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1.
J Water Process Eng ; 50: 103279, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2095724

ABSTRACT

Glucocorticoids (GCs) are widely used in the treatment of the coronavirus disease of 2019 (COVID-19), and the toxicity of GCs to aquatic organisms has aroused widespread concern. Powdered activated carbon (PAC) has proven effective in removing various trace organic pollutants. In this study, the adsorption behaviors of 20 typical GCs onto PACs were investigated at environmentally relevant concentrations (ng/L) in real wastewater, using four commercially available PACs (HDB, WPH, 20BF, PWA). The results showed that PAC adsorption was feasible for GC removal at ng/L concentrations. After adsorption for 60 min, the GC removal efficiencies obtained by HDB, WPH, 20BF, and PWA were 90-98 %, 89-97 %, 84-96 %, and 71-90 %, respectively. The adsorption processes of 20 GCs on PACs were well fitted by the pseudo-second-order kinetics model (with R 2 >0.98). Among the four PACs, HDB achieved the highest rates because of the electrostatic attraction between HDB (positively charged) and the complex of GCs and natural organic matter (GC-NOM, negatively charged). Among the 20 GCs, compounds with substitutions of halogen atoms or five-membered rings at C-17 achieved higher adsorption rates because of the enhanced formation of hydrogen bonds and a resulting increase in electron density. In addition, surrogate models with total fluorescence (TF) and ultraviolet absorbance at 254 nm (UV254) were developed to monitor the attenuation trend of GCs during adsorption processes. Compared with the UV254 model, the TF model showed better sensitivity to GC monitoring, which could greatly simplify the water quality monitoring process and facilitate online monitoring of GCs in water.

2.
Biosensors (Basel) ; 12(11)2022 Oct 29.
Article in English | MEDLINE | ID: covidwho-2090001

ABSTRACT

Biolayer interferometry (BLI) is a well-established laboratory technique for studying biomolecular interactions important for applications such as drug development. Currently, there are interesting opportunities for expanding the use of BLI in other fields, including the development of rapid diagnostic tools. To date, there are no detailed frameworks for implementing BLI in target-recognition studies that are pivotal for developing point-of-need biosensors. Here, we attempt to bridge these domains by providing a framework that connects output(s) of molecular interaction studies with key performance indicators used in the development of point-of-need biosensors. First, we briefly review the governing theory for protein-ligand interactions, and we then summarize the approach for real-time kinetic quantification using various techniques. The 2020 PRISMA guideline was used for all governing theory reviews and meta-analyses. Using the information from the meta-analysis, we introduce an experimental framework for connecting outcomes from BLI experiments (KD, kon, koff) with electrochemical (capacitive) biosensor design. As a first step in the development of a larger framework, we specifically focus on mapping BLI outcomes to five biosensor key performance indicators (sensitivity, selectivity, response time, hysteresis, operating range). The applicability of our framework was demonstrated in a study of case based on published literature related to SARS-CoV-2 spike protein to show the development of a capacitive biosensor based on truncated angiotensin-converting enzyme 2 (ACE2) as the receptor. The case study focuses on non-specific binding and selectivity as research goals. The proposed framework proved to be an important first step toward modeling/simulation efforts that map molecular interactions to sensor design.


Subject(s)
Biosensing Techniques , COVID-19 , Humans , Dielectric Spectroscopy , SARS-CoV-2 , COVID-19/diagnosis , Interferometry/methods , Biosensing Techniques/methods
3.
ChemMedChem ; : e202200399, 2022 Oct 02.
Article in English | MEDLINE | ID: covidwho-2085004

ABSTRACT

Repurposing of antiviral drugs affords a rapid and effective strategy to develop therapies to counter pandemics such as COVID-19. SARS-CoV-2 replication is closely linked to the metabolism of cytosine-containing nucleotides, especially cytidine-5'-triphosphate (CTP), such that the integrity of the viral genome is highly sensitive to intracellular CTP levels. CTP synthase (CTPS) catalyzes the rate-limiting step for the de novo biosynthesis of CTP. Hence, it is of interest to know the effects of the 5'-triphosphate (TP) metabolites of repurposed antiviral agents on CTPS activity. Using E. coli CTPS as a model enzyme, we show that ribavirin-5'-TP is a weak allosteric activator of CTPS, while sofosbuvir-5'-TP and adenine-arabinofuranoside-5'-TP are both substrates. ß-d-N4 -Hydroxycytidine-5'-TP is a weak competitive inhibitor relative to CTP, but induces filament formation by CTPS. Alternatively, sofosbuvir-5'-TP prevented CTP-induced filament formation. These results reveal the underlying potential for repurposed antivirals to affect the activity of a critical pyrimidine nucleotide biosynthetic enzyme.

