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1.
Sci Data ; 9(1): 654, 2022 10 26.
Article in English | MEDLINE | ID: covidwho-2087255

ABSTRACT

SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2), a virus causing severe acute respiratory disease in humans, emerged in late 2019. This respiratory virus can spread via aerosols, fomites, contaminated hands or surfaces as for other coronaviruses. Studying their persistence under different environmental conditions represents a key step for better understanding the virus transmission. This work aimed to present a reproducible procedure for collecting data of stability and inactivation kinetics from the scientific literature. The aim was to identify data useful for characterizing the persistence of viruses in the food production plants. As a result, a large dataset related to persistence on matrices or in liquid media under different environmental conditions is presented. This procedure, combining bibliographic survey, data digitalization techniques and predictive microbiological modelling, identified 65 research articles providing 455 coronaviruses kinetics. A ranking step as well as a technical validation with a Gage Repeatability & Reproducibility process were performed to check the quality of the kinetics. All data were deposited in public repositories for future uses by other researchers.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Food Handling , Kinetics , Plants, Edible , Reproducibility of Results , Databases, Factual
2.
Gigascience ; 112022 10 17.
Article in English | MEDLINE | ID: covidwho-2077749

ABSTRACT

BACKGROUND: Recent studies have disclosed the genome, transcriptome, and epigenetic compositions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the effect of viral infection on gene expression of the host cells. It has been demonstrated that, besides the major canonical transcripts, the viral genome also codes for noncanonical RNA molecules. While the structural characterizations have revealed a detailed transcriptomic architecture of the virus, the kinetic studies provided poor and often misleading results on the dynamics of both the viral and host transcripts due to the low temporal resolution of the infection event and the low virus/cell ratio (multiplicity of infection [MOI] = 0.1) applied for the infection. It has never been tested whether the alteration in the host gene expressions is caused by aging of the cells or by the viral infection. FINDINGS: In this study, we used Oxford Nanopore's direct cDNA and direct RNA sequencing methods for the generation of a high-coverage, high temporal resolution transcriptomic dataset of SARS-CoV-2 and of the primate host cells, using a high infection titer (MOI = 5). Sixteen sampling time points ranging from 1 to 96 hours with a varying time resolution and 3 biological replicates were used in the experiment. In addition, for each infected sample, corresponding noninfected samples were employed. The raw reads were mapped to the viral and to the host reference genomes, resulting in 49,661,499 mapped reads (54,62 Gbs). The genome of the viral isolate was also sequenced and phylogenetically classified. CONCLUSIONS: This dataset can serve as a valuable resource for profiling the SARS-CoV-2 transcriptome dynamics, the virus-host interactions, and the RNA base modifications. Comparison of expression profiles of the host gene in the virally infected and in noninfected cells at different time points allows making a distinction between the effect of the aging of cells in culture and the viral infection. These data can provide useful information for potential novel gene annotations and can also be used for studying the currently available bioinformatics pipelines.


Subject(s)
COVID-19 , Nanopore Sequencing , Animals , COVID-19/genetics , DNA, Complementary/genetics , Kinetics , RNA , SARS-CoV-2/genetics
3.
Anal Chem ; 94(45): 15553-15557, 2022 Nov 15.
Article in English | MEDLINE | ID: covidwho-2076957

ABSTRACT

Macromolecular association is crucial to many fields in biomedical sciences, including drug development, gene editing, and diagnostics. In particular, protein-protein association and dissociation rate constants are typically determined using surface plasmon resonance systems, which require costly instrumentation and cumbersome procedures (e.g., blocking, washing, and separation). Herein, we demonstrate that protein-binding constants can be readily determined using a real-time biosensing platform facilitated by graphene oxide-modified microwell plates and fluorophore-labeled proteins, where the fluorescent probes remain highly fluorescent during protein association, whereas fluorescent bioprobes that are not associated with their counterparts are quenched by graphene oxide. Binding data of three pairs of proteins were systematically determined employing this single-step platform and compared with those data reported by the suppliers or the literature, suggesting that this approach is comparable and consistent with the existing ones. Such pairs include (i) human immunoglobulin G (H-IgG)-fluorophore-labeled anti-H-IgG, (ii) prostate-specific antigen (PSA)-quantum dot-labeled anti-PSA, and (iii) anti-RBD-fluorophore-labeled SARS-CoV-2 spike receptor-binding domain recombinant protein. We also offer an open-source software that automatically determines the binding kinetics constants of proteins. This Technical Note introduces a simple, yet effective, platform to determine relevant information on protein kinetics, which can be performed using a microwell plate reader and economical materials like graphene oxide. We foresee a new generation of diagnostics based on our affordable protein kinetics analysis.


