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1.
COVID ; 2(1):5-17, 2022.
Article in English | MDPI | ID: covidwho-1580968

ABSTRACT

Human coronaviruses (HCoVs) are associated with a range of respiratory symptoms. The discovery of severe acute respiratory syndrome (SARS)-CoV, Middle East respiratory syndrome, and SARS-CoV-2 pose a significant threat to human health. In this study, we developed a method (HCoV-MS) that combines multiplex PCR with matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), to detect and differentiate seven HCoVs simultaneously. The HCoV-MS method had high specificity and sensitivity, with a 1–5 copies/reaction detection limit. To validate the HCoV-MS method, we tested 163 clinical samples, and the results showed good concordance with real-time PCR. Additionally, the detection sensitivity of HCoV-MS and real-time PCR was comparable. The HCoV-MS method is a sensitive assay, requiring only 1 μL of a sample. Moreover, it is a high-throughput method, allowing 384 samples to be processed simultaneously in 30 min. We propose that this method be used to complement real-time PCR for large-scale screening studies.

2.
Preprint in English | Other preprints | ID: ppcovidwho-295527

ABSTRACT

The STimulator of INterferon Genes (STING) protein is a cornerstone of the human immune response. Its activation by cGAMP upon the presence of cytosolic DNA stimulates the production of type I interferons and inflammatory cytokines which are crucial for protecting cells from infections. STING signaling pathway can also influence both tumor-suppressive and tumor-promoting mechanisms, rendering it an appealing target for drug design. In the human population, several STING variants exist and exhibit dramatic differences in their activity, impacting the efficiency of the host defense against infections. Understanding the differential molecular mechanisms exhibited by these variants is of utmost importance notably towards personalized medicine treatments against diseases such as viral infections (COVID-19, Dengue…), cancers, or auto-inflammatory diseases. Owing to micro-seconds scale molecular modeling simulations and post-processing by contacts analysis and Machine Learning techniques, we reveal the dynamical behavior of four STING variants (wild type, G230A, R293Q, and G230A-R293Q) and we rationalize the variability of efficiency observed experimentally. Our results show that the decrease of STING activity is linked to a stiffening of key-structural features of the binding cavity, together with changes of the interaction patterns within the protein.

3.
Clin Infect Dis ; 2021 Nov 12.
Article in English | MEDLINE | ID: covidwho-1522157

ABSTRACT

BACKGROUND: To combat the COVID-19 pandemic, nonpharmaceutical interventions (NPI) were implemented worldwide, which impacted a broad spectrum of acute respiratory infections (ARI). METHODS: Etiologically diagnostic data from 142 559 cases with ARIs, who were tested for eight viral pathogens (influenza virus, IFV; respiratory syncytial virus, RSV; human parainfluenza virus, HPIV; human adenovirus; human metapneumovirus; human coronavirus, HCoV; human bocavirus, HBoV, and human rhinovirus, HRV) between 2012 and 2021, were analyzed to assess the changes of respiratory infections in China during the first COVID-19 pandemic year compared to pre-pandemic years. RESULTS: Test positive rates of all respiratory viruses decreased during 2020, compared to the average levels during 2012-2019, with changes ranging from -17·2% for RSV to -87·6% for IFV. Sharp decreases mostly occurred between February and August when massive NPIs remained active, although HRV rebounded to the historical level during the summer. While IFV and HMPV were consistently suppressed year round, RSV, HPIV, HCoV, HRV HBov resurged and went beyond historical levels during September, 2020-January, 2021, after NPIs were largely relaxed and schools reopened. Resurgence was more prominent among children younger than 18 years and in Northern China. These observations remain valid after accounting for seasonality and long-term trend of each virus. CONCLUSIONS: Activities of respiratory viral infections were reduced substantially in the early phases of the COVID-19 pandemic, and massive NPIs were likely the main driver. Lifting of NPIs can lead to resurgence of viral infections, particularly in children.