4.
Vaccines (Basel) ; 10(10)2022 Oct 12.
Article in English | MEDLINE | ID: covidwho-2071934

ABSTRACT

INTRODUCTION: We tested the total spike antibody (S-Ab), IgG/IgM S-Ab, and neutralizing antibody (N-Ab) responses of COVID-19-naïve subjects from before their first BNT162b2 vaccination up to 210 days after boosting. METHODS: We studied 136 COVID-19-naïve subjects who received three doses of the Pfizer mRNA vaccine (39 males, 97 females, mean age 43.8 ± 13.5 years) from January 2021 to May 2022. Serum was assessed for total S-Ab (Roche), IgG/M (Abbott), and N-Ab (Snibe). RESULTS: Peak antibody levels were measured 20-30 days after each dose, with booster dosing eliciting significantly higher peak antibodies than the second dose: total S-Ab 2219 vs. 19,551 BAU/mL (difference 16,667 BAU/mL, p < 0.0001); IgG 2270 vs. 2932 BAU/mL (difference 660 BAU/mL, p = 0.04); and N-Ab 3.52 vs. 26.4 µg/mL (difference 21.4 µg/mL, p < 0.0001). Only IgM showed a lower peak post-booster antibody titer (COI 2.11 vs. 0.23, difference 1.63, 95% CI 1.05 to 2.38, p < 0.0001). By 180-210 days after the second or third vaccination, total S-Ab/IgG/N-Ab had decreased by 68.7/93.8/73.6% vs. 82.8/86.3/79.5%. The half-lives of IgG and N-Ab antibodies were longer after the third vaccination (IgG: 65 vs. 34 days, N-Ab: 99 vs. 78 days). CONCLUSION: Total S-Ab/IgG/N-Ab showed a greater increase post-booster, with IgG/N-Ab having a longer half-life.

5.
BioTech (Basel) ; 11(4)2022 Oct 11.
Article in English | MEDLINE | ID: covidwho-2071231

ABSTRACT

Omicron BA.2.75 may become the next globally dominant strain of COVID-19 in 2022. The BA.2.75 sub-variant has acquired more mutations (9) in spike protein and other genes of SARS-CoV-2 than any other variant. Thus, its chemical composition and thermodynamic properties have changed compared with earlier variants. In this paper, the Gibbs energy of the binding and antigen-receptor binding rate was reported for the BA.2.75 variant. Gibbs energy of the binding of the Omicron BA.2.75 variant is more negative than that of the competing variants BA.2 and BA.5.

6.
BMC Med ; 20(1): 379, 2022 10 13.
Article in English | MEDLINE | ID: covidwho-2064796

ABSTRACT

This study evaluated the persistence of IgM, IgA, and IgG to SARS-CoV-2 spike and nucleocapsid antigens up to 616 days since the onset of symptoms in a longitudinal cohort of 247 primary health care workers from Barcelona, Spain, followed up since the start of the pandemic. The study also assesses factors affecting antibody levels, including comorbidities and the responses to variants of concern as well as the frequency of reinfections. Despite a gradual and significant decline in antibody levels with time, seropositivity to five SARS-CoV-2 antigens combined was always higher than 90% over the whole study period. In a subset of 23 participants who had not yet been vaccinated by November 2021, seropositivity remained at 95.65% (47.83% IgM, 95.65% IgA, 95.65% IgG). IgG seropositivity against Alpha and Delta predominant variants was comparable to that against the Wuhan variant, while it was lower for Gamma and Beta (minority) variants and for IgA and IgM. Antibody levels at the time point closest to infection were associated with age, smoking, obesity, hospitalization, fever, anosmia/hypogeusia, chest pain, and hypertension in multivariable regression models. Up to 1 year later, just before the massive roll out of vaccination, antibody levels were associated with age, occupation, hospitalization, duration of symptoms, anosmia/hypogeusia, fever, and headache. In addition, tachycardia and cutaneous symptoms associated with slower antibody decay, and oxygen supply with faster antibody decay. Eight reinfections (3.23%) were detected in low responders, which is consistent with a sustained protective role for anti-spike naturally acquired antibodies. Stable persistence of IgG and IgA responses and cross-recognition of the predominant variants circulating in the 2020-2021 period indicate long-lasting and largely variant-transcending humoral immunity in the initial 20.5 months of the pandemic, in the absence of vaccination.


