RESUMO
BACKGROUND: Cardiac troponin is commonly raised in patients presenting with malignancy. The prognostic significance of raised troponin in these patients is unclear. OBJECTIVES: We sought to investigate the relation between troponin and mortality in a large, well characterised cohort of patients with a routinely measured troponin and a primary diagnosis of malignancy. METHODS: We used the National Institute for Health Research (NIHR) Health Informatics Collaborative data of 5571 patients, who had troponin levels measured at 5 UK cardiac centres between 2010 and 2017 and had a primary diagnosis of malignancy. Patients were classified into solid tumour or haematological malignancy subgroups. Peak troponin levels were standardised as a multiple of each laboratory's 99th -percentile upper limit of normal (xULN). RESULTS: 4649 patients were diagnosed with solid tumours and 922 patients with haematological malignancies. Raised troponin was an independent predictor of mortality in all patients (Troponin > 10 vs. <1 adjusted HR 2.01, 95% CI 1.73 to 2.34), in solid tumours (HR 1.84, 95% CI 1.55 to 2.19), and in haematological malignancy (HR 2.72, 95% CI 1.99 to 3.72). There was a significant trend in increasing mortality risk across troponin categories in all three subgroups (p < 0.001). CONCLUSION: Raised troponin level is associated with increased mortality in patients with a primary diagnosis of malignancy regardless of cancer subtype. Mortality risk is stable for patients with a troponin level below the ULN but increases as troponin level increases above the ULN in the absence of acute coronary syndrome.
RESUMO
BACKGROUND AND AIMS: Waist circumference (WC) is a significant indicator of body adiposity and is associated with increased mortality and morbidity of cardiovascular diseases. Although, single nutrient intake and candidate genes were previously associated with WC. Little is known about WC association with overall diet quality, genetic risk score and gene-nutrient interaction. This study aims to investigate the influence of overall diet quality and multiple WC-associated single nucleotide polymorphisms on WC. In addition to investigating gene-nutrient interaction association with WC. METHODS: This study explored cross-sectional data from two large sample-size studies, to provide reproducible results. As a representation of the UK population, the Airwave Health Monitoring Study (n = 6,502) and the UK-Biobank Cohort Study (n = 171,129) were explored for factors associated with WC. Diet quality was evaluated based on the Mellen Index for Dietary Approaches to Stop Hypertension (Mellen-DASH). The genetic risk score for WC (GRS-Waist) was calculated by screening the population genotype for WC-associated single nucleotide polymorphisms. Multivariate linear regression models were built to explore WC association with diet quality and genetic risk score. Gene-nutrient interaction was explored by introducing the interaction term (GRS-Waist X Mellen-DASH score) to multivariate linear regression analysis. RESULTS: The prevalence of high WC (Female > 80 cm, Male > 94 cm) was 46.5% and 51.7% in both populations. Diet quality and genetic risk score of WC were significantly associated with WC. There was no evidence of interaction between GRS-Waist, DASH diet scores and nutrient intake on WC. CONCLUSION: This study's findings provided reproducible results on waist circumference association with diet and genetics and tested the possibility of gene-nutrient interaction. These reproducible results are successful in building the foundation for using diet and genetics for early identification of those at risk of having high WC and WC-associated diseases. In addition, evidence on gene-diet interactions on WC is limited and lacks replication, therefore our findings may guide future research in investigating this interaction and investigating its application in precision nutrition.
Assuntos
Polimorfismo de Nucleotídeo Único , Circunferência da Cintura , Humanos , Estudos Transversais , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Dieta , Reino Unido , Idoso , Predisposição Genética para Doença , Fatores de RiscoRESUMO
The COVID-19 pandemic has highlighted the need to upgrade systems for infectious disease surveillance and forecasting and modeling of the spread of infection, both of which inform evidence-based public health guidance and policies. Here, we discuss requirements for an effective surveillance system to support decision making during a pandemic, drawing on the lessons of COVID-19 in the U.S., while looking to jurisdictions in the U.S. and beyond to learn lessons about the value of specific data types. In this report, we define the range of decisions for which surveillance data are required, the data elements needed to inform these decisions and to calibrate inputs and outputs of transmission-dynamic models, and the types of data needed to inform decisions by state, territorial, local, and tribal health authorities. We define actions needed to ensure that such data will be available and consider the contribution of such efforts to improving health equity.
Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Estados Unidos/epidemiologia , SARS-CoV-2 , Pandemias , Vigilância da População , Saúde PúblicaRESUMO
BACKGROUND: Early age at menarche (AAM) has been associated with a higher risk of carotid artery intima-media thickness (cIMT), an indicator of subclinical vascular disease, albeit the mechanisms underlying this association remain elusive. A better understanding of the relationship between AAM, modifiable cardiometabolic risk factors, and subclinical atherosclerosis may contribute to improved primary prevention and cardiovascular disease treatment. We aimed to investigate the putative causal role of AAM on cIMT, and to identify and quantify the potentially mediatory effects of cardiometabolic risk factors underlying this relationship. METHODS AND RESULTS: We conducted linkage disequilibrium score regression analyses between our exposure of interest, AAM, our outcome of interest, cIMT and potential mediators of the AAM-cIMT association to gauge cross-trait genetic overlap. We considered as mediators the modifiable anthropometric risk factors body mass index (BMI), systolic blood pressure (SBP), lipid traits (total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol), and glycemic traits (fasting glucose). We then leveraged the paradigm of Mendelian randomization to infer causality between AAM and cIMT, and to identify whether cardiometabolic risk factors served as potential mediators of this effect. Our analyses showed that genetically predicted AAM was inversely associated with cIMT, BMI, SBP, and triglycerides, and positively associated with high-density lipoprotein, low-density lipoprotein, and total cholesterol. We showed that the effect of genetically predicted AAM on cIMT may be partially mediated through BMI (20.1% [95% CI, 1.4% to 38.9%]) and SBP (13.5% [95% CI, 0.5%-26.6%]). Our cluster-specific Mendelian randomization revealed heterogeneous causal effect estimates of age at menarche on BMI and SBP. CONCLUSIONS: We highlight supporting evidence for a potential causal association between earlier AAM and cIMT, and almost one third of the effect of AAM on cIMT may be mediated by BMI and SBP. Early intervention aimed at lowering BMI and hypertension may be beneficial in reducing the risk of developing subclinical atherosclerosis due to earlier age at menarche.
Assuntos
Índice de Massa Corporal , Espessura Intima-Media Carotídea , Hipertensão , Menarca , Análise da Randomização Mendeliana , Humanos , Feminino , Menarca/genética , Hipertensão/genética , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Fatores Etários , Masculino , Doenças das Artérias Carótidas/genética , Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/diagnóstico por imagem , Aterosclerose/genética , Aterosclerose/epidemiologia , Fatores Sexuais , Fatores de Risco , Adolescente , Pressão Sanguínea/genética , Medição de Risco , Doenças Assintomáticas , Fatores de Risco CardiometabólicoRESUMO
Background: The effect of Ramadan intermittent fasting (RIF) on the metabolic profile, anthropometry and blood pressure has been investigated in multiple studies. However, it is still unknown to what extent changes in nutrient intakes contribute to these changes. Methods: This observational study was conducted in London (UK) in 2019. The study collected diverse data from a community-based sample in London before and during/after Ramadan. Collected data included a 3-day food diary (before and during Ramadan), as well as blood samples, anthropometric measurements and blood pressure (before and after Ramadan). The food diary was translated into nutritional data using nutrition software "Nutritics." The changes in nutrient intakes were investigated using a mixed-effects regression model. The impact of adjusting for nutrient intake change was investigated on the absolute difference of metabolites (Nightingale platform), systolic/diastolic blood pressure and anthropometric measures. Results: The study collected data on food intake before and during Ramadan from 56 participants; the mean age was 44.7 ± 17.3, and 51.8% (n = 29) were females. We found a change in the intake of 11 nutritional factors, glucose, fructose, betaine, sugars, sugars as monosaccharide equivalents, lutein/zeaxanthin, starch, starch as monosaccharide equivalents, proline, glutamic acid and lycopene. No changes in quantities or proportions of macronutrients, carbohydrates, protein and fat. Mainly, the changes in diet during Ramadan are characterized by more consumption of sugars (62%, p < 0.001) and a lower intake of starch (-21%, p = 0.012). The changes in 14 metabolite levels (two glycolysis-related metabolites, one amino acid, two ketone bodies, two triglyceride, six lipoprotein subclasses, and an inflammation marker) after Ramadan were partially associated with some changes in nutrient intakes during Ramadan, especially betaine, fructose, glucose, starches and sugars. The lutein/zeaxanthin intake change explained inversely 14% of systolic blood pressure changes. Moreover, BMI and weight changes were partially explained by changes in intake of fat (7%; 9%), monounsaturated fat (6%; 7%), starch (8%; 9%), and starch as monosaccharide equivalents (8%; 9%) intakes in a direct relationship. Conclusion: Diet changes during Ramadan were associated partially with the observed changes in the metabolic profile, blood pressure and anthropometry. This confirms the changes associated with RIF in the metabolic profile, blood pressure and anthropometry are not an absolute physiological response to the diet transition occurring during Ramadan.
