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1.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1012296

ABSTRACT

Objective: To investigate the clinical characteristics and maternal and fetal prognosis of pregnant women with acute fatty liver of pregnancy (AFLP). Methods: The clinical data of 86 AFLP pregnant women admitted to the Third Affiliated Hospital of Guangzhou Medical University from September 2017 to August 2022 were collected, and their general data, clinical characteristics, laboratory tests and maternal and fetal outcomes were retrospectively analyzed. Results: (1) General information: the age of the 86 pregnant women with AFLP was (30.8±5.4) years, and the body mass index was (21.0±2.5) kg/m2. There were 50 primiparas (58.1%, 50/86) and 36 multiparas (41.9%, 36/86). There were 64 singleton pregnancies (74.4%, 64/86) and 22 twin pregnancies (25.6%, 22/86). (2) Clinical characteristics: the main complaints of AFLP pregnant women were gastrointestinal symptoms, including epigastric pain (68.6%, 59/86), nausea (47.7%, 41/86), anorexia (46.5%, 40/86), vomiting (39.5%, 34/86). The main non-gastrointestinal symptoms were jaundice of skin and/or scleral (54.7%, 47/86), edema (38.4%, 33/86), fatigue (19.8%, 17/86), bleeding tendency (16.3%, 14/86), polydipsia or polyuria (14.0%, 12/86), skin itching (8.1%, 7/86), and 17.4% (15/86) AFLP pregnant women had no obvious symptoms. (3) Laboratory tests: the incidence of liver and kidney dysfunction and abnormal coagulation function in AFLP pregnant women was high, and the levels of blood ammonia, lactate dehydrogenase and lactic acid were increased, and the levels of hemoglobin, platelet and albumin decreased. However, only 24 cases (27.9%, 24/86) of AFLP pregnant women showed fatty liver by imageology examination. (4) Pregnancy outcomes: ① AFLP pregnant women had a high incidence of pregnancy complications, mainly including renal insufficiency (95.3%, 82/86), preterm birth (46.5%, 40/86), hypertensive disorders in pregnancy (30.2%, 26/86), gestational diabetes mellitus (36.0%, 31/86), fetal distress (24.4%, 21/86), pulmonary infection (23.3%, 20/86), disseminated intravascular coagulation (16.3%, 14/86), multiple organ dysfunction syndrome (16.3%, 14/86), hepatic encephalopathy (9.3%, 8/86), and intrauterine fetal death (2.3%, 2/86). ② Treatment and outcome of AFLP pregnant women: the intensive care unit transfer rate of AFLP pregnant women was 66.3% (57/86). 82 cases were improved and discharged after treatment, 2 cases were transferred to other hospitals for follow-up treatment, and 2 cases (2.3%, 2/86) died. ③ Neonatal outcomes: except for 2 cases of intrauterine death, a total of 106 neonates were delivered, including 39 cases (36.8%, 39/106) of neonatal asphyxia, 63 cases (59.4%, 63/106) of neonatal intensive care unit admission, and 3 cases (2.8%, 3/106) of neonatal death. Conclusions: AFLP is a severe obstetric complication, which is harmful to mother and fetus. In the process of clinical diagnosis and treatment, attention should be paid to the clinical manifestations and laboratory tests of pregnant women, early diagnosis and active treatment, so as to improve maternal and fetal outcomes.


Subject(s)
Pregnancy , Infant, Newborn , Female , Humans , Adult , Retrospective Studies , Premature Birth/epidemiology , Pregnancy Complications/diagnosis , Fatty Liver/diagnosis , Fetal Death , Stillbirth
2.
Preprint in English | medRxiv | ID: ppmedrxiv-22276948

