Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 166
Filter
1.
PLoS One ; 17(8): e0272034, 2022.
Article in English | MEDLINE | ID: covidwho-2079709

ABSTRACT

RATIONALE: Inhaled antimicrobials enable high local concentrations where needed and, compared to orally administration, greatly reduce the potential for systemic side effects. In SARS-CoV-2 infections, hydroxychloroquine sulphate (HCQ) administered as dry powder via inhalation could be safer than oral HCQ allowing higher and therefore more effective pulmonary concentrations without dose limiting toxic effects. OBJECTIVES: To assess the local tolerability, safety and pharmacokinetic parameters of HCQ inhalations in single ascending doses of 5, 10 and 20 mg using the Cyclops dry powder inhaler. METHODS: Twelve healthy volunteers were included in the study. Local tolerability and safety were assessed by pulmonary function tests, electrocardiogram and recording adverse events. To estimate systemic exposure, serum samples were collected before and 0.5, 2 and 3.5 h after inhalation. RESULTS AND DISCUSSION: Dry powder HCQ inhalations were well tolerated by the participants, except for transient bitter taste in all participants and minor coughing irritation. There was no significant change in QTc-interval or drop in FEV1 post inhalation. The serum HCQ concentration remained below 10 µg/L in all samples. CONCLUSION: Single doses of inhaled dry powder HCQ up to 20 mg are safe and well tolerated. Our data support that further studies with inhaled HCQ dry powder to evaluate pulmonary pharmacokinetics and efficacy are warranted.


Subject(s)
COVID-19 , Hydroxychloroquine , Administration, Inhalation , COVID-19/drug therapy , Dry Powder Inhalers , Healthy Volunteers , Humans , Hydroxychloroquine/adverse effects , Powders , SARS-CoV-2
2.
Sci Rep ; 12(1): 16294, 2022 09 29.
Article in English | MEDLINE | ID: covidwho-2050543

ABSTRACT

Several factors related to anti-spike(S) IgG antibody titers after mRNA COVID-19 vaccination have been elucidated, but the magnitude of the effects of each factor has not been fully understood. This cross-sectional study assessed anti-S and anti-nucleocapsid (N) antibody titers on 3744 healthy volunteers (median age, 36 years; IQR, 24-49 years; females, 59.0%) who received two doses of mRNA-1273 or BNT162b2 vaccine and completed a survey questionnaire. Multiple regression was conducted to identify factors associated with antibody titers. All but one participant tested positive for anti-S antibodies (99.97%). The following factors were independently and significantly associated with high antibody titer: < 3 months from vaccination (ratio of means 4.41); mRNA-1273 vaccine (1.90, vs BNT162b2); anti-N antibody positivity (1.62); age (10's: 1.50, 20's: 1.37, 30's: 1.26, 40's: 1.16, 50's: 1.15, vs ≧60's); female (1.07); immunosuppressive therapy (0.54); current smoking (0.85); and current drinking (0.96). The largest impact on anti-S IgG antibody titers was found in elapsed time after vaccination, followed by vaccine brand, immunosuppressants, previous SARS-CoV-2 infection (anti-N antibody positive), and age. Although the influence of adverse reactions after the vaccine, gender, smoking, and drinking was relatively small, they were independently related factors.


Subject(s)
COVID-19 Vaccines , COVID-19 , Immunoglobulin G , 2019-nCoV Vaccine mRNA-1273/administration & dosage , 2019-nCoV Vaccine mRNA-1273/adverse effects , 2019-nCoV Vaccine mRNA-1273/immunology , Adult , BNT162 Vaccine/administration & dosage , BNT162 Vaccine/adverse effects , BNT162 Vaccine/immunology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Cross-Sectional Studies , Female , Healthy Volunteers , Humans , Immunization Schedule , Immunoglobulin G/blood , Immunosuppressive Agents , Japan/epidemiology , Male , Middle Aged , Seroepidemiologic Studies , Vaccination , Young Adult
3.
Antimicrob Agents Chemother ; 66(10): e0063222, 2022 10 18.
Article in English | MEDLINE | ID: covidwho-2019711

