Rapid luminescence-based screening method for SARS- CoV-2 inhibitors discovery

SLAS DISCOVERY, Journal Year: 2025, Volume and Issue: 31, P. 100211 - 100211

Published: Jan. 15, 2025

The COVID-19 pandemic has emphasized the necessity for rapid and adaptable drug screening platforms against live pathogenic viruses that require high levels of biosafety containment. Conventional antiviral testing is time-consuming labor-intensive. Here, we outline design validation a semi-automated drug-screening platform SARS-CoV-2 utilizes multiple liquid handlers, stable A549 cell line expressing ACE2 TMPRSS2 receptors, recombinant strain harboring nano-luciferase gene. This allows accelerated low-, mid-, high-throughput screenings by bypassing virus inactivation staining steps compared to assays utilizing fluorescent reporter or immunofluorescence. First, demonstrated luminescence signal obtained at 24 h post-infection robust can be used as surrogate immunofluorescence 48 incubation post infection. We confirmed susceptibility panel reference drugs validated in 96- 384-well plates accordance with NIH criteria screening. showed reproducible results, Z factor ≥0.5, coefficient variation <20% achieved both 96 plate formats. Lastly, assessed assay's performance 240 compounds from MMV Global Health Library, using format remdesivir control compound. single point resulted identification hits inhibited more than 50% viral growth. selected 15 most active evaluate their inhibitory concentration cytotoxicity, which confirmation 3 potent least toxic were never reported antivirals. These results confirm our reliably employed easily adapted other viruses.

Language: Английский

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Potential Biases in Test-Negative Design Studies of COVID-19 Vaccine Effectiveness Arising from the Inclusion of Asymptomatic Individuals

American Journal of Epidemiology, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 19, 2024

The test-negative design (TND) is a popular method for evaluating vaccine effectiveness (VE). A "classical" TND study includes symptomatic individuals tested the disease targeted by to estimate VE against infection. However, recent applications of have attempted infection including all individuals, regardless their symptoms. In this article, we use directed acyclic graphs and simulations investigate potential biases in studies COVID-19 arising from "alternative" approach, particularly when applied during periods widespread testing. We show that inclusion asymptomatic can potentially lead collider stratification bias, uncontrolled confounding health healthcare-seeking behaviors (HSBs), differential outcome misclassification. While our focus on setting, issues discussed here may also be relevant context other infectious diseases. This true scenarios where there either high baseline prevalence infection, strong correlation between HSBs vaccination, different testing practices vaccinated unvaccinated or settings both under attenuates symptoms diagnostic accuracy modified presence

Language: Английский

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Immunity against conserved and non-conserved Spike epitopes after COVID-19 booster vaccination provides long-term protection against symptomatic Omicron infections

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

The objective of this study was to investigate the features immune protection against SARS-CoV-2 infection in a single cohort during 6–17 months following booster immunization with an mRNA-based vaccine. results illustrate influence humoral and cellular immunity on efficacy Notably, neutralizing antibody titers were found serve as reasonably reliable correlate prior immunization. However, predictive power largely lost after boosting. loss appears be due critical remodeling response Our findings support hypothesis that both conserved non-conserved epitopes viral Spike protein's receptor-binding domain (RBD) is crucial for optimal long-term Omicron infection. While may provide cross-variant protection, antibodies targeting RBD play pivotal role achieving maximum protection. These observations highlight repeated shaping landscape reinforce necessity considering components, alongside intended use considerations, when assessing vaccine developing future strategies.

