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1.
Preprint in English | medRxiv | ID: ppmedrxiv-21268499

ABSTRACT

BackgroundThe increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccinations. In this study, we reported the safety and immunogenicity of a heterologous boost with a recombinant COVID-19 vaccine (CHO cells), named NVSI-06-07, as a third dose in participants who have previously received two doses of the inactivated vaccine (BBIBP-CorV) at pre-specified time intervals. Using homologous boost with BBIBP-CorV as control, the safety and immunogenicity of the heterologous boost with NVSI-06-07 against various SARS-CoV-2 strains, including Omicron, were characterized. MethodsThis study is a single-center, randomised, double-blinded, controlled phase 2 trial for heterologous boost of NVSI-06-07 in BBIBP-CorV recipients from the United Arab Emirates (UAE). Healthy adults (aged [≥]18 years) were enrolled and grouped by the specified prior vaccination interval of BBIBP-CorV, i.e., 1-3 months, 4-6 months or [≥]6 months, respectively, with 600 individuals per group. For each group, participants were randomly assigned at 1:1 ratio to receive either a heterologous boost of NVSI-06-07 or a homologous booster dose of BBIBP-CorV. The primary outcome was to comparatively assess the immunogenicity between heterologous and homologous boosts at 14 and 28 days post-boosting immunization, by evaluation of the geometric mean titers (GMTs) of IgG and neutralizing antibodies as well as the corresponding seroconversion rate ([≥]4-fold rise in antibody titers). The secondary outcomes were the safety profile of the boosting strategies within 30 days post vaccination. The exploratory outcome was the immune efficacy against Omicron and other variants of concern (VOCs) of SARS-CoV-2. This trial is registered with ClinicalTrials.gov, NCT05033847. FindingsA total of 1800 individuals who have received two doses of BBIBP-CorV were enrolled, of which 899 participants received a heterologous boost of NVSI-06-07 and 901 received a homologous boost for comparison. No vaccine-related serious adverse event (SAE) and no adverse events of special interest (AESI) were reported. 184 (20{middle dot}47%) participants in the heterologous boost groups and 177 (19{middle dot}64%) in the homologous boost groups reported at least one adverse reaction within 30 days. Most of the local and systemic adverse reactions reported were grades 1 (mild) or 2 (moderate), and there was no significant difference in the overall safety between heterologous and homologous boosts. Immunogenicity assays showed that the seroconversion rates in neutralizing antibodies against prototype SARS-CoV-2 elicited by heterologous boost were 89{middle dot}96% - 97{middle dot}52% on day 28 post-boosting vaccination, which was much higher than what was induced by homologous boost (36{middle dot}80% - 81{middle dot}75%). Similarly, in heterologous NVSI-06-07 booster groups, the neutralizing geometric mean titers (GMTs) against the prototype strain increased by 21{middle dot}01 - 63{middle dot}85 folds from baseline to 28 days post-boosting vaccination, whereas only 4{middle dot}20 - 16{middle dot}78 folds of increases were observed in homologous BBIBP-CorV booster group. For Omicron variant, the neutralizing antibody GMT elicited by the homologous boost of BBIBP-CorV was 37{middle dot}91 (95%CI, 30{middle dot}35-47{middle dot}35), however, a significantly higher level of neutralizing antibodies with GMT 292{middle dot}53 (95%CI, 222{middle dot}81-384{middle dot}07) was induced by the heterologous boost of NVSI-06-07, suggesting that it may serve as an effective boosting strategy combating the pandemic of Omicron. The similar results were obtained for other VOCs, including Alpha, Beta and Delta, in which the neutralizing response elicited by the heterologous boost was also significantly greater than that of the homologous boost. In the participants primed with BBIBP-CorV over 6 months, the largest increase in the neutralizing GMTs was obtained both in the heterologous and homologous boost groups, and thus the booster vaccination with over 6 months intervals was optimal. InterpretationOur findings indicated that the heterologous boost with NVSI-06-07 was safe, well-tolerated and immunogenic in adults primed with a full regimen of BBIBP-CorV. Compared to homologous boost with a third dose of BBIBP-CorV, incremental increases in immune responses were achieved by the heterologous boost with NVSI-06-07 against SARS-CoV-2 prototype strain, Omicron variant, and other VOCs. The heterologous BBIBP-CorV/NVSI-06-07 prime-boosting vaccination may be valuable in preventing the pandemic of Omicron. The optimal booster strategy was the heterologous boost with NVSI-06-07 over 6 months after a priming with two doses of BBIBP-CorV. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for clinical trials or prospective/cohort studies involving heterologous booster vaccination in non-immunocompromised population published up to Dec 25, 2021, using the term "(COVID) AND (vaccin*) AND (clinical trial OR cohort OR prospective) AND (heterologous) AND (booster OR prime-boost OR third dose)" with no language restrictions. Nine studies of heterologous prime-boost vaccinations with adenovirus-vector vaccines (ChAdOx1 nCov-19, Oxford-AstraZeneca, Ad26.COV2.S, Janssen) and mRNA vaccines (BNT162b2, Pfizer-BioNtech; mRNA1273, Moderna) were identified. The adenovirus-vector and mRNA heterologous prime-boost vaccination was found to be well tolerated and immunogenic. In individuals primed with adenovirus-vector vaccine, mRNA booster vaccination led to greater immune response than homologous boost. However, varied results were obtained on whether heterologous boost was immunogenically superior to the homologous mRNA prime-boost vaccination. Besides that, A preprint trial in population previously immunized with inactivated vaccines (CoronaVac, Sinovac Biotech) showed that the heterologous boost with adenovirus-vector vaccine (Convidecia, CanSino Biologicals) was safe and induced higher level of live-virus neutralizing antibodies than by the homogeneous boost. A pilot study reported that boosting with BNT162b2 in individuals primed with two doses of inactivated vaccines (BBIBP-CorV) was significantly more immunogenic than homologous vaccination with two-dose of BNT162b2. In addition, a preprint paper demonstrated that heterologous boost of ZF2001, a recombinant protein subunit vaccine, after CoronaVac or BBIBP-CorV vaccination potently improved the immunogenicity. But only a small size of samples was tested in this study and the live-virus neutralization was not detected. Till now, it is still lacking a formal clinical trial to evaluate the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated vaccine followed by a recombinant protein subunit-based vaccine. Added value of this studyTo our knowledge, this is the first reported result of a large-scale randomised, controlled clinical trial of heterologous prime-boost vaccination with an inactivated vaccine followed by a recombinant protein subunit vaccine. This trial demonstrated that the heterologous prime-booster vaccination with BBIBP-CorV/NVSI-06-07 is safe and immunogenic. Its immunoreactivity is similar to that of homologous vaccination with BBIBP-CorV. Compared to homologous boost, heterologous boost with NVSI-06-07 in BBIBP-CorV recipients elicited significantly higher immunogenicity not only against the SARS-CoV-2 prototype strain but also against Omicron and other variants of concern (VOCs). Implications of all the available evidenceBooster vaccination is considered an effective strategy to improve the protection efficacy of COVID-19 vaccines and control the epidemic waves of SARS-CoV-2. Data from our trial suggested that the booster vaccination of NVSI-06-07 in BBIBP-CorV recipients significantly improved the immune responses against various SARS-CoV-2 strains, including Omicron. Due to no Omicron-specific vaccine available currently, the BBIBP-CorV/NVSI-06-07 heterologous prime-boost might serve as an effective strategy combating Omicron variant. Besides that, BBIBP-CorV has been widely inoculated in population, and thus further boosting vaccination with NVSI-06-07 is valuable in preventing the COVID-19 pandemic. But further studies are needed to assess the long-term protection of BBIBP-CorV/NVSI-06-07 prime-booster vaccination.