ABSTRACT

Ensitrelvir is a novel selective inhibitor of the 3C-like protease of SARS-CoV-2, which is essential for viral replication. This phase 1 study of ensitrelvir assessed its safety, tolerability, and pharmacokinetics of single (part 1, n = 50) and multiple (part 2, n = 33) ascending oral doses. Effect of food on the pharmacokinetics of ensitrelvir, differences in pharmacokinetics of ensitrelvir between Japanese and white participants, and effect of ensitrelvir on the pharmacokinetics of midazolam (a cytochrome P450 3A [CYP3A] substrate) were also assessed. In part 1, Japanese participants were randomized to placebo or ensitrelvir at doses of 20, 70, 250, 500, 1,000, or 2,000 mg. In part 2, Japanese and white participants were randomized to placebo or once-daily ensitrelvir at loading/maintenance dose 375/125 mg or 750/250 mg for 5 days. Most treatment-related adverse events observed were mild in severity and were resolved without treatment. Plasma exposures showed almost dose proportionality, and geometric mean half-life of ensitrelvir following the single dose was 42.2 to 48.1 h. Food intake reduced Cmax and delayed Tmax of ensitrelvir but did not impact the area under the curve (AUC), suggesting suitability for administration without food restriction. Compared with Japanese participants, plasma exposures were slightly lower for white participants. Ensitrelvir affected the pharmacokinetics of CYP3A substrates because of increase in AUC of midazolam coadministered with ensitrelvir 750/250 mg on day 6. In conclusion, ensitrelvir was well-tolerated and demonstrated favorable pharmacokinetics, including a long half-life, supporting once-daily oral dosing. These results validate further assessments of ensitrelvir in participants with SARS-CoV-2 infection.


Subject(s)
Antiviral Agents , COVID-19 , Indazoles , Triazines , Adult , Humans , Administration, Oral , Antiviral Agents/pharmacokinetics , Antiviral Agents/therapeutic use , Area Under Curve , COVID-19/drug therapy , Cytochrome P-450 CYP3A , Dose-Response Relationship, Drug , Double-Blind Method , Enzyme Inhibitors , Healthy Volunteers , Midazolam/therapeutic use , Peptide Hydrolases , Protease Inhibitors , SARS-CoV-2 , Indazoles/pharmacokinetics , Indazoles/therapeutic use , Triazines/pharmacokinetics , Triazines/therapeutic use , Triazoles/pharmacokinetics , Triazoles/therapeutic use
4.
Clin Transl Sci ; 15(11): 2697-2708, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2019194

ABSTRACT

Molnupiravir (MK-4482) is an oral prodrug of the antiviral ribonucleoside analog, N-hydroxycytidine (NHC), which has activity against RNA viruses, including severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). We conducted a phase I safety and pharmacokinetic study of molnupiravir in healthy Japanese adult participants. A sample size larger than typically used in pharmacokinetic studies was implemented to collect additional safety data in the Japanese population to support special approval for emergency use in Japan. Single doses of molnupiravir up to 1600 mg and multiple doses of 400 and 800 mg administered every 12 h (q12h) for 5.5 days were generally well-tolerated. NHC appeared rapidly in plasma and reached maximum concentration (Cmax ), with a median time to Cmax (Tmax ) between 1.00 and 2.00 h. Area under the concentration versus time curve from zero to infinity (AUC0-inf ), area under the concentration versus time curve from zero to 12 h (AUC0-12 ), and Cmax of plasma NHC increased approximately dose proportionally. With q12h dosing, the geometric mean (GM) accumulation ratios for NHC AUC0-12 and Cmax were ~1 for 400 and 800 mg. Pharmacokinetics of NHC triphosphate (NHC-TP), the active metabolite of NHC was assessed in peripheral blood mononuclear cells and also demonstrated roughly dose proportional pharmacokinetics. The GM accumulation ratios for NHC-TP AUC0-12 and Cmax were ~2.5 for 400 and 800 mg. Following administration with food, only a modest reduction (24%) in plasma NHC Cmax with comparable AUC0-inf was seen, supporting administration without regard to food.