Subject(s)
Biosensing Techniques , COVID-19 , Humans , Male , SARS-CoV-2 , Kinetics , Fluorescent Dyes , Immunoglobulin G/chemistry
4.
Biosensors (Basel) ; 12(10)2022 Oct 17.
Article in English | MEDLINE | ID: covidwho-2071230

ABSTRACT

In March 2020, the World Health Organization (WHO) declared COVID-19 a pandemic, and the spike protein has been reported to be an important drug target for anti-COVID-19 treatment. As such, in this study, we successfully developed a novel electrochemical receptor biosensor by immobilizing the SARS-CoV-2 spike protein and using AuNPs-HRP as an electrochemical signal amplification system. Moreover, the time-current method was used to quantify seven antiviral drug compounds, such as arbidol and chloroquine diphosphate. The results show that the spike protein and the drugs are linearly correlated within a certain concentration range and that the detection sensitivity of the sensor is extremely high. In the low concentration range of linear response, the kinetics of receptor-ligand interactions are similar to that of an enzymatic reaction. Among the investigated drug molecules, bromhexine exhibits the smallest Ka value, and thus, is most sensitively detected by the sensor. Hydroxychloroquine exhibits the largest Ka value. Molecular docking simulations of the spike protein with six small-molecule drugs show that residues of this protein, such as Asp, Trp, Asn, and Gln, form hydrogen bonds with the -OH or -NH2 groups on the branched chains of small-molecule drugs. The electrochemical receptor biosensor can directly quantify the interaction between the spike protein and drugs such as abidor and hydroxychloroquine and perform kinetic studies with a limit of detection 3.3 × 10-20 mol/L, which provides a new research method and idea for receptor-ligand interactions and pharmacodynamic evaluation.


Subject(s)
Bromhexine , COVID-19 , Metal Nanoparticles , Humans , Spike Glycoprotein, Coronavirus/chemistry , Hydroxychloroquine/pharmacology , SARS-CoV-2 , Molecular Docking Simulation , Kinetics , Ligands , Gold , Antiviral Agents/pharmacology
5.
Front Immunol ; 13: 968105, 2022.
Article in English | MEDLINE | ID: covidwho-2065511

ABSTRACT

Introduction: Despite vaccine development, the COVID-19 pandemic is ongoing due to immunity-escaping variants of concern (VOCs). Estimations of vaccine-induced protective immunity against VOCs are essential for setting proper COVID-19 vaccination policy. Methods: We performed plaque-reduction neutralizing tests (PRNTs) using sera from healthcare workers (HCWs) collected from baseline to six months after COVID-19 vaccination and from convalescent COVID-19 patients. The 20.2% of the mean PRNT titer of convalescent sera was used as 50% protective value, and the percentage of HCWs with protective immunity for each week (percent-week) was compared among vaccination groups. A correlation equation was deduced between a PRNT 50% neutralizing dose (ND50) against wild type (WT) SARS-CoV-2 and that of the Delta variant. Results: We conducted PRNTs on 1,287 serum samples from 297 HCWs (99 HCWs who received homologous ChAdOx1 vaccination (ChAd), 99 from HCWs who received homologous BNT162b2 (BNT), and 99 from HCWs who received heterologous ChAd followed by BNT (ChAd-BNT)). Using 365 serum samples from 116 convalescent COVID-19 patients, PRNT ND50 of 118.25 was derived as 50% protective value. The 6-month cumulative percentage of HCWs with protective immunity against WT SARS-CoV-2 was highest in the BNT group (2297.0 percent-week), followed by the ChAd-BNT (1576.8) and ChAd (1403.0) groups. In the inter-group comparison, protective percentage of the BNT group (median 96.0%, IQR 91.2-99.2%) was comparable to the ChAd-BNT group (median 85.4%, IQR 15.7-100%; P =0.117) and significantly higher than the ChAd group (median 60.1%, IQR 20.0-87.1%; P <0.001). When Delta PRNT was estimated using the correlation equation, protective immunity at the 6-month waning point was markedly decreased (28.3% for ChAd group, 52.5% for BNT, and 66.7% for ChAd-BNT). Conclusion: Decreased vaccine-induced protective immunity at the 6-month waning point and lesser response against the Delta variant may explain the Delta-dominated outbreak of late 2021. Follow-up studies for newly-emerging VOCs would also be needed.


