2021-02-11

Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.; Department of Pathology, Anhui Medical University, Hefei, China.; Zhejiang University, Hangzhou, China.; Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.; Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.; Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Objective: The prognosis of mild and severe patients has prominent differences during the prevalence of COVID-19, and it will be significant to identify patients' potential risk of progressing to severe cases according to their first clinical presentations. Therefore, we aim to review the clinical symptoms of the COVID-19 epidemic systematically. Methods:We searched PubMed, Embase, Web of Science, and CNKI (Chinese Database) for studies about the clinical features of COVID-19 in China from March 18 to April 18. Then we used REVMAN to conduct a meta-analysis. Results: After screening, 20 articles including 3,326 COVID-19 confirmed cases were selected from 142 articles we retrieved at the beginning of our research. We divided all the cases into a severe group (including severe and critically severe patients) and a mild group according to the "Diagnosis and Treatment Protocol for Novel Coronavirus Infection-Induced Pneumonia" version 4 (trial). Of all the initial symptoms (including

2020-03-15

College of Horticulture, Shenyang Agricultural University, Shenyang, Liaoning,; 110866, People’s Republic of China College of Horticulture, Shenyang Agricultural University, Shenyang, Liaoning,; 110866, People’s Republic of China College of Horticulture, Shenyang Agricultural University, Shenyang, Liaoning,; 110866, People’s Republic of China College of Horticulture, Shenyang Agricultural University, Shenyang, Liaoning,; 110866, People’s Republic of China College of Horticulture, Shenyang Agricultural University, Shenyang, Liaoning,; 110866, People’s Republic of China Institute of Pomology, Shandong Academy of Agricultural Sciences, Tai’an, 271000,; People’s Republic of China College of Horticulture, Shenyang Agricultural University, Shenyang, Liaoning,; 110866, People’s Republic of China

To examine the potential roles of melatonin in Cd uptake, accumulation and detoxification in Malus plants, we exposed two different apple rootstocks varying greatly in Cd uptake and accumulation to either 0 or 30 μM Cd together with 0 or 100 μM melatonin. Cd stress stimulated endogenous melatonin production to a greater extent in the Cd-tolerant M. baccata than in the Cd-susceptible M. micromalus ‘qingzhoulinqin’. Melatonin application attenuated Cd-induced reductions in growth, photosynthesis, and enzyme activity, as well as ROS and MDA accumulation. Melatonin treatment more effectively restored photosynthesis, photosynthetic pigments, and biomass in Cd-challenged M. micromalus ‘qingzhoulinqin’ than in Cd-stressed M. baccata. Exogenous melatonin lowered root Cd2+ uptake, reduced leaf Cd accumulation, decreased Cd translocation factors (Tfs), and increased root, stem, and leaf melatonin contents in both Cd-exposed rootstocks

2020-03-15

College of Horticulture, Shenyang Agricultural University, Shenyang, Liaoning,; 110866, People’s Republic of China College of Horticulture, Shenyang Agricultural University, Shenyang, Liaoning,; 110866, People’s Republic of China College of Horticulture, Shenyang Agricultural University, Shenyang, Liaoning,; 110866, People’s Republic of China College of Horticulture, Shenyang Agricultural University, Shenyang, Liaoning,; 110866, People’s Republic of China College of Horticulture, Shenyang Agricultural University, Shenyang, Liaoning,; 110866, People’s Republic of China Institute of Pomology, Shandong Academy of Agricultural Sciences, Tai’an, 271000,; People’s Republic of China College of Horticulture, Shenyang Agricultural University, Shenyang, Liaoning,; 110866, People’s Republic of China

To examine the potential roles of melatonin in Cd uptake, accumulation and detoxification in Malus plants, we exposed two different apple rootstocks varying greatly in Cd uptake and accumulation to either 0 or 30 μM Cd together with 0 or 100 μM melatonin. Cd stress stimulated endogenous melatonin production to a greater extent in the Cd-tolerant M. baccata than in the Cd-susceptible M. micromalus ‘qingzhoulinqin’. Melatonin application attenuated Cd-induced reductions in growth, photosynthesis, and enzyme activity, as well as ROS and MDA accumulation. Melatonin treatment more effectively restored photosynthesis, photosynthetic pigments, and biomass in Cd-challenged M. micromalus ‘qingzhoulinqin’ than in Cd-stressed M. baccata. Exogenous melatonin lowered root Cd2+ uptake, reduced leaf Cd accumulation, decreased Cd translocation factors (Tfs), and increased root, stem, and leaf melatonin contents in both Cd-exposed rootstocks