Subject(s)
Ageusia , COVID-19 , Anosmia , Antibodies, Viral , COVID-19/epidemiology , Humans , Immunoglobulin A , Immunoglobulin G , Immunoglobulin M , Oxygen , Reinfection , SARS-CoV-2
7.
Microbiol Spectr ; : e0059722, 2022 Oct 12.
Article in English | MEDLINE | ID: covidwho-2063980

ABSTRACT

Determination of antibody levels against the nucleocapsid (N) and spike (S) proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are used to estimate the humoral immune response after SARS-CoV-2 infection or vaccination. Differences in the design and specification of antibody assays challenge the interpretation of test results, and comparative studies are often limited to single time points per patient. We determined the longitudinal kinetics of antibody levels of 145 unvaccinated coronavirus disease 2019 (COVID-19) patients at four visits over 1 year upon convalescence using 8 commercial SARS-CoV-2 antibody assays (from Abbott, DiaSorin, Roche, Siemens, and Technoclone), as well as a virus neutralization test (VNT). A linear regression model was used to investigate whether antibody results obtained in the first 6 months after disease onset could predict the VNT results at 12 months. Spike protein-specific antibody tests showed good correlation to the VNT at individual time points (rS, 0.74 to 0.92). While longitudinal assay comparison with the Roche Elecsys anti-SARS-CoV-2 S test showed almost constant antibody concentrations over 12 months, the VNT and all other tests indicated a decline in serum antibody levels (median decrease to 14% to 36% of baseline). The antibody level at 3 months was the best predictor of the VNT results at 12 months after disease onset. The current standardization to a WHO calibrator for normalization to binding antibody units (BAU) is not sufficient for the harmonization of SARS-CoV-2 antibody tests. Assay-specific differences in absolute values and trends over time need to be considered when interpreting the course of antibody levels in patients. IMPORTANCE Determination of antibodies against SARS-CoV-2 will play an important role in detecting a sufficient immune response. Although all the manufacturers expressed antibody levels in binding antibody units per milliliter, thus suggesting comparable results, we found discrepant behavior between the eight investigated assays when we followed the antibody levels in a cohort of 145 convalescent patients over 1 year. While one assay yielded constant antibody levels, the others showed decreasing antibody levels to a varying extent. Therefore, the comparability of the assays must be improved regarding the long-term kinetics of antibody levels. This is a prerequisite for establishing reliable antibody level cutoffs for sufficient individual protection against SARS-CoV-2.

8.
American Journal of Transplantation ; 22(Supplement 3):643, 2022.
Article in English | EMBASE | ID: covidwho-2063436

ABSTRACT

Purpose: Understanding the dynamics of antibody response to a third dose (D3) of anti-SARS-CoV-2 vaccine in solid organ transplant recipients (SOTRs) is important to inform booster strategies. Method(s): We studied the the dynamics of anti-RBD (Roche, <0.8 to >2500 U/dL) and anti-S (Euroimmun, 0.1 to >8.9 AU) antibody levels in a cohort of SOTRs at 2 weeks, 1 month and 3 months after D3. We compared the proportion of seroconversion at 1 month or 3 months after D3 between mRNA and Ad.26.COV2.S D3 recipients, using Poisson regression with robust standard error, adjusting for age and numbers of immunosuppressants. Result(s): Among 928 SOTRs with 2-week (n=655), 1-month (n=651) or 3-month (n=404) post-D3 titer, 78%, 82% and 86% tested positive for antibodies. The median (IQR) anti-RBD at the three timepoints were >2500 (73, >2500), 2494 (49, >2500) and 1234 (59, >2500) U/mL (Figure 1A, blue), and there were 61% (n=436), 60% (n=491) and 53% (n=313) with anti-RBD> 1000 u/mL, respectively. The median (IQR) anti-S at the three timepoints were 3.2 (0.3, 8.4), 8 (2, >8.9) and 7.4 (2, >8.9) AU (Figure 1B, blue), and there were 47% (n=218), 61% (n=161) and 64% (n=91) who developed anti-S>4 AU. Among patients with no or minimal immune response at 2 weeks post-D3 (n=102), 3/41 (7%) had increased anti-RBD by 1 month while 11/18 (61%) had increased anti-S (Fisher exact p<0.001). 6/29 (21%) had increased anti-RBD by 3 months while 12/20 (60%) had increased anti-S (p<0.01) (Figure 1A&B, yellow). 27/102 (27%) of them seroconverted at 1 or 3 months after D3. Having received Ad.26.COV2.S as D3 is associated with 3.9X increased proportion of seroconversion at 1 month or 3 months among patients with no or minimal immune response at 2 weeks after D3 (aIRR=2.223.926.92, p<0.001). Conclusion(s): Among SOTRs who received a booster anti-SARS-CoV-2 vaccination, dynamics of Anti-RBD and Anti-S antibodies differed substantially. Anti-RBD titers on average declined only slightly after 14 days post-D3, while anti-S increased up through 30-60 days post-D3. After the peak, average titer values for both antibodies declined slightly through three months post-D3.