2.
Preprint in English | bioRxiv | ID: ppbiorxiv-474432

ABSTRACT

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019, viral variants with greater transmissibility or immune evasion properties have arisen, which could jeopardize recently deployed vaccine and antibody-based countermeasures. Here, we evaluated in mice and hamsters the efficacy of preclinical non-GMP Moderna mRNA vaccine (mRNA-1273) and the Johnson & Johnson recombinant adenoviral-vectored vaccine (Ad26.COV2.S) against the B.1.621 (Mu) South American variant of SARS-CoV-2, which contains spike mutations T95I, Y144S, Y145N, R346K, E484K, N501Y, D614G, P681H, and D950N. Immunization of 129S2 and K18-human ACE2 transgenic mice with mRNA-1273 vaccine protected against weight loss, lung infection, and lung pathology after challenge with B.1.621 or WA1/2020 N501Y/D614G SARS-CoV-2 strain. Similarly, immunization of 129S2 mice and Syrian hamsters with a high dose of Ad26.COV2.S reduced lung infection after B.1.621 virus challenge. Thus, immunity induced by mRNA-1273 or Ad26.COV2.S vaccines can protect against the B.1.621 variant of SARS-CoV-2 in multiple animal models.

3.
Zhongguo Yaolixue yu Dulixue Zazhi = Chinese Journal of Pharmacology and Toxicology ; - (10):737, 2021.
Article in English | ProQuest Central | ID: covidwho-1564981

ABSTRACT

OBJECTIVE Since the coronavirus disease 2019(COVID-19) outbreak in December 2019, the search for a potential treatment for COVID-19 has been a constant focus. Therefore, we identified potential treatments for COVID-19 from Hippophae Fructus, a Tibetan medicine that may act on COVID-19, using a network pharmacology approach.METHODS We collected the chemical constituents and corresponding targets of Hippophae Fructus from traditional Chinese medicine system pharmacology(TCMSP). COVID-19 related genes were predicted in pubmed-Gene, OMIM and GeneCards databases. Then, protein-protein interactions(PPIs) of key genes were analyzed by STRING database.Compound-target-diseases network was constructed using Cytoscape software. The potential pathways were determined by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analyses. Additionally,molecular docking was used to verify the binding effect between the active component and the target. RESULTS A total of 33 components and 192 corresponding targets in Hippophae Fructus were found. 50 genes were obtained from the intersection of component targets and disease targets. These genes include IL-6, TNF, MAPK8 and PTGS2, which regulate several pathways associated with COVID-19, involving Hepatitis B, Influenza A, TNF signaling pathway and Tuberculosis. More importantly, high-node compounds such as quercetin and beta-sitosterol can well bind to key targets.CONCLUSION Some components in Hippophae Fructus can act on COVID-19 related genes and regulate multiple pathways. Perhaps Hippophae Fructus has the effect in treating COVID-19.

4.
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
5.
Pathogens ; 10(9)2021 Sep 08.
Article in English | MEDLINE | ID: covidwho-1410521

ABSTRACT

SARS-CoV-2 infection has caused a global pandemic that has severely damaged both public health and the economy. The nucleocapsid protein of SARS-CoV-2 is multifunctional and plays an important role in ribonucleocapsid formation and viral genome replication. In order to elucidate its functions, interaction partners of the SARS-CoV-2 N protein in human cells were identified via affinity purification and mass spectrometry. We identified 160 cellular proteins as interaction partners of the SARS-CoV-2 N protein in HEK293T and/or Calu-3 cells. Functional analysis revealed strong enrichment for ribosome biogenesis and RNA-associated processes, including ribonucleoprotein complex biogenesis, ribosomal large and small subunits biogenesis, RNA binding, catalysis, translation and transcription. Proteins related to virus defence responses, including MOV10, EIF2AK2, TRIM25, G3BP1, ZC3HAV1 and ZCCHC3 were also identified in the N protein interactome. This study comprehensively profiled the viral-host interactome of the SARS-CoV-2 N protein in human cells, and the findings provide the basis for further studies on the pathogenesis and antiviral strategies for this emerging infection.

6.
Preprint in English | bioRxiv | ID: ppbiorxiv-457693

ABSTRACT

Although mRNA vaccines prevent COVID-19, variants jeopardize their efficacy as immunity wanes. Here, we assessed the immunogenicity and protective activity of historical (mRNA-1273, designed for Wuhan-1 spike) or modified (mRNA-1273.351, designed for B.1.351 spike) preclinical Moderna mRNA vaccines in 129S2 and K18-hACE2 mice. Immunization with high or low dose formulations of mRNA vaccines induced neutralizing antibodies in serum against ancestral SARS-CoV-2 and several variants, although levels were lower particularly against the B.1.617.2 (Delta) virus. Protection against weight loss and lung pathology was observed with all high-dose vaccines against all viruses. Nonetheless, low-dose formulations of the vaccines, which produced lower magnitude antibody and T cell responses, and serve as a possible model for waning immunity, showed breakthrough lung infection and pneumonia with B.1.617.2. Thus, as levels of immunity induced by mRNA vaccines decline, breakthrough infection and disease likely will occur with some SARS-CoV-2 variants, suggesting a need for additional booster regimens.

7.
Traditional Med.Res. ; 4(5): 201-215, 20200702.
Article in English | ELSEVIER | ID: covidwho-1352968

ABSTRACT

Background: To evaluate the mechanism of Chinese patent drug Xuebijing (XBJ) injection in the treatment of a new coronavirus disease 2019 (COVID-19) based on network pharmacology and molecular docking technology. Methods: The TCMSP database was employed to collect and screen the active ingredients of the Chinese herb contained in the XBJ injection. The GeneCards database and STRING database were applied to collect and expand the targets of COVID-19 and compare and screen the related targets of COVID-19 by XBJ injection. Cytoscape was employed to build a network connecting Chinese medicine, compounds, targets, disease, and topology analysis was performed via the Network Analyzer to screen the key ingredients and targets. The software of Schrödinger molecular docking was used to verify the binding activity of the key ingredients of XBJ injection and the key targets of COVID-19. Metascape platform and DAVID database were utilized to conduct Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis on the key targets of COVID-19 treated by XBJ injection. Results: Eight key compounds and 15 key targets were screened and verified by molecular docking; these key compounds included luteolin, quercetin, baicalein, and kaempferol. The key targets included DPP4, AR, ESR1, CALM1, and protein kinase 1. Gene Ontology analysis involved an apoptosis and hypoxia reaction and the changes in blood vessel morphology. Kyoto Encyclopedia of Genes and Genomes analysis involved signaling pathways of hypoxia inducible factor-1, VEGF, and PI3K/AKT/NF-κB. Conclusion: The mechanism of XBJ injection when used to treat COVID-19 should be further investigated as the key compounds in XBJ regulated the expression of key targets such as protein kinase 1, VEGF-A, B-cell lymphoma-2, and TNF, which affected the COVID-19 receptors such as angiotensin-converting enzyme 2 and signaling pathways like hypoxia inducible factor-1, PI3K-Akt, and NF-κB, which alleviated the inflammation, respiratory distress, and hypoxia caused by COVID-19 infection.