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Neutralizing , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19/therapy , COVID-19 Vaccines , Cohort Studies , Humans , Immunization, Passive , Kinetics , Pandemics , Prospective Studies , Republic of Korea/epidemiology , SARS-CoV-2 , Vaccination
6.
Int J Mol Sci ; 23(18)2022 Sep 14.
Article in English | MEDLINE | ID: covidwho-2032989

ABSTRACT

The emergence of new SARS-CoV-2 lineages able to escape antibodies elicited by infection or vaccination based on the Spike protein of the Wuhan isolates has reduced the ability of Spike-specific antibodies to protect previously infected or vaccinated individuals from infection. Therefore, the role played by T cells in the containment of viral replication and spread after infection has taken a more central stage. In this brief review, we will discuss the role played by T cells in the protection from COVID-19, with a particular emphasis on the kinetics of the T cell response and its localization at the site of primary infection.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , Humans , Kinetics , Spike Glycoprotein, Coronavirus , T-Lymphocytes , Vaccination
7.
Int J Mol Sci ; 23(16)2022 Aug 12.
Article in English | MEDLINE | ID: covidwho-2023734

ABSTRACT

Heavy metal ions can disrupt biological functions via multiple molecular mechanisms, including inhibition of enzymes. We investigate the interactions of human papain-like cysteine endopeptidases cathepsins L, K, and S with gallium and cerium ions, which are associated with medical applications. We compare these results with zinc and lead, which are known to inhibit thiol enzymes. We show that Ga3+, Ce3+, and Ce4+ ions inhibit all tested peptidases with inhibition constants in the low micromolar range (between 0.5 µM and 10 µM) which is comparable to Zn2+ ions, whereas inhibition constants of Pb2+ ions are one order of magnitude higher (30 µM to 150 µM). All tested ions are linear specific inhibitors of cathepsin L, but cathepsins K and S are inhibited by Ga3+, Ce3+, and Ce4+ ions via hyperbolic inhibition mechanisms. This indicates a mode of interaction different from that of Zn2+ and Pb2+ ions, which act as linear specific inhibitors of all peptidases. All ions also inhibit the degradation of insoluble elastin, which is a common target of these peptidases in various inflammatory diseases. Our results suggest that these ions and their compounds have the potential to be used as cysteine cathepsin inhibitors in vitro and possibly in vivo.


Subject(s)
Cerium , Gallium , Cathepsin K/metabolism , Cathepsins/metabolism , Cysteine , Cysteine Proteinase Inhibitors/metabolism , Cysteine Proteinase Inhibitors/pharmacology , Endopeptidases/metabolism , Humans , Ions , Kinetics , Lead
8.
Pathog Dis ; 80(1)2022 10 03.
Article in English | MEDLINE | ID: covidwho-2017915

ABSTRACT

Effective vaccination is a key element in the exit strategy from the current severe acute respiratory syndrome-CoV coronavirus-2 (SARS-CoV-2) pandemic, and may also offer protection against severe disease from future variants of concern. Here, we prospectively monitored T-cell responses over time, using ELISpot interferon-γ (INF-y) release assays, and B-cell responses, using serological tests, after vaccination and booster with BioNTech/Pfizer mRNA (Pfizer) and Janssen vector (Janssen/Johnson & Johnson) vaccines in hospital health care workers. Vaccine recipients were divided into seropositive and seronegative individuals at baseline, in order to determine the effect of natural immunity on vaccine-induced immune kinetics. We found that convalescent individuals mounted higher spike-specific INF-y-secreting T-cell responses and B-cell-mediated IgG responses, after receiving the Janssen vaccine or the first dose of the Pfizer vaccine. IgG levels corresponded to the virus neutralization capacity as measured by VNT assay. At 8 months postvaccination, spike-specific cellular immunity waned to low levels in individuals with or without prior natural immunity, whereas waning of humoral immunity occurred predominantly in naive individuals. The booster shot effectively reinduced both cellular and humoral immune responses. To conclude, our data supports the implemented single-dose mRNA booster strategy employed in the Netherlands. Furthermore, the level of pre-existing natural immunity may be factored into determining the optimal time window between future booster vaccines.


