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1.
Aging Dis ; 13(3): 884-898, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1870135

ABSTRACT

COVID-19 emerged in Wuhan in December 2019 and soon became a worldwide pandemic. We collected and analyzed the data from 1077 patients with COVID-19 who were admitted to the west campus of Wuhan Union Hospital from January 16 to April 16, 2020. Sixty (5.6%) of the 1077 COVID-19 patients were diagnosed with acute kidney injury (AKI) during hospitalization, and 18 of them (30%) had AKI on chronic kidney disease (AKI/CKD). COVID-19 patients with AKI had a worse prognosis, with higher intensive care unit (ICU) admission (28.3%) and fatality (65%) rates than patients without AKI (3.4% and 10.7%, respectively). Among the COVID-19 patients, AKI was more likely to occur in male patients, the elderly, patients with more severe disease states and those with comorbidities (such as hypertension, diabetes, coronary heart disease (CHD), chronic obstructive pulmonary disease (COPD) and CKD). COVID-19 patients with AKI were more likely to develop respiratory failure, gastrointestinal bleeding, acute liver injury, acute myocardial injury, heart failure, acute respiratory distress syndrome (ARDS), cerebrovascular accident, and disseminated intravascular coagulation (DIC) than those without AKI. Compared with patients without AKI, COVID-19 patients with AKI had lower platelet counts, lymphocyte counts, albumin levels and serum calcium levels but had elevated leukocyte counts, neutrophil counts and serum potassium levels. Inflammatory indicators, such as C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT), were significantly higher in patients with AKI than in those without AKI. COVID-19 patients with AKI also exhibited a longer prothrombin time (PT), a longer activated partial thromboplastin time (APTT), and a higher D-dimer level than those without AKI. Survival analysis revealed that COVID-19 patients with AKI had a reduced survival rate compared with those without AKI. Furthermore, COVID-19 patients with AKI/CKD had a lower survival rate than those with AKI or CKD only. Multiple logistic regression indicated that the predictors of AKI in COVID-19 patients included complications, such as respiratory failure and acute myocardial injury, and higher creatinine and PCT levels during hospitalization.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-337032

ABSTRACT

ABSTRACT Recent studies found that Omicron variant escapes vaccine-elicited immunity. Interestingly, potent cross-clade pan-sarbecovirus neutralizing antibodies were found in survivors of the infection by SARS-CoV-1 after BNT162b2 mRNA vaccination ( N Engl J Med. 2021 Oct 7;385(15):1401-1406 ). These pan-sarbecovirus neutralizing antibodies were observed to efficiently neutralize the infection driven by the S protein from both SARS-CoV and multiple SARS-CoV-2 variants of concern (VOC) including B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.2 (Delta). However, whether these cross-reactive antibodies could neutralize the Omicron variant is still unknown. Based on the data collected from a cohort of SARS-CoV-1 survivors received 3-dose of immunization, our studies reported herein showed that a high level of neutralizing antibodies against both SARS-CoV-1 and SARS-CoV-2 were elicited by a 3rd-dose of booster vaccination of protein subunit vaccine ZF2001. However, a dramatically reduced neutralization of SARS-CoV-2 Omicron Variant (B.1.1.529) is observed in sera from these SARS-CoV-1 survivors received 3-dose of Vaccination. Our results indicates that the rapid development of pan-variant adapted vaccines is warranted.

3.
iScience ; 25(6): 104431, 2022 Jun 17.
Article in English | MEDLINE | ID: covidwho-1851361

ABSTRACT

The different variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have attracted most public concern because they caused "wave and wave" COVID-19 pandemic. The initial step of viral infection is mediated by the SARS-CoV-2 Spike (S) protein, which mediates the receptor recognition and membrane fusion between virus and host cells. Neutralizing antibodies (nAbs) targeting the S protein of SARS-CoV-2 have become promising candidates for clinical intervention strategy, while multiple studies have shown that different variants have enhanced infectivity and antibody resistance. Here, we explore the structure and function of STS165, a broadly inter-Spike bivalent nAb against SARS-CoV-2 variants and even SARS-CoV, contributing to further understanding of the working mechanism of nAbs.