5.
Nat Commun ; 12(1): 5026, 2021 08 18.
Article in English | MEDLINE | ID: covidwho-1363491

ABSTRACT

Nationwide prospective surveillance of all-age patients with acute respiratory infections was conducted in China between 2009‒2019. Here we report the etiological and epidemiological features of the 231,107 eligible patients enrolled in this analysis. Children <5 years old and school-age children have the highest viral positivity rate (46.9%) and bacterial positivity rate (30.9%). Influenza virus, respiratory syncytial virus and human rhinovirus are the three leading viral pathogens with proportions of 28.5%, 16.8% and 16.7%, and Streptococcus pneumoniae, Mycoplasma pneumoniae and Klebsiella pneumoniae are the three leading bacterial pathogens (29.9%, 18.6% and 15.8%). Negative interactions between viruses and positive interactions between viral and bacterial pathogens are common. A Join-Point analysis reveals the age-specific positivity rate and how this varied for individual pathogens. These data indicate that differential priorities for diagnosis, prevention and control should be highlighted in terms of acute respiratory tract infection patients' demography, geographic locations and season of illness in China.


Subject(s)
Bacteria/isolation & purification , Bacterial Infections/microbiology , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/virology , Virus Diseases/virology , Viruses/isolation & purification , Adolescent , Adult , Bacteria/classification , Bacteria/genetics , Bacterial Infections/epidemiology , Child , Child, Preschool , China/epidemiology , Female , Humans , Infant , Male , Prospective Studies , Respiratory Tract Infections/epidemiology , Seasons , Virus Diseases/epidemiology , Viruses/classification , Viruses/genetics , Young Adult
6.
Cell Res ; 31(1): 25-36, 2021 01.
Article in English | MEDLINE | ID: covidwho-1387275

ABSTRACT

Structural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic antibody cocktail against SARS-CoV-2. On the basis of our previously identified humanized cross-neutralizing antibody H014, we systematically analyzed a fully human naive antibody library and rationally identified a potent neutralizing antibody partner, P17, which confers effective protection in animal model. Cryo-EM studies dissected the nature of the P17 epitope, which is SARS-CoV-2 specific and distinctly different from that of H014. High-resolution structure of the SARS-CoV-2 spike in complex with H014 and P17, together with functional investigations revealed that in a two-antibody cocktail, synergistic neutralization was achieved by S1 shielding and conformational locking, thereby blocking receptor attachment and viral membrane fusion, conferring high potency as well as robustness against viral mutation escape. Furthermore, cluster analysis identified a hypothetical 3rd antibody partner for further reinforcing the cocktail as pan-SARS-CoVs therapeutics.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 , Epitopes/immunology , SARS-CoV-2/immunology , Single-Chain Antibodies/immunology , Animals , Antibodies, Neutralizing/pharmacology , Antibodies, Viral/pharmacology , COVID-19/immunology , COVID-19/prevention & control , Chlorocebus aethiops , Disease Models, Animal , Humans , Single-Chain Antibodies/pharmacology , Vero Cells
7.
PLoS One ; 16(8): e0255592, 2021.
Article in English | MEDLINE | ID: covidwho-1346329

ABSTRACT

We predicted that people with compassionate goals to support others and not harm them practiced more COVID-19 health behaviors during the SARS-CoV-2 pandemic to protect both themselves and others from infection. Three studies (N = 1,143 American adults) supported these predictions and ruled out several alternative explanations. Compassionate goals unrelated to the health context predicted COVID-19 health behaviors better than the general motivation to be healthy (Studies 2 and 3). In contrast, general health motivation predicted general health behaviors better than did compassionate goals. Compassionate goals and political ideology each explained unique variance in COVID-19 health behaviors (Studies 1-3). Compassionate goals predict unique variance in COVID-19 health behaviors beyond empathic concern, communal orientation, and relational self-construal (Study 3), supporting the unique contribution of compassionate goals to understanding health behaviors. Our results suggest that ecosystem motivation is an important predictor of health behaviors, particularly in the context of a highly contagious disease.


Subject(s)
COVID-19 , Empathy , Health Behavior , Adult , COVID-19/epidemiology , COVID-19/prevention & control , Female , Goals , Humans , Male , Middle Aged , Motivation
8.
Environ Sci Technol ; 55(16): 10911-10922, 2021 08 17.
Article in English | MEDLINE | ID: covidwho-1345524

ABSTRACT

Air pollution composed of the complex interactions among particular matter, chemicals, and pathogens is an emerging and global environmental issue that closely correlates with a variety of diseases and adverse health effects, especially increasing incidences of neurodegenerative diseases. However, as one of the prevalent health outcomes of air pollution, chemosensory dysfunction has not attracted enough concern until recently. During the COVID-19 pandemic, multiple scientific studies emphasized the plausibly essential roles of the chemosensory system in the airborne transmission airway of viruses into the human body, which can also be utilized by pollutants. In this Review, in addition to summarizing current progress regarding the contributions of traditional air pollutants to chemosensory dysfunction, we highlight the roles of emerging contaminants. We not only sum up clarified mechanisms, such as inflammation and apoptosis but also discuss some not yet completely identified mechanisms, e.g., disruption of olfactory signal transduction. Although the existing evidence is not overwhelming, the chemosensory system is expected to be a useful indicator in neurotoxicology and neural diseases based on accumulating studies that continually excavate the deep link between chemosensory dysfunction and neurodegenerative diseases. Finally, we argue the importance of studies concerning chemosensory dysfunction in understanding the health effects of air pollution and provide comments for some future directions of relevant research.