8.
BMC Med ; 19(1): 191, 2021 08 09.
Article in English | MEDLINE | ID: covidwho-1344106

ABSTRACT

BACKGROUND: Knowledge about the 1-year outcome of COVID-19 is limited. The aim of this study was to follow-up and evaluate lung abnormalities on serial computed tomography (CT) scans in patients with COVID-19 after hospital discharge. METHODS: A prospective cohort study of patients with COVID-19 from the First Affiliated Hospital, Zhejiang University School of Medicine was conducted, with assessments of chest CT during hospitalization and at 2 weeks, 1 month, 3 months, 6 months, and 1 year after hospital discharge. Risk factors of residual CT opacities and the influence of residual CT abnormalities on pulmonary functions at 1 year were also evaluated. RESULTS: A total of 41 patients were followed in this study. Gradual recovery after hospital discharge was confirmed by the serial CT scores. Around 47% of the patients showed residual aberration on pulmonary CT with a median CT score of 0 (interquartile range (IQR) of 0-2) at 1 year after discharge, with ground-glass opacity (GGO) with reticular pattern as the major radiologic pattern. Patients with residual radiological abnormalities were older (p = 0.01), with higher rate in current smokers (p = 0.04), higher rate in hypertensives (p = 0.05), lower SaO2 (p = 0.004), and higher prevalence of secondary bacterial infections during acute phase (p = 0.02). Multiple logistic regression analyses indicated that age was a risk factor associated with residual radiological abnormalities (OR 1.08, 95% CI 1.01-1.15, p = 0.02). Pulmonary functions of total lung capacity (p = 0.008) and residual volume (p < 0.001) were reduced in patients with residual CT abnormalities and were negatively correlated with CT scores. CONCLUSION: During 1-year follow-up after discharge, COVID-19 survivors showed continuous improvement on chest CT. However, residual lesions could still be observed and correlated with lung volume parameters. The risk of developing residual CT opacities increases with age.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Adult , COVID-19/diagnostic imaging , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Retrospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed
9.
BMC Med Educ ; 21(1): 397, 2021 Jul 23.
Article in English | MEDLINE | ID: covidwho-1322933

ABSTRACT

BACKGROUND: The purpose of this study is to understand the influencing factors of Chinese college students' satisfaction with online teaching and psychological pressure on learning during the novel coronavirus epidemic. METHODS: We assessed the effect of online teaching of 7084 medical students from wannan medical college in March 5 to April 2, 2020 using cluster sampling. The respondents were asked to complete a 7-item self-compiled online teaching satisfaction questionnaire. Chi-square test and multivariate logistic regression analysis are used. RESULTS: Sex is female (OR = 1.257, 95%CI: 1.132 ~ 1.396), grades are second and third grades (second grades: OR = 1.228, 95%CI: 1.080 ~ 1.397; third grades: OR = 1.197, 95%CI: 1.048 ~ 1.367), normal/unfamiliar learning platform operation (OR = 3.692, 95%CI: 3.321 ~ 4.103) were risk factors for satisfactory teaching effect. In addition, students whose school year system is four-year (OR = 0.870, 95%CI: 0.781 ~ 0.969) and grade 4 and above (OR = 0.594, 95%CI: 0.485 ~ 0.727) were more satisfied with the teaching effect of teachers. And, during the period of the COVID-19 epidemic, the risk factors for college students to have psychological stress were: female (OR = 1.258, 95%CI: 1.096 ~ 1.442), from rural areas (OR = 1.511, 95%CI: 1.312 ~ 1.740), and the academic year system is four-year system (OR = 1.191, 95%CI: 1.028 ~ 1.380), using mobile phones and other learning tools (OR = 1.388, 95%CI: 1.205 ~ 1.600), general/unfamiliar with learning platform operations (OR = 2.273), 95%CI: 1.888 ~ 2.735). While the protective factors for college students' psychological stress included: grade three and four and above (OR = 0.463, 95%CI: 0.387 ~ 0.554; OR = 0.232, 95%CI: 0.187 ~ 0.286), and they think that the teaching effect is satisfactory (OR = 0.314, 95%CI: 0.261 ~ 0.379). CONCLUSION: This survey shows that compared with male college students, female college students were more dissatisfied with the teaching effect of teachers and havd greater psychological pressure on learning. Psychological counseling should be strengthened for students in rural areas and those who were not familiar with the operating platform to relieve their psychological pressure on learning.