2021-11-17

Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.; Department of Epidemiology, University of North Carolina at Chapel Hillgrid.10698.36, Chapel Hill, North Carolina, USA.; Department of Epidemiology, University of North Carolina at Chapel Hillgrid.10698.36, Chapel Hill, North Carolina, USA.; Department of Epidemiology, University of North Carolina at Chapel Hillgrid.10698.36, Chapel Hill, North Carolina, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.; Department of Epidemiology, University of North Carolina at Chapel Hillgrid.10698.36, Chapel Hill, North Carolina, USA.; Department of Epidemiology, University of North Carolina at Chapel Hillgrid.10698.36, Chapel Hill, North Carolina, USA.; Department of Epidemiology, University of North Carolina at Chapel Hillgrid.10698.36, Chapel Hill, North Carolina, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.; Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA.; Massachusetts Consortium on Pathogen Readiness, Boston, Massachusetts, USA.

The global COVID-19 pandemic has sparked intense interest in the rapid development of vaccines as well as animal models to evaluate vaccine candidates and to define immune correlates of protection. We recently reported a mouse-adapted SARS-CoV-2 virus strain (MA10) with the potential to infect wild-type laboratory mice, driving high levels of viral replication in respiratory tract tissues as well as severe clinical and respiratory symptoms, aspects of COVID-19 disease in humans that are important to capture in model systems. We evaluated the immunogenicity and protective efficacy of novel rhesus adenovirus serotype 52 (RhAd52) vaccines against MA10 challenge in mice. Baseline seroprevalence is lower for rhesus adenovirus vectors than for human or chimpanzee adenovirus vectors, making these vectors attractive candidates for vaccine development. We observed that RhAd52 vaccines elicited robust binding and neutralizing antibody titers, which inversely correlated with viral replication

2021-07-04

Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Division of Infectious Diseases, Massachusetts General Hospital and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Program in Immunology, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA.; Massachusetts Consortium on Pathogen Readiness, Boston, Massachusetts, USA.

Emerging SARS-CoV-2 variants of concern that overcome natural and vaccine-induced immunity threaten to exacerbate the COVID-19 pandemic. Increasing evidence suggests that neutralizing antibody (NAb) responses are a primary mechanism of protection against infection. However, little is known about the extent and mechanisms by which natural immunity acquired during the early COVID-19 pandemic confers cross-neutralization of emerging variants. In this study, we investigated cross-neutralization of the B.1.1.7 and B.1.351 SARS-CoV-2 variants in a well-characterized cohort of early pandemic convalescent subjects. We observed modestly decreased cross-neutralization of B.1.1.7 but a substantial 4.8-fold reduction in cross-neutralization of B.1.351. Correlates of cross-neutralization included receptor binding domain (RBD) and N-terminal domain (NTD) binding antibodies, homologous NAb titers, and membrane-directed T cell responses. These data shed light on the cross-neutralization of emerging