9.
American Journal of Transplantation ; 22(Supplement 3):768-769, 2022.
Article in English | EMBASE | ID: covidwho-2063432

ABSTRACT

Purpose: nti-spike antibody response to SARS-CoV-2 vaccination is diminished in LT recipients compared to the general population so understanding durability for those that do respond is critical to mitigating risks of infection. We measured serial antibody titers in LT recipients for 6 months after two-dose mRNA vaccine series to describe kinetics and sero-reversion rates. Method(s): LT recipients without known prior COVID-19 had anti-spike antibody testing at 1, 3, and 6 months after the second dose of mRNA vaccine (D2) using two commercial assays (Roche Elecsys anti-receptor binding domain immunoassay (EIA) [positive >=0.8 U/mL] or EUROIMMUN anti-S1 EIA [positive >=1.1 AU]). We compared titer distributions over time and identified factors associated with sero-reversion. Result(s): 180 LT recipients received BNT162b2 (48%) or mRNA-1273 (52%) 2-dose series between 1/7/2021-5/7/2021. At 1 month post-D2 (n=173), 146 (84%) had positive antibody levels at a median (IQR) of 30 (28, 32) days post-D2. At 3 months post-D2 (n=164), 149 (91%) had positive levels at a median of 92 (90, 96) days post-D2. At 6 months post-D2 (n=73), 62 (85%) had positive levels at a median of 180 (176, 185) days post-D2. Among the 66 seropositive at 1 or 3 months post-D2, 58 (88%) remained seropositive by 6 months post-D2. Neither age, years since transplant, vaccine type, nor mycophenolate (MMF) use were associated with sero-reversion, though there was a trend toward more triple immunosuppressive use (25% vs 3%, p=0.07). Of those Roche-tested, the median anti-RBD levels were >=250 U/mL (14, >=250;n=120) at 1 month post-D2, >=250 U/mL (58, >=250;n=113) at 3 months, and >=250 U/mL (30, >=250;n=49) at 6 months . Of those EUROIMMUN-tested, the median anti-S1 levels were 7.25 AU (4.31, 8.71;n=53) at 1 month, 5.71 AU (1.27, 7.90;n=51) at 3 months, and 1.73 AU (0.76, 6.01;n=25) at 6 months. Conclusion(s): Overall, most LT recipients demonstrated 6 month durability of anti-spike antibody following vaccination, but a subset did sero-revert, potentially associated with heavier immunosuppression. Further investigation into clinical consequences of waning antibody levels is key to guide timing of additional vaccine doses.

10.
American Journal of Transplantation ; 22(Supplement 3):1035, 2022.
Article in English | EMBASE | ID: covidwho-2063413

ABSTRACT

Purpose: Evolving data suggests booster vaccine doses enhance the immunogenicity of SARS-CoV-2 vaccines in solid organ transplant recipients with higher IgG responses, neutralizing antibodies titers, and greater SARS-CoV-2-specific T-cell counts. Currently, there is no recommended framework for monitoring potential vaccine-related immunological graft injury. Here, we describe kinetics of dd-cfDNA pre- and post-booster vaccination in kidney transplant recipients (KTRs). Method(s): Electronic medical records were reviewed to identify KTRs that received a SARS-CoV-2 booster vaccine dose in 2021 and were monitored with dd-cfDNA pre- and post-vaccination. dd-cfDNA was collected as part of standard of care assessment. Pre-booster dd-cfDNA levels were defined as the most recent result prior to booster administration. Post-vaccination results were collected up to 30 days post-booster administration. Result(s): 116 KTRs were identified for analysis. Patient demographics are summarized in Table 1. Median time from transplant to SARS-CoV-2 booster administration was 463 days (IQR 333-787.25, Table 1). Pre-booster dd-cfDNA levels were established a median of 9 days (IQR 2.25 - 16) pre-booster. The median level of dd-cfDNA pre-booster was 0.17% (IQR 0.12% - 0.25%). There was no significant difference in median levels of dd-cfDNA up to 30 days post-booster administration (Kruskal Wallis test with multiple comparisons, all p values >0.99, Figure 1). No adverse clinical events or acute rejection episodes were reported within 30 days of SARS-CoV-2 booster administration in this cohort. Conclusion(s): Median dd-cfDNA levels were not impacted by SARS-CoV-2 booster administration, suggesting that patterns of subclinical injury that may potentiate inflammation, allosensitization or allograft rejection are unlikely in this setting. The stability of dd-cfDNA demonstrated here further reinforces the safety profile of SARS-CoV-2 vaccine booster administration in KTRs.

