. An independent group of translators validated the questionnaire translations and any discrepancies were addressed. The final survey instrument in each language was programmed in SurveyCTO software, incorporating appropriate routing, conditional logic and other controls and uploaded on handheld mobile tablets. Bench testing of the survey questionnaire was conducted, and adjustments made before actual data collection.
0 for further cleaning. Data analysis was conducted in Rstudio V.1.4.1106 . Descriptive statistics have been provided in the form of means for continuous variables while categorical variables have been expressed as frequencies and percentages. Socioeconomic status was generated as an additive index from six variables on household ownership of television, computer, sofa set, refrigerator and cassette/CD/DVD player, and access to electricity.
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Previous BCG vaccination is associated with less severe clinical progression of COVID-19 - BMC MedicineBackground BCG vaccination, originally used to prevent tuberculosis, is known to “train” the immune system to improve defence against viral respiratory infections. We investigated whether a previous BCG vaccination is associated with less severe clinical progression of COVID-19 Methods A case-control study comparing the proportion with a BCG vaccine scar (indicating previous vaccination) in cases and controls presenting with COVID-19 to health units in Brazil. Cases were subjects with severe COVID-19 (O2 saturation | 90%, severe respiratory effort, severe pneumonia, severe acute respiratory syndrome, sepsis, and septic shock). Controls had COVID-19 not meeting the definition of “severe” above. Unconditional regression was used to estimate vaccine protection against clinical progression to severe disease, with strict control for age, comorbidity, sex, educational level, race/colour, and municipality. Internal matching and conditional regression were used for sensitivity analysis. Results BCG was associated with high protection against COVID-19 clinical progression, over 87% (95% CI 74–93%) in subjects aged 60 or less and 35% (95% CI − 44–71%) in older subjects. Conclusions This protection may be relevant for public health in settings where COVID-19 vaccine coverage is still low and may have implications for research to identify vaccine candidates for COVID-19 that are broadly protective against mortality from future variants. Further research into the immunomodulatory effects of BCG may inform COVID-19 therapeutic research.
Source: BioMedCentral - 🏆 22. / 71 Read more »
Nationwide health, socio-economic and genetic predictors of COVID-19 vaccination status in Finland - Nature Human BehaviourThe authors use data on the entire Finnish population to develop a machine learning model for predicting COVID-19 vaccination uptake. Important predictors are proxies of socio-economic status, and those at high risk for COVID-19 consequences are less likely to get vaccinated.
Source: medical_xpress - 🏆 101. / 51 Read more »
Observational cohort study of long COVID among 2 million elderly adultsResearch estimates the incidence of long COVID and long Flu among Medicare patients using the World Health Organization (WHO) consensus definition. The study compares the incidence, symptomatology, and healthcare utilization between long COVID and long flu patients.
Source: NewsMedical - 🏆 19. / 71 Read more »
Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19 - Genome MedicineBackground We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.
Source: BioMedCentral - 🏆 22. / 71 Read more »
A modeling-based approach to optimize COVID-19 vaccine dosing schedules for improved protectionWhile the development of different vaccines has slowed the dissemination of SARS-CoV-2, the occurrence of breakthrough infections continues to fuel the pandemic. As a strategy to secure at least partial protection, with a single dose of a given COVID-19 vaccine to maximum possible fraction of the population, delayed administration of subsequent doses (or boosters) has been implemented in many countries. However, waning immunity and emergence of new variants of SARS-CoV-2 suggest that such measures may jeopardize the attainment of herd immunity due to intermittent lapses in protection. Optimizing vaccine dosing schedules could thus make the difference between periodic occurrence of breakthrough infections or effective control of the pandemic. To this end, we have developed a mechanistic mathematical model of adaptive immune response to vaccines and demonstrated its applicability to COVID-19 mRNA vaccines as a proof-of-concept for future outbreaks. The model was thoroughly calibrated against multiple clinical datasets involving immune response to SARS-CoV-2 infection and mRNA vaccines in healthy and immunocompromised subjects (cancer patients undergoing therapy); the model showed robust clinical validation by accurately predicting neutralizing antibody kinetics, a correlate of vaccine-induced protection, in response to multiple doses of mRNA vaccines. Importantly, we estimated population vulnerability to breakthrough infections and predicted tailored vaccination dosing schedules to maximize protection and thus minimize breakthrough infections, based on the immune status of a sub-population. We have identified a critical waiting window for cancer patients (or, immunocompromised subjects) to allow recovery of the immune system (particularly CD4+ T-cells) for effective differentiation of B-cells to produce neutralizing antibodies and thus achieve optimal vaccine efficacy against variants of concern, especially between the first and second doses. Also, we have obtained op
Source: medical_xpress - 🏆 101. / 51 Read more »