Language: Английский

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Adult vaccinations against respiratory infections

Expert Review of Anti-infective Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Lower respiratory infections have a huge impact on global health, especially in older individuals, immunocompromised people, and those with chronic comorbidities. The COVID-19 pandemic highlights the importance of vaccination. However, there are lower rates vaccination adult population that commonly due to missed opportunity vaccinate. Vaccination offers best strategy prevent hospitalization, complications, death caused by infections. In this review, authors provide an overview vaccines for population. review available data about preventing infections, focusing pneumococcal vaccine, influenza vaccines, syncytial virus (RSV) vaccines. discuss currently scientific evidence role against Finally, current recommendations Scientific effectiveness is important. An efficient implementation immunization strategies will decrease burden Recognizing existing their essential achieve high rate

Language: Английский

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Effectiveness of COVID-19 vaccines against SARS-CoV-2 infection and severe outcomes in adults: a systematic review and meta-analysis of European studies published up to 22 January 2024

European Respiratory Review, Journal Year: 2025, Volume and Issue: 34(175), P. 240222 - 240222

Published: Jan. 1, 2025

Background Up-to-date evidence from European studies on long-term vaccine effectiveness (VE) of COVID-19 vaccines is lacking. This review aimed to evaluate and durability primary series boosters in preventing infection severe outcomes the population. Methods We conducted systematic searches PubMed Embase up 22 January 2024. included observational that evaluated VE against acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or disease (hospitalisation, intensive care unit admission death) for Europe. applied a random-effects meta-analysis model. Results 33 over 56 million participants. The overall complete with any SARS-CoV-2 variant was 70.7%. lower Omicron, at 26.1%, than pre-Omicron strains, 77.0%. Over time, by decreased 68.9% 38.9% after 6 months. Boosters restored 76.4% maintained 58.4% 3 due 87.4%, 93.3% 62.8% Omicron strains. Protection declined less infection. months series, still provided 50% protection caused Omicron. 87.9% 78.5% Conclusion declines markedly time variants. more durable resistant viral mutation. protection, emphasising need timely booster vaccination vulnerable populations.

Language: Английский

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COVID-19 Vaccination Effectiveness in the General Population of an Italian Province: Two Years of Follow-Up

Vaccines, Journal Year: 2023, Volume and Issue: 11(8), P. 1325 - 1325

Published: Aug. 4, 2023

We carried out a cohort study on the overall population of province Pescara, Italy, to assess real-world effectiveness SARS-CoV-2 vaccination against infection, severe, or lethal COVID-19, two years after start campaign. included all resident domiciled subjects, and extracted official demographic, vaccination, hospital co-pay exemption datasets from 1 January 2021, up 15 February 2023. Cox proportional hazards analyses were adjusted for gender, age, diabetes, hypertension, COPD, major cardio- cerebrovascular events, cancer, kidney diseases. Throughout follow-up (466 days average), 186,676 subjects received greater than equal three vaccine doses (of ChAdOx1 nCoV-19, BNT162b2, mRNA-1273, NVX-CoV2373, JNJ-78436735), 47,610 doses, 11,452 one dose, 44,989 none. Overall, 40.4% infected with SARS-CoV-2. Of them, 2.74% had severe (1.30%) COVID-19. As compared unvaccinated, individuals who booster dose showed ≥85% lower risk A massive impact was found among elderly: 22.0% died, as opposed less 3% those doses. No protection infection observed, although this finding certainly influenced by Italian restriction policies control pandemic. Importantly, during Omicron predominance period, only group at least reduced COVID-19-related death.

Language: Английский

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Regional Differences in Uptake of Vaccination against COVID-19 and Influenza in Germany: Results from the DigiHero Cohort

Vaccines, Journal Year: 2023, Volume and Issue: 11(11), P. 1640 - 1640

Published: Oct. 26, 2023

During the COVID-19 pandemic in Germany, vaccination uptake exhibited considerable regional disparities. To assess factors contributing to this variation, we examined association of sociodemographic variables with COVID-19, booster, and influenza status within a cohort 37,078 participants from 13 German federal states digital health study commonly known as DigiHero. Our findings revealed variations rates based on factors. However, these had limited explanatory power regarding differences vaccine uptake. In contrast, found substantial correlations between support specific parties during last local elections at level each administrative district. conclusion, alone did not suffice explain disparities Political stances can play major role, although current investigation individual political orientations but rather used only an ecological approach.