Subject(s)
Air Pollutants , Air Pollution , COVID-19 , Environmental Pollutants , Air Pollutants/analysis , Air Pollutants/toxicity , Air Pollution/adverse effects , Air Pollution/analysis , Humans , Pandemics , SARS-CoV-2
9.
Chin J Acad Radiol ; : 1-9, 2021 Jun 28.
Article in English | MEDLINE | ID: covidwho-1286228

ABSTRACT

Background: Coronary artery calcification (CAC) is an independent risk factor of major adverse cardiovascular events; however, the impact of CAC on in-hospital death and adverse clinical outcomes in patients with coronavirus disease 2019 (COVID-19) remains unclear. Objective: To explore the association between CAC and in-hospital mortality and adverse events in patients with COVID-19. Methods: This multicenter retrospective cohort study enrolled 2067 laboratory-confirmed COVID-19 patients with definitive clinical outcomes (death or discharge) admitted from 22 tertiary hospitals in China between January 3, 2020 and April 2, 2020. Demographic, clinical, laboratory results, chest CT findings, and CAC on admission were collected. The primary outcome was in-hospital death and the secondary outcome was composed of in-hospital death, admission to intensive care unit (ICU), and requiring mechanical ventilation. Multivariable Cox regression analysis and Kaplan-Meier plots were used to explore the association between CAC and in-hospital death and adverse clinical outcomes. Results: The mean age was 50 years (SD,16) and 1097 (53.1%) were male. A total of 177 patients showed high CAC level, and compared with patients with low CAC, these patients were older (mean age: 49 vs. 69 years, P < 0.001) and more likely to be male (52.0% vs. 65.0%, P = 0.001). Comorbidities, including cardiovascular disease (CVD) ([33.3%, 59/177] vs. [4.7%, 89/1890], P < 0.001), presented more often among patients with high CAC, compared with patients with low CAC. As for laboratory results, patients with high CAC had higher rates of increased D-dimer, LDH, as well as CK-MB (all P < 0.05). The mean CT severity score in high CAC group was also higher than low CAC group (12.6 vs. 11.1, P = 0.005). In multivariable Cox regression model, patients with high CAC were at a higher risk of in-hospital death (hazard ratio [HR], 1.731; 95% CI 1.010-2.971, P = 0.046) and adverse clinical outcomes (HR, 1.611; 95% CL 1.087-2.387, P = 0.018). Conclusion: High CAC is a risk factor associated with in-hospital death and adverse clinical outcomes in patients with confirmed COVID-19, which highlights the importance of calcium load testing for hospitalized COVID-19 patients and calls for attention to patients with high CAC. Supplementary Information: The online version contains supplementary material available at 10.1007/s42058-021-00072-4.

10.
Front Med (Lausanne) ; 8: 582299, 2021.
Article in English | MEDLINE | ID: covidwho-1268254

ABSTRACT

Background: Most COVID-19 patients cannot provide a clear exposure time; therefore, this study was designed to predict the progression of COVID-19 by using the definite departure time from Wuhan. Methods: In this retrospective study, all cases were selected from Northwestern China, which has the lowest population density. As our study endpoints, the incubation period was defined as the date of departure from Wuhan City to the date of symptom onset; we defined the confirmed time as the interval from symptom onset to positive results (samples from the respiratory tract). Both of them were estimated by fitting a Weibull distribution on the departure date and symptom onset. The differences among the variables were analyzed. Results: A total of 139 patients were ultimately enrolled, and ~10.1% of patients (14 patients) had no symptoms during their disease course. We estimated the median incubation period to be 4.0 days (interquartile intervals, 2.0-8.0), and the 95th percentile of the distribution was 15.0 days. Moreover, ~5.6% of patients (7 patients) experienced symptoms 2 weeks after leaving. Furthermore, the estimation median interval from symptom onset to final diagnosis was 4.0 days (interquartile intervals, 2.0-6.0), and the 95th percentile of the distribution was 12.0 days. Finally, the median hospitalization time was 16.0 days, ranging from 3.0 to 45.0 days. Univariate analysis showed that age (P = 0.021) and severity status (P = 0.001) were correlated significantly with hospitalization time. Conclusions: We provide evidence that departure time can be used to estimate the incubation and confirmed times of patients infected with COVID-19 when they leave an epidemic area.