4.
Biomed Res Int ; 2022: 8920117, 2022.
Article in English | MEDLINE | ID: covidwho-1822116

ABSTRACT

The coronavirus disease (COVID-19) which emerged in Wuhan, China, in December 2019, is widely controlled now in China. However, the global epidemic is still severe. To study and comment on Hubei's approaches for responding to the disease, the paper considered some factors such as suspected cases (part of them are influenza patients or common pneumonia patients, etc.), quarantine, patient classification (three types), clinically diagnosed cases, and lockdown of Wuhan and Hubei. After that, the paper established an SELIHR model based on the surveillance data of Hubei published by the Hubei Health Commission from 10 January 2020 to 30 April 2020 and used the fminsearch optimization method to estimate the optimal parameters of the model. We obtained the basic reproduction number ℛ 0 = 3.1571 from 10 to 22 January. ℛ 0 was calculated as 2.0471 from 23 to 27 January. From 28 January to 30 April, ℛ 0 = 1.5014. Through analysis, it is not hard to find that the patients without classification during the period of confirmed cases will result in the cumulative number of cases in Hubei to increase. In addition, regarding the lockdown measures implemented by Hubei during the epidemic, our simulations also show that if the lockdown time of either Hubei or Wuhan is advanced, it will effectively curb the spread of the epidemic. If the lockdown measures are not taken, the total cumulative number of cases will increase substantially. From the results of the study, it can be concluded that the lockdown, patient classification, and the large-scale case screening are essential to slow the spread of COVID-19, which can provide references for other countries or regions.


Subject(s)
COVID-19 , Basic Reproduction Number , COVID-19/epidemiology , China/epidemiology , Communicable Disease Control/methods , Humans , Quarantine , SARS-CoV-2
5.
Signal Transduct Target Ther ; 7(1): 139, 2022 04 27.
Article in English | MEDLINE | ID: covidwho-1815514

ABSTRACT

The SARS-CoV-2 Omicron variant shows substantial resistance to neutralization by infection- and vaccination-induced antibodies, highlighting the demands for research on the continuing discovery of broadly neutralizing antibodies (bnAbs). Here, we developed a panel of bnAbs against Omicron and other variants of concern (VOCs) elicited by vaccination of adenovirus-vectored COVID-19 vaccine (Ad5-nCoV). We also investigated the human longitudinal antibody responses following vaccination and demonstrated how the bnAbs evolved over time. A monoclonal antibody (mAb), named ZWD12, exhibited potent and broad neutralization against SARS-CoV-2 variants Alpha, Beta, Gamma, Kappa, Delta, and Omicron by blocking the spike protein binding to the angiotensin-converting enzyme 2 (ACE2) and provided complete protection in the challenged prophylactic and therapeutic K18-hACE2 transgenic mouse model. We defined the ZWD12 epitope by determining its structure in complex with the spike (S) protein via cryo-electron microscopy. This study affords the potential to develop broadly therapeutic mAb drugs and suggests that the RBD epitope bound by ZWD12 is a rational target for the design of a broad spectrum of vaccines.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Monoclonal/genetics , Antibodies, Viral , Broadly Neutralizing Antibodies , COVID-19/prevention & control , COVID-19 Vaccines/genetics , Cryoelectron Microscopy , Epitopes , Humans , Mice , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Vaccination , Viral Envelope Proteins
6.
Cell Discov ; 8(1): 36, 2022 Apr 21.
Article in English | MEDLINE | ID: covidwho-1805604

ABSTRACT

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529) has aroused concerns over their increased infectivity and transmissibility, as well as decreased sensitivity to SARS-CoV-2-neutralizing antibodies (NAbs) and the current coronavirus disease 2019 (COVID-19) vaccines. Such exigencies call for the development of pan-sarbecovirus vaccines or inhibitors to combat the circulating SARS-CoV-2 NAb-escape variants and other sarbecoviruses. In this study, we isolated a broadly NAb against sarbecoviruses named GW01 from a donor who recovered from COVID-19. Cryo-EM structure and competition assay revealed that GW01 targets a highly conserved epitope in a wide spectrum of different sarbecoviruses. However, we found that GW01, the well-known sarbecovirus NAb S309, and the potent SARS-CoV-2 NAbs CC12.1 and REGN10989 only neutralize about 90% of the 56 tested currently circulating variants of SARS-CoV-2 including Omicron. Therefore, to improve efficacy, we engineered an IgG-like bispecific antibody GW01-REGN10989 (G9) consisting of single-chain antibody fragments (scFv) of GW01 and REGN10989. We found that G9 could neutralize 100% of NAb-escape mutants (23 out of 23), including Omicron variant, with a geometric mean (GM) 50% inhibitory concentration of 8.8 ng/mL. G9 showed prophylactic and therapeutic effects against SARS-CoV-2 infection of both the lung and brain in hACE2-transgenic mice. Site-directed mutagenesis analyses revealed that GW01 and REGN10989 bind to the receptor-binding domain in different epitopes and from different directions. Since G9 targets the epitopes for both GW01 and REGN10989, it was effective against variants with resistance to GW01 or REGN10989 alone and other NAb-escape variants. Therefore, this novel bispecific antibody, G9, is a strong candidate for the treatment and prevention of infection by SARS-CoV-2, NAb-escape variants, and other sarbecoviruses that may cause future emerging or re-emerging coronavirus diseases.