Assuntos
COVID-19 , Cognição , Memória , Humanos , COVID-19/complicações , COVID-19/psicologia , Reino Unido , Noruega , Adulto , Síndrome de COVID-19 Pós-Aguda/complicações , CriançaRESUMO
AIMS: Evaluate sex differences in cardiovascular disease (CVD) risk prediction, including use of i) optimal sex-specific risk predictors and ii) sex-specific risk thresholds. METHODS AND RESULTS: Prospective cohort study using UK Biobank, including 121,724 and 182,632 healthy men and women, respectively, aged 38-73 years at baseline. There were 11,899 (men) and 9,110 (women) incident CVD cases (hospitalization or mortality) with median 12.1 years follow-up. We used recalibrated Pooled Cohort Equations (PCE, 7.5% 10-year risk threshold as per US guidelines), QRISK3 (10% 10-year risk threshold as per UK guidelines) and Cox survival models using sparse sex-specific variable sets (via LASSO stability selection) to predict CVD risk separately in men and women. LASSO stability selection included 12 variables in common between men and women, with three additional variables selected for men and one for women. C-statistics were slightly lower for PCE than QRISK3 and models using stably-selected variables, but were similar between men and women: 0.67 [0.66-0.68], 0.70 [0.69-0.71], and 0.71 [0.70-0.72] in men and 0.69 [0.68-0.70], 0.72 [0.71-0.73], and 0.72 [0.71-0.73] in women for PCE, QRISK3 and models using stably-selected variables, respectively. At current clinically implemented risk thresholds, test sensitivity was markedly lower in women than men for all models: at 7.5% 10-year risk, sensitivity was 65.1% and 68.2% in men and 24.0% and 33.4% in women for PCE and models using stably-selected variables, respectively; at 10% 10-year risk, sensitivity was 53.7% and 52.3% in men and 16.8% and 20.2% in women for QRISK3 and models using stably-selected variables, respectively. Specificity was correspondingly higher in women than men. However, the sensitivity in women at 5% 10-year risk threshold increased to 50.1%, 58.5% and 55.7% for PCE, QRISK3 and models using stably-selected variables, respectively. CONCLUSIONS: Use of sparse sex-specific variables improved CVD risk prediction compared with PCE but not QRISK3. At current risk thresholds, PCE and QRISK3 work less well for women than men but sensitivity was improved in women using a 5% 10-year risk threshold. Use of sex-specific risk thresholds should be considered in any re-evaluation of CVD risk calculators. TRANSLATIONAL PERSPECTIVE: Cardiovascular disease (CVD) risk prediction is an important component of clinical risk management and disease prevention. We find that at risk prediction thresholds used by currently applied risk prediction algorithms (PCE 7.5% 10-year risk threshold in the US and QRISK3 10% risk threshold in the UK), sensitivity of these risk prediction tools is markedly lower in women than in men. This sex inequality implies that women are proportionately less likely to receive appropriate clinical management including lipid-lowering therapy. If the risk prediction threshold is lowered to 5% 10-year risk in women, then sensitivity in women is substantially increased.
