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Aojie Wang

Bio: Aojie Wang is an academic researcher from Fudan University. The author has contributed to research in topics: Interquartile range & Neutralizing antibody. The author has an hindex of 2, co-authored 3 publications receiving 705 citations.

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Posted ContentDOI
TL;DR: The correlation of NAb titers with age, lymphocyte counts, and blood CRP levels suggested that the interplay between virus and host immune response in coronavirus infections should be further explored for the development of effective vaccine against SARS-CoV-2 virus.
Abstract: Background The COVID-19 pandemic caused by SARS-CoV-2 coronavirus threatens global public health. Currently, neutralizing antibodies (NAbs) versus this virus are expected to correlate with recovery and protection of this disease. However, the characteristics of these antibodies have not been well studied in association with the clinical manifestations in patients. Methods Plasma collected from 175 COVID-19 recovered patients with mild symptoms were screened using a safe and sensitive pseudotyped-lentiviral-vector-based neutralization assay. Spike-binding antibody in plasma were determined by ELISA using RBD, S1, and S2 proteins of SARS-CoV-2. The levels and the time course of SARS-CoV-2-specific NAbs and the spike-binding antibodies were monitored at the same time. Findings SARS-CoV-2 NAbs were unable to cross-reactive with SARS-CoV virus. SARS-CoV-2-specific NAbs were detected in patients from day 10-15 after the onset of the disease and remained thereafter. The titers of NAb among these patients correlated with the spike-binding antibodies targeting S1, RBD, and S2 regions. The titers of NAbs were variable in different patients. Elderly and middle-age patients had significantly higher plasma NAb titers (P<0.0001) and spike-binding antibodies (P=0.0003) than young patients. Notably, among these patients, there were ten patients whose NAb titers were under the detectable level of our assay (ID50: < 40); while in contrast, two patients, showed very high titers of NAb, with ID50 :15989 and 21567 respectively. The NAb titers were positive correlated with plasma CRP levels but negative correlated with the lymphocyte counts of patients at the time of admission, indicating an association between humoral response and cellular immune response. Interpretation The variations of SARS-CoV-2 specific NAbs in recovered COVID-19 patients may raise the concern about the role of NAbs on disease progression. The correlation of NAb titers with age, lymphocyte counts, and blood CRP levels suggested that the interplay between virus and host immune response in coronavirus infections should be further explored for the development of effective vaccine against SARS-CoV-2 virus. Furthermore, titration of NAb is helpful prior to the use of convalescent plasma for prevention or treatment. Funding Ministry of Science and Technology of China, National Natural Science Foundation of China, Shanghai Municipal Health Commission, and Chinese Academy of Medical Sciences

639 citations

Journal ArticleDOI
TL;DR: NAbs were unable to cross-react with SARS-associated CoV and NAb titers correlated with the spike-binding antibodies targeting S1, and S2 regions, and reached peak levels from day 10 to 15 after disease onset.
Abstract: Importance The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health. The association between clinical characteristics of the virus and neutralizing antibodies (NAbs) against this virus have not been well studied. Objective To examine the association between clinical characteristics and levels of NAbs in patients who recovered from COVID-19. Design, Setting, and Participants In this cohort study, a total of 175 patients with mild symptoms of COVID-19 who were hospitalized from January 24 to February 26, 2020, were followed up until March 16, 2020, at Shanghai Public Health Clinical Center, Shanghai, China. Exposures SARS-CoV-2 infections were diagnosed and confirmed by reverse transcriptase–polymerase chain reaction testing of nasopharyngeal samples. Main Outcomes and Measures The primary outcome was SARS-CoV-2–specific NAb titers. Secondary outcomes included spike-binding antibodies, cross-reactivity against SARS-associated CoV, kinetics of NAb development, and clinical information, including age, sex, disease duration, length of stay, lymphocyte counts, and blood C-reactive protein level. Results Of the 175 patients with COVID-19, 93 were female (53%); the median age was 50 (interquartile range [IQR], 37-63) years. The median length of hospital stay was 16 (IQR, 13-21) days, and the median disease duration was 22 (IQR, 18-26) days. Variable levels of SARS-CoV-2–specific NAbs were observed at the time of discharge (50% inhibitory dose [ID50], 1076 [IQR, 448-2048]). There were 10 patients whose NAb titers were less than the detectable level of the assay (ID50, Conclusions and Relevance In this cohort study, among 175 patients who recovered from mild COVID-19 in Shanghai, China, NAb titers to SARS-CoV-2 appeared to vary substantially. Further research is needed to understand the clinical implications of differing NAb titers for protection against future infection.

199 citations


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01 Jan 2020
TL;DR: Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

4,408 citations

Journal ArticleDOI
TL;DR: A cohort of asymptomatic patients infected with SARS-CoV-2 had significantly lower levels of virus-specific IgG antibodies compared to a cohort of age- and sex-matched symptomatic infected patients.
Abstract: The clinical features and immune responses of asymptomatic individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been well described We studied 37 asymptomatic individuals in the Wanzhou District who were diagnosed with RT-PCR-confirmed SARS-CoV-2 infections but without any relevant clinical symptoms in the preceding 14 d and during hospitalization Asymptomatic individuals were admitted to the government-designated Wanzhou People's Hospital for centralized isolation in accordance with policy1 The median duration of viral shedding in the asymptomatic group was 19 d (interquartile range (IQR), 15-26 d) The asymptomatic group had a significantly longer duration of viral shedding than the symptomatic group (log-rank P = 0028) The virus-specific IgG levels in the asymptomatic group (median S/CO, 34; IQR, 16-107) were significantly lower (P = 0005) relative to the symptomatic group (median S/CO, 205; IQR, 58-382) in the acute phase Of asymptomatic individuals, 933% (28/30) and 811% (30/37) had reduction in IgG and neutralizing antibody levels, respectively, during the early convalescent phase, as compared to 968% (30/31) and 622% (23/37) of symptomatic patients Forty percent of asymptomatic individuals became seronegative and 129% of the symptomatic group became negative for IgG in the early convalescent phase In addition, asymptomatic individuals exhibited lower levels of 18 pro- and anti-inflammatory cytokines These data suggest that asymptomatic individuals had a weaker immune response to SARS-CoV-2 infection The reduction in IgG and neutralizing antibody levels in the early convalescent phase might have implications for immunity strategy and serological surveys