Subject(s)
COVID-19 , Epidemics , Students, Medical , Female , Humans , Male , SARS-CoV-2 , Schools, Medical
10.
Placenta ; 111: 91-96, 2021 08.
Article in English | MEDLINE | ID: covidwho-1272664

ABSTRACT

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mainly transmitted by droplets and close contact, has caused a pandemic worldwide as of March 2020. According to the current case reports and cohort studies, the symptoms of pregnant women infected with SARS-CoV-2 were similar to normal adults and may cause a series of adverse consequences of pregnancy (placental abruption, fetal distress, epilepsy during pregnancy, etc.). However, whether SARS-CoV-2 can be transmitted to the fetus through the placental barrier is still a focus of debate. METHODS: In this study, in order to find out whether SARS-CoV-2 can infect fetus through the placental barrier, we performed qualitative detection of virus structural protein (spike protein and nucleoprotein) and targeted receptor protein Angiotensin Converting Enzyme 2 (ACE2), Basigin (CD147) and molecular chaperone GRP78 expression on the placental tissue of seven pregnant women diagnosed with COVID-19 through immunohistochemistry. Amniotic fluid, neonatal throat, anal swab and breastmilk samples were collected immediately in the operating room or delivery room for verification after delivery, which were all tested for SARS-CoV-2 by reverse transcriptionpolymerase chain reaction (RT-PCR). RESULTS/DISCUSSION: The result showed that CD147 was expressed on the basal side of the chorionic trophoblast cell membrane and ACE2 was expressed on the maternal side, while GRP78 was strongly expressed in the cell membrane and cytoplasm. The RT-PCR results of Amniotic fluid, neonatal throat, anal swab and breastmilk samples were all negative. On the basis of these findings, we speculated that it may be due to the placental barrier between mother and baby, for example, villous matrix and interstitial blood vessels have low expression of virus-related receptors (ACE2, CD147, GRP78), the probability of vertical transmission of SARS-CoV-2 through the placenta is low.


Subject(s)
COVID-19/transmission , Infectious Disease Transmission, Vertical , Placenta/virology , Pregnancy Complications, Infectious/virology , SARS-CoV-2 , Adult , Amniotic Fluid/virology , Angiotensin-Converting Enzyme 2/analysis , Basigin/analysis , COVID-19 Testing , China , Female , Fetal Diseases/virology , Heat-Shock Proteins/analysis , Humans , Infant, Newborn , Nucleoproteins/analysis , Placenta/chemistry , Pregnancy , Reverse Transcriptase Polymerase Chain Reaction , Spike Glycoprotein, Coronavirus/analysis
11.
Preprint in English | bioRxiv | ID: ppbiorxiv-448958

ABSTRACT

The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 is an attractive target for COVID-19 vaccine developments, which naturally exists in a trimeric form. Here, guided by structural and computational analyses, we present a mutation-integrated trimeric form of RBD (mutI tri-RBD) as a broadly protective vaccine candidate, in which three RBDs were individually grafted from three different circulating SARS-CoV-2 strains including the prototype, Beta (B.1.351) and Kappa (B.1.617). The three RBDs were then connected end-to-end and co-assembled to possibly mimic the native trimeric arrangements in the natural S protein trimer. The recombinant expression of the mutI tri-RBD, as well as the homo-tri-RBD where the three RBDs were all truncated from the prototype strain, by mammalian cell exhibited correct folding, strong bio-activities, and high stability. The immunization of both the mutI tri-RBD and homo-tri-RBD plus aluminum adjuvant induced high levels of specific IgG and neutralizing antibodies against the SARS-CoV-2 prototype strain in mice. Notably, regarding to the "immune-escape" Beta (B.1.351) variant, mutI tri-RBD elicited significantly higher neutralizing antibody titers than homo-tri-RBD. Furthermore, due to harboring the immune-resistant mutations as well as the evolutionarily convergent hotspots, the designed mutI tri-RBD also induced strong broadly neutralizing activities against various SARS-CoV-2 variants, especially the variants partially resistant to homo-tri-RBD. Homo-tri-RBD has been approved by the China National Medical Products Administration to enter clinical trial (No. NCT04869592), and the superior broad neutralization performances against SARS-CoV-2 support the mutI tri-RBD as a more promising vaccine candidate for further clinical developments.