7.
Curr Opin Struct Biol ; 74: 102388, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1796139

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as a public health crisis and led to tremendous economic devastation. The spike protein (S) of SARS-CoV-2 hijacks the angiotensin converting enzyme 2 (ACE2) as a receptor for virus entry, representing the initial step of viral infection. S is one of the major targets for development of the antiviral drugs, antibodies, and vaccines. ACE2 is a peptidase that plays a physiologically important role in the renin-angiotensin system. Concurrently, it also forms dimer of heterodimer with the neutral amino acid transporter B0AT1 to regulate intestinal amino acid metabolism. The symptoms of COVID-19 are closely correlated with the physiological functions of ACE2. In this review, we summarize the functional and structural studies on ACE2, B0AT1, and their complex with S of SARS-CoV-2, providing insights into the various symptoms caused by viral infection and the development of therapeutic strategies.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Angiotensin-Converting Enzyme 2 , Humans , Peptidyl-Dipeptidase A/chemistry , Peptidyl-Dipeptidase A/metabolism , Protein Binding , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism
8.
Cell Discov ; 8(1): 16, 2022 Feb 15.
Article in English | MEDLINE | ID: covidwho-1692632

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) continue to wreak havoc across the globe. Higher transmissibility and immunologic resistance of VOCs bring unprecedented challenges to epidemic extinguishment. Here we describe a monoclonal antibody, 2G1, that neutralizes all current VOCs and has surprising tolerance to mutations adjacent to or within its interaction epitope. Cryo-electron microscopy structure showed that 2G1 bound to the tip of receptor binding domain (RBD) of spike protein with small contact interface but strong hydrophobic effect, which resulted in nanomolar to sub-nanomolar affinities to spike proteins. The epitope of 2G1 on RBD partially overlaps with angiotensin converting enzyme 2 (ACE2) interface, which enables 2G1 to block interaction between RBD and ACE2. The narrow binding epitope but high affinity bestow outstanding therapeutic efficacy upon 2G1 that neutralized VOCs with sub-nanomolar half maximal inhibitory concentration in vitro. In SARS-CoV-2, Beta or Delta variant-challenged transgenic mice and rhesus macaque models, 2G1 protected animals from clinical illness and eliminated viral burden, without serious impact to animal safety. Mutagenesis experiments suggest that 2G1 is potentially capable of dealing with emerging SARS-CoV-2 variants in the future. This report characterized the therapeutic antibodies specific to the tip of spike against SARS-CoV-2 variants and highlights the potential clinical applications as well as for developing vaccine and cocktail therapy.

9.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-317878

ABSTRACT

The COVID-19 pandemic has by-and-large prevented in-person meetings since March 2020. While the increasing deployment of effective vaccines around the world is a very positive development, the timeline and pathway to "normality" is uncertain and the "new normal" we will settle into is anyone's guess. Particle physics, like many other scientific fields, has more than a year of experience in holding virtual meetings, workshops, and conferences. A great deal of experimentation and innovation to explore how to execute these meetings effectively has occurred. Therefore, it is an appropriate time to take stock of what we as a community learned from running virtual meetings and discuss possible strategies for the future. Continuing to develop effective strategies for meetings with a virtual component is likely to be important for reducing the carbon footprint of our research activities, while also enabling greater diversity and inclusion for participation. This report summarizes a virtual two-day workshop on Virtual Meetings held May 5-6, 2021 which brought together experts from both inside and outside of high-energy physics to share their experiences and practices with organizing and executing virtual workshops, and to develop possible strategies for future meetings as we begin to emerge from the COVID-19 pandemic. This report outlines some of the practices and tools that have worked well which we hope will serve as a valuable resource for future virtual meeting organizers in all scientific fields.