2021-04-13

Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School Medicine, New Haven, Connecticut, United States of America.; Department of Computer Science, Yale University, New Haven, Connecticut, United States of America.; Department of Laboratory Medicine, Yale University, New Haven, Connecticut, United States of America.; Department of Immunobiology, Yale University, New Haven, Connecticut, United States of America.; Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School Medicine, New Haven, Connecticut, United States of America.; Department of Computer Science, Yale University, New Haven, Connecticut, United States of America.; Universite Claude Bernard Lyon 1, Faculte de Medecine Lyon Est, Lyon, France.; Department de Bioinformatique, Univ Evry, Universite Paris-Saclay, Paris, France.; Department of Molecular Biophysics & Biochemistry, Yale School of Medicine, New Haven, Connecticut, United States of America.; Department of Molecular, Cellular, and Developmental Biology, Yale School of Medicine, New Haven, Connecticut, United States of America.; Department of Comparative Medicine, Yale School of Medicine, New Haven, Connecticut, United States of America.; Department of Neuroscience, Yale School of Medicine, New Haven, Connecticut, United States of America.; Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut, United of States of America.; Department of Comparative Medicine, Yale School of Medicine, New Haven, Connecticut, United States of America.; Department of Neuroscience, Yale School of Medicine, New Haven, Connecticut, United States of America.; Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut, United of States of America.; Department of Biomedical Engineering, Yale University, New Haven, Connecticut, United States of America.; Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut, United States of America.; Department of Genetics, Yale School of Medicine, New Haven, Connecticut, United States of America.; Department of Laboratory Medicine, Yale University, New Haven, Connecticut, United States of America.; Department of Immunobiology, Yale University, New Haven, Connecticut, United States of America.; Department of Laboratory Medicine, Yale University, New Haven, Connecticut, United States of America.; Department of Immunobiology, Yale University, New Haven, Connecticut, United States of America.; Department of Laboratory Medicine, Yale University, New Haven, Connecticut, United States of America.; Department of Immunobiology, Yale University, New Haven, Connecticut, United States of America.; Department of Laboratory Medicine, Yale University, New Haven, Connecticut, United States of America.; Department of Immunobiology, Yale University, New Haven, Connecticut, United States of America.; Yale Center for Genome Analysis, Yale School of Medicine, New Haven, Connecticut, United States of America.; Department of Biomedical Engineering, Yale University, New Haven, Connecticut, United States of America.; Department of Anesthesiology, Yale University, New Haven, Connecticut, United States of America.; Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, United States of America.; Department of Laboratory Medicine, Yale University, New Haven, Connecticut, United States of America.; Department of Immunobiology, Yale University, New Haven, Connecticut, United States of America.; Department of Laboratory Medicine, Yale University, New Haven, Connecticut, United States of America.; Department of Immunobiology, Yale University, New Haven, Connecticut, United States of America.; Department of Genetics, Yale School of Medicine, New Haven, Connecticut, United States of America.; The Jackson Laboratory, Farmington, Connecticut, United States of America.; Department of Immunobiology, Yale University, New Haven, Connecticut, United States of America.; Howard Hughes Medical Institute, Chevy Chase, Maryland, United States of America.; Department of Comparative Medicine, Yale School of Medicine, New Haven, Connecticut, United States of America.; Department of Neuroscience, Yale School of Medicine, New Haven, Connecticut, United States of America.; Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut, United of States of America.; Department of Laboratory Medicine, Yale University, New Haven, Connecticut, United States of America.; Department of Immunobiology, Yale University, New Haven, Connecticut, United States of America.; Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut, United States of America.; Department of Genetics, Yale School of Medicine, New Haven, Connecticut, United States of America.; Howard Hughes Medical Institute, Chevy Chase, Maryland, United States of America.; Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School Medicine, New Haven, Connecticut, United States of America.; Department of Computer Science, Yale University, New Haven, Connecticut, United States of America.; Department of Laboratory Medicine, Yale University, New Haven, Connecticut, United States of America.; Department of Immunobiology, Yale University, New Haven, Connecticut, United States of America.

There are currently limited Food and Drug Administration (FDA)-approved drugs and vaccines for the treatment or prevention of Coronavirus Disease 2019 (COVID-19). Enhanced understanding of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and pathogenesis is critical for the development of therapeutics. To provide insight into viral replication, cell tropism, and host-viral interactions of SARS-CoV-2, we performed single-cell (sc) RNA sequencing (RNA-seq) of experimentally infected human bronchial epithelial cells (HBECs) in air-liquid interface (ALI) cultures over a time course. This revealed novel polyadenylated viral transcripts and highlighted ciliated cells as a major target at the onset of infection, which we confirmed by electron and immunofluorescence microscopy. Over the course of infection, the cell tropism of SARS-CoV-2 expands to other epithelial cell types including basal and club cells. Infection induces cell-intrinsic expression of type I and type