Subject(s)
COVID-19 , Adult , Humans , Japan/epidemiology , COVID-19/drug therapy , Leukocytes, Mononuclear , SARS-CoV-2 , Healthy Volunteers
5.
Biomed Chromatogr ; 36(11): e5456, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2013374

ABSTRACT

Paxlovid, a copackaged medication of nirmatrelvir tablets (150 mg) and ritonavir tablets (100 mg) developed by Pfizer, is one of the first orally accessible COVID-19 antiviral medicines to be approved for emergency usage. In this research, an efficient LC-MS/MS method for simultaneous determination of nirmatrelvir and ritonavir in human plasma was established and validated with remdesivir as an internal standard. Chromatographic separations were carried out on a Thermo BDS Hypersil C18 column (4.6 × 100 mm, 2.4 µm) using deionized water and methanol as mobile phase, both added with 0.1% (v/v) formic acid. Based on the positive electrospray ionization mode, nirmatrelvir and ritonavir were analyzed by selective reaction monitoring. Excellent precision, accuracy, recovery, and linearity were demonstrated, covering the range of 50-5000 ng/mL for nirmatrelvir and 10-1000 ng/mL for ritonavir. Then, the established method was used for determining the pharmacokinetic profile of Paxlovid in healthy Chinese volunteers. The pharmacokinetic parameters, including Cmax , Tmax , t1/2 , and AUC0 - ∞ of Western volunteers, correspond well with the results of this pharmacokinetic investigation.


Subject(s)
COVID-19 , Ritonavir , Antiviral Agents , COVID-19/drug therapy , China , Chromatography, High Pressure Liquid/methods , Chromatography, Liquid/methods , Healthy Volunteers , Humans , Methanol/chemistry , Reproducibility of Results , Tablets , Tandem Mass Spectrometry/methods , Water/chemistry
6.
PLoS One ; 17(8): e0272572, 2022.
Article in English | MEDLINE | ID: covidwho-1987158

ABSTRACT

BACKGROUND: Venous phlebotomy performed by trained personnel is critical for patient diagnosis and monitoring of chronic disease, but has limitations in resource-constrained settings, and represents an infection control challenge during outbreaks. Self-collection devices have the potential to shift phlebotomy closer to the point of care, supporting telemedicine strategies and virtual clinical trials. Here we assess a capillary blood micro-sampling device, the Tasso Serum Separator Tube (SST), for measuring blood protein levels in healthy subjects and non-hospitalized COVID-19 patients. METHODS: 57 healthy controls and 56 participants with mild/moderate COVID-19 were recruited at two U.S. military healthcare facilities. Healthy controls donated Tasso SST capillary serum, venous plasma and venous serum samples at multiple time points, while COVID-19 patients donated a single Tasso SST serum sample at enrolment. Concentrations of 17 protein inflammatory biomarkers were measured in all biospecimens by Ella multi-analyte immune-assay. RESULTS: Tasso SST serum protein measurements in healthy control subjects were highly reproducible, but their agreements with matched venous samples varied. Most of the selected proteins, including CRP, Ferritin, IL-6 and PCT, were well-correlated between Tasso SST and venous serum with little sample type bias, but concentrations of D-dimer, IL-1B and IL-1Ra were not. Self-collection at home with delayed sample processing was associated with significant concentrations differences for several analytes compared to supervised, in-clinic collection with rapid processing. Finally, Tasso SST serum protein concentrations were significantly elevated in in non-hospitalized COVID-19 patients compared with healthy controls. CONCLUSIONS: Self-collection of capillary blood with micro-sampling devices provides an attractive alternative to routine phlebotomy. However, concentrations of certain analytes may differ significantly from those in venous samples, and factors including user proficiency, temperature control and time lags between specimen collection and processing need to be considered for their effect on sample quality and reproducibility.


Subject(s)
COVID-19 , Blood Proteins , Blood Specimen Collection , COVID-19/diagnosis , Healthy Volunteers , Humans , Reproducibility of Results , Specimen Handling
7.
Sleep Med ; 100: 89-102, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1977826