ABSTRACT

SARS-CoV-2 vaccines have proven effective in eliciting an immune response capable of providing protective immunity in healthy individuals. However, whether SARS-CoV-2 vaccination induces a long-lived immune response in immunocompromised individuals is poorly understood. Primary antibody deficiency (PAD) syndromes are among the most common immunodeficiency disorders in adults and are characterized by an impaired ability to mount robust antibody responses following infection or vaccination. Here, we present data from a prospective study in which we analyzed the B and T cell response in PAD patients following SARS-COV-2 vaccination. Unexpectedly, individuals with PAD syndromes mounted a SARS-CoV-2 specific B and CD4+ T cell response that was comparable in magnitude to healthy individuals. Many individuals with PAD syndromes displayed reduced IgG1+ and CD11c+ memory B cell responses following the primary vaccination series. However, the IgG1 class-switching defect was largely rescued following mRNA booster vaccination. Boosting also elicited an increase in the SARS-CoV-2-specific B and T cell response and the development of Omicron-specific memory B cells in COVID-19-naive PAD patients. Together, these data indicate that SARS-CoV-2 vaccines elicit memory B and T cells in PAD patients that may contribute to long-term protective immunity.

3.
Preprint in English | bioRxiv | ID: ppbiorxiv-494559

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a generalist virus, infecting and evolving in numerous mammals, including captive and companion animals, free-ranging wildlife, and humans. Transmission among non-human species poses a risk for the establishment of SARS-CoV-2 reservoirs, makes eradication difficult, and provides the virus with opportunities for new evolutionary trajectories, including selection of adaptive mutations and emergence of new variant lineages. Here we use publicly available viral genome sequences and phylogenetic analysis to systematically investigate transmission of SARS-CoV-2 between human and non-human species and to identify mutations associated with each species. We found the highest frequency of animal-to-human transmission from mink, compared with negligible transmission from other sampled species (cat, dog, and deer). Although inferred transmission events could be limited by sampling biases, our results provide a useful baseline for further studies. Using genome-wide association studies, no single nucleotide variants (SNVs) were significantly associated with cats and dogs, potentially due to small sample sizes. However, we identified three SNVs statistically associated with mink and 26 with deer. Of these SNVs, [~][2/3] were plausibly introduced into these animal species from local human populations, while the remaining [~][1/3] were more likely derived in animal populations and are thus top candidates for experimental studies of species-specific adaptation. Together, our results highlight the importance of studying animal-associated SARS-CoV-2 mutations to assess their potential impact on human and animal health. ImportanceSARS-CoV-2, the causative agent of COVID-19, can infect many animal species, making eradication difficult because it can be reseeded from different reservoirs. When viruses replicate in different species, they may be faced with different evolutionary pressures and acquire new mutations, with unknown consequences for transmission and virulence in humans. Here we analyzed SARS-CoV-2 genome sequences from cats, dogs, deer, and mink to estimate transmission between each of these species and humans. We found several transmission events from humans to each animal, but very few detectable transmissions from animals back to humans, with the exception of mink. We also identified three mutations more likely to be found in mink than humans, and 26 in deer. These mutations could help the virus adapt to life in these different species. Ongoing surveillance of SARS-CoV-2 from animals will be important to understand their potential impacts on both human and animal health.

4.
PLoS Comput Biol ; 18(2): e1009856, 2022 02.
Article in English | MEDLINE | ID: mdl-35130267

ABSTRACT

Dendrodendritic interactions between excitatory mitral cells and inhibitory granule cells in the olfactory bulb create a dense interaction network, reorganizing sensory representations of odors and, consequently, perception. Large-scale computational models are needed for revealing how the collective behavior of this network emerges from its global architecture. We propose an approach where we summarize anatomical information through dendritic geometry and density distributions which we use to calculate the connection probability between mitral and granule cells, while capturing activity patterns of each cell type in the neural dynamical systems theory of Izhikevich. In this way, we generate an efficient, anatomically and physiologically realistic large-scale model of the olfactory bulb network. Our model reproduces known connectivity between sister vs. non-sister mitral cells; measured patterns of lateral inhibition; and theta, beta, and gamma oscillations. The model in turn predicts testable relationships between network structure and several functional properties, including lateral inhibition, odor pattern decorrelation, and LFP oscillation frequency. We use the model to explore the influence of cortex on the olfactory bulb, demonstrating possible mechanisms by which cortical feedback to mitral cells or granule cells can influence bulbar activity, as well as how neurogenesis can improve bulbar decorrelation without requiring cell death. Our methodology provides a tractable tool for other researchers.


