AbstractObjectivesTo determine the clinical sequelae of long covid for a year after infection in patients with mild disease and to evaluate its association with age, sex, SARS-CoV-2 variants, and ...vaccination status.DesignRetrospective nationwide cohort study.SettingElectronic medical records from an Israeli nationwide healthcare organisation.Population1 913 234 Maccabi Healthcare Services members of all ages who did a polymerase chain reaction test for SARS-CoV-2 between 1 March 2020 and 1 October 2021.Main outcome measuresRisk of an evidence based list of 70 reported long covid outcomes in unvaccinated patients infected with SARS-CoV-2 matched to uninfected people, adjusted for age and sex and stratified by SARS-CoV-2 variants, and risk in patients with a breakthrough SARS-CoV-2 infection compared with unvaccinated infected controls. Risks were compared using hazard ratios and risk differences per 10 000 patients measured during the early (30-180 days) and late (180-360 days) time periods after infection.ResultsCovid-19 infection was significantly associated with increased risks in early and late periods for anosmia and dysgeusia (hazard ratio 4.59 (95% confidence interval 3.63 to 5.80), risk difference 19.6 (95% confidence interval 16.9 to 22.4) in early period; 2.96 (2.29 to 3.82), 11.0 (8.5 to 13.6) in late period), cognitive impairment (1.85 (1.58 to 2.17), 12.8, (9.6 to 16.1); 1.69 (1.45 to 1.96), 13.3 (9.4 to 17.3)), dyspnoea (1.79 (1.68 to 1.90), 85.7 (76.9 to 94.5); 1.30 (1.22 to 1.38), 35.4 (26.3 to 44.6)), weakness (1.78 (1.69 to 1.88), 108.5, 98.4 to 118.6; 1.30 (1.22 to 1.37), 50.2 (39.4 to 61.1)), and palpitations (1.49 (1.35 to 1.64), 22.1 (16.8 to 27.4); 1.16 (1.05 to 1.27), 8.3 (2.4 to 14.1)) and with significant but lower excess risk for streptococcal tonsillitis and dizziness. Hair loss, chest pain, cough, myalgia, and respiratory disorders were significantly increased only during the early phase. Male and female patients showed minor differences, and children had fewer outcomes than adults during the early phase of covid-19, which mostly resolved in the late period. Findings remained consistent across SARS-CoV-2 variants. Vaccinated patients with a breakthrough SARS-CoV-2 infection had a lower risk for dyspnoea and similar risk for other outcomes compared with unvaccinated infected patients.ConclusionsThis nationwide study suggests that patients with mild covid-19 are at risk for a small number of health outcomes, most of which are resolved within a year from diagnosis.
Identifying patients at increased risk for severe COVID-19 is of high priority during the pandemic as it could affect clinical management and shape public health guidelines. In this study we assessed ...whether a second PCR test conducted 2-7 days after a SARS-CoV-2 positive test could identify patients at risk for severe illness. Analysis of a nationwide electronic health records data of 1683 SARS-CoV-2 positive individuals indicated that a second negative PCR test result was associated with lower risk for severe illness compared to a positive result. This association was seen across different age groups and clinical settings. More importantly, it was not limited to recovering patients but also observed in patients who still had evidence of COVID-19 as determined by a subsequent positive PCR test. Our study suggests that an early second PCR test may be used as a supportive risk-assessment tool to improve disease management and patient care.
The natural history of allergic diseases suggests bidirectional and progressive relationships between allergic disorders of the skin, lung, and gut indicative of mucosal organ crosstalk. However, ...impacts of local allergic inflammation on the cellular landscape of remote mucosal organs along the skin:lung:gut axis are not yet known. Eosinophils are tissue-dwelling innate immune leukocytes associated with allergic diseases. Emerging data suggest heterogeneous phenotypes of tissue-dwelling eosinophils contribute to multifaceted roles that favor homeostasis or disease. This study investigated the impact of acute local allergen exposure on the frequency and phenotype of tissue eosinophils within remote mucosal organs. Our findings demonstrate allergen challenge to skin, lung, or gut elicited not only local eosinophilic inflammation, but also increased the number and frequency of eosinophils within remote, allergen nonexposed lung, and intestine. Remote allergen-elicited lung eosinophils exhibited an inflammatory phenotype and their presence associated with enhanced susceptibility to airway inflammation induced upon subsequent inhalation of a different allergen. These data demonstrate, for the first time, a direct effect of acute allergic inflammation on the phenotype and frequency of tissue eosinophils within antigen nonexposed remote mucosal tissues associated with remote organ priming for allergic inflammation.
Assessing the impact of cesarean delivery (CD) on long-term childhood outcomes is challenging as conducting a randomized controlled trial is rarely feasible and inferring it from observational data ...may be confounded. Utilizing data from electronic health records of 737,904 births, we defined and emulated a target trial to estimate the effect of CD on predefined long-term pediatric outcomes. Causal effects were estimated using pooled logistic regression and standardized survival curves, leveraging data breadth to account for potential confounders. Diverse sensitivity analyses were performed including replication of results in an external validation set from the UK including 625,044 births. Children born in CD had an increased risk to develop asthma (10-year risk differences (95% CI) 0.64% (0.31, 0.98)), an average treatment effect of 0.10 (0.07–0.12) on body mass index (BMI) z-scores at age 5 years old and 0.92 (0.68–1.14) on the number of respiratory infection events until 5 years of age. A positive 10-year risk difference was also observed for atopy (10-year risk differences (95% CI) 0.74% (-0.06, 1.52)) and allergy 0.47% (-0.32, 1.28)). Increased risk for these outcomes was also observed in the UK cohort. Our findings add to a growing body of evidence on the long-term effects of CD on pediatric morbidity, may assist in the decision to perform CD when not medically indicated and paves the way to future research on the mechanisms underlying these effects and intervention strategies targeting them.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Assessing the impact of cesarean delivery (CD) on long-term childhood outcomes is challenging as conducting a randomized controlled trial is rarely feasible and inferring it from observational data ...may be confounded. Utilizing data from electronic health records of 737,904 births, we defined and emulated a target trial to estimate the effect of CD on predefined long-term pediatric outcomes. Causal effects were estimated using pooled logistic regression and standardized survival curves, leveraging data breadth to account for potential confounders. Diverse sensitivity analyses were performed including replication of results in an external validation set from the UK including 625,044 births. Children born in CD had an increased risk to develop asthma (10-year risk differences (95% CI) 0.64% (0.31, 0.98)), an average treatment effect of 0.10 (0.07–0.12) on body mass index (BMI) z-scores at age 5 years old and 0.92 (0.68–1.14) on the number of respiratory infection events until 5 years of age. A positive 10-year risk difference was also observed for atopy (10-year risk differences (95% CI) 0.74% (-0.06, 1.52)) and allergy 0.47% (-0.32, 1.28)). Increased risk for these outcomes was also observed in the UK cohort. Our findings add to a growing body of evidence on the long-term effects of CD on pediatric morbidity, may assist in the decision to perform CD when not medically indicated and paves the way to future research on the mechanisms underlying these effects and intervention strategies targeting them.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
While immunological memory has long been considered the province of T- and B-lymphocytes, it has recently been reported that innate cell populations are capable of mediating memory responses. We now ...show that an innate memory immune response is generated in mice following infection with vaccinia virus, a poxvirus for which no cognate germline-encoded receptor has been identified. This immune response results in viral clearance in the absence of classical adaptive T and B lymphocyte populations, and is mediated by a Thy1(+) subset of natural killer (NK) cells. We demonstrate that immune protection against infection from a lethal dose of virus can be adoptively transferred with memory hepatic Thy1(+) NK cells that were primed with live virus. Our results also indicate that, like classical immunological memory, stronger innate memory responses form in response to priming with live virus than a highly attenuated vector. These results demonstrate that a defined innate memory cell population alone can provide host protection against a lethal systemic infection through viral clearance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Youth mental distress has substantially increased during the COVID-19 pandemic. However, it is unclear if mental symptoms are directly related to SARS-CoV-2 infection or to social restrictions. We ...aimed to investigate mental health outcomes in infected versus uninfected adolescents, for up to two years after an index polymerase chain reaction (PCR) test.
A retrospective cohort study, based on electronic health records from a large nationally representative Israeli health fund, among adolescents aged 12–17 years with a PCR test for SARS-CoV-2 between March 1, 2020 and March 1, 2021. Infected and uninfected individuals were matched by age, sex, test date, sector, and socioeconomic status. Cox regression was used to derive hazard ratios (HRs) for mental health outcomes within two years from PCR test for infected versus uninfected individuals, while accounting for pre-existing psychiatric history. External validation was performed on UK primary care data.
Among 146,067 PCR-tested adolescents, 24,009 were positive and 22,354 were matched with negative adolescents. SARS-CoV-2 infection was significantly associated with reduced risks for dispensation of antidepressants (HR 0.74, 95% confidence interval CI 0.66–0.83), diagnoses of anxiety (HR 0.82, 95% CI 0.71–0.95), depression (HR 0.65, 95% CI 0.53–0.80), and stress (HR 0.80, 95% CI 0.69–0.92). Similar results were obtained in the validation dataset.
This large, population-based study suggests that SARS-CoV-2 infection is not associated with elevated risk for mental distress in adolescents. Our findings highlight the importance of taking a holistic view on adolescents' mental health during the pandemic, with consideration of both SARS-CoV-2 infection and response measures.
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e18092
Background: Value-based healthcare requires integration of real-world data (RWD) generated by patients in parallel to clinical documentation. This gives a holistic perspective of ...the patients’ health and care and could lead to reduced costs and better patient care and safety. Belong digital patient-powered network (PPN) is a social network for cancer patients and caregivers providing them access to other patients, healthcare professionals and disease management tools. In this study we compared the clinical data generated by Belong users with classical clinical documentation. Furthermore we explored the additional information generated in the PPN and its value. Methods: RWD collected from users of the Belong PPN was retrospectively analyzed. We evaluated patient-reported outcomes in parallel to medical records provided voluntarily and anonymously. Data of patient journeys was extracted and mapped from medical records and social engagement in our platform using artificial intelligence (AI) engines. Data was further validated manually by the research team to assure accuracy. Results: We compared 40 treatment journeys reported by patients in Belong to their doctor summary. The data showed that patients can accurately describe their cancer diagnosis and treatment, mentioning 85% and 90% of their diagnosis and treatment, respectively. In 38% of the cases, patients’ engagement data provided additional insights in the categories of OTC drugs, supplements, diet, alternative treatments, lifestyle changes and emotional health. Complementary information from patients with possible clinical consequences (changes in sugar levels, blood pressure, body minerals levels etc.) was also reported and could affect patients’ treatment and well-being. Conclusions: RWD collected in the Belong PPN recreated a comparable clinical description of standard medical documents and provided additional insights that created a more comprehensive picture of patients’ health. Superimposing the social data layer onto the clinical one could provide significant advancement of how we treat patients and result in better cost-efficiency, improved healthcare services and patients’ outcomes.
Chitosan microparticles as carriers for GRA-1 protein vaccine were prepared and characterized with respect to loading efficiency and GRA-1 stability after short-term storage. Chitosan nanoparticles ...as carriers for GRA-1 pDNA vaccine were prepared and characterized with respect to size, zeta potential, and protection of the pDNA vaccine against degradation by DNase I. Both protein and pDNA vaccine preparations were tested with regard to their potential to elicit GRA-1-specific immune response after intragastric administration using different prime/boost regimen. The immune response was measured by determination of IgG2a and IgG1 antibody titers. It was shown that priming with GRA1 protein vaccine loaded chitosan particles and boosting with GRA1 pDNA vaccine resulted in high anti-GRA1 antibodies, characterized by a mixed IgG2a/IgG1 ratio. These results showed that oral delivery of vaccines using chitosan as a carrier material appears to be beneficial for inducing an immune response against
Toxoplasma gondii. The type of immune response, however, will largely depend on the prime/boost regimen and the type of vaccine used.
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![Thy1+ NK [corrected] cells ...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1553-7374_1553-7366/small "Thy1+ NK [corrected] cells from vaccinia virus-primed mice confer protection against vaccinia virus challenge in the absence of adaptive lymphocytes")