2,463 citations

Journal ArticleDOI
TL;DR: Key cell entry mechanisms of SARS-CoV-2 that potentially contribute to the immune evasion, cell infectivity, and wide spread of the virus are identified using biochemical and pseudovirus entry assays and the potency and evasiveness are highlighted.
Abstract: A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) is causing the global coronavirus disease 2019 (COVID-19) pandemic. Understanding how SARS-CoV-2 enters human cells is a high priority for deciphering its mystery and curbing its spread. A virus surface spike protein mediates SARS-CoV-2 entry into cells. To fulfill its function, SARS-CoV-2 spike binds to its receptor human ACE2 (hACE2) through its receptor-binding domain (RBD) and is proteolytically activated by human proteases. Here we investigated receptor binding and protease activation of SARS-CoV-2 spike using biochemical and pseudovirus entry assays. Our findings have identified key cell entry mechanisms of SARS-CoV-2. First, SARS-CoV-2 RBD has higher hACE2 binding affinity than SARS-CoV RBD, supporting efficient cell entry. Second, paradoxically, the hACE2 binding affinity of the entire SARS-CoV-2 spike is comparable to or lower than that of SARS-CoV spike, suggesting that SARS-CoV-2 RBD, albeit more potent, is less exposed than SARS-CoV RBD. Third, unlike SARS-CoV, cell entry of SARS-CoV-2 is preactivated by proprotein convertase furin, reducing its dependence on target cell proteases for entry. The high hACE2 binding affinity of the RBD, furin preactivation of the spike, and hidden RBD in the spike potentially allow SARS-CoV-2 to maintain efficient cell entry while evading immune surveillance. These features may contribute to the wide spread of the virus. Successful intervention strategies must target both the potency of SARS-CoV-2 and its evasiveness.

2,450 citations

Journal ArticleDOI
Nicolas Vabret1, Graham J. Britton1, Conor Gruber1, Samarth Hegde1, Joel Kim1, Maria Kuksin1, Rachel Levantovsky1, Louise Malle1, Alvaro Moreira1, Matthew D. Park1, Luisanna Pia1, Emma Risson1, Miriam Saffern1, Bérengère Salomé1, Myvizhi Esai Selvan1, Matthew P. Spindler1, Jessica Tan1, Verena van der Heide1, Jill Gregory1, Konstantina Alexandropoulos1, Nina Bhardwaj1, Brian D. Brown1, Benjamin Greenbaum1, Zeynep H. Gümüş1, Dirk Homann1, Amir Horowitz1, Alice O. Kamphorst1, Maria A. Curotto de Lafaille1, Saurabh Mehandru1, Miriam Merad1, Robert M. Samstein1, Manasi Agrawal, Mark Aleynick, Meriem Belabed, Matthew Brown1, Maria Casanova-Acebes, Jovani Catalan, Monica Centa, Andrew Charap, Andrew K Chan, Steven T. Chen, Jonathan Chung, Cansu Cimen Bozkus, Evan Cody, Francesca Cossarini, Erica Dalla, Nicolas F. Fernandez, John A. Grout, Dan Fu Ruan, Pauline Hamon, Etienne Humblin, Divya Jha, Julia Kodysh, Andrew Leader, Matthew Lin, Katherine E. Lindblad, Daniel Lozano-Ojalvo, Gabrielle Lubitz, Assaf Magen, Zafar Mahmood2, Gustavo Martinez-Delgado, Jaime Mateus-Tique, Elliot Meritt, Chang Moon1, Justine Noel, Timothy O'Donnell, Miyo Ota, Tamar Plitt, Venu Pothula, Jamie Redes, Ivan Reyes Torres, Mark P. Roberto, Alfonso R. Sanchez-Paulete, Joan Shang, Alessandra Soares Schanoski, Maria Suprun, Michelle Tran, Natalie Vaninov, C. Matthias Wilk, Julio A. Aguirre-Ghiso, Dusan Bogunovic1, Judy H. Cho, Jeremiah J. Faith, Emilie K. Grasset, Peter S. Heeger, Ephraim Kenigsberg, Florian Krammer1, Uri Laserson1 
16 Jun 2020-Immunity
TL;DR: The current state of knowledge of innate and adaptive immune responses elicited by SARS-CoV-2 infection and the immunological pathways that likely contribute to disease severity and death are summarized.

1,350 citations

Journal ArticleDOI
12 Nov 2020-Cell
TL;DR: A combined examination of all three branches of adaptive immunity at the level of SARS-CoV-2-specific CD4+ and CD8+ T cell and neutralizing antibody responses in acute and convalescent subjects suggested roles for both CD4 plus T cells in protective immunity in COVID-19.

1,298 citations