ABSTRACT

OBJECTIVE: We conducted a systematic review and meta-analysis to provide an update on sleep quality in different world areas and better characterize subjective sleep alterations during the COVID-19 pandemic. Considering gender distribution and specific pandemic-related parameters, we also intend to identify significant predictors of sleep problems. METHODS: Six electronic databases were searched from December 2019 to November 2021 for studies investigating sleep during COVID-19 employing the Pittsburgh Sleep Quality Index, the Medical Outcomes Study Sleep, the Insomnia Severity Index or the Epworth Sleepiness Scale. Random-effects models were implemented to estimate the pooled raw means of subjective sleep alterations. Also, we considered the role of several pandemic-related parameters (i.e., days from the first COVID-19 case, government stringency index, new cases for a million people, new deaths for a million people) by means of meta-regression analyses. RESULTS: A total of 139 studies were selected. The pooled mean of the global Pittsburgh Sleep Quality Index score (PSQIgen) was 6.73 (95% CI, 6.61-6.85). The insomnia severity index score was reported from 50 studies with a pooled mean of 8.44 (95% CI, 7.53-9.26). Subgroup analyses confirmed that most subcategories had poor sleep quality and subclinical insomnia. Meta-regressions showed that PSQIgen was predicted by days from the first COVID-19 case and government restrictions with a negative slope and by female gender with a positive slope. The government stringency index was positively correlated with the direct subjective evaluation of sleep quality. CONCLUSIONS: We found an overall impaired sleep and widespread subthreshold insomnia during the COVID-19 pandemic. The female percentage seems to be the best predictor of impaired sleep quality, consistently to the available literature. Noteworthy, sleep alterations were inversely associated with governmental restrictions and decreased during the pandemic. Our results give a contribution to critically orienting further studies on sleep since COVID-19 pandemic.


Subject(s)
COVID-19 , Sleep Initiation and Maintenance Disorders , Female , Humans , Sleep Initiation and Maintenance Disorders/epidemiology , Pandemics , Healthy Volunteers , Sleep
8.
Int J Neuropsychopharmacol ; 25(11): 933-935, 2022 Nov 17.
Article in English | MEDLINE | ID: covidwho-1973164

ABSTRACT

Chemosensory (i.e., olfaction and taste) dysfunction is common in neurodegenerative (e.g., Parkinson's disease, Alzheimer's disease, and dementia), psychiatric (e.g., depression, bipolar disorders, other conditions), and postinfectious (i.e., long COVID) diseases and in the elderly. Despite its impact on patients' quality of life, no established treatment for taste disorders exists so far. A recent report on the effect of pramipexole, a D2/D3 agonist, on taste performance in healthy participants provides support for a new potential therapeutic target for taste dysfunction to be tested in future randomized, placebo-controlled, clinical trials across several populations reporting gustatory symptoms.


Subject(s)
COVID-19 , Parkinson Disease , Humans , Aged , Pramipexole , Dopamine Agonists/therapeutic use , Receptors, Dopamine D3 , Parkinson Disease/complications , Parkinson Disease/drug therapy , Parkinson Disease/physiopathology , Dopamine , Healthy Volunteers , Taste , Quality of Life , Benzothiazoles , Taste Disorders/drug therapy , Taste Disorders/etiology
9.
Sci Rep ; 12(1): 12998, 2022 07 29.
Article in English | MEDLINE | ID: covidwho-1967626

ABSTRACT

To investigate whether diurnal changes in noninvasive ocular surface parameters and subjective symptoms occur in healthy subjects wearing face mask who were analyzed before and after 8 h of continuous use. In this prospective cross-sectional study, healthy volunteers attending the same workplace environment underwent a noninvasive ocular surface workup by means of Keratograph 5 M (Oculus, Wetzlar, Germany) in the same day at 2 different time points: (i) in the early morning before wearing face mask (T0); (ii) after 8 h of continuous face mask use (T1). Noninvasive break-up time (NIBUT), tear meniscus height (TMH), ocular redness and meibomian gland dropout were measured. All subjects were asked to complete the Ocular Surface Disease Index (OSDI) questionnaire before and after 8 h of face mask wearing. Data from 20 healthy subjects (10 males and 10 females, mean age 25.1 ± 3.9 years) were included. Mean value of TMH decreased significantly from 0.29 ± 0.07 at T0 to 0.23 ± 0.07 mm at T1 (P < 0.001); conversely, mean values of NIBUT, redness score and meibomian gland dropout did not change significantly after continuous face mask wearing (always P > 0.532). Concerning ocular discomfort symptoms, mean value of OSDI score worsened significantly at T1 compared to T0 (from 12.9 ± 12.6 to 19.4 ± 12.0; P = 0.017). Continuous face mask wearing for 8 h led to decreased TMH associated with the onset of ocular discomfort symptoms in young healthy subjects.