10.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315681

ABSTRACT

As of August15, 2020, more than 21,155,600 people were infected and about 761,264 were expired due to SARS-CoV-2 infection worldwide. The extreme spread of the emerging virus makes the disease a serious problem for public health. However, a curative treatment or effective specific vaccine againstSARS-CoV-2 infection is unavailable. Recently, several studies have been performed to evaluate the effects of COVID-19 convalescent plasma transfusion on the clinical outcomes in patients with severe/critical COVID-19 [1-5]. However, the results from these studies aredatable, and thus its useremains investigational.

11.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-324132

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) has brought major harm and challenges to the world. Although many studies have suggested that IFN-I could affect the life cycle of the virus by regulating the expression level of microRNAs, the expression characteristics of plasma IFN-I signaling-related miRNAs at the acute and recovery phase of COVID-19 remain unclear.MethodsDemographic characteristics and fasting blood samples were collected from the acute and recovery phases of 29 COVID-19 patients and 29 healthy controls matched by age (± 5years) and gender (1:1). Expression levels of 12 IFN signaling-related miRNAs were analyzed using RT-qPCR. The receptor-binding domain (RBD) IgG antibody in the convalescent plasma samples was detected using competitive ELISA.ResultsCompared with healthy controls, patients with COVID-19 presented increased levels of miR-29b-3p (~ 5.91-fold), miR-497-5p (~ 2.28-fold), and miR-1246 (~ 7.97-fold), and decreased expression levels of miR-186-5p (~ 6.39-fold) and miR-15a-5p (~ 3.26-fold) at the acute phase of infection. However, the expression levels of miR-29b-3p and miR-1246, which significantly elevated at the acute phase, were not different between individuals at the recovery phase and healthy controls. The expression levels of miR-30b-5p, miR-497-5p, miR-409-3p and miR-548c-5p in convalescent plasma samples were significantly lower than those in healthy controls. However, the concentration of miR-186-5p in the convalescent plasma samples was significantly higher than that in healthy controls and patients with acute infection. Furthermore, competitive ELISA results showed that the plasma level of miR-497-5p at the acute phase positively correlated with RBD-IgG antibody response (r=0.48, P =0.038).ConclusionsThe present study firstly reported that timely and appropriate regulation of IFN signaling-related miRNA expression plays a critical role during both acute and recovery phase of SARS-CoV-2 infection. Furthermore, the circulating miR-497-5p level was positively correlated to RBD-IgG antibody response in COVID-19 patients.

12.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323646

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a new emerging public health crisis to the world. However, data are still limited on the clinical features and laboratory findings in COVID-19 patients. Methods: : Medical records including demographics characteristics, clinical features, laboratory findings and radiological materials of 66 hospitalized COVID-19 patients were collected between Jan 23 and Mar 9, 2020. Symptoms/signs with potential association with the disease severity were analyzed. Results: : Of 66 hospitalized COVID-19 patients, the male-to-female ratio was 44:22. There were eight cases potentially exposed to one single patient. The most common initial symptoms of SARS-CoV-2 infection were fever (77.3%) and cough (74.2%). Compared to those with non-severe infection, the severe patients were more likely to be older (62.6 ± 15.1 vs 46.9 ± 13.3 years. P = 0.001) and with more infected lobes. As the results shown, higher initial (on admission) and peak (during hospitalization) counts of lymphocyte were inversely associated with the severe SARS-CoV-2 infection (both OR: 0.01 every 1´10 9 /L decrease). However, the elevated initial neutrophil counts (OR: 1.63 every 1´10 9 /L increase), initial and peak levels of LDH (OR: 1.02 and 1.01 every 1 U/L increase), peak levels of CRP (OR: 1.03 every 1 mg/L increase), AST (OR: 1.06 every 1 U/L increase) and ALT (OR: 1.02 every 1 U/L increase) were significantly associated with COVID-19 severity. Conclusion: Our present study indicated that fever and cough were the most common initial symptoms of SARS-CoV-2 infection, and the virus could be efficiently spread by person-to-person transmission. In addition, lymphocyte and neutrophil counts, and serum levels of AST, ALT, CRP and LDH should be useful for the evaluation on COVID-19 severity.