Language: Английский

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Knowledge of COVID-19 symptoms, transmission, and prevention: Evidence from health and demographic surveillance in Southern Mozambique

PLOS Global Public Health, Journal Year: 2023, Volume and Issue: 3(11), P. e0002532 - e0002532

Published: Nov. 1, 2023

Understanding community members' knowledge of SARS-CoV-2 transmission and prevention is essential for directing public health interventions to reduce disease spread improve vaccination coverage. Here, we describe COVID-19 transmission, prevention, symptoms among residents in Mozambique. We conducted a cross-sectional survey 33,087 households Health Demographic Surveillance System Manhiça, Participants were recruited April 2021 before the Delta variant wave peak Omicron cases February 2022. Principal components analysis was used create scores representing symptoms, prevention. Multiple imputation quasi-Poisson regression examine associations between demographic characteristics sources information, examined whether information mediated relationship educational attainment Across this rural community, 98.2%, 97.0%, 85.1% respondents reported knowing how could be prevented, that can cause disease, transmitted, respectively. The most recognized cough (51.2%), headaches (44.9%), fever (44.5%); mechanisms saliva droplets (50.5%) or aerosol (46.9%) from an infected person; measures handwashing (91.9%) mask-wearing (91.8%). Characteristics associated with greater included having at least primary education, older age, employment, higher wealth, Christian religion. Respondents who had experienced also more likely possess Receiving television, WhatsApp, radio, hospital, scores. These findings support need outreach community-engaged messaging promote measures, particularly people low education.

Language: Английский

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Knowledge of COVID-19 prevention in Eastern Ethiopia

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 29, 2023

ABSTRACT Objectives As of May 2023, over 500,000 COVID-19 cases and 7,500 deaths have been reported in Ethiopia. Understanding community members’ knowledge perception SARS-CoV-2 prevention is essential for directing public health interventions to reduce transmission improve vaccination coverage. Here, we aimed describe factors associated with among residents Eastern Methods We conducted a cross-sectional survey random sample 880 participants Health Demographic Surveillance System the Harari Region, Ethiopia, from August September 2021. Principal components analysis was used create score representing prevention. Quasi-Poisson regression examine associations between demographic characteristics Our also included information regarding or government measures prevent COVID-19, healthcare services children under five, pregnant women. Results The most cited individual risk contracting were washing hands soap (91.5%) wearing facemask (89.2%), whereas least mentioned avoiding domestic international travel (22.2%) medical gloves (20.3%). recognized closure schools universities (77.0%), advice avoid gatherings (75.2%), stay home (62.3%). Adjusted analyses demonstrated that higher rural areas than urban areas, those aged ≥65 years (<25 as reference), secondary education (no formal monthly income ≥2,001 Birr (0-1,200 farmers domestic/subsistence workers employees (unemployed reference). Knowledge lower households ≥5 household members (1-2 Of five women, 9.4% 12.3% missed at one care visit since mid-March 2020 consequent pandemic, respectively. Conclusions Public infectious disease depend on perceptions knowledge. found adults had good methods reducing risks although differed groups. A substantial number respondents missing important visits. these may help Ethiopian authorities plan effective programs control SARS-CoV-2.

Language: Английский

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The Effectiveness of Bivalent COVID-19 Vaccination: A Preliminary Report

Life, Journal Year: 2023, Volume and Issue: 13(10), P. 2094 - 2094

Published: Oct. 21, 2023

Vaccination has been a game-changer in the long battle against COVID-19. However, waning vaccine-induced immunity and immune evasion of emerging variants create challenges. The rapid-fire development bivalent vaccines (BVs), comprising ancestral strains new variant, was authorized to prevent COVID-19, but effectiveness updated remains largely unclear. Electronic databases were searched investigate immunogenicity reactogenicity BVs humans. As March 2023, 20 trials identified. Compared with monovalent vaccination, induced similar. demonstrated approximately 33-50% higher values additional variant strains. An observational cohort study showed clinical BVs. adverse events In conclusion, our systematic review found that had equal without safety concerns. Approximately increased antibody titers observed subjects BV vaccine moderate heterogeneity, especially for BA.1-containing

Language: Английский

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