019 (COVID-19) is being reported, yet the spectrum of disease severity and expression patterns of angiotensin- converting enzyme 2 (ACE2) in children at different developmental stages are largely unknow. Methods: We analysed clinical features in a cohort of 173 children with COVID-19 (0-15 yrs.-old) between January 22, 2020 and March 25, 2020. We systematically examined the expression and distribution of ACE2 in different developmental stages of children by using a combination of children’s lung biopsies, pluripotent stem cell-derived lung cells, RNA-sequencing profiles, and ex vivo SARS-CoV-2 pseudoviral infections. Findings: It revealed that infants (<1yrs.-old), with a weaker potency of immune response, are more vulnerable to develop pneumonia whereas older children (>1 yrs.-old) are more resistant to lung injury. The expression levels of ACE2 however do not vary by age in children’s lung. ACE2 is notably expressed not only in Alveolar Type II (AT II) cells, but also in SOX9 positive lung progenitor cells detected in both pluripotent stem cell derivatives and infants’ lungs. The ACE2+ SOX9+ cells are readily infected by SARS-CoV-2 pseudovirus and the numbers of the double positive cells are significantly decreased in older children. Interpretation: Infants (<1 yrs.-old) with COVID-19 infection are more vulnerable to lung injuries. ACE2 expression in multiple types of lung cells including SOX9 positive progenitor cells, in cooperation with an unestablished immune system, could be risk factors contributing to vulnerability of infants with COVID-19. There is a need to continue monitoring lung development in young children who have recovered from COVID-19 infection. Funding: National Natural Science Grant of China (No 31571407; 31970910); Hong Kong Health and Medical Research Fund (HMRF) (No:06172956), and Stem Cell and Regenerative Medicine Fund (Guangzhou Women and Children's Medical Centre, Grant No:5001-4001010)Declaration of Interests: The authors declare no competing interest.Ethics Approval Statement: This study was approved by the respective Institutional Review Board. Written informed consent was obtained from patients and/or guardians before data collected.