Subject(s)
Olfactory Bulb/physiology , Humans , Smell/physiology
5.
Preprint in English | medRxiv | ID: ppmedrxiv-22269848

ABSTRACT

Patients with primary antibody deficiency syndromes (PAD) have poor humoral immune responses requiring immunoglobulin replacement therapy. We followed PAD patients after SARS-CoV-2 vaccination by evaluating their immunoglobulin replacement products and serum for anti-spike binding, Fc{gamma}R binding, and neutralizing activities. Immunoglobulin replacement products had low anti-spike and receptor binding domain (RBD) titers and neutralizing activity. In COVID-19-naive PAD patients, anti-spike and RBD titers increased after mRNA vaccination but decreased to pre-immunization levels by 90 days. Patients vaccinated after SARS-CoV-2 infection developed higher responses comparable to healthy donors. Most vaccinated PAD patients had serum neutralizing antibody titers above an estimated correlate of protection against ancestral SARS-CoV-2 and Delta virus but not against Omicron virus, although this was improved by boosting. Thus, currently used immunoglobulin replacement products likely have limited protective activity, and immunization and boosting of PAD patients with mRNA vaccines should confer at least short-term immunity against SARS-CoV-2 variants, including Omicron.

6.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-930601

ABSTRACT

Objective:To investigate the status quo of thriving at work, career resilience and voice behavior in organ transplantation nurses, and mediation effects of thriving at work between the latter two.Methods:From June to August 2018,180 nurses with organ transplant qualification departments in two Grade A hospitals in Fuzhou, Fujian Province were investigated by the general situation survey form, Thriving At Work Scale, Career Resilience Scale and Voice Behavior Scale.Results:The scores of thriving at work, career resilience and voice behavior were 3.68 ± 0.65, 3.56 ± 0.61 and 3.42 ± 0.62. There was a pairwise positive correlation among the three: thriving at work, career resilience and voice behavior( r values were 0.270-0.664, all P<0.05). Thriving at work played a partial mediating role between career resilience and voice behavior ( B values were 0.138-0.611, all P<0.05). Conclusions:Ii is necessary to improve thriving at work, career resilience and voice behavior in organ transplantation nurses. Thriving at work is the intermediary factor between the latter two. The improvement of thriving at work and career resilience will help to promote organ transplant specialist nurses to make positive voice behavior.

7.
Preprint in English | bioRxiv | ID: ppbiorxiv-471198

ABSTRACT

Viral vaccines can lose their efficacy as the genomes of targeted viruses rapidly evolve, resulting in new variants that may evade vaccine-induced immunity. This process is apparent in the emergence of new SARS-CoV-2 variants which have the potential to undermine vaccination efforts and cause further outbreaks. Predictive vaccinology points to a future of pandemic preparedness in which vaccines can be developed preemptively based in part on predictive models of viral evolution. Thus, modeling the trajectory of SARS-CoV-2 spike protein evolution could have value for mRNA vaccine development. Traditionally, in silico sequence evolution has been modeled discretely, while there has been limited investigation into continuous models. Here we present the Viral Predictor for mRNA Evolution (VPRE), an open-source software tool which learns from mutational patterns in viral proteins and models their most statistically likely evolutionary trajectories. We trained a variational autoencoder with real-time and simulated SARS-CoV-2 genome data from Australia to encode discrete spike protein sequences into continuous numerical variables. To simulate evolution along a phylogenetic path, we trained a Gaussian process model with the numerical variables to project spike protein evolution up to five months in advance. Our predictions mapped primarily to a sequence that differed by a single amino acid from the most reported spike protein in Australia within the prediction timeframe, indicating the utility of deep learning and continuous latent spaces for modeling viral protein evolution. VPRE can be readily adapted to investigate and predict the evolution of viruses other than SARS-CoV-2 in temporal, geographic, and lineage-specific pathways.