11.
Front Med (Lausanne) ; 8: 573726, 2021.
Article in English | MEDLINE | ID: covidwho-1259349

ABSTRACT

Background: Overseas imported cases of COVID-19 continue to increase in China, so we conducted this study to review the epidemiological characteristics of these patients. Methods: From February 26 to April 4, 2020, the imported cases from abroad were enrolled in this study. The effect of prevention countermeasures in curbing the spread of COVID-19 was assessed in this study. Moreover, we defined incubation period and confirmed time as from the date of leaving the epicenter to date of symptom onset and date of final diagnosed, respectively, and the interval of symptom onset to final diagnosed time was defined as diagnostic time. Categorical variables were summarized as numbers and percentages, and the difference among the variables were analyzed. Results: For 670 cases imported from abroad, 555 were Chinese and 115 were foreigners. Apparently, confirmed cases had significantly decreased after China was compelled to temporarily suspend the entry of foreign passport holders with valid visas or residence permits; 6 days after implement of controlled measures, the daily new confirmed cases were reduced to 13 cases. Moreover, about 84.3% of patients (166/197) presented symptoms 1 week after leaving the epicenter, and notably seven patients (3.6%) had symptoms 2 weeks after leaving the epicenter. The median incubation period was 3.0 days (inter quartile range, 1.0 to 6.0), the 95th percentile was 11.6 days. Additionally, most of cases (92.9%) were detected positively of nucleic acid after symptom onset with 4 days, the median diagnostic time was 2.0 days (interquartile range, 1.0 to 3.0), and the 95th percentile of the distribution was 5.0 days. Finally, about 5.8% of patients were healthy carriers, and the median confirmed time of asymptomatic patients was 4.0 days (interquartile range, 2.0 to 9.0). The following variables might be associated with confirmed time: symptom type (P = 0.005), exported regions (P < 0.001), and symptom onset time (P < 0.001). Conclusions: The prevention countermeasures for imported cases implemented by the Chinese government played an indispensable role in curbing the spread of COVID-19; the time of departure from epicenter could provide an estimate of the incubation period; and a confirmed time, 2-week quarantine period might need to be prolonged, while asymptomatic patients should be closely monitored.

12.
Front Psychiatry ; 12: 557611, 2021.
Article in English | MEDLINE | ID: covidwho-1201856

ABSTRACT

Background: The 2019 novel coronavirus disease (COVID-19) is an extremely rapidly spreading respiratory infection caused by SARS-CoV-2. Many schizophrenic patients were infected with COVID-19 in Wuhan City, Hubei Province. This study took hospitalized schizophrenia patients with COVID-19 as the research subjects and observed the changes in psychopathology and stress of patients with COVID-19 and the accompanying social isolation. Methods: To sort and isolate potential COVID-19-infected patients, an isolated ward was set up from January 30, 2020, to March 30, 2020. Schizophrenia patients with COVID-19 were referred to this ward, and long-term hospitalized cases were included in this study. The Positive and Negative Syndrome Scale and Perceived Stress Scale were used to evaluate the severity of mental symptoms and psychological stress in the early stage of the outbreak of COVID-19, after the diagnosis of COVID-19 and after recovery. At the time of diagnosis, we also extracted the patient's routine blood, biochemical and other indicators and asked the patient's perception of COVID-19. Results: 21 hospitalized schizophrenia patients with COVID-19 were recruited in this study. The changes in PANSS scores were not significant (p = 0.225 baseline vs. diagnosed, p = 0.399 cured vs. diagnosed). The CPSS scores increased significantly after diagnosis and transfer to the isolation ward (p < 0.001 baseline vs. diagnosed, p < 0.001 cured vs. diagnosed). The course of schizophrenia was a protective factor of stress levels to cases (t = -3.25, p = 0.006), and patients' perception of COVID-19 was a risk factor (t = 2.48, p = 0.038). The final multiple linear regression model was statistically significant (F = 8.16, p < 0.001). Conclusion: Hospitalized schizophrenia patients with COVID-19 had increased stress levels and negative symptoms but alleviated positive symptoms after medical isolated treatment. This reminds us that in the face of major epidemics, we must specifically alleviate the psychological burden at the peak of the epidemic and improve the prognosis of patients after the epidemic.

