is deputy chief of the Department of Control and Prevention for Infectious Disease at the Guangzhou Center for Disease Control and Prevention. His research interests are the surveillance, control, and prevention of respiratory infectious diseases, including influenza, avian influenza, and scarlet fever. References 1. Han Y, Zhang Z, Zhu J, Yu P. A familial cluster of infection associated with the 2019 novel coronavirus indicating possible person-to-person transmission during the incubation period.
The discovery of novel drug candidates with anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) potential is critical for the control of the global COVID-19 pandemic. Artemisinin, an old antimalarial drug derived from Chinese herbs, has saved millions of lives. Artemisinins are a cluster of artemisinin-related drugs developed for the treatment of malaria and have been reported to have multiple pharmacological activities, including anticancer, antiviral, and immune modulation. Considering the reported broad-spectrum antiviral potential of artemisinins, researchers are interested in whether they could be used to combat COVID-19. We systematically evaluated the anti-SARS-CoV-2 activities of nine artemisinin-related compounds in vitro and carried out a time-of-drug-addition assay to explore their antiviral mode of action. Finally, a pharmacokinetic prediction model was established to predict the therapeutic potential of selected compounds against COVID-19. Arteannuin B showed the highest anti-SARS-CoV-2 potential with an EC 50 of 10.28 ± 1.12 μM. Artesunate and dihydroartemisinin showed similar EC 50 values of 12.98 ± 5.30 μM and 13.31 ± 1.24 μM, respectively, which could be clinically achieved in plasma after intravenous administration. Interestingly, although an EC 50 of 23.17 ± 3.22 μM was not prominent among the tested compounds, lumefantrine showed therapeutic promise due to high plasma and lung drug concentrations after multiple dosing. Further mode of action analysis revealed that arteannuin B and lumefantrine acted at the post-entry step of SARS-CoV-2 infection. This research highlights the anti-SARS-CoV-2 potential of artemisinins and provides leading candidates for anti-SARS-CoV-2 drug research and development.
The coronavirus disease-19 (COVID-19) caused by SARS-CoV-2 infection can lead to a series of clinical settings from non-symptomatic viral carriers/spreaders to severe illness characterized by acute respiratory distress syndrome (ARDS)1,2. A sizable part of patients with COVID-19 have mild clinical symptoms at the early stage of infection, but the disease progression may become quite rapid in the later stage with ARDS as the common manifestation and followed by critical multiple organ failure, causing a high mortality rate of 7-10% in the elderly population with underlying chronic disease1-3. The pathological investigation in the lungs and other organs of fatal cases is fundamental for the mechanistic understanding of severe COVID-19 and the development of specific therapy in these cases. Gross anatomy and molecular markers allowed us to identify, in two fatal patients subject to necropsy, the main pathological features such as exudation and hemorrhage, epithelium injuries, infiltration of macrophages and fibrosis in the lungs. The mucous plug with fibrinous exudate in the alveoli and the activation of alveolar macrophages were characteristic abnormalities. These findings shed new insights into the pathogenesis of COVID-19 and justify the use of interleukin 6 (IL6) receptor antagonists and convalescent plasma with neutralizing antibodies against SARS-CoV-2 for severe patients.Authors Chaofu Wang, Jing Xie, Lei Zhao, Xiaochun Fei, Heng Zhang, and Yun Tan contributed equally to this work. Authors Chaofu Wang, Jun Cai, Rong Chen, Zhengli Shi, and Xiuwu Bian jointly supervised this work.
BACKGROUND The lack of effective treatments against the 2019 coronavirus disease (COVID‐19) has led to the exploratory use of convalescent plasma for treating COVID‐19. Case reports and case series have shown encouraging results. This study investigated SARS‐CoV‐2 antibodies and epidemiological characteristics in convalescent plasma donors, to identify criteria for donor selection. METHODS Recovered COVID‐19 patients, aged 18‐55 years, who had experienced no symptoms for more than 2 weeks, were recruited. Donor characteristics such as disease presentations were collected and SARS‐CoV‐2 N‐specific IgM, IgG, and S‐RBD‐specific IgG levels were measured by enzyme‐linked immunosorbent assay (ELISA). RESULTS Whereas levels of N‐specific IgM antibody declined after recovery, S‐RBD‐specific and N‐specific IgG antibodies increased after 4 weeks from the onset of symptoms, with no significant correlation to age, sex, or ABO blood type. Donors with the disease presentation of fever exceeding 38.5°C or lasting longer than 3 days exhibited higher levels of S‐RBD‐specific IgG antibodies at the time of donation. Of the 49 convalescent plasma donors, 90% had an S‐RBD‐specific IgG titer of ≥1:160 and 78% had a titer of ≥1:640 at the time of plasma donation. Of the 30 convalescent plasma donors, who had donated plasma later than 28 days after the onset of symptoms and had a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5°C, 100% had an S‐RBD‐specific IgG titer of ≥1:160 and 93% had a titer of ≥1:640. CONCLUSION This study indicates that the S‐RBD‐specific IgG antibody reaches higher levels after 4 weeks from the onset of COVID‐19 symptoms. We recommend the following selection criteria for optimal donation of COVID‐19 convalescent plasma: 28 days after the onset of symptoms and with a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5°C. Selection based on these criteria can ensure a high likelihood of achieving sufficiently high S‐RBD‐specific IgG titers.
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