8.
PLoS Comput Biol ; 17(10): e1009479, 2021 10.
Article in English | MEDLINE | ID: mdl-34634035

ABSTRACT

A central question in neuroscience is how context changes perception. In the olfactory system, for example, experiments show that task demands can drive divergence and convergence of cortical odor responses, likely underpinning olfactory discrimination and generalization. Here, we propose a simple statistical mechanism for this effect based on unstructured feedback from the central brain to the olfactory bulb, which represents the context associated with an odor, and sufficiently selective cortical gating of sensory inputs. Strikingly, the model predicts that both convergence and divergence of cortical odor patterns should increase when odors are initially more similar, an effect reported in recent experiments. The theory in turn predicts reversals of these trends following experimental manipulations and in neurological conditions that increase cortical excitability.


Subject(s)
Feedback, Physiological/physiology , Models, Neurological , Olfactory Pathways/physiology , Olfactory Perception/physiology , Alzheimer Disease/physiopathology , Brain/physiology , Computational Biology , Humans
9.
Preprint in English | medRxiv | ID: ppmedrxiv-21264250

ABSTRACT

Although vaccines effectively prevent COVID-19 in healthy individuals, they appear less immunogenic in individuals with chronic inflammatory diseases (CID) and/or under chronic immunosuppression, and there is uncertainty of their activity against emerging variants of concern in this population. Here, we assessed a cohort of 74 CID patients treated as monotherapy with chronic immunosuppressive drugs for functional antibody responses in serum against historical and variant SARS-CoV-2 viruses after immunization with Pfizer mRNA BNT162b2 vaccine. Longitudinal analysis showed the greatest reductions in neutralizing antibodies and Fc effector function capacity in individuals treated with TNF- inhibitors, and this pattern appeared worse against the B.1.617.2 Delta virus. Within five months of vaccination, serum neutralizing titers of the majority of CID patients fell below the presumed threshold correlate for antibody-mediated protection. Thus, further vaccine boosting or administration of long-acting prophylaxis (e.g., monoclonal antibodies) likely will be required to prevent SARS-CoV-2 infection in this susceptible population.

10.
Preprint in English | bioRxiv | ID: ppbiorxiv-462074

ABSTRACT

Human monoclonal antibody (mAb) treatments are promising for COVID-19 prevention, post-exposure prophylaxis, or therapy. However, the titer of neutralizing antibodies required for protection against SARS-CoV-2 infection remains poorly characterized. We previously described two potently neutralizing mAbs COV2-2130 and COV2-2381 targeting non-overlapping epitopes on the receptor-binding domain of SARS-CoV-2 spike protein. Here, we engineered the Fc-region of these mAbs with mutations to extend their persistence in humans and reduce interactions with Fc gamma receptors. Passive transfer of individual or combinations of the two antibodies (designated ADM03820) given prophylactically by intravenous or intramuscular route conferred virological protection in a non-human primate (NHP) model of SARS-CoV-2 infection, and ADM03820 potently neutralized SARS-CoV-2 variants of concern in vitro. We defined 6,000 as a protective serum neutralizing antibody titer in NHPs against infection for passively transferred human mAbs that acted by direct viral neutralization, which corresponded to a concentration of 20 g/mL of circulating mAb.

11.
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.