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Viral , COVID-19/prevention & control , Health Personnel , Humans , Immunity, Cellular , Immunity, Humoral , Immunoglobulin G , Interferon-gamma , Kinetics , RNA, Messenger , SARS-CoV-2 , Vaccination
9.
Water Res ; 223: 119021, 2022 Sep 01.
Article in English | MEDLINE | ID: covidwho-2004603

ABSTRACT

Due to the Covid-19 pandemic, the worldwide biocides application has been increased, which will eventually result in enhanced residuals in treated wastewater. At the same time, chlorine disinfection of secondary effluents and hospital wastewaters has been intensified. With respect to predicted elevated exposure in wastewater, the chlorination kinetics, transformation pathways and toxicity evolution were investigated in this study for two typical isothiazolinone biocides, methyl-isothiazolinone (MIT) and chloro-methyl-isothiazolinone (CMIT). Second-order rate constants of 0.13 M-1·s-1, 1.95 × 105 M-1·s-1 and 5.14 × 105 M-1·s-1 were determined for the reaction of MIT with HOCl, Cl2O and Cl2, respectively, while reactivity of CMIT was around 1-2 orders of magnitude lower. While chlorination of isothiazolinone biocides at pH 7.1 was dominated by Cl2O-oxidation, acidic pH and elevated Cl- concentration favored free active chlorine (FAC) speciation into Cl2 and increased overall isothiazolinone removal. Regardless of the dominant FAC species, the elimination of MIT and CMIT resulted in an immediate loss of acute toxicity under all experimental conditions, which was attributed to a preferential attack at the S-atom resulting in subsequent formation of sulfoxides and sulfones and eventually an S-elimination. However, chlorination of isothiazolinone biocides in secondary effluent only achieved <10% elimination at typical disinfection chlorine exposure 200 mg·L-1·min, but was predicted to be remarkably increased by acidizing solution to pH 5.5. Alternative measures might be needed to minimize the discharge of these toxic chemicals into the aquatic environment.


Subject(s)
COVID-19 , Disinfectants , Water Pollutants, Chemical , Water Purification , Chlorine , Disinfectants/toxicity , Halogenation , Halogens , Humans , Hydrogen-Ion Concentration , Kinetics , Pandemics , Sulfones , Sulfoxides , Thiazoles , Waste Water , Water Pollutants, Chemical/analysis , Water Purification/methods
10.
Am J Physiol Heart Circ Physiol ; 323(3): H569-H576, 2022 09 01.
Article in English | MEDLINE | ID: covidwho-2001931

ABSTRACT

The post-acute phase of coronavirus disease 2019 (COVID-19) is often marked by several persistent symptoms and exertional intolerance, which compromise survivors' exercise capacity. This was a cross-sectional study aiming to investigate the impact of COVID-19 on oxygen uptake (V̇o2) kinetics and cardiopulmonary function in survivors of severe COVID-19 about 3-6 mo after intensive care unit (ICU) hospitalization. Thirty-five COVID-19 survivors previously admitted to ICU (5 ± 1 mo after hospital discharge) and 18 controls matched for sex, age, comorbidities, and physical activity level with no prior history of SARS-CoV-2 infection were recruited. Subjects were submitted to a maximum-graded cardiopulmonary exercise test (CPX) with an initial 3-min period of a constant, moderate-intensity walk (i.e., below ventilatory threshold, VT). V̇o2 kinetics was remarkably impaired in COVID-19 survivors as evidenced at the on-transient by an 85% (P = 0.008) and 28% (P = 0.001) greater oxygen deficit and mean response time (MRT), respectively. Furthermore, COVID-19 survivors showed an 11% longer (P = 0.046) half-time of recovery of V̇o2 (T1/2V̇o2) at the off-transient. CPX also revealed cardiopulmonary impairments following COVID-19. Peak oxygen uptake (V̇o2peak), percent-predicted V̇o2peak, and V̇o2 at the ventilatory threshold (V̇o2VT) were reduced by 17%, 17%, and 12% in COVID-19 survivors, respectively (all P < 0.05). None of the ventilatory parameters differed between groups (all P > 0.05). In addition, COVID-19 survivors also presented with blunted chronotropic responses (i.e., chronotropic index, maximum heart rate, and heart rate recovery; all P < 0.05). These findings suggest that COVID-19 negatively affects central (chronotropic) and peripheral (metabolic) factors that impair the rate at which V̇o2 is adjusted to changes in energy demands.NEW & NOTEWORTHY Our findings provide novel data regarding the impact of COVID-19 on submaximal and maximal cardiopulmonary responses to exercise. We showed that V̇o2 kinetics is significantly impaired at both the onset (on-transient) and the recovery phase (off-transient) of exercise in these patients. Furthermore, our results suggest that survivors of severe COVID-19 may have a higher metabolic demand at a walking pace. These findings may partly explain the exertional intolerance frequently observed following COVID-19.