Subject(s)
COVID-19 , Dry Eye Syndromes , Adult , Cross-Sectional Studies , Dry Eye Syndromes/diagnosis , Female , Healthy Volunteers , Humans , Male , Masks/adverse effects , Meibomian Glands , Pandemics , Prospective Studies , Tears , Young Adult
10.
Front Immunol ; 13: 851765, 2022.
Article in English | MEDLINE | ID: covidwho-1963441

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19), has caused a global crisis. Patients with COVID-19 present with a range of clinical manifestations, from no symptoms to severe illness. However, little is known about the profiles of immune cells required to protect against SARS-CoV-2. This study was performed to determine the immune cells profiles in the peripheral blood of COVID-19 patients with moderate to severe disease (n=52), and compare the findings with those from healthy subjects vaccinated with Pfizer BioNTech mRNA vaccine (VS) (n=62), and non-vaccinated healthy subjects (HS) (n=30) from Kuwait. Absolute counts and percentages of total lymphocytes and lymphocyte subsets (CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD16+CD56+ NK cells) in the peripheral blood of the three groups were analyzed using flow cytometry. The results showed that the absolute counts of total lymphocytes, CD3+, CD4+, and CD8+ T cells, CD19+ B cells, and CD56+ NK cells, were significantly lower in COVID-19 patients than normal healthy controls and vaccinated subjects. The percentages of CD3+ and CD4+ T lymphocytes were also significantly lower in the COVID-19 patients. However, the percentage of CD16+CD56+ NK cells was significantly higher in the peripheral blood of COVID-19 patients, compared to the HS and VS groups with no detectable differences in the percentages of CD8+ T cells and CD19+ B cells between the three groups. Analysis of the monocyte subsets has showed a significantly higher percentage of CD14+HLA-DR+ monocytes in COVID-19 patients compared to HS whereas the inflammatory CD14+CD16+ HLA-DR+ monocytes, and the non-classical CD16+HLA-DR+ monocytes showed significantly lower frequency in the blood of the patients than that of HS. These findings demonstrate perturbations of both innate and adaptive immune cell subsets that reflect dysregulated host responses in COVID-19 patients with moderate to severe disease.


Subject(s)
COVID-19 , COVID-19/prevention & control , HLA-DR Antigens , Healthy Volunteers , Humans , SARS-CoV-2 , Vaccination , Vaccines, Synthetic , mRNA Vaccines
12.
Int J Environ Res Public Health ; 19(11)2022 05 24.
Article in English | MEDLINE | ID: covidwho-1924216

ABSTRACT

BACKGROUND: During the COVID-19 pandemic, the fear of being infected was a major concern, resulting in both physical and psychological effects. Despite several studies on fear of COVID-19 in the general population, the effects on healthy volunteers who face COVID-19 on the frontlines have not yet been investigated. METHODS: An online survey on specific psychological variables related to COVID-19 was administered to 720 healthy volunteers, and gender differences were investigated. RESULTS: The primary finding was that females showed higher scores in all dimensions assessed. A multiple linear regression conducted on both genders exhibited a similar pattern of predictors, highlighting the pivotal role of negative affect in the male group. CONCLUSIONS: The findings suggest that COVID-19 had significant effects on healthy volunteers, especially in the female group. Although the previous literature did not report the crucial role played by the negative affect in the male sample, these results highlight the need to deepen how both genders use different emotional strategies to cope with stressful situations. This study may be useful in the development of specific psychological support and ad hoc training for healthy volunteers.


Subject(s)
COVID-19 , Anxiety/epidemiology , COVID-19/epidemiology , Depression/epidemiology , Fear , Female , Healthy Volunteers , Humans , Male , Pandemics , Sex Factors
13.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1206: 123363, 2022 Aug 15.
Article in English | MEDLINE | ID: covidwho-1914562