12.
Preprint in English | bioRxiv | ID: ppbiorxiv-451375

ABSTRACT

Escape variants of SARS-CoV-2 are threatening to prolong the COVID-19 pandemic. To address this challenge, we developed multivalent protein-based minibinders as potential prophylactic and therapeutic agents. Homotrimers of single minibinders and fusions of three distinct minibinders were designed to geometrically match the SARS-CoV-2 spike (S) trimer architecture and were optimized by cell-free expression and found to exhibit virtually no measurable dissociation upon binding. Cryo-electron microscopy (cryoEM) showed that these trivalent minibinders engage all three receptor binding domains on a single S trimer. The top candidates neutralize SARS-CoV-2 variants of concern with IC50 values in the low pM range, resist viral escape, and provide protection in highly vulnerable human ACE2-expressing transgenic mice, both prophylactically and therapeutically. Our integrated workflow promises to accelerate the design of mutationally resilient therapeutics for pandemic preparedness. One-Sentence SummaryWe designed, developed, and characterized potent, trivalent miniprotein binders that provide prophylactic and therapeutic protection against emerging SARS-CoV-2 variants of concern.

13.
Preprint in English | bioRxiv | ID: ppbiorxiv-443267

ABSTRACT

SARS-CoV-2 variants that attenuate antibody neutralization could jeopardize vaccine efficacy and the end of the COVID-19 pandemic. We recently reported the protective activity of a single-dose intranasally-administered spike protein-based chimpanzee adenovirus-vectored vaccine (ChAd-SARS-CoV-2-S) in animals, which has advanced to human trials. Here, we assessed its durability, dose-response, and cross-protective activity in mice. A single intranasal dose of ChAd-SARS-CoV-2-S induced durably high neutralizing and Fc effector antibody responses in serum and S-specific IgG and IgA secreting long-lived plasma cells in the bone marrow. Protection against a historical SARS-CoV-2 strain was observed across a 100-fold vaccine dose range and over a 200-day period. At 6 weeks or 9 months after vaccination, serum antibodies neutralized SARS-CoV-2 strains with B.1.351 and B.1.1.28 spike proteins and conferred almost complete protection in the upper and lower respiratory tracts after challenge. Thus, in mice, intranasal immunization with ChAd-SARS-CoV-2-S provides durable protection against historical and emerging SARS-CoV-2 strains.

14.
Preprint in English | bioRxiv | ID: ppbiorxiv-441501

ABSTRACT

With the emergence of SARS-CoV-2 variants with increased transmissibility and potential resistance, antibodies and vaccines with broadly inhibitory activity are needed. Here we developed a panel of neutralizing anti-SARS-CoV-2 mAbs that bind the receptor binding domain of the spike protein at distinct epitopes and block virus attachment to cells and its receptor, human angiotensin converting enzyme-2 (hACE2). While several potently neutralizing mAbs protected K18-hACE2 transgenic mice against infection caused by historical SARS-CoV-2 strains, others induced escape variants in vivo and lost activity against emerging strains. We identified one mAb, SARS2-38, that potently neutralizes all SARS-CoV-2 variants of concern tested and protects mice against challenge by multiple SARS-CoV-2 strains. Structural analysis showed that SARS2-38 engages a conserved epitope proximal to the receptor binding motif. Thus, treatment with or induction of inhibitory antibodies that bind conserved spike epitopes may limit the loss of potency of therapies or vaccines against emerging SARS-CoV-2 variants.

15.
Preprint in English | bioRxiv | ID: ppbiorxiv-439166

ABSTRACT

Emergence of novel variants of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) underscores the need for next-generation vaccines able to elicit broad and durable immunity. Here we report the evaluation of a ferritin nanoparticle vaccine displaying the receptor-binding domain of the SARS-CoV-2 spike protein (RFN) adjuvanted with Army Liposomal Formulation QS-21 (ALFQ). RFN vaccination of macaques using a two-dose regimen resulted in robust, predominantly Th1 CD4+ T cell responses and reciprocal peak mean neutralizing antibody titers of 14,000-21,000. Rapid control of viral replication was achieved in the upper and lower airways of animals after high-dose SARS-CoV-2 respiratory challenge, with undetectable replication within four days in 7 of 8 animals receiving 50 {micro}g RFN. Cross-neutralization activity against SARS-CoV-2 variant B.1.351 decreased only [~]2-fold relative to USA-WA1. In addition, neutralizing, effector antibody and cellular responses targeted the heterotypic SARS-CoV-1, highlighting the broad immunogenicity of RFN-ALFQ for SARS-like betacoronavirus vaccine development. Significance StatementThe emergence of SARS-CoV-2 variants of concern (VOC) that reduce the efficacy of current COVID-19 vaccines is a major threat to pandemic control. We evaluate a SARS-CoV-2 Spike receptor-binding domain ferritin nanoparticle protein vaccine (RFN) in a nonhuman primate challenge model that addresses the need for a next-generation, efficacious vaccine with increased pan-SARS breadth of coverage. RFN, adjuvanted with a liposomal-QS21 formulation (ALFQ), elicits humoral and cellular immune responses exceeding those of current vaccines in terms of breadth and potency and protects against high-dose respiratory tract challenge. Neutralization activity against the B.1.351 VOC within two-fold of wild-type virus and against SARS-CoV-1 indicate exceptional breadth. Our results support consideration of RFN for SARS-like betacoronavirus vaccine development.