13.
Front Med (Lausanne) ; 7: 564250, 2020.
Article in English | MEDLINE | ID: covidwho-1186808

ABSTRACT

Background: Few studies have reported the transmission characteristics of coronavirus disease (COVID-19) in low-density populations. This study has therefore analyzed the epidemiological characteristics and clinical outcomes of COVID-19 patients in Northwestern China, an area with low population density. Methods: From January 21 to March 11, 2020, data from patients diagnosed with novel coronavirus pneumonia (NCP) in areas of Northwestern China with lower population densities were retrospectively analyzed. Certain variables were categorized as numbers and percentages, with the ratio between resident patients (no history of going out during the epidemic) and imported patients representing the contagiousness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for COVID-19. Hospitalization time was also calculated. Results: A total of 617 COVID-19 patients were reported in Northwestern China, and the morbidity and mortality rates of 0.000005 and 0.011, respectively. Further analysis showed that the morbidity was inversely proportional to population density and distance from Wuhan City. This study enrolled 473 confirmed cases; among these patients, there were 248 residents and 225 imported cases with a ratio of 1:1. The youngest and oldest patients were 1 and 94 years of age, respectively, with a median age of 42 years. Fifteen (3.2%) patients were children or infants. Two patients were pregnant, and one patient gave birth to a healthy baby with negative results during her disease course. About 17.3% of patients (82 cases) were healthy carriers without any symptoms during their disease course. One male patient (0.2%) had recurrence of a positive test result 4 days after discharge. The median hospitalization time was 16.0 days, ranging from 2.0 to 43.0 days. Further analysis showed that age (P = 0.03) and severity status (P < 0.001) were significantly correlated with hospitalization time. Conclusions: The morbidity and mortality rates of COVID-19 patients in the regions with a low population density were lower than those of the national average in China. All populations were susceptible to infection by SARS-CoV-2. Asymptomatic patients with positive results should be taken seriously, and the hospitalization time of patients is associated with their age and severity status.

14.
Int J Gen Med ; 14: 381-385, 2021.
Article in English | MEDLINE | ID: covidwho-1143343

ABSTRACT

Objective: This study aimed to investigate the clinical manifestation and treatment effects of extrapulmonary complications in cases of novel coronavirus pneumonia. Methods: The clinical data of patients with novel coronavirus pneumonia who were admitted to Hanchuan People's Hospital between January and March 2020 were retrospectively analyzed, and the clinical characteristics, laboratory test results, and treatment pathways of patients with extrapulmonary complications were analyzed and summarized. Results: Of the 500 patients in this study, 97 patients with a history of chronic diseases were excluded, and 152 patients had extrapulmonary complications. Common extrapulmonary syndromes: 98 patients (64.47%) suffered from digestive system involvement; 43 patients (28.29%) suffered from cardiovascular system damage; 32 patients (21.05%) had urinary system damage; 25 patients (16.45%) had nervous system damage; and 30 patients (19.74%) had more than two kinds of system damage. In all cases, these patients were treated with comprehensive measures, and effective outcomes were achieved. Conclusion: According to the clinical characteristics and laboratory test results of this sample group, early evaluation of patients with extrapulmonary complications and timely symptomatic treatment can effectively improve outcomes of pneumonia treatment, accelerate the alleviation of symptoms, and improve patients' condition.