12.
J Clin Med ; 10(10)2021 May 13.
Article in English | MEDLINE | ID: covidwho-1256577

ABSTRACT

Despite numerous technological and medical advances, out-of-hospital cardiac arrests (OHCAs) still suffer from suboptimal survival rates and poor subsequent neurological and functional outcomes amongst survivors. Multiple studies have investigated the implementation of high-quality prehospital resuscitative efforts, and across these studies, different terms describing high-quality resuscitative efforts have been used, such as high-performance CPR (HP CPR), multi-tiered response (MTR) and minimally interrupted cardiac resuscitation (MICR). There is no universal definition for HP CPR, and dissimilar designs have been employed. This systematic review thus aimed to review current evidence on HP CPR implementation and examine the factors that may influence OHCA outcomes. Eight studies were systematically reviewed, and seven were included in the final meta-analysis. Random-effects meta-analysis found a significantly improved likelihood of prehospital return of spontaneous circulation (pooled odds ratio (OR) = 1.46, 95% CI: 1.16 to 1.82, p < 0.001), survival-to-discharge (pooled OR = 1.32, 95% CI: 1.16 to 1.50, p < 0.001) and favourable neurological outcomes (pooled OR = 1.24, 95% CI: 1.11 to 1.39, p < 0.001) with HP CPR or similar interventions. However, the studies had generally high heterogeneity (I2 greater than 50%) and overall moderate-to-severe risk for bias. Moving forward, a randomised, controlled trial is necessary to shed light on the subject.

13.
Educ Inf Technol (Dordr) ; : 1-15, 2021 Jun 05.
Article in English | MEDLINE | ID: covidwho-1252157

ABSTRACT

With the rapid advancement of China's "Internet plus Education" plan, "Internet plus Education" has become a research hotspot. The outbreak of COVID-19 pandemic has brought great opportunities, tests and inspections for online education. All schools earnestly implemented the relevant requirements of the Ministry of Education and leverage the strengths of the Internet to ensure that "suspension of classes and non-stop teaching". Taking a middle school in the west part of China as an example, the online survey was conducted to investigate its live broadcast teaching. The independent sample test and one-way analysis of variance were used to statistically analyze the differences among the students' genders, grades, home location, type of device used and parental companionship. Finally, the implications were put forward to provide a reference for live teaching practice.

14.
Front Cell Infect Microbiol ; 11: 650487, 2021.
Article in English | MEDLINE | ID: covidwho-1167306

ABSTRACT

Background: Convalescent plasma (CP) transfusion is considered to be the priority therapeutic option for COVID-19 inpatients when no specific drugs are available for emerging infections. An alternative, simple, and sensitive method is urgently needed for clinical use to detect neutralization activity of the CP to avoid the use of inconvenient micro-neutralization assay. Method: This study aims to explore optimal index in predicting the COVID-19 CP neutralization activity (neutralizing antibody titers, NAb titers) in an indirect ELISA format. Fifty-seven COVID-19-recovered patients plasma samples were subjected to anti-SARS-CoV-2 RBD, S1, and N protein IgG antibody by indirect ELISA. Results: ELISA-RBD exhibited high specificity (96.2%) and ELISA-N had high sensitivity (100%); while ELISA-S1 had low sensitivity (86.0%) and specificity (73.1%). Furthermore, ELISA-RBD IgG titers and pseudovirus-based NAb titers correlated significantly, with R2 of 0.2564 (P < 0.0001). Conclusion: ELISA-RBD could be a substitute for the neutralization assay in resource-limited situations to screen potential plasma donors for further plasma infusion therapy.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/blood , COVID-19/therapy , Immunization, Passive/methods , Plasma/immunology , Animals , Antibodies, Viral/therapeutic use , Antiviral Agents/therapeutic use , Blood Donors , China , Chlorocebus aethiops , Cohort Studies , Enzyme-Linked Immunosorbent Assay , HEK293 Cells , Humans , Immunoglobulin G/blood , SARS-CoV-2 , Sensitivity and Specificity , Vero Cells
15.
Health Qual Life Outcomes ; 19(1): 103, 2021 Mar 22.
Article in English | MEDLINE | ID: covidwho-1147072

ABSTRACT

BACKGROUND: More than 210,000 medical workers have fought against the outbreak of Coronavirus Disease 2019 (COVID-19) in Hubei in China since December 2019. However, the prevalence of mental health problems in frontline medical staff after fighting COVID-19 is still unknown. METHODS: Medical workers in Wuhan and other cities in Hubei Province were invited to participate a cross-sectional and convenience sampling online survey, which assessed the prevalence of anxiety, insomnia, depression, and post-traumatic stress disorder (PTSD). RESULTS: A total of 1,091 responses (33% male and 67% female) were valid for statistical analysis. The prevalence was anxiety 53%, insomnia 79%, depression 56%, and PTSD 11%. Healthcare workers in Wuhan were more likely to face risks of anxiety (56% vs. 52%, P = 0.03) and PTSD (15% vs. 9%, P = 0.03) than those in other cities of Hubei. In terms of educational attainment, those with doctoral and masters' (D/M) degrees may experience more anxiety (median of 7.0, [interquartile range (IQR) 2.0-8.5] vs. median 5.0 [IQR 5.0-8.0], P = 0.02) and PTSD (median 26.0 [IQR 19.5-33.0] vs. median 23.0 [IQR 19.0-31.0], P = 0.04) than those with lower educational degrees. CONCLUSIONS: The mental problems were an important issue for the healthcare workers after COVID-19. Thus, an early intervention on such mental problems is necessary for healthcare workers.