ABSTRACT

A fully validated, simple, rapid and reproducible liquid chromatography-tandem mass spectrometry method was developed to determine NHC (N-hydroxycytidine), the active metabolite of Molnupiravir (MOL) in human plasma; one of the limited treatment options for SARS-CoV-2 in plasma of healthy volunteers. The internal standard (IS) used was ribavirin. The extraction of analyte and IS from plasma was performed using acetonitrile as a solvent for protein precipitation. Agilent Zorbax Eclipse plus C18, 4.6 × 150 mm, (5 µm) was used for chromatographic separation using a mixture of methanol0.2 % acetic acid (5:95, v/v) as a mobile phase that was pumped at a flow rate of 0.9 mL/min. Detection was performed on a triple quadrupole mass spectrometer operating in multiple reaction monitoring (MRM) employing positive ESI interface using API4500 triple quadrupole tandem mass spectrometer system, with the transitions set at m/z 260.10 â†’ 128.10 and 245.10 â†’ 113.20 for NHC and IS respectively. Method validation was performed in accordance with United States FDA bioanalytical guidance. The concentration range of 20.0-10000.0 ng/mL was used to establish linearity via weighted linear regression approach (1/x2). Moreover, the analyzed pharmacokinetic data from twelve Egyptian healthy volunteers were used to develop a population pharmacokinetic model for NHC. The developed model was used to perform simulations and evaluate the current MOL dosing recommendations through calculating the maximum concentration (Cmax) "the safety metric" and area under the curve (AUC0-12 h) "the efficacy metric" for 1000 virtual subjects. Geometric mean ratios (GMR) with their associated 90% confidence intervals (CI) compared to literature values were computed. Geometric means of simulation-based Cmax and AUC0-12 were 3827 ng/mL (GMR = 1.05; 90% CI = 0.96-1.15) and 9320 ng.h/mL (GMR = 1.04; 90% CI = 0.97-1.11), respectively indicating that current MOL dosage can achieve the therapeutic targets and dose adjustment may not be required for the Egyptian population. The developed model could be used in the future to refine MOL dosage once further therapeutic targets are identified.


Subject(s)
Antiviral Agents , COVID-19 , Prodrugs , Tandem Mass Spectrometry , Antiviral Agents/blood , Chromatography, Liquid/methods , Cytidine/analogs & derivatives , Egypt , Healthy Volunteers , Humans , Hydroxylamines/blood , Reproducibility of Results , SARS-CoV-2 , Tandem Mass Spectrometry/methods
14.
PLoS One ; 17(6): e0270023, 2022.
Article in English | MEDLINE | ID: covidwho-1910666

ABSTRACT

BACKGROUND: The roles of literacy, fear and hesitancy were investigated for acceptance of COVID-19 vaccine (AV) types among village health volunteers (VHVs) in Thailand. MATERIALS AND METHODS: A cross-sectional study was conducted using an unidentified online questionnaire to assess literacy, fear and hesitancy of COVID-19 vaccine acceptance among Thai VHVs between 1 and 15 October 2021. The questionnaire was developed based on the HLVa-IT (Health Literacy Vaccinale degli adulti in Italiano) for vaccine literacy (VL), using an adult Vaccine Hesitancy Scale (aVHS) for COVID-19 vaccine hesitancy (VH) and Fear of COVID-19 scale (FCoV-19S) for the distress of COVID-19 vaccine. The effects of VL, VH and vaccine fear (VF) on AV were estimated using multivariable logistic regression. RESULTS: A total of 5,312 VHVs completed the questionnaire. After adjustment with variables in the multivariable analysis, the VL score was insignificantly associated with increased vaccination (aOR = 1.002; (95%CI: 0.994-1.01)), while VF and VH significantly decreased the chance of vaccination, aOR = 0.966 (95%CI: 0.953-0.978) and aOR = 0.969; (95%CI: 0.960-0.979), respectively and VF and VH were negatively associated with AV for all types of vaccine preference, with VL showing a reverse relationship only for mRNA-based vaccines. CONCLUSION: VL may not increase AV among VHVs. To increase attitudes toward receiving COVID-19 vaccination in Thailand, the government and health-related organizations should instigate policies to significantly reduce VF and VH among Thai VHVs.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , COVID-19/epidemiology , COVID-19/prevention & control , Cross-Sectional Studies , Fear , Healthy Volunteers , Humans , Thailand , Vaccination , mRNA Vaccines
15.
Front Immunol ; 13: 832501, 2022.
Article in English | MEDLINE | ID: covidwho-1902988