Subject(s)
COVID-19 , Oxygen Consumption , Cross-Sectional Studies , Exercise , Exercise Test/methods , Exercise Tolerance/physiology , Humans , Kinetics , Oxygen/metabolism , Oxygen Consumption/physiology , SARS-CoV-2 , Survivors
11.
J Immunol Methods ; 506: 113293, 2022 07.
Article in English | MEDLINE | ID: covidwho-2000542

ABSTRACT

BACKGROUND: Real-world population studies have shown waning immunity, over time, after receiving the two doses of the BNT162b2 COVID-19 vaccine. Studies reporting the long-term humoral response are important to drive future vaccination strategies like the introduction of the booster dose. Yet, available literature on long follow-up periods is scarce. Covidiagnostix is a multicenter study aiming to assess the antibody response in >1000 healthcare professionals (HCPs) who received the BNT162b2 vaccine. METHODS: Serum was tested at time-0 (T0), before the first dose and then at T1, T2, T3 and T4, respectively, 21, 42, 177 and 302 days after T0. Antibodies against the SARS-CoV-2 nucleocapsid-protein were measured to assess SARS-CoV-2 infections, whereas antibodies against the receptor-binding domain of the spike protein were measured to assess vaccine response. RESULTS: The antibody titer observed 10 months post-vaccination showed a decrease of approximately 80% from the peak measured at T2, yet the median titer of the seronegatives HCPs was still higher than seropositives before vaccination. We identified 12 post-vaccination infected HCPs within 6 months after receiving the first dose and another 12 post-vaccination infected HCPs between 6 and 10 months post-vaccination. CONCLUSION: Vaccination induced a humoral response which is well detectable even 10 months post-vaccination. Yet a high anti-spike serum antibody titer does not guarantee protection from infection. Differences in symptomatology between SARS-CoV-2 infections occurred within the first 6 months post-vaccination and the following 4 months, and differences in COVID-19 prevalence and vaccination coverage observed in these two time intervals were consistent with a decrease in vaccine efficacy 6 months after receiving the first dose.


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , Delivery of Health Care , Humans , Kinetics , SARS-CoV-2
13.
PLoS Pathog ; 18(6): e1010569, 2022 06.
Article in English | MEDLINE | ID: covidwho-1987162

ABSTRACT

We describe the longitudinal kinetics of the serological response in COVID-19 recovered patients over a period of 14 months. The antibody kinetics in a cohort of 192 recovered patients, including 66 patients for whom follow-up serum samples were obtained at two to four clinic visits, revealed that RBD-specific antibodies decayed over the 14 months following the onset of symptoms. The decay rate was associated with the robustness of the response in that antibody levels that were initially highly elevated after the onset of symptoms subsequently decayed more rapidly. An exploration of the differences in the longitudinal kinetics between recovered patients and naïve vaccinees who had received two doses of the BNT162b2 vaccine showed a significantly faster decay in the naïve vaccinees, indicating that serological memory following natural infection is more robust than that following to vaccination. Our data highlighting the differences between serological memory induced by natural infection vs. vaccination contributed to the decision-making process in Israel regarding the necessity for a third vaccination dose.