Subject(s)
COVID-19 , Depressive Disorder/epidemiology , Disease Outbreaks , Health Personnel/psychology , Occupational Diseases/epidemiology , SARS-CoV-2 , Adult , China/epidemiology , Cross-Sectional Studies , Depressive Disorder/psychology , Female , Humans , Male , Middle Aged , Occupational Diseases/psychology , Prevalence , Psychometrics , Quality of Life , Surveys and Questionnaires , Young Adult
16.
Results Phys ; 24: 104046, 2021 May.
Article in English | MEDLINE | ID: covidwho-1144914

ABSTRACT

This manuscript addressing the dynamics of fractal-fractional type modified SEIR model under Atangana-Baleanu Caputo (ABC) derivative of fractional order y and fractal dimension p for the available data in Pakistan. The proposed model has been investigated for qualitative analysis by applying the theory of non-linear functional analysis along with fixed point theory. The fractional Adams-bashforth iterative techniques have been applied for the numerical solution of the said model. The Ulam-Hyers (UH) stability techniques have been derived for the stability of the considered model. The simulation of all compartments has been drawn against the available data of covid-19 in Pakistan. The whole study of this manuscript illustrates that control of the effective transmission rate is necessary for stoping the transmission of the outbreak. This means that everyone in the society must change their behavior towards self-protection by keeping most of the precautionary measures sufficient for controlling covid-19.

17.
Preprint in English | bioRxiv | ID: ppbiorxiv-431566

ABSTRACT

The pandemic of the COVID-19 disease caused by SARS-CoV-2 has led to more than 100 million infections and over 2 million deaths worldwide. The progress in the developments of effective vaccines and neutralizing antibody therapeutics brings hopes to eliminate the threat of COVID-19. However, SARS-CoV-2 continues to mutate, and several new variants have been emerged. Among the various naturally-occurring mutations, the E484K mutation shared by both the 501Y.V2 and 501Y.V3 variants attracted serious concerns, which may potentially enhance the receptor binding affinity and reduce the immune response. In the present study, the molecular mechanism behind the impacts of E484K mutation on the binding affinity of the receptor-binding domain (RBD) with the receptor human angiotensin-converting enzyme 2 (hACE2) was investigated by using the molecular dynamics (MD) simulations combined with the molecular mechanics-generalized Born surface area (MMGBSA) method. Our results indicate that the E484K mutation results in more favorable electrostatic interactions compensating the burial of the charged and polar groups upon the binding of RBD with hACE2, which significantly improves the RBD-hACE2 binding affinity. Besides that, the E484K mutation also causes the conformational rearrangements of the loop region containing the mutant residue, which leads to more tight binding interface of RBD with hACE2 and formation of some new hydrogen bonds. The more tight binding interface and the new hydrogen bonds formation also contribute to the improved binding affinity of RBD to the receptor hACE2. In addition, six neutralizing antibodies and nanobodies complexed with RBD were selected to explore the effects of E484K mutation on the recognition of these antibodies to RBD. The simulation results show that the E484K mutation significantly reduces the binding affinities to RBD for most of the studied neutralizing antibodies, and the decrease in the binding affinities is mainly owing to the unfavorable electrostatic interactions caused by the mutation. Our studies revealed that the E484K mutation may improve the binding affinity between RBD and the receptor hACE2, implying more transmissibility of the E484K-containing variants, and weaken the binding affinities between RBD and the studied neutralizing antibodies, indicating reduced effectiveness of these antibodies. Our results provide valuable information for the effective vaccine development and antibody drugs design.

18.
J Med Virol ; 93(7): 4446-4453, 2021 07.
Article in English | MEDLINE | ID: covidwho-1064383

ABSTRACT

This study aims to comparatively analyze the therapeutic efficacy upon multiple medication plans over lopinavir/ritonavir (LPV/r), arbidol (ARB), and methylprednisolone on patients with coronavirus disease 2019 (COVID-19). Totally, 75 COVID-19 patients admitted to The First Affiliated Hospital, Zhejiang University School of Medicine from January 22, 2020 to February 29, 2020 were recruited and grouped based on whether or not LPV/r and ARB were jointly used and whether or not methylprednisolone was used. Indexes including body temperature, time for nucleic acid negative conversion, hospital stays, and laboratory indexes were examined and compared. For all patients, there were no significant differences in the change of body temperature, the time for negative conversion, and hospital stays whether LPV/r and ARB were jointly used or not. While for severe and critically severe patients, methylprednisolone noticeably reduced the time for negative conversion. Meanwhile, the clinical efficacy was superior on patients receiving methylprednisolone within 3 days upon admission, and the duration of hospital stays was much shorter when methylprednisolone was given at a total dose of 0-400 mg than a higher dose of >400 mg if all patients received a similar dose per day. Nonetheless, no significant changes across hepatic, renal, and myocardial function indexes were observed. LPV/r combined with ARB produced no noticeably better effect on COVID-19 patients relative to the single-agent treatment. Additionally, methylprednisolone was efficient in severe and critically severe cases, and superior efficacy could be realized upon its early, appropriate, and short-term application.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Indoles/therapeutic use , Lopinavir/therapeutic use , Methylprednisolone/therapeutic use , Ritonavir/therapeutic use , China , Drug Combinations , Female , Fever/drug therapy , Humans , Length of Stay , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/drug effects
19.
Int Immunopharmacol ; 90: 107120, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1065209