15.
Front Cell Infect Microbiol ; 11: 613304, 2021.
Article in English | MEDLINE | ID: covidwho-1088903

ABSTRACT

Background: The emerging Coronavirus Disease-2019 (COVID-19) has challenged the public health globally. With the increasing requirement of detection for SARS-CoV-2 outside of the laboratory setting, a rapid and precise Point of Care Test (POCT) is urgently needed. Methods: Targeting the nucleocapsid (N) gene of SARS-CoV-2, specific primers, and probes for reverse transcription recombinase-aided amplification coupled with lateral flow dipstick (RT-RAA/LFD) platform were designed. For specificity evaluation, it was tested with human coronaviruses, human influenza A virus, influenza B viruses, respiratory syncytial virus, and hepatitis B virus, respectively. For sensitivity assay, it was estimated by templates of recombinant plasmid and pseudovirus of SARS-CoV-2 RNA. For clinical assessment, 100 clinical samples (13 positive and 87 negatives for SARS-CoV-2) were tested via quantitative reverse transcription PCR (RT-qPCR) and RT-RAA/LFD, respectively. Results: The limit of detection was 1 copies/µl in RT-RAA/LFD assay, which could be conducted within 30 min at 39°C, without any cross-reaction with other human coronaviruses and clinical respiratory pathogens. Compared with RT-qPCR, the established POCT assay offered 100% specificity and 100% sensitivity in the detection of clinical samples. Conclusion: This work provides a convenient POCT tool for rapid screening, diagnosis, and monitoring of suspected patients in SARS-CoV-2 endemic areas.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , Real-Time Polymerase Chain Reaction/methods , SARS-CoV-2/genetics , COVID-19/virology , COVID-19 Nucleic Acid Testing/instrumentation , Coronavirus Nucleocapsid Proteins/genetics , DNA Primers/genetics , Humans , Phosphoproteins/genetics , Point-of-Care Testing , RNA, Viral/genetics , Real-Time Polymerase Chain Reaction/instrumentation , Recombinases/metabolism , Reverse Transcription , SARS-CoV-2/isolation & purification , Sensitivity and Specificity
16.
R Soc Open Sci ; 7(11): 200958, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-1005759

ABSTRACT

Angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 have been implicated in cell entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). The expression of ACE2 and TMPRSS2 in the lung epithelium might have implications for the risk of SARS-CoV-2 infection and severity of COVID-19. We use human genetic variants that proxy angiotensin-converting enzyme (ACE) inhibitor drug effects and cardiovascular risk factors to investigate whether these exposures affect lung ACE2 and TMPRSS2 gene expression and circulating ACE2 levels. We observed no consistent evidence of an association of genetically predicted serum ACE levels with any of our outcomes. There was weak evidence for an association of genetically predicted serum ACE levels with ACE2 gene expression in the Lung eQTL Consortium (p = 0.014), but this finding did not replicate. There was evidence of a positive association of genetic liability to type 2 diabetes mellitus with lung ACE2 gene expression in the Gene-Tissue Expression (GTEx) study (p = 4 × 10-4) and with circulating plasma ACE2 levels in the INTERVAL study (p = 0.03), but not with lung ACE2 expression in the Lung eQTL Consortium study (p = 0.68). There were no associations of genetically proxied liability to the other cardiometabolic traits with any outcome. This study does not provide consistent evidence to support an effect of serum ACE levels (as a proxy for ACE inhibitors) or cardiometabolic risk factors on lung ACE2 and TMPRSS2 expression or plasma ACE2 levels.

17.
Cell Res ; 31(1): 25-36, 2021 01.
Article in English | MEDLINE | ID: covidwho-952976

ABSTRACT

Structural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic antibody cocktail against SARS-CoV-2. On the basis of our previously identified humanized cross-neutralizing antibody H014, we systematically analyzed a fully human naive antibody library and rationally identified a potent neutralizing antibody partner, P17, which confers effective protection in animal model. Cryo-EM studies dissected the nature of the P17 epitope, which is SARS-CoV-2 specific and distinctly different from that of H014. High-resolution structure of the SARS-CoV-2 spike in complex with H014 and P17, together with functional investigations revealed that in a two-antibody cocktail, synergistic neutralization was achieved by S1 shielding and conformational locking, thereby blocking receptor attachment and viral membrane fusion, conferring high potency as well as robustness against viral mutation escape. Furthermore, cluster analysis identified a hypothetical 3rd antibody partner for further reinforcing the cocktail as pan-SARS-CoVs therapeutics.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 , Epitopes/immunology , SARS-CoV-2/immunology , Single-Chain Antibodies/immunology , Animals , Antibodies, Neutralizing/pharmacology , Antibodies, Viral/pharmacology , COVID-19/immunology , COVID-19/prevention & control , Chlorocebus aethiops , Disease Models, Animal , Humans , Single-Chain Antibodies/pharmacology , Vero Cells
19.
Preprint | SSRN | ID: ppcovidwho-1098

ABSTRACT

Background: In mainland China, no new domestic cases of COVID-19 had been reported for several weeks, it was current priority to prevent and control imported ca

20.
Preprint | SSRN | ID: ppcovidwho-675

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) has become a pandemic. Despite of the growing number of patients with COVID-19 infection, data on the clinical c

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