RESUMO
A leading explanation for translational failure in neurodegenerative disease is that new drugs are evaluated late in the disease course when clinical features have become irreversible. Here, to address this gap, we cognitively profiled 21,051 people aged 17-85 years as part of the Genes and Cognition cohort within the National Institute for Health and Care Research BioResource across England. We describe the cohort, present cognitive trajectories and show the potential utility. Surprisingly, when studied at scale, the APOE genotype had negligible impact on cognitive performance. Different cognitive domains had distinct genetic architectures, with one indicating brain region-specific activation of microglia and another with glycogen metabolism. Thus, the molecular and cellular mechanisms underpinning cognition are distinct from dementia risk loci, presenting different targets to slow down age-related cognitive decline. Participants can now be recalled stratified by genotype and cognitive phenotype for natural history and interventional studies of neurodegenerative and other disorders.
Assuntos
Cognição , Genótipo , Humanos , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Adolescente , Adulto , Adulto Jovem , Feminino , Estudos de Coortes , Masculino , Apolipoproteínas E/genética , Envelhecimento/genética , InglaterraRESUMO
Photochemical ligand release from metal complexes may be exploited in the development of novel photoactivated chemotherapy agents for the treatment of cancer and other diseases. Highly intriguing photochemical behavior is reported for two ruthenium(II) complexes bearing conformationally flexible 1,2,3-triazole-based ligands incorporating a methylene spacer to form 6-membered chelate rings. [Ru(bpy)2(pictz)]2+ (1) and [Ru(bpy)2(btzm)]2+ (2) (bpy = 2,2'-bipyridyl; pictz = 1-(picolyl)-4-phenyl-1,2,3-triazole; btzm = bis(4-phenyl-1,2,3-triazol-4-yl)methane) exhibit coordination by the triazole ring through the less basic N2 atom as a consequence of chelation and readily undergo photochemical release of the pictz and btzm ligands (Ï = 0.079 and 0.091, respectively) in acetonitrile solution to form cis-[Ru(bpy)2(NCMe)2]2+ (3) in both cases. Ligand-loss intermediates of the form [Ru(bpy)2(κ1-pictz or κ1-btzm)(NCCD3)]2+ are detected by 1H NMR spectroscopy and mass spectrometry. Photolysis of 1 yields three ligand-loss intermediates with monodentate pictz ligands, two of which form through simple decoordination of either the pyridine or triazole donor with subsequent solvent coordination (4-tz(N2) and 4-py, respectively). The third intermediate, shown to be able to form photochemically directly from 1, arises through linkage isomerism in which the monodentate pictz ligand is coordinated by the triazole N3 atom (4-tz(N3)) with a comparable ligand-loss intermediate with an N3-bound κ1-btzm ligand also observed for 2.
RESUMO
Photoluminescent coordination complexes of Cr(III) are of interest as near-infrared spin-flip emitters. Here, we explore the preparation, electrochemistry, and photophysical properties of the first two examples of homoleptic N-heterocyclic carbene complexes of Cr(III), featuring 2,6-bis(imidazolyl)pyridine (ImPyIm) and 2-imidazolylpyridine (ImPy) ligands. The complex [Cr(ImPy)3]3+ displays luminescence at 803 nm on the microsecond time scale (13.7 µs) from a spin-flip doublet excited state, which transient absorption spectroscopy reveals to be populated within several picoseconds following photoexcitation. Conversely, [Cr(ImPyIm)2]3+ is nonemissive and has a ca. 500 ps excited-state lifetime.
RESUMO
The Cohort Study of Mobile Phone Use and Health (COSMOS) has repeatedly collected self-reported and operator-recorded data on mobile phone use. Assessing health effects using self-reported information is prone to measurement error, but operator data were available prospectively for only part of the study population and did not cover past mobile phone use. To optimize the available data and reduce bias, we evaluated different statistical approaches