ABSTRACT

OBJECTIVE: To explore the application value of artificial liver support system in the clinical treatment of coronavirus disease 2019 (COVID-19) patients with cytokine storm. METHODS: Six cases of severe or critically severe COVID-19 patients treated in The First Affiliated Hospital, College of Medicine, Zhejiang University from January 22 to February 4, 2020 were recruited, and all of them received artificial liver support treatment. Statistical analysis was carried out on the change of cytokines (TNF-α, IL-10, IL-6, IFN-γ, IL-2, IL-4), inflammation-related indicators (white blood cell, neutrophil, lymphocyte, C-reactive protein and procalcitonin), immune-related indicators (B lymphocyte percentage, natural killer cell percentage, CD3+CD4+CD8 T cell percentage), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the 6 patients before and after treatment, and the proportions of patients with abnormal indicators were analyzed as well. In addition, computed tomography (CT) was used to observe the absorption of pulmonary lesions before and after the artificial liver support treatment. RESULTS: The levels of cytokines (IL-6 and IL-10) were effectively reduced in the 6 patients after treatment with the artificial liver support system. Meanwhile, the proportions of patients with abnormal TNF-α, IL-10, IL-6 and IFN-γ were all decreased (p < 0.05). The levels of inflammation-related indicators including white blood cell, C-reactive protein and procalcitonin, and the proportions of patients with these abnormal indicators were both significantly reduced (p < 0.05). The level of neutrophil was not effectively reduced before and after the treatment, but the proportion was significantly reduced (p < 0.05). However, the abnormality of lymphocyte in the patients was not improved. There was no significant difference in immune-related indicators, AST and ALT before and after the treatment (p > 0.05). CT imaging showed that the artificial liver support treatment contributed to absorption of pulmonary lesions. CONCLUSIONS: The artificial liver support system had a great clinical effect in the treatment of cytokine storm and inflammation in COVID-19 patients, and it could promote the absorption of infected lesions.


Subject(s)
COVID-19/therapy , Cytokine Release Syndrome/therapy , Life Support Care/methods , Liver, Artificial , Lung/pathology , Lymphocytes/pathology , SARS-CoV-2/physiology , Aged , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Cytokines/blood , Female , Humans , Lung/diagnostic imaging , Male , Middle Aged
20.
Clin Transl Med ; 11(2): e297, 2021 02.
Article in English | MEDLINE | ID: covidwho-1049592

ABSTRACT

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in December 2019 and has subsequently spread worldwide. Currently, there is no effective method to cure COVID-19. Mesenchymal stromal cells (MSCs) may be able to effectively treat COVID-19, especially for severe and critical patients. Menstrual blood-derived MSCs have recently received much attention due to their superior proliferation ability and their lack of ethical problems. Forty-four patients were enrolled from January to April 2020 in a multicenter, open-label, nonrandomized, parallel-controlled exploratory trial. Twenty-six patients received allogeneic, menstrual blood-derived MSC therapy, and concomitant medications (experimental group), and 18 patients received only concomitant medications (control group). The experimental group was treated with three infusions totaling 9 × 107 MSCs, one infusion every other day. Primary and secondary endpoints related to safety and efficacy were assessed at various time points during the 1-month period following MSC infusion. Safety was measured using the frequency of treatment-related adverse events (AEs). Patients in the MSC group showed significantly lower mortality (7.69% died in the experimental group vs 33.33% in the control group; P = .048). There was a significant improvement in dyspnea while undergoing MSC infusion on days 1, 3, and 5. Additionally, SpO2 was significantly improved following MSC infusion, and chest imaging results were improved in the experimental group in the first month after MSC infusion. The incidence of most AEs did not differ between the groups. MSC-based therapy may serve as a promising alternative method for treating severe and critical COVID-19.


Subject(s)
COVID-19/therapy , Menstruation , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , SARS-CoV-2/metabolism , Adolescent , Adult , Aged , Allografts , COVID-19/blood , COVID-19/mortality , Critical Illness , Disease-Free Survival , Female , Humans , Male , Middle Aged , Severity of Illness Index , Survival Rate
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