ABSTRACT

Background: Previous studies have indicated inferior responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination in solid organ transplant (SOT) recipients. We examined the development of anti-receptor-binding domain (RBD) immunoglobulin G (IgG) after two doses of BNT162b2b in SOT recipients 6 months after vaccination and compared to that of immunocompetent controls. Methods: We measured anti-RBD IgG after two doses of BNT162b2 in 200 SOT recipients and 200 matched healthy controls up to 6 months after first vaccination. Anti-RBD IgG concentration and neutralizing capacity of antibodies were measured at first and second doses of BNT162b2 and 2 and 6 months after the first dose. T-cell responses were measured 6 months after the first dose. Results: In SOT recipients, geometric mean concentration (GMC) of anti-RBD IgG increased from first to second dose (1.14 AU/ml, 95% CI 1.08-1.24 to 11.97 AU/ml, 95% CI 7.73-18.77) and from second dose to 2 months (249.29 AU/ml, 95% CI 153.70-385.19). Six months after the first vaccine, anti-RBD IgG declined (55.85 AU/ml, 95% CI 36.95-83.33). At all time points, anti-RBD IgG was lower in SOT recipients than that in controls. Fewer SOT recipients than controls had a cellular response (13.1% vs. 59.4%, p < 0.001). Risk factors associated with humoral non-response included age [relative risk (RR) 1.23 per 10-year increase, 95% CI 1.11-1.35, p < 0.001], being within 1 year from transplantation (RR 1.55, 95% CI 1.30-1.85, p < 0.001), treatment with mycophenolate (RR 1.54, 95% CI 1.09-2.18, p = 0.015), treatment with corticosteroids (RR 1.45, 95% CI 1.10-1.90, p = 0.009), kidney transplantation (RR 1.70, 95% CI 1.25-2.30, p = 0.001), lung transplantation (RR 1.63, 95% CI 1.16-2.29, p = 0.005), and de novo non-skin cancer comorbidity (RR 1.52, 95% CI, 1.26-1.82, p < 0.001). Conclusion: Immune responses to BNT162b2 are inferior in SOT recipients compared to healthy controls, and studies aiming to determine the clinical impact of inferior vaccine responses are warranted.


Subject(s)
/immunology , COVID-19/immunology , Organ Transplantation , SARS-CoV-2/physiology , Transplant Recipients , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Cohort Studies , Healthy Volunteers , Humans , Male , Prospective Studies , Vaccination
17.
Sensors (Basel) ; 22(11)2022 May 30.
Article in English | MEDLINE | ID: covidwho-1892940

ABSTRACT

Static balance tests are conducted in various clinics for diagnosis and treatment adjustment. As a result of population aging, the accessibility of these tests should be increased, in the clinic, and for remote patient examination. A number of publications have already conducted static balance evaluations using the sensors embedded in a smartphone. This study focuses on the applicability of using smartphone-based balance assessment on a large scale while considering ease of use, safety, and reliability. The Mon4t® app was used to acquire the postural motion using different smartphone devices, different smartphone locations, and various standing postures. The signals derived from the app were compared to the center of pressure displacement derived from a force plate. The results showed moderate to high agreement between the two methods, particularly at the tandem stance (0.69 ≤ r ≤ 0.91). Preliminary data collection was conducted on three healthy participants, followed by 50 additional healthy volunteers, aged 65+. The results demonstrated that the Mon4t app can serve as an accessible and inexpensive static balance assessment tool, both in clinical settings and for remote patient monitoring, which is key for enabling telehealth.


Subject(s)
Postural Balance , Smartphone , Healthy Volunteers , Humans , Posture , Reproducibility of Results
18.
Clin Transl Sci ; 15(9): 2159-2171, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1891527

ABSTRACT

Ribavirin is an inosine monophosphate dehydrogenase inhibitor. Studies suggest ribavirin aerosol could be a safe and efficacious treatment option in the fight against coronaviruses. However, current treatment is long (12-18 h per day, 3-7 days), limiting clinical utility. A reduction in treatment time would reduce treatment burden. We aimed to evaluate safety and pharmacokinetics (PK) of four, single-dose regimens of ribavirin aerosol in healthy volunteers. Thirty-two subjects were randomized, to four cohorts of aerosolized ribavirin (active) or placebo. Cohort 1 received 50 mg/ml ribavirin/placebo (10 ml total volume); cohort 2, 50 mg/ml ribavirin/placebo (20 ml total volume); cohort 3, 100 mg/ml ribavirin/placebo (10 ml total volume); and cohort 4, 100 mg/ml ribavirin/placebo (20 ml total volume). Intense safety monitoring and PK sampling took place on days 1, 2, 3, and 40. Subjects were (mean ± SD, active vs. placebo) aged 57 ± 4.5 vs. 60 ± 2.5 years; 83% vs. 88% were female; and 75% vs. 50% were Caucasian. Some 12.5% (3/24) and 25% (2/8) experienced at least one treatment-emergent adverse event (TEAE) (two moderate; five mild) in the active and placebo groups, respectively. No clinically significant safety concerns were reported. Mean maximum observed concentration (Cmax ) and area under the curve (AUC) values were higher in cohort 4, whereas cohorts 2 and 3 showed similar PK values. Ribavirin absorption reached Cmax within 2 h across cohorts. Four single-dose regimens of ribavirin aerosol demonstrated systemic exposure with minimal systemic effects. Results support continued clinical development of ribavirin aerosol as a treatment option in patients with coronaviruses.