16.
Preprint in English | bioRxiv | ID: ppbiorxiv-436864

ABSTRACT

The emergence of antigenically distinct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility is a public health threat. Some of these variants show substantial resistance to neutralization by SARS-CoV-2 infection- or vaccination-induced antibodies, which principally target the receptor binding domain (RBD) on the virus spike glycoprotein. Here, we describe 2C08, a SARS-CoV-2 mRNA vaccine-induced germinal center B cell-derived human monoclonal antibody that binds to the receptor binding motif within the RBD. 2C08 broadly neutralizes SARS-CoV-2 variants with remarkable potency and reduces lung inflammation, viral load, and morbidity in hamsters challenged with either an ancestral SARS-CoV-2 strain or a recent variant of concern. Clonal analysis identified 2C08-like public clonotypes among B cell clones responding to SARS-CoV-2 infection or vaccination in at least 20 out of 78 individuals. Thus, 2C08-like antibodies can be readily induced by SARS-CoV-2 vaccines and mitigate resistance by circulating variants of concern. One Sentence SummaryProtection against SARS-CoV-2 variants by a potently neutralizing vaccine-induced human monoclonal antibody.

17.
Preprint in English | bioRxiv | ID: ppbiorxiv-436523

ABSTRACT

The emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants stresses the continued need for next-generation vaccines that confer broad protection against coronavirus disease 2019 (COVID-19). We developed and evaluated an adjuvanted SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine in nonhuman primates (NHPs). High-dose (50 {micro}g) SpFN vaccine, given twice within a 28 day interval, induced a Th1-biased CD4 T cell helper response and a peak neutralizing antibody geometric mean titer of 52,773 against wild-type virus, with activity against SARS-CoV-1 and minimal decrement against variants of concern. Vaccinated animals mounted an anamnestic response upon high-dose SARS-CoV-2 respiratory challenge that translated into rapid elimination of replicating virus in their upper and lower airways and lung parenchyma. SpFNs potent and broad immunogenicity profile and resulting efficacy in NHPs supports its utility as a candidate platform for SARS-like betacoronaviruses. One-Sentence SummaryA SARS-CoV-2 Spike protein ferritin nanoparticle vaccine, co-formulated with a liposomal adjuvant, elicits broad neutralizing antibody responses that exceed those observed for other major vaccines and rapidly protects against respiratory infection and disease in the upper and lower airways and lung tissue of nonhuman primates.

18.
Preprint in English | bioRxiv | ID: ppbiorxiv-433110

ABSTRACT

Despite the introduction of public health measures and spike protein-based vaccines to mitigate the COVID-19 pandemic, SARS-CoV-2 infections and deaths continue to rise. Previously, we used a structural design approach to develop picomolar range miniproteins targeting the SARS-CoV-2 receptor binding domain. Here, we investigated the capacity of modified versions of one lead binder, LCB1, to protect against SARS-CoV-2-mediated lung disease in human ACE2-expressing transgenic mice. Systemic administration of LCB1-Fc reduced viral burden, diminished immune cell infiltration and inflammation, and completely prevented lung disease and pathology. A single intranasal dose of LCB1v1.3 reduced SARS-CoV-2 infection in the lung even when given as many as five days before or two days after virus inoculation. Importantly, LCB1v1.3 protected in vivo against a historical strain (WA1/2020), an emerging B.1.1.7 strain, and a strain encoding key E484K and N501Y spike protein substitutions. These data support development of LCB1v1.3 for prevention or treatment of SARS-CoV-2 infection.