13.
International Journal of Financial Studies ; 9(4):70, 2021.
Article in English | ProQuest Central | ID: covidwho-1599427

ABSTRACT

The aim of this study is to investigate the herding of beta transmission between return and volatility. We have used the dynamic conditional correlation model with the mixed-data sampling (DCC-MIDAS) model for the analysis. The evidence demonstrates that herding is a key transmitter in Taiwan’s stock market. The significant estimation of DCC-MIDAS explains that the herding phenomenon is highly dynamic and time-varying in herding behavior. By means of time-varying beta of herding based on our rolling forecasting method and robustness check of the Markov-switching regression approach using four types of portfolios, the evidence indicates that there are conditional correlations between betas and herding. In addition, it also reveals that herding forms in Taiwan’s markets during the subprime crisis period.

14.
BMC Public Health ; 21(1): 2239, 2021 12 09.
Article in English | MEDLINE | ID: covidwho-1566517

ABSTRACT

BACKGROUND: COVID-19 patients with long incubation period were reported in clinical practice and tracing of close contacts, but their epidemiological or clinical features remained vague. METHODS: We analyzed 11,425 COVID-19 cases reported between January-August, 2020 in China. The accelerated failure time model, Logistic and modified Poisson regression models were used to investigate the determinants of prolonged incubation period, as well as their association with clinical severity and transmissibility, respectively. RESULT: Among local cases, 268 (10.2%) had a prolonged incubation period of > 14 days, which was more frequently seen among elderly patients, those residing in South China, with disease onset after Level I response measures administration, or being exposed in public places. Patients with prolonged incubation period had lower risk of severe illness (ORadjusted = 0.386, 95% CI: 0.203-0.677). A reduced transmissibility was observed for the primary patients with prolonged incubation period (50.4, 95% CI: 32.3-78.6%) than those with an incubation period of ≤14 days. CONCLUSIONS: The study provides evidence supporting a prolonged incubation period that exceeded 2 weeks in over 10% for COVID-19. Longer monitoring periods than 14 days for quarantine or persons potentially exposed to SARS-CoV-2 should be justified in extreme cases, especially for those elderly.


Subject(s)
COVID-19 , Epidemics , Infectious Disease Incubation Period , COVID-19/epidemiology , China/epidemiology , Humans , Quarantine , SARS-CoV-2
15.
Cardiol Discov ; 1(4): 233-258, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1566076

ABSTRACT

COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection likely ranks among the deadliest diseases in human history. As with other coronaviruses, SARS-CoV-2 infection damages not only the lungs but also the heart and many other organs that express angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV-2. COVID-19 has upended lives worldwide. Dietary behaviors have been altered such that they favor metabolic and cardiovascular complications, while patients have avoided hospital visits because of limited resources and the fear of infection, thereby increasing out-hospital mortality due to delayed diagnosis and treatment. Clinical observations show that sex, age, and race all influence the risk for SARS-CoV-2 infection, as do hypertension, obesity, and pre-existing cardiovascular conditions. Many hospitalized COVID-19 patients suffer cardiac injury, acute coronary syndromes, or cardiac arrhythmia. SARS-CoV-2 infection may lead to cardiomyocyte apoptosis and necrosis, endothelial cell damage and dysfunction, oxidative stress and reactive oxygen species production, vasoconstriction, fibrotic and thrombotic protein expression, vascular permeability and microvascular dysfunction, heart inflammatory cell accumulation and activation, and a cytokine storm. Current data indicate that COVID-19 patients with cardiovascular diseases should not discontinue many existing cardiovascular therapies such as ACE inhibitors, angiotensin receptor blockers, steroids, aspirin, statins, and PCSK9 inhibitors. This review aims to furnish a framework relating to COVID-19 and cardiovascular pathophysiology.