11.
American Journal of Transplantation ; 22(Supplement 3):762, 2022.
Article in English | EMBASE | ID: covidwho-2063411

ABSTRACT

Purpose: Heart and lung transplant (HT/LT) recipients have impaired humoral responses to SARS-CoV-2 vaccination compared to other solid organ transplant recipients (SOTRs). The purpose of this study is to describe antibody titer kinetics and durability among HT and LT recipients. Method(s): HT or LT recipients (> 18 years) with no known COVID-19 infection were included. Demographics and clinical characteristics were collected via survey. Serologic testing was performed on the Roche Elecsys anti-SARS-CoV-2 enzyme immuno-assay (EIA) or the EUROIMMUN EIA pre- and post-dose 2 (D2). Result(s): Among 93 HT recipients, 59 (63%) were seropositive 1 month and 66 (71%) 3 months post-D2 (Table 1). Seropositive HT recipients had a higher median length of time from transplant to vaccination. 7/66 (11%) had delayed seroconversion (were negative for antibodies 1-month post-D2). Median(IQR) anti-RBD was 81 (8, 250) 1-month post-D2 (n=38) and 231 (48, 438) U/mL 3-months post-D2 (n=43) (Figure 1). Among 68 LT recipients, 29/68 (43%) were seropositive 1-month and 30 (44%) 3-months post-D2. Seronegative LT recipients were more likely to younger (18-39 years old, 15% vs 3%), or older (> 60 years, 74% vs. 50%, p=0.01). Seronegative LT recipients were more likely to be on anti-metabolite therapy (79% vs. 53%, p=0.04) and had a lower median length of time from transplant to vaccination. Among seropositive LT recipients at 3-months, 3 (10%) had delayed seroconversion. Median (IQR) anti-RBD was 61 (4, 233) U/mL 1-month post-D2 (n=26) and 45(11, 299) U/mL 3-months post-D2. Conclusion(s): HT and LT recipients develop a delayed and variable antibody response to mRNA SARS-CoV-2 vaccination. HT recipients more frequently seroconverted, and had higher anti-RBD levels, than LT recipients. Persistent negative and low antibody titers may place LT recipients at the highest risk of breakthrough SARSCoV- 2 infection among SOTRs.

12.
American Journal of Transplantation ; 22(Supplement 3):1064-1065, 2022.
Article in English | EMBASE | ID: covidwho-2063403

ABSTRACT

Purpose: Some solid-organ transplant recipients (SOTRs) with low or negative antibody levels after a 2-dose mRNA vaccine series against SARS-CoV-2 experience boosting after a third dose (D3), but long-term antibody durability after D3 is unknown. We describe six-month SARS-CoV-2 antibody kinetics and durability in 31 SOTRs who received D3. Method(s): 31 SOTRs without prior COVID-19 were identified within our national observational study. Serologic testing was performed a median of 30 (IQR 27-40) days after D3 and repeated at a median of 166 (148-184) days after D3. Semiquantitative anti-spike serologic testing using the Roche Elecsys anti-S enzyme immunoassay (EIA) or EUROIMMUN anti-S1 EIA was performed. Result(s): Over 6 months of follow-up, antibody levels increased in 16/27(59%), remained stable in 6/27(22%) (one negative, the others above the assay limit), and decreased in 5/27(19%). One-month post-D3, 24/31(77%) were seropositive and 7/31(23%) were seronegative. Six-months post-D3, 29/31(94%) were seropositive and 2/31(6%) remained seronegative. Both nonresponders received the BNT-162b2 primary series;one received Ad.26.CoV2.S and the other mRNA-1273 for D3. This difference in seroconversion after D3 was not statistically significant (Fisher exact = 0.49, between primary series). There were no reported cases of COVID-19 during the study period. Conclusion(s): We observed a very high rate of seroconversion after D3 in SOTRs, with marked heterogeneity in timing and strength of response depending on baseline antibody level and vaccine platform received. These results are encouraging evidence for the durable immunogenicity of additional vaccine doses in most SOTRs, and demonstrate the need for dedicated analysis of heterologous boosting strategies.