Subject(s)
COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , BNT162 Vaccine , Humans , Kinetics , Vaccination
14.
Environ Res ; 214(Pt 3): 113943, 2022 11.
Article in English | MEDLINE | ID: covidwho-1983018

ABSTRACT

The global pandemic situation due to COVID-19 has given rise to the massive use of disinfectant products, many of them based on silver atoms. After the use of these products, the silver passes into the aqueous effluents, becoming an emerging contaminant in waters. In this work, a novel procedure for the total and simultaneous removal of ionic and nanomeric silver in aqueous samples is introduced, employing magnetic nanoparticles wrapped with an ionic liquid (Fe3O4@IL) as a removal agent. Experimental variables such as pH, contact time, temperature, as well as pollutant and removal agent doses were studied to achieve the total elimination, exhibiting exceptional conditions for the removal of different concentrations of silvers species in water. The approach achieves 100% removal efficiency for the simultaneous removal of both silver species, goal not achieved previously. Also, 100% removal efficiency is reached for the both species separately, since ionic silver is adsorbed onto the Fe3O4, while nanomeric silver is extracted in the IL. Particularly, for concentrations within the range 50-200 µg L-1, total removal efficiency was reached for a wide range of temperatures and a pH range 7-9, achieved in just 15 min, for all cases. Additionally, the doses of Fe3O4@IL employed to remove all concentrations of silver were 13.7 mg. Characterization of Fe3O4@IL surfaces before and after the process was performed by means of Field Effect Scanning Electron Microscopy and Energy Dispersive X-ray Spectroscopy. Fe3O4@IL was recycled by employing 100 µL of 1% HNO3 solution, allowing its use for 10 additional silver removal cycles without loss of efficiency. The study of adsorption kinetics and equilibrium isotherms reveal a Freundlich-type adsorption, which suggests affinity between sites in the complex surface of Fe3O4@IL, and Elovich kinetics, indicative of chemisorption onto a heterogeneous surface, while the temperature shows no effect on the results.


Subject(s)
COVID-19 , Ionic Liquids , Magnetite Nanoparticles , Water Pollutants, Chemical , Adsorption , Humans , Hydrogen-Ion Concentration , Ionic Liquids/chemistry , Kinetics , Magnetite Nanoparticles/chemistry , Silver/chemistry , Water/chemistry , Water Pollutants, Chemical/analysis
15.
Emerg Infect Dis ; 28(9): 1859-1862, 2022 09.
Article in English | MEDLINE | ID: covidwho-1963356

ABSTRACT

Given widespread use of spike antibody in generating coronavirus disease vaccines, SARS-CoV-2 nucleocapsid antibodies are increasingly used to indicate previous infection in serologic surveys. However, longitudinal kinetics and seroreversion are poorly defined. We found substantial seroreversion of nucleocapsid total immunoglobulin, underscoring the need to account for seroreversion in seroepidemiologic studies.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19/epidemiology , Coronavirus Nucleocapsid Proteins/immunology , Humans , Kinetics , Nucleocapsid , Phosphoproteins/immunology , Seroepidemiologic Studies
17.
PLoS Negl Trop Dis ; 14(6): e0008407, 2020 06.
Article in English | MEDLINE | ID: covidwho-1962982

ABSTRACT

Confronted with the challenge of understanding population-level processes, disease ecologists and epidemiologists often simplify quantitative data into distinct physiological states (e.g. susceptible, exposed, infected, recovered). However, data defining these states often fall along a spectrum rather than into clear categories. Hence, the host-pathogen relationship is more accurately defined using quantitative data, often integrating multiple diagnostic measures, just as clinicians do to assess their patients. We use quantitative data on a major neglected tropical disease (Leptospira interrogans) in California sea lions (Zalophus californianus) to improve individual-level and population-level understanding of this Leptospira reservoir system. We create a "host-pathogen space" by mapping multiple biomarkers of infection (e.g. serum antibodies, pathogen DNA) and disease state (e.g. serum chemistry values) from 13 longitudinally sampled, severely ill individuals to characterize changes in these values through time. Data from these individuals describe a clear, unidirectional trajectory of disease and recovery within this host-pathogen space. Remarkably, this trajectory also captures the broad patterns in larger cross-sectional datasets of 1456 wild sea lions in all states of health but sampled only once. Our framework enables us to determine an individual's location in their time-course since initial infection, and to visualize the full range of clinical states and antibody responses induced by pathogen exposure. We identify predictive relationships between biomarkers and outcomes such as survival and pathogen shedding, and use these to impute values for missing data, thus increasing the size of the useable dataset. Mapping the host-pathogen space using quantitative biomarker data enables more nuanced understanding of an individual's time course of infection, duration of immunity, and probability of being infectious. Such maps also make efficient use of limited data for rare or poorly understood diseases, by providing a means to rapidly assess the range and extent of potential clinical and immunological profiles. These approaches yield benefits for clinicians needing to triage patients, prevent transmission, and assess immunity, and for disease ecologists or epidemiologists working to develop appropriate risk management strategies to reduce transmission risk on a population scale (e.g. model parameterization using more accurate estimates of duration of immunity and infectiousness) and to assess health impacts on a population scale.


Subject(s)
Biomarkers/blood , Host-Pathogen Interactions/physiology , Leptospira/pathogenicity , Leptospirosis/diagnosis , Leptospirosis/veterinary , Sea Lions/microbiology , Animal Diseases/diagnosis , Animal Diseases/immunology , Animal Diseases/microbiology , Animals , Antibodies, Bacterial/blood , Bacterial Shedding , California , Cross-Sectional Studies , Host-Pathogen Interactions/immunology , Immunity , Kinetics , Leptospira interrogans , Leptospirosis/immunology , Survival Rate
19.
Sci Rep ; 12(1): 12403, 2022 07 20.
Article in English | MEDLINE | ID: covidwho-1947496

ABSTRACT

The comprehension of a long-term humoral immune response against SARS-CoV-2 can shed light on the treatment and vaccination strategies of COVID-19 disease, improving the knowledge about this virus infection and/or re-infection. We assessed the IgG antibodies against SARS-CoV-2 nucleocapsid (N) protein (anti-SARS-CoV-2 (N) IgG) in 1441 COVID-19 convalescent patients within 15 months longitudinal study from middle-developed country. The main inclusion criteria was positive RT- PCR result on nasopharyngeal swab samples at least one month before antibody testing and absence of any induced or inherited immunodeficiency. 92.7% of convalescent patients' serum contained anti-SARS-CoV-2 (N) IgG and only 1.3% of patients had a delayed antibody response. In the majority of convalescent patients' the durability of antibodies lasted more than one year. The kinetics of anti-SARS-CoV-2 (N) IgG took a bell-shaped character-increased first 25-30 weeks, then started to decrease, but were still detectable for more than 15 months. We found that on the one hand anti-SARS-CoV-2 humoral response level correlates with disease severity, on the other, in particular, the level of peak antibodies correlates with age-older patients develop more robust humoral response regardless of sex, disease severity and BMI.


Subject(s)
COVID-19 , Antibodies, Viral , Humans , Immunoglobulin G , Kinetics , Longitudinal Studies , SARS-CoV-2
20.
J Membr Biol ; 255(2-3): 211-224, 2022 06.
Article in English | MEDLINE | ID: covidwho-1935761

ABSTRACT

Membrane fusion is an essential process for the survival of eukaryotes and the entry of enveloped viruses into host cells. A proper understanding of the mechanism of membrane fusion would provide us a handle to manipulate several biological pathways, and design efficient vaccines against emerging and re-emerging viral infections. Although fusion proteins take the central stage in catalyzing the process, role of lipid composition is also of paramount importance. Lipid composition modulates membrane organization and dynamics and impacts the lipid-protein (peptide) interaction. Moreover, the intrinsic curvature of lipids has strong impact on the formation of stalk and hemifusion diaphragm. Detection of transiently stable intermediates remains the bottleneck in the understanding of fusion mechanism. In order to circumvent this challenge, analytical methods can be employed to determine the kinetic parameters from ensemble average measurements of observables, such as lipid mixing, content mixing, and content leakage. The current review aims to present an analytical method that would aid our understanding of the fusion mechanism, provides a better insight into the role of lipid shape, and discusses the interplay of lipid and peptide in membrane fusion.


Subject(s)
Membrane Fusion , Peptides , Kinetics , Lipids/chemistry
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