16.
Virol J ; 18(1): 244, 2021 12 07.
Article in English | MEDLINE | ID: covidwho-1559217

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a huge challenge worldwide. Although previous studies have suggested that type I interferon (IFN-I) could inhibit the virus replication, the expression characteristics of IFN-I signaling-related miRNAs (ISR-miRNAs) during acute severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and its relationship with receptor-binding domain (RBD) IgG antibody response at the recovery phase remain unclear. METHODS: Expression profiles of 12 plasma ISR-miRNAs in COVID-19 patients and healthy controls were analyzed using RT-qPCR. The level of RBD-IgG antibody was determined using the competitive ELISA. Spearman correlation was done to measure the associations of plasma ISR-miRNAs with clinical characteristics during acute SARS-CoV-2 infection and RBD-IgG antibody response at the recovery phase. RESULTS: Compared with the healthy controls, COVID-19 patients exhibited higher levels of miR-29b-3p (Z = 3.15, P = 0.002) and miR-1246 (Z = 4.98, P < 0.001). However, the expression of miR-186-5p and miR-15a-5p were significantly decreased. As the results shown, miR-30b-5p was negatively correlated with CD4 + T cell counts (r = - 0.41, P = 0.027) and marginally positively correlated with fasting plasma glucose in COVID-19 patients (r = 0.37, P = 0.052). The competitive ELISA analysis showed the plasma level of miR-497-5p at the acute phase was positively correlated with RBD-IgG antibody response (r = 0.48, P = 0.038). CONCLUSIONS: Our present results suggested that the expression level of ISR-miRNAs was not only associated with acute SARS-CoV-2 infection but also with RBD-IgG antibody response at the recovery phase of COVID-19. Future studies should be performed to explore the biological significance of ISR-miRNAs in SARS-CoV-2 infection.


Subject(s)
Antibodies, Viral/immunology , COVID-19/diagnosis , Immunoglobulin G/immunology , Interferon Type I/genetics , MicroRNAs , Virus Replication/genetics , COVID-19/blood , COVID-19 Nucleic Acid Testing , Case-Control Studies , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Immunoglobulin G/blood , Interferon Type I/blood , Male , MicroRNAs/blood , MicroRNAs/genetics , MicroRNAs/metabolism , Middle Aged , Pregnancy , SARS-CoV-2
17.
Complex Intell Systems ; : 1-8, 2021 Feb 10.
Article in English | MEDLINE | ID: covidwho-1516944

ABSTRACT

The distribution of relief materials is an important part of post-disaster emergency rescue. To meet the needs of the relief materials in the affected areas after a sudden disaster and ensure its smooth progress, an optimized dispatch model for multiple periods and multiple modes of transportation supported by the Internet of Things is established according to the characteristics of relief materials. Through the urgent production of relief materials, market procurement, and the use of inventory collection, the needs of the disaster area are met and the goal of minimizing system response time and total cost is achieved. The model is solved using CPLX software, and numerical simulation and results are analyzed using the example of the COVID-19 in Wuhan City, and the dispatching strategies are given under different disruption scenarios. The results show that the scheduling optimization method can meet the material demand of the disaster area with shorter time and lower cost compared with other methods, and can better cope with the supply interruptions that occur in post-disaster rescue.

18.
Signal Transduct Target Ther ; 6(1): 315, 2021 08 25.
Article in English | MEDLINE | ID: covidwho-1442755

ABSTRACT

The evolution of coronaviruses, such as SARS-CoV-2, makes broad-spectrum coronavirus preventional or therapeutical strategies highly sought after. Here we report a human angiotensin-converting enzyme 2 (ACE2)-targeting monoclonal antibody, 3E8, blocked the S1-subunits and pseudo-typed virus constructs from multiple coronaviruses including SARS-CoV-2, SARS-CoV-2 mutant variants (SARS-CoV-2-D614G, B.1.1.7, B.1.351, B.1.617.1, and P.1), SARS-CoV and HCoV-NL63, without markedly affecting the physiological activities of ACE2 or causing severe toxicity in ACE2 "knock-in" mice. 3E8 also blocked live SARS-CoV-2 infection in vitro and in a prophylactic mouse model of COVID-19. Cryo-EM and "alanine walk" studies revealed the key binding residues on ACE2 interacting with the CDR3 domain of 3E8 heavy chain. Although full evaluation of safety in non-human primates is necessary before clinical development of 3E8, we provided a potentially potent and "broad-spectrum" management strategy against all coronaviruses that utilize ACE2 as entry receptors and disclosed an anti-coronavirus epitope on human ACE2.


Subject(s)
Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Antibodies, Monoclonal, Murine-Derived/pharmacology , Antiviral Agents/pharmacology , COVID-19/drug therapy , SARS-CoV-2/immunology , Angiotensin-Converting Enzyme 2/immunology , Animals , Antibodies, Monoclonal, Murine-Derived/immunology , Antiviral Agents/immunology , Chlorocebus aethiops , Disease Models, Animal , HEK293 Cells , Humans , Mice , Mice, Inbred BALB C , Mice, Transgenic , Vero Cells
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