13.
Tissue Engineering - Part A ; 28:228-229, 2022.
Article in English | EMBASE | ID: covidwho-2062829

ABSTRACT

Purpose/Objectives: Bioprinted models of lung tissue are in high demand but in short supply, particularly for addressing the research needs in response to COVID-19 pandemic. The lung is arguably one of the most complex organs in the body, with a multiscale cytoarchitectural organization serving its multiple functions. In particular, the cellular structure of the alveolar sacs poses a big challenge to extrusion bioprinting, which is more adept at capturing the external shape of biological objects than their cell-level details.Methodology: Recently, we proposed a constructive compromise, attainable by bioprinting of equivalent 3D constructs derived from individual (such as 'precision cut lung slices') or stackable (serial histological sections) anatomic images. The advantage of this approach is that in these images, which can be obtained either from regular histology, or confocal fluorescence or electron microscopy (EM), is already incorporated a wealth of structural information. This can be first transferred to '2.5 dimensional' models (by giving them a finite thickness), and then these can be printed layer-by-layer and stacked as tissue-equivalent 3D volumes. Here we illustrate this proposed workflow with 3D printed human lung sections, and with a lung fragment reconstituted from serial sections, while also simulating the infection with SARS-CoV-2 virus in the same constructs by an agent-based modeling approach.Results: As proof of concept, we processed a human lung histological section in CAD, converted it as .stl file and then 3D printed it using as materials both polycaprolactone (by fused filament fabrication), and by the FRESH method using alginate as hydrogel bioink. Similarly, we extracted from a serial EM stack an image selection which was imported in CAD as well and printed as a self-standing object by photolithography. Here we also report the re-purposing of a simulation program of SARS-CoV-2 infection created on the CompuCell 3D (CC3D) platform, to analyze the propagation of infection in cellular patterns derived from the same histological and ultrastructural sections of human lungs. Using it, we explored the spatial distribution and kinetics of several cell classes (infected, virus shedding, apoptotic), the associated viral and cytokine fields, as well as the impact of the presence of generic inflammatory cells, in comparison with the comparable situations when the cell distribution was a uniform epithelial monolayer. We noted a good reproducibility of these simulations, in spite of the section-characteristic cell distribution patterns, and of the initial locations ('seeding') of the viral infection. In addition, we reconstructed thicker virtual tissue slices from multiple single-cell layers for the study of their viral infection as well.Conclusion/Significance: In conclusion, while more sophisticated methods to capture the tissue structure in 3D constructs certainly exist, the extrusion bioprinting is shown here to be capable to offer a simpler, more practical, and more affordable alternative. We also demonstrated how computational simulations on the same images as used in bioprinting, can be used as a useful heuristic instrument to anticipate the results of the interaction of viruses with bioprinted structures that are more complex than cellular monolayers.

14.
Clinical Toxicology ; 60(Supplement 2):133, 2022.
Article in English | EMBASE | ID: covidwho-2062724

ABSTRACT

Background: Metformin is the most commonly used diabetes medication and at supratherapeutic levels can result in a severe type-A metabolic lactic acidosis known as metformin-associated lactic acidosis (MALA). Treatment of MALA includes aggressive fluid resuscitation, supporting blood pressure and correcting acidosis. Renal replacement therapy (RRT), usually hemodialysis (HD) is recommended in severe cases with refractory acidosis (with elevated lactate), altered mental status, or shock. To our knowledge, this is the second report of metformin half-life during treatment with continuous veno-venous hemodiafiltration (CVVHDF). Case report: A 53-year-old man died following a reported acute on chronic ingestion of 80 g of his metformin tablets resulting in severe, refractory shock and MALA. His peak serum metformin concentration was 53mcg/mL (therapeutic range 1-2mcg/mL), peak lactic acid concentration was 49.7 mmol/L, and arterial pH nadir was 7.06. Serial serum metformin concentrations were obtained while on RRT;both HD and CVVHDF. The switch from HD to CVVHDF was done due to staffing shortages during the COVID-19 pandemic. The patient died despite aggressive therapy with renal replacement therapy and multiple vasopressors on hospital day five. Serial metformin concentrations during CVVHDF suggested a half-life of 33-h. Discussion(s): Hemodialysis has been reported to clear metformin at a rate greater than 200mL/min and continuous venous-venous hemofiltration (CVVH) at greater than 50mL/min. In this case, metformin levels appear to follow first-order elimination kinetics during CVVHDF with an estimated half-life of 33 h. Comparatively, metformin has a half-life of 4.7-5.5 h during HD. To our knowledge, this is the second report of estimated metformin half-life while using the CVVHDF form of continuous renal replacement. The previous case report measured a half-life of 16.5 h on CVVHDF. This case report shows CVVHDF decreases half-life of metformin and provides first order elimination in the setting of overdose. Conclusion(s): The early initiation of HD appears warranted but prognostic indicators have not been well established. In the absence of HD availability, other forms of RRT (e.g., CCVHDF) can be used and may provide first-order elimination of metformin.