Subject(s)
Ribavirin , Area Under Curve , Cohort Studies , Double-Blind Method , Female , Healthy Volunteers , Humans , Male , Ribavirin/adverse effects
19.
Med Sci Monit ; 28: e936069, 2022 May 30.
Article in English | MEDLINE | ID: covidwho-1876158

ABSTRACT

BACKGROUND Face masks have become an important part of the COVID-19 prevention approach. This study aimed to explore the effect of wearing masks on exercise ability and ventilatory anaerobic threshold (VAT). MATERIAL AND METHODS Thirty-four young, healthy volunteers were included in this study, consisting of 18 men and 16 women. The subjects were randomized to perform 2 cardiopulmonary exercise tests (CPET) on a cycle ergometer with gas exchange analysis, one with and another without wearing a face mask (cross-over design). The general data for all subjects and indicators from the 2 exercise tests performed with and without wearing a face mask were collected. RESULTS In cardiopulmonary exercise tests, wearing a mask significantly (P<0.05) decreased peak indexes (eg, work rate (WR), oxygen consumption per kg body weight (VO2/kg), heart rate (HR), ventilation per minute (VE) and carbon dioxide ventilation equivalent (VE/VCO2)) and anaerobic threshold indexes (eg, WR, HR, VE, breath frequency (BF), dead space ratio (VD/VT), and VE/VCO2). However, the PETCO2 at peak was significantly higher. There was a positive linear correlation between WR difference and VO2 difference at VAT (abbreviated as deltaWR@VAT and deltaVO2@VAT, respectively) (r=0.495, P=0.003). Subgroup analysis of the VAT indexes showed that WR, VO2/kg, and VE were significantly decreased in the advanced VAT group with mask compared with the stable VAT group with mask (P<0.05). Logistic regression showed that deltaVE, deltaBF, and deltaVE/VCO2 had independent influences on VAT. CONCLUSIONS Wearing masks advances VAT in healthy young subjects during CPET. The advanced VAT was associated with changes in VE, BF, and VE/VCO2 while wearing masks.


Subject(s)
Anaerobic Threshold , COVID-19 , Exercise Tolerance , Female , Healthy Volunteers , Humans , Male , Masks
20.
Bull Exp Biol Med ; 173(1): 133-138, 2022 May.
Article in English | MEDLINE | ID: covidwho-1872575

ABSTRACT

We studied the differences in the characteristics of T-cell immunity in clinically healthy volunteers of three groups: "no previous COVID-19, not vaccinated", "recovered", and "vaccinated" as well as the relationship between the presence of IFNγ-releasing T cells in response to stimulation with peptide pools overlapping the main S, N, M, ORF3, and ORF7 protein sequences and the presence of IgG to the SARS-CoV-2 S protein. In the "no previous COVID-19, non-vaccinated" group, T cells specific to both S protein and other virus proteins were absent in 95% subjects. In the "recovered from COVID-19" group, T cells specific to the spike protein were present in samples from 39% subjects. In the same group, T-cell immunity to other viral proteins was present in 58% subjects. In vaccinated subjects, specific T cells responding to stimulation with S protein peptides were found in 47% cases and Т cells specific to N, M, ORF3, ORF7 proteins were detected in only 22% subjects.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Healthy Volunteers , Humans , Immunity, Humoral , Spike Glycoprotein, Coronavirus , T-Lymphocytes
SELECTION OF CITATIONS
SEARCH DETAIL