19.
Preprint in English | medRxiv | ID: ppmedrxiv-21254427

ABSTRACT

The COVID-19 pandemic has been accompanied by the largest mobilization of therapeutic convalescent plasma (CCP) in over a century. Initial identification of high titer units was based on dose-response data using the Ortho VITROS IgG assay. The proliferation of SARS-CoV-2 serological assays and non-uniform application has led to uncertainty about their interrelationships. The purpose of this study was to establish correlations and analogous cutoffs between commercially available serological tests (Ortho, Abbott, Roche), a spike ELISA, and a virus neutralization assay using convalescent plasma from a cohort of 79 donors from April 2020. Relationships relative to FDA-approved cutoffs under the CCP EUA were identified by linear regression and receiver operator characteristic curves. Relative to the Ortho VITROS assay, the r2 of the Abbott, Roche, the anti-Spike ELISA and the neutralizing assay were 0.58, 0.5, 0.82, and 0.44, respectively. The best correlative index for establishing high-titer units was 3.82 S/C for the Abbott, 10.89 COI for the Roche, 1:1,202 for the anti-Spike ELISA, and 1:200 by the neutralization assay. The overall agreement using derived cutoffs compared to the CCP EUA Ortho VITROS cutoff of 9.5 was 92.4% for Abbott, 84.8% for Roche, 87.3% for the anti-S ELISA and 78.5% for the neutralization assay. Assays based on antibodies against the nucleoprotein (Roche, Abbott) and neutralizing antibody tests were positively associated with the Ortho assay, although their ability to distinguish FDA high-titer specimens was imperfect. The resulting relationships help reconcile results from the large body of serological data generated during the COVID-19 pandemic.

20.
Chinese Journal of School Health ; (12): 1582-1585, 2021.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-904613

ABSTRACT

Objective@#To investigate the changes of environmental sanitation, health knowledge and behavior of students and diarrhea in rural schools in Henan and Sichuan Provinces from 2016 to 2018, and to provide data for improving environmental sanitation, health literacy, as well as reducing diarrhea and other infectious diseases among rural students.@*Methods@#Based on the "Community Approach to Total Sanitation (CATS)", a total of 13 rural primary schools were selected in 2016 and 2018 respectively, including 8 in Henan and 5 in Sichuan. One class of fourth grade students was selected from each school. Totally 450 students were surveyed in 2016 and 2018, respectively. The drinking water, environmental hygiene, students personal hygiene and behavior, and the incidence of diarrhea in recent 3 months were investigated by interview, observation, inquiry and questionnaire.@*Results@#Between 2016 and 2018, the number of schools providing safe drinking water for students increased from 6 to 8, the number of schools with proper hand washing facilities increased from 9 to 12, the number of schools with hand washing facilities equipped with soap or hand sanitizer increased from 2 to 9, and the number of schools with sanitary toilet type increased from 9 to 12. The awareness rate of students total health knowledge increased from 58.74% (793/1 350) to 64.96% (877/1 350), the formation rate of students total health behavior increased from 67.78% (1 220/1 800) to 75.28 % (1 355/1 800), the proportion of diarrhea in recent 3 months decreased from 36.89% (166/450) to 21.11% (95/450), the differences were statistically significant( χ 2=11.08, 24.86, 27.20, P <0.05).@*Conclusion@#The basic environmental sanitation facilities of rural schools in Henan and Sichuan has improved substantially, together with increased students health knowledge and hygiene behavior, and decreased incidence of students diarrhea.

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