15.
Co-Kinetic Journal ; - (94):44-47, 2022.
Article in English | CINAHL | ID: covidwho-2057714

ABSTRACT

The fact that we are talking about how to survive recession for the second time in two years is a timely reminder that we must not take our clients or our businesses for granted. This article describes the key aspects of your business to think about and some simple marketing plans to put in place that will help you to win customers and survive this current storm in the best financial shape possible.

16.
J Taiwan Inst Chem Eng ; 139: 104538, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2049588

ABSTRACT

Nowadays, wearing a 3-layered face mask (3LFM) to protect against coronavirus illness (COVID-19) has become commonplace, resulting in massive, hazardous solid waste. Since most of them are infected with viruses, a secure way of disposal is necessary to prevent further virus spread. Pyrolysis treatment has recently developed as an effective method for disposing of such hazardous waste and consequently converting them into energy products. In this regard, the goal of the present study is to physicochemically characterize the 3LFM followed by pyrolysis in a TGA to evaluate the pyrolysis performance, kinetic, and thermodynamic parameters and in a semi-batch reactor to characterize the volatile product. Furthermore, an artificial neural network (ANN) was used to forecast thermal deterioration data. The results demonstrated a strong correlation between real and anticipated values. The study proved the relevance of the ANN model and the applicability of pyrolysis for disposing of 3LFM while simultaneously producing energy products.

17.
Acta Biomater ; 151: 491-500, 2022 10 01.
Article in English | MEDLINE | ID: covidwho-2048831

ABSTRACT

Current vaccination schedules, including COVID-19 vaccines, require multiple doses to be administered. Single injection vaccines eliciting equivalent immune response are highly desirable. Unfortunately because unconventional release kinetics are difficult to achieve it still remains a huge challenge. Herein a single-injection COVID-19 vaccine was designed using a highly programmable release system based on dynamic layer-by-layer (LBL) films. The antigen, S1 subunit of SARS-CoV-2 spike protein, was loaded in CaCO3 microspheres, which were further coated with tannic acid (TA)/polyethylene glycol (PEG) LBL films. The single-injection vaccine was obtained by mixing the microspheres coated with different thickness of TA/PEG films. Because of the unique constant-rate erosion behavior of the TA/PEG coatings, this system allows for distinct multiple pulsatile release of antigen, closely mimicking the release profile of antigen in conventional multiple dose vaccines. Immunization with the single injection vaccine induces potent and persistent S1-specific humoral and cellular immune responses in mice. The sera from the vaccinated animal exhibit robust in vitro viral neutralization ability. More importantly, the immune response and viral inhibition induced by the single injection vaccine are as strong as that induced by the corresponding multiple dose vaccine, because they share the same antigen release profile. STATEMENT OF SIGNIFICANCE: Vaccines are the most powerful and cost-effective weapons against infectious diseases such as COVID-19. However, current vaccination schedules, including the COVID-19 vaccines, require multiple doses to be administered. Herein a single-injection COVID-19 vaccine is designed using a highly programmable release system. This vaccine releases antigens in a pulsatile manner, closely mimicking the release pattern of antigens in conventional multiple dose vaccines. As a result, one single injection of the new vaccine induces an immune response and viral inhibition similar to that induced by the corresponding multiple-dose vaccine approach.


