Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 46
Filter
1.
Commun Biol ; 5(1): 262, 2022 03 24.
Article in English | MEDLINE | ID: covidwho-1799550

ABSTRACT

Understanding the underlying molecular mechanisms behind ADE of SARS-CoV-2 is critical for development of safe and effective therapies. Here, we report that two neutralizing mAbs, MW01 and MW05, could enhance the infection of SARS-CoV-2 pseudovirus on FcγRIIB-expressing B cells. X-ray crystal structure determination and S trimer-binding modeling showed that MW01 and MW05 could bind to RBDs in S trimer with both "up" and "down" states. While, the neutralizing mAb MW07, which has no ADE activity only binds to RBD in S trimer with "up" state. Monovalent MW01 and MW05 completely diminished the ADE activity compared with their bivalent counterparts. Moreover, both macropinocytosis and endocytosis are confirmed involving in ADE of SARS-CoV-2 pseudoviral infection. Blocking endosome transportation and lysosome acidification could inhibit the ADE activity mediated by MW05. Together, our results identified a novel ADE mechanism of SARS-CoV-2 pseudovirus in vitro, FcγRIIB-mediated uptake of SARS-CoV-2/mAb complex with bivalent interaction.


Subject(s)
Antibody-Dependent Enhancement , COVID-19 , Antibodies, Viral , Humans , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
2.
Parasit Vectors ; 15(1): 78, 2022 Mar 05.
Article in English | MEDLINE | ID: covidwho-1789129

ABSTRACT

BACKGROUND: This study explored the effect of a continuous mitigation and containment strategy for coronavirus disease 2019 (COVID-19) on five vector-borne diseases (VBDs) in China from 2020 to 2021. METHODS: Data on VBDs from 2015 to 2021 were obtained from the National Health Commission of the People's Republic of China, and the actual trend in disease activity in 2020-2021 was compared with that in 2015-2019 using a two-ratio Z-test and two proportional tests. Similarly, the estimated trend in disease activity was compared with the actual trend in disease activity in 2020. RESULTS: There were 13,456 and 3684 average yearly cases of VBDs in 2015-2019 and 2020, respectively. This represents a decrease in the average yearly incidence of total VBDs of 72.95% in 2020, from 0.9753 per 100,000 population in 2015-2019 to 0.2638 per 100,000 population in 2020 (t = 75.17, P < 0.001). The observed morbidity rates of the overall VBDs were significantly lower than the predicted rates (47.04% reduction; t = 31.72, P < 0.001). The greatest decline was found in dengue, with a 77.13% reduction (observed rate vs predicted rate: 0.0574 vs. 0.2510 per 100,000; t = 41.42, P < 0.001). Similarly, the average yearly mortality rate of total VBDs decreased by 77.60%, from 0.0064 per 100,000 population in 2015-2019 to 0.0014 per 100,000 population in 2020 (t = 6.58, P < 0.001). A decreasing trend was also seen in the monthly incidence of total VBDs in 2021 compared to 2020 by 43.14% (t = 5.48, P < 0.001). CONCLUSIONS: The results of this study verify that the mobility and mortality rates of VBDs significantly decreased from 2015-2019 to 2020-2021, and that they are possibly associated to the continuous COVID-19 mitigation and contamination strategy implemented in China in 2020-2021.


Subject(s)
COVID-19 , Epidemics , Vector Borne Diseases , COVID-19/epidemiology , COVID-19/prevention & control , China/epidemiology , Humans , SARS-CoV-2 , Vector Borne Diseases/epidemiology , Vector Borne Diseases/prevention & control
3.
J Med Virol ; 94(5): 2201-2211, 2022 May.
Article in English | MEDLINE | ID: covidwho-1777589

ABSTRACT

The public health interventions to mitigate coronavirus disease 2019 (COVID-19) could also potentially reduce the global activity of influenza. However, this strategy's impact on other common infectious diseases is unknown. We collected data of 10 respiratory infectious (RI) diseases, influenza-like illnesses (ILIs), and seven gastrointestinal infectious (GI) diseases during 2015-2020 in China and applied two proportional tests to check the differences in the yearly incidence and mortality, and case-fatality rates (CFRs) over the years 2015-2020. The results showed that the overall RI activity decreased by 7.47%, from 181.64 in 2015-2019 to 168.08 per 100 000 in 2020 (p < 0.001); however, the incidence of influenza was seen to have a 16.08% escalation (p < 0.001). In contrast, the average weekly ILI percentage and positive influenza virus rate decreased by 6.25% and 61.94%, respectively, in 2020 compared to the previous 5 years (all p < 0.001). The overall incidence of GI decreased by 45.28%, from 253.73 in 2015-2019 to 138.84 in 2020 per 100 000 (p < 0.001), and with the greatest decline seen in hand, foot, and mouth disease (HFMD) (64.66%; p < 0.001). The mortality and CFRs from RI increased by 128.49% and 146.95%, respectively, in 2020, compared to 2015-2019 (p < 0.001). However, the mortality rates and CFRs of seven GI decreased by 70.56% and 46.12%, respectively (p < 0.001). In conclusion, China's COVID-19 elimination/containment strategy is very effective in reducing the incidence rates of RI and GI, and ILI activity, as well as the mortality and CFRs of GI diseases.


Subject(s)
COVID-19 , Communicable Diseases , Influenza, Human , COVID-19/epidemiology , COVID-19/prevention & control , China/epidemiology , Communicable Diseases/epidemiology , Humans , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Public Health , SARS-CoV-2
4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325501

ABSTRACT

Background: Many COVID-19 patients have been discharged, but lung injury, including pulmonary fibrosis, might lead to long-term impairment. This study aimed to evaluate predictors and monitors of pulmonary fibrosis in patients with COVID-19. Methods Thirty-five convalescent patients with severe COVID-19, after appropriate medical treatments, were recruited. According to evidence of fibrosis on initial computed tomography (CT), the patients were divided into mild-to-moderate and severe groups. Levels of transforming growth factor beta (TGF-β), chemokine ligand 18 (CCL18), type III procollagen peptide (PⅢP), hyaluronic acid (HA), laminin (LN), and type IV collagen (CⅣ) were determined. Laboratory tests, clinical data, and CT features at different stages were collected and analyzed, and the prognostic performance of these parameters was evaluated. Results Severe fibrosis was found in 76.29% (26/35) of patients. However, most baseline laboratory characteristics were normal. Fibrosis indicators (TGF-β: 66.67 ± 158.57 vs 55.84 ± 126.43 pg/mL, P = 0.006;CCL18: 364.27 ± 167.70 vs 84.47 ± 60.67 ng/mL, P = 0.000;PⅢP: 54.12 ± 55.34 vs 17.15 ± 2.48 ng/mL, P = 0.000;HA: 122.47 ± 78.84 vs 59.74 ± 18.01 ng/mL, p = 0.000;LN: 55.43 ± 46.44 vs 24.25 ± 7.79 ng/mL, P = 0.000;CⅣ: 24.77 ± 14.97 vs 15.32 ± 1.15 ng/mL, P = 0.001) were elevated in patients compared with controls. Over 90 days’ follow-up, HRCT scores gradually decreased from 22.48 ± 16.13 to 10.33 ± 11.11 (P < 0.001), and mMRC scores decreased from 3.27 ± 0.32 to 1.48 ± 0.33, and all fibrosis indicators, except for PⅢP, gradually declined with the improvement of pulmonary fibrosis. Moreover, TGF-β and CCL18 levels were lower in the mild-to-moderate than severe fibrosis group (88.16 ± 97.45 vs 205.93 ± 170.57 pg/mL, P = 0.024;241.84 ± 125.37 vs 366.64 ± 161.06 ng/mL, P = 0.038), and patients with elevated baseline levels of serum TGF-β and CCL18 had longer rehabilitation times. Conclusions TGF-β and CCL18 may be promising biomarkers for predicting and monitoring the development of pulmonary fibrosis in patients with COVID-19.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325217

ABSTRACT

Objectives: The pandemic of the coronavirus disease 2019 (COVID-19) continuously poses a serious threat to public health, highlighting an urgent need for simple and efficient early detection and prediction. Methods: : We comprehensively investigated and reanalyzed the published indexes and models for predicting severe illness among COVID‑19 patients in our dataset, and validated them on an independent dataset. Results: : 696 COVID-19 cases in the discovery stage and 337 patients in the validation stage were involved. The AuROC of neutrophil to lymphocyte ratio (NLR) (0.782) was significantly higher than that of the other 11 independent risk indexes in severe outcome prediction. The combination of NLR and oxygen saturation (SaO 2 ) (NLR+SaO 2 ) showed the biggest AuROC calculations with a value of 0.901;with a cut-off value of 0.532, it exhibited 84.2% sensitivity, 88.4% specificity and 86.8% correct classification ratio. Moreover, we first identified that principal component analysis (PCA) is an effective tool to predict the severity of COVID-19. We obtained 86.5% prediction accuracy with 86% sensitivity when PCA was applied to predict severe illness. In addition, to evaluate the performance of NLR+SaO 2 and PCA, we compared them with currently published predictive models in the same dataset. Conclusions: : It showed that NLR+SaO 2 is an appropriate and promising method for predicting severe illness, followed by PCA. We then validated the results on an independent dataset and revealed that they remained robust accuracy in outcome prediction. This study is significant for early treatment, intervention, triage and saving limited resources.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324309

ABSTRACT

Background: The coronavirus disease 2019 (COVID-19) is a newly recognized illness that has spread rapidly all over the world. Severe hypoxemic respiratory failure from COVID-19 will bring high risk of venous thromboembolism (VTE). Our study aims to identify in-hospital VTE risk and bleeding risk in COVID-19 patients. Methods We retrospectively studied 138 consecutively enrolled patients with COVID-19 and identified in-hospital VTE and bleeding risk by Padua Prediction Score and Improve bleed risk assessment model. The clinical data and features were analyzed in VTE patients. Results Our findings identified that 23 (16.67%) patients with COVID-19 were at high risk for VTE according to Padua prediction score, and 9(6.52%) patients were at high risk of bleeding for VTE prophylaxis according to Improve prediction score. Fifteen critically ill patients faced double high risk from thrombosis (Padua score more than 4 points in all 15[100%] patients) and hemorrhage (Improve score more than 7 points in 9[60.0%] patients). Thrombotic events were identified in four patients (2.9%) of all COVID-19 patients. All of them were diagnosed as deep vein thrombosis by ultrasound after 3 to 18 days after admission. Three (75.0%) were critically ill patients, which means the incidence of VTE among critically ill patients was 20%. One major hemorrhage was happened in critically ill patients during VTE treatment. Conclusion Critically ill patients with COVID-19 suffered both high risk of thrombosis and bleeding risks. More effective VTE prevention strategies based on an individual assessment of bleeding risks were necessary for critically ill patients with COVID-19.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323643

ABSTRACT

The elevated level of D-dimer and its relationship with poor outcomes in COVID-19 pneumonia patients have been demonstrated. In addition to a hypercoagulable state, D-dimer is also a biomarker of inflammation. We investigated the relationship between D-dimer level and chest computed tomography (CT) severity score, which could reflect the severity of inflammation in COVID-19 pneumonia patients. We retrospectively enrolled 86 consecutive COVID-19 pneumonia patients. CT severity scores were computed to quantify the overall lung involvement. The D-dimer level among CT score tertiles and the association of the D-dimer level with CT score were analyzed. Our results showed that the median D-dimer level was 0.70 mg/L (IQR: 0.35-1.76). 49 patients (57.0%) had D-dimer level above the normal range (≤ 0.55mg/L). The D-dimer levels were significantly different across CT score tertiles (0.37 mg/l [IQR, 0.31-0.87], 0.66 mg/l [IQR, 0.39-1.43], 1.83 mg/l [IQR, 0.85-4.41], P<0.001). The natural logarithm of the D-dimer level was significantly associated with the CT score (r s =0.586, P <0.001). In conclusion, the D-dimer level may predict the severity of inflammation of COVID-19 pneumonia prior to coagulopathy/thrombosis. This could be an additional explanation for the mechanism of elevated D-dimer level predicting higher mortality.

8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323639

ABSTRACT

To investigate the changes of the respiratory infectious diseases (RID) and air quality during the COVID-19 outbreak over Yangtze River Delta Region, China. We investigate the impact of COVID-19 control measures on changes of RID and air quality by constructing two proportional test and fitting ARIMA and piecewise regression models. A total of 81,345 and 1,048,511 cases of RID were identified in Shanghai and Zhejiang Province, respectively. The incidence of seven RID and influenza decreased by 37.80% and 49.57% in 2020 in Shanghai and decreased by 20.39% and 43.40% in Zhejiang Province, respectively. The monthly concentrations of overall air pollutants decreased by 12.7% and 12.85% in 2020 Shanghai and Zhejiang compared to the 2017–2019 period;the most rapid decrease was observed in SO 2 concentrations (32.39% and 33.37% in Shanghai Province and Zhejiang Province, respectively). A moderate correlation was seen between influenza incidence and monthly SO 2 concentrations in Shanghai (r = 0.59). A 10 μg/m 3 decrease of SO 2 was significantly associated with the reduction of influenza incidence(2907.76 per 100,000). This study provided the additional evidences that the measures taken for COVID-19 were effective in improving the air quality and reducing spread of other common respiratory diseases, but direct causality is not established.

9.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323568

ABSTRACT

Background: There is limited information on the difference in epidemiology, clinical characteristics and outcomes of the initial outbreak of the coronavirus disease (COVID-19) in Wuhan (the epicenter) and Sichuan (the peripheral area) in the early phase of the COVID-19 pandemic. This study was conducted to investigate the differences in the epidemiological and clinical characteristics of patients with COVID-19 between the epicenter and peripheral areas of pandemic and thereby generate information that would be potentially helpful in formulating clinical practice recommendations to tackle the COVID-19 pandemic. Methods: The Sichuan & Wuhan Collaboration Research Group for COVID-19 established two retrospective cohorts that separately reflect the epicenter and peripheral area during the early pandemic. The epidemiology, clinical characteristics and outcomes of patients in the two groups were compared. Multivariate regression analyses were used to estimate the adjusted odds ratios (aOR) with regard to the outcomes. Results: The Wuhan (epicenter) cohort included 710 randomly selected patients, and the peripheral (Sichuan) cohort included 474 consecutive patients. A higher proportion of patients from the periphery had upper airway symptoms, whereas a lower proportion of patients in the epicenter had lower airway symptoms and comorbidities. Patients in the epicenter had a higher risk of death (aOR=7.64), intensive care unit (ICU) admission (aOR=1.66), delayed time from illness onset to hospital and ICU admission (aOR=6.29 and aOR=8.03, respectively), and prolonged duration of viral shedding (aOR=1.64). Conclusions: The worse outcomes in the epicenter could be explained by the prolonged time from illness onset to hospital and ICU admission. This could potentially have been associated with elevated systemic inflammation secondary to organ dysfunction and prolonged duration of virus shedding independent of age and comorbidities. Thus, early supportive care could achieve better clinical outcomes.

10.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-312185

ABSTRACT

Background: This study aims to identify some biomarkers for monitoring the recovery of lung injury in severe COVID-19 patients from stabilized stage toward convalescence. Methods: : We enrolled participants who diagnosed with severe COVID-19 (n = 28) and health volunteers (n = 25) from Taikang Tongji (Wuhan) Hospital. The patients were in a stabilized stage and had a course of 48.1±12.8 days. We followed these patients for 90 days. The blood routine, cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-17A, TNF-α, IFN-α, IFN-γ), type II alveolar epithelium injury indicators (Surfactant protein A (SP-A), Krebs von den Lungen-6 (KL-6)) and chest CT were tested on the 1, 30, 60, and 90 days after enrollment. Results: : In stabilized stage, the parameters of blood routine and some cytokines (IL-1β, IL-2, IL-4, IL-12p70, TNF-α) had bounced back to normal (p>0.05). Some cytokines (IL-5, IL-6, IL-10, IL-17A, IFN-α, IFN-γ) and type II alveolar epithelium injury indicators (SP-A and KL-6) were still higher than normal (p<0.05). During the stabilized stage to convalescence, in spite of the variation of monocyte count, monocyte/lymphocyte ratio, IL-5, IL-10, IL-12p70, IL-17A, IFN-γ, IFN-α, SP-A and KL-6 were downward trend (p<0.05), only KL-6 level (p<0.05) could simultaneously reflect the lung injury volume which be measured by CT. Conclusions: : Our preliminary data indicated that KL-6 could be an effective prognostic biomarker for monitoring the recovery of lung function in patients with severe COVID-19 from stabilized stage toward convalescence.

11.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-309675

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic, which has resulted in ~1,119,431 deaths. There is currently no approved vaccines or therapeutics for treating COVID-19. The SARS-CoV-2 Spike protein promotes entry into host cells and is considered a key therapeutic target by many researchers. Here we describe the identification of several monoclonal antibodies that target the SARS-CoV-2 Spike protein. One human antibody, CA521 LALA , demonstrated neutralization potential by immunizing human antibody transgenic mice. CA521 LALA showed potent SARS-CoV-2-specific neutralization activity against SARS-CoV-2 pseudovirus and authentic SARS-CoV-2 infection in vitro . The LALA mutation introduced to CA521 abrogates the binding with Fc receptors or complement receptors reducing antibody-dependent enhancement seen with anti-SARS-CoV antibodies. CA521 LALA also demonstrated having a long half-life of 9.5 days in mice and 9.3 days in rhesus monkeys. CA521 LALA inhibited SARS-CoV-2 infection in SARS-CoV-2 susceptible mice at a therapeutic setting with the virus titer of the lung reduced by 4.5 logs. Structural analysis by cryo-EM revealed that CA521 LALA recognizes an epitope overlapping with angiotensin converting enzyme 2 (ACE2)-binding sites in SARS-CoV-2 receptor binding domain (RBD) in the Spike protein. CA521 LALA blocks the interaction by binding all three RBDs of one SARS CoV-2 spike trimer simultaneously. These results demonstrate the importance for antibody-based therapeutic interventions in the treatment of COVID-19 and identifies CA521 LALA a promising antibody that reacts with SARS-CoV-2 Spike protein to strongly neutralize its activity.

12.
Int J Environ Res Public Health ; 19(3)2022 01 24.
Article in English | MEDLINE | ID: covidwho-1649078

ABSTRACT

The Yangtze River Delta is one of the top five Chinese regions affected by COVID-19, as it is adjacent to Hubei Province, where COVID-19 first emerged. We investigated the impact of COVID-19 non-pharmaceutical interventions (NPIs) on changes in respiratory infectious diseases (RIDs) incidence and air quality in the Yangtze River Delta by constructing two proportional tests and fitting ARIMA and linear regression models. Compared with the pre-COVID-19 period, the average monthly incidence of seven RIDs decreased by 37.80% (p < 0.001) and 37.11% (p < 0.001) during the COVID-19 period and the post-vaccination period, respectively, in Shanghai, and decreased by 20.39% (p < 0.001) and 22.86% (p < 0.001), respectively, in Zhejiang. Similarly, compared with the pre-COVID-19 period, the monthly overall concentrations of six air pollutants decreased by 12.7% (p = 0.003) and 18.79% (p < 0.001) during the COVID-19 period and the post-vaccination period, respectively, in Shanghai, and decreased by 12.85% (p = 0.008) and 15.26% (p = 0.001), respectively, in Zhejiang. Interestingly, no significant difference in overall incidence of RIDs and concentrations of air quality was shown between the COVID-19 period and the post-vaccination period in either Shanghai or Zhejiang. This study provides additional evidence that the NPIs measures taken to control COVID-19 were effective in improving air quality and reducing the spread of RIDs. However, a direct causal relationship has not been established.


Subject(s)
Air Pollutants , Air Pollution , COVID-19 , Communicable Diseases , Air Pollutants/analysis , Air Pollution/analysis , Air Pollution/prevention & control , China/epidemiology , Environmental Monitoring , Humans , Incidence , Particulate Matter/analysis , SARS-CoV-2
13.
Clin Respir J ; 16(3): 182-189, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1642633

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) is a newly recognized illness that has spread rapidly all over the world. More and more reports highlight the risk of venous thromboembolism (VTE) in COVID-19. Our study aims to identify in-hospital VTE risk and bleeding risk in COVID-19 patients. METHODS: We retrospectively studied 138 consecutively enrolled patients with COVID-19 and identified in-hospital VTE and bleeding risk by Padua Prediction Score and Improve bleed risk assessment model. The clinical data and features were analyzed in VTE patients. RESULTS: Our findings identified that 23 (16.7%) patients with COVID-19 were at high risk for VTE according to Padua prediction score and 9 (6.5%) patients were at high risk of bleeding for VTE prophylaxis according to Improve prediction score. Fifteen critically ill patients faced double high risk from thrombosis (Padua score more than 4 points in all 15 [100%] patients) and hemorrhage (Improve score more than 7 points in 9 [60.0%] patients). Thrombotic events were identified in four patients (2.9%) of all COVID-19 patients. All of them were diagnosed with deep vein thrombosis by ultrasound 3 to 18 days after admission. Three (75.0%) were critically ill patients, which means that the incidence of VTE among critically ill patients was 20%. One major hemorrhage happened in critically ill patients during VTE treatment. CONCLUSION: Critically ill patients with COVID-19 suffered both a high risk of thrombosis and bleeding risks. More effective VTE prevention strategies based on an individual assessment of bleeding risks were necessary for critically ill patients with COVID-19.


Subject(s)
COVID-19 , Venous Thromboembolism , Anticoagulants/therapeutic use , COVID-19/complications , COVID-19/epidemiology , Hemorrhage/epidemiology , Hemorrhage/etiology , Humans , Retrospective Studies , Risk Assessment , Risk Factors , SARS-CoV-2 , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control
14.
BMJ Glob Health ; 7(1)2022 01.
Article in English | MEDLINE | ID: covidwho-1612993

ABSTRACT

BACKGROUND: It has been reported that strict non-pharmaceutical measures can significantly reduce the incidence and mortality of respiratory and intestinal infectious diseases during the COVID-19 pandemic, but there are limited reports on the impact in terms of the rates of zoonotic diseases. METHODS: We extracted the incidence and mortality data of eight notifiable infectious zoonotic diseases from the website of the National Health Commission of the People's Republic of China for the period of January 2015 to April 2021. RESULTS: First, the overall incidence of zoonotic diseases decreased from 0.3714 per 100 000 in 2015-2019 to 0.2756 in 2020 (25.79% reduction, p<0.001); however, a dramatic increase in activity was seen in 2021 compared with 2020 (0.4478 per 100 000 in 2021, 62.47% increase, p<0.001). Anthrax, brucellosis, leptospirosis and hydatid disease exhibited significant upward trends in 2021. Second, analysed further by stages, the monthly incidence in the routine stage (from May to December 2020) was much higher than that in the emergency stage of the COVID-19 (from January to April 2020) (55.33% increase, p<0.001). We also found that the monthly observed incidence was significantly lower than the predicted incidence of a 10.29% reduction in the emergency stage. Third, no differences were seen in mortality between 2021 and 2020, while a significant decline was found in 2020 compared with the previous 5 years (72.70%, p<0.001). CONCLUSIONS: Strict containment and feasible suppression strategies during the 2020 period of the COVID-19 pandemic had positive impacts on the overall incidence of zoonotic diseases in China. However, anthrax, brucellosis, leptospirosis and hydatid diseases might increase with the relaxation of non-pharmacological interventions in 2021.


Subject(s)
COVID-19 , Animals , China/epidemiology , Humans , Incidence , Pandemics , SARS-CoV-2 , Zoonoses/epidemiology
15.
MAbs ; 14(1): 2005507, 2022.
Article in English | MEDLINE | ID: covidwho-1585297

ABSTRACT

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a serious public health crisis worldwide, and considering the novelty of the disease, preventative and therapeutic measures alike are urgently needed. To accelerate such efforts, the development of JS016, a neutralizing monoclonal antibody directed against the SARS-CoV-2 spike protein, was expedited from a typical 12- to 18-month period to a 4-month period. During this process, transient Chinese hamster ovary cell lines are used to support preclinical, investigational new drug-enabling toxicology research, and early Chemistry, Manufacturing and Controls development; mini-pool materials to supply Phase 1 clinical trials; and a single-clone working cell bank for late-stage and pivotal clinical trials were successively adopted. Moreover, key process performance and product quality investigations using a series of orthogonal and state-of-the-art techniques were conducted to demonstrate the comparability of products manufactured using these three processes, and the results indicated that, despite observed variations in process performance, the primary and high-order structures, purity and impurity profiles, biological and immunological functions, and degradation behaviors under stress conditions were largely comparable. The study suggests that, in particular situations, this strategy can be adopted to accelerate the development of therapeutic biopharmaceuticals and their access to patients.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/therapeutic use , Antibody Affinity/immunology , Antibody Specificity/immunology , CHO Cells , COVID-19/prevention & control , COVID-19/virology , Chromatography, High Pressure Liquid/methods , Circular Dichroism , Clone Cells , Cricetinae , Cricetulus , Humans , Immunoglobulin G/chemistry , Immunoglobulin G/immunology , Immunoglobulin G/therapeutic use , Isoelectric Point , SARS-CoV-2/metabolism , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/metabolism
16.
Urban Studies ; : 00420980211049350, 2021.
Article in English | Sage | ID: covidwho-1488337

ABSTRACT

The ongoing coronavirus disease (COVID-19) pandemic has had a far-reaching impact on urban living, prompting emergency preparedness and response from public health governance at multiple levels. The Chinese government has adopted a series of policy measures to control infectious disease, for which cities are the key spatial units. This research traces and reports analyses of those policy measures and their evolution in four Chinese cities: Zhengzhou, Hangzhou, Shanghai and Chengdu. The theoretical framework stems from conceptualisations of urban governance and its role in public health emergencies, wherein crisis management and emergency response are highlighted. In all four cities, the trend curves of cumulative diagnosed cases, critical policies launched in key time nodes and local governance approaches in the first wave were identified and compared. The findings suggest that capable local leadership is indispensable for controlling the coronavirus epidemic, yet local governments? approaches are varied, contributing to dissimilar local epidemic control policy pathways and positive outcomes in the fight against COVID-19. The effectiveness of disease control is determined by how local governments? measures have adapted to geospatial and socioeconomic heterogeneity. The coordinated actions from central to local governments also reveal an efficient, top-down command transmission and execution system for coping with the pandemic. This article argues that effective control of pandemics requires both a holistic package of governance strategies and locally adaptive governance measures/processes, and concludes with proposals for both a more effective response at the local level and identification of barriers to achieving these responses within diverse subnational institutional contexts.

17.
Cities ; 118: 103396, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1330695

ABSTRACT

Effective control of the COVID-19 pandemic via appropriate management of the built environment is an urgent issue. This study develops a research framework to explore the relationship between COVID-19 incidence and influential factors related to protection of vulnerable populations, intervention in transmission pathways, and provision of healthcare resources. Relevant data for regression analysis and structural equation modeling is collected during the first wave of the pandemic in the United States, from counties with over 100 confirmed cases. In addition to confirming certain factors found in the existing literature, we uncover six new factors significantly associated with COVID-19 incidence. Furthermore, incidence during the lockdown is found to significantly affect incidence after the reopening, highlighting that timely quarantining and treating of patients is essential to avoid the snowballing transmission over time. These findings suggest ways to mitigate the negative effects of subsequent waves of the pandemic, such as special attention of infection prevention in neighborhoods with unsanitary and overcrowded housing, minimization of social activities organized by neighborhood associations, and contactless home delivery service of healthy food. Also worth noting is the need to provide support to people less capable of complying with the stay-at-home order because of their occupations or socio-economic disadvantage.

18.
Emerg Microbes Infect ; 10(1): 1519-1529, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1316787

ABSTRACT

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated continuously and newly emerging variants escape from antibody-mediated neutralization raised great concern. S protein is heavily glycosylated and the glycosylation sites are relatively conserved, thus glycans on S protein surface could be a target for the development of anti-SARS-CoV-2 strategies against variants. Here, we collected 12 plant-derived lectins with different carbohydrate specificity and evaluated their anti-SARS-CoV-2 activity against mutant strains and epidemic variants using a pseudovirus-based neutralization assay. The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1. Lentil lectin also showed antiviral activity against SARS-CoV and MERS-CoV. We found lentil lectin could block the binding of ACE2 to S trimer and inhibit SARS-CoV-2 at the early steps of infection. Using structural information and determined N-glycan profile of S trimer, taking together with the carbohydrate specificity of lentil lectin, we provide a basis for the observed broad spectrum anti-SARS-CoV-2 activity. Lentil lectin showed weak haemagglutination activity at 1 mg/mL and no cytotoxicity activity, and no weight loss was found in single injection mouse experiment. This report provides the first evidence that lentil lectin strongly inhibit infection of SARS-COV-2 variants, which should provide valuable insights for developing future anti-SARS-CoV-2 strategies.


Subject(s)
Antiviral Agents/pharmacology , Lens Plant/chemistry , Plant Extracts/pharmacology , Plant Lectins/pharmacology , SARS-CoV-2/drug effects , Animals , Antiviral Agents/chemistry , Humans , Mice , Mice, Inbred BALB C , Plant Extracts/chemistry , Plant Lectins/chemistry , SARS-CoV-2/growth & development , Seeds/chemistry
19.
Cardiol Res Pract ; 2021: 5537275, 2021.
Article in English | MEDLINE | ID: covidwho-1304290

ABSTRACT

In this study, we investigated the association between the plasma NT-proBNP level at admission and the severity of COVID-19 pneumonia. For this retrospective, single-centre cohort study, we enrolled consecutive patients from February 9 to March 4, 2020, in a COVID-19 ward of Hubei General Hospital (East Branch) in Wuhan, which is a government-assigned centre for COVID-19 treatment. Diagnosis was confirmed by microbiological and radiographic findings following the interim guidance of the World Health Organization (WHO). A total of 91 (92.9%) patients were finally included in this study. The median age of the patients was 61 years (IQR, 47-69), and 39 (43.0%) of them were male. Two cases of death were reported (2.3%). Twenty-three patients (25.3%) had NT-proBNP levels above 300 pg/ml. Higher NT-proBNP levels were associated with worse PSI and CT scores. The natural logarithm of the NT-proBNP level was positively correlated with the PSI and CT scores (PSI score: r S = 0.396, P=0.001; CT score: r S = 0.440, P < 0.001). Patients with NT-proBNP ≥300 pg/ml showed a potential risk for higher mortality than patients with NT-proBNP <300 pg/ml (mortality rate, 8.7% vs. 0%; P=0.062). The plasma NT-proBNP level of COVID-19 patients was significantly related to the severity of pneumonia.

20.
Sci Rep ; 11(1): 11636, 2021 06 02.
Article in English | MEDLINE | ID: covidwho-1253991

ABSTRACT

The elevated level of D-dimer and its relationship with poor outcomes in SARS-COV-2 pneumonia patients have been demonstrated. In addition to a hypercoagulable state, D-dimer is also a biomarker of inflammation. We investigated the relationship between D-dimer level and chest computed tomography (CT) severity score, which could reflect the severity of inflammation in SARS-COV-2 pneumonia patients. We retrospectively enrolled 86 consecutive SARS-COV-2 pneumonia patients. CT severity scores were computed to quantify the overall lung involvement. The D-dimer level among CT score tertiles and the association of the D-dimer level with CT score were analyzed. Our results showed that the median D-dimer level was 0.70 mg/L (IQR 0.35-1.76). 42 patients (48.8%) had D-dimer levels above the median level. The D-dimer levels were significantly different across CT score tertiles (0.37 mg/l [IQR 0.31-0.87], 0.66 mg/l [IQR 0.39-1.43], 1.83 mg/l [IQR 0.85-4.41], P < 0.001). The natural logarithm of the D-dimer level was significantly associated with the CT score (rs = 0.586, P < 0.001). In conclusion, the D-dimer level may be associated with the severity of inflammation of SARS-COV-2 pneumonia prior to coagulopathy/thrombosis. This could be an additional explanation for the mechanism of the relationship between elevated D-dimer level and higher mortality.


Subject(s)
COVID-19/diagnostic imaging , COVID-19/etiology , Fibrin Fibrinogen Degradation Products/analysis , Adult , Aged , COVID-19/blood , Female , Humans , Lung/diagnostic imaging , Lung/pathology , Lung/virology , Male , Middle Aged , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/virology , Respiration, Artificial , Retrospective Studies , Tomography, X-Ray Computed/methods
SELECTION OF CITATIONS
SEARCH DETAIL