Subject(s)
COVID-19 , Viral Vaccines , Animals , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunity , Mice , Polyethylene Glycols , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Tannins , Vaccines, Subunit
18.
J Med Virol ; 2022 Sep 30.
Article in English | MEDLINE | ID: covidwho-2047795

ABSTRACT

Developing reliable, rapid, and quantitative point-of-care testing (POCT) technology of SARS-CoV-2-specific antibodies and understanding longitudinal vaccination response kinetics are highly required to restrain the ongoing coronavirus disease 2019 (COVID-19) pandemic. We demonstrate a novel portable, sensitive, and rapid chemiluminescent lab-on-fiber detection platform for detection of anti-SARS-CoV-2 antibodies: the chemiluminescent lab-on-fiber immunosensor (c-LOFI). Using SARS-CoV-2 Spike S1 RBD protein functionalized fiber bio-probe, the c-LOFI can detect anti-SARS-CoV-2 immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies with high sensitivity based on their respective horseradish peroxidase-labeled secondary antibodies. The limits of detection of anti-SARS-CoV-2 IgG and IgM antibodies were 0.6 and 0.3 ng/ml, respectively. The c-LOFI was successfully applied for direct detection of anti-SARS-CoV-2 antibodies in whole blood samples with simple dilution, which can serve as a finger prick test to rapidly detect antibodies. Furthermore, the longitudinal immune response (>12 months) kinetics following three-dose inactivated virus vaccines was evaluated based on anti-SARS-CoV-2 IgG detection results, which can provide important significance for understanding the immune mechanism against COVID-19 and identify individuals who may benefit from the vaccination and booster vaccination. The c-LOFI has great potential to become a sensitive, low-cost, rapid, high-frequency POCT tool for the detection of both SARS-CoV-2-specific antibodies and other biomarkers.

19.
Biosensors (Basel) ; 12(10)2022 Sep 23.
Article in English | MEDLINE | ID: covidwho-2043580

ABSTRACT

The global pandemic of COVID-19 has created an unrivalled need for sensitive and rapid point-of-care testing (POCT) methods for the detection of infectious viruses. For the novel coronavirus SARS-CoV-2, the nucleocapsid protein (N-protein) is one of the most abundant structural proteins of the virus and it serves as a useful diagnostic marker for detection. Herein, we report a fiber optic particle plasmon resonance (FOPPR) biosensor which employed a single-stranded DNA (ssDNA) aptamer as the recognition element to detect the SARS-CoV-2 N-protein in 15 min with a limit of detection (LOD) of 2.8 nM, meeting the acceptable LOD of 106 copies/mL set by the WHO target product profile. The sensor chip is a microfluidic chip based on the balance between the gravitational potential and the capillary force to control fluid loading, thus enabling the power-free auto-flowing function. It also has a risk-free self-contained design to avoid the risk of the virus leaking into the environment. These findings demonstrate the potential for designing a low-cost and robust POCT device towards rapid antigen detection for early screening of SARS-CoV-2 and its related mutants.


Subject(s)
Biosensing Techniques , COVID-19 , Humans , SARS-CoV-2 , DNA, Single-Stranded , Microfluidics , COVID-19/diagnosis , Nucleocapsid Proteins/genetics
20.
Swiss Medical Weekly ; 152:29S, 2022.
Article in English | EMBASE | ID: covidwho-2040854

ABSTRACT

Background: Since end Dec. 2021, the Omicron SARS-CoV-2 strains have appeared while previous β,g,α or d strains have disappeared. Methods: Analysis of clinical, humoral, cellular and inflammation responses in known patients from the Clinical Immunology Unit [CIU] after Omicron COVID. Recruitment January 1st to June 30th, 2022. Comparison with data of 54 CIU COVID patients from the first wave [1stW]. Measured parameters: β2microglobulin [β2m], C3, C4, ferritin, ECP, anti Spike1 [S1] for Wuhan and Omicron B1.159, ab anti NCP (nucleocapsids) and neutralizing antibodies [NeuAb], Ab phenotyping, leucocyte repartition, lymphocyte phenotyping. Patients: 118 Omicron infected [OmiP]: M 31%, F 69% (Vac 64%, noVac 36%): 24 previously “Naïve COVID” [NaCOV], 18 noVac with a previous β,g,α or d COVID, 64 Vac with no previous COVID and 12 Vac with a previous COVID. Results: No difference between OmiP and 1stW in the kinetics of response to S1 (Omicron or WT) in the first 6 months. It peaks between 45 to 60 d. Anti-NCP ab peaks at 30 to 45 d and is still present ≥ 5 months. Prior infection and/or vaccination is associated with a 2- 3-fold increase of previously detected anti-S1 Wuhan and anti- S1 Omicron. NaCOV develop ab to S1 Wuhan but in much lesser amounts than 1stW. Among OmiP no increased counts of eosinophils and NK as observed in 1stW, neither any increase in β2m and CRP. The majority of OmiP have elevated serum ECP and increased polyclonal ab production for ≥ 4 months. Conclusions: Omicron induces a different immune response than previous strains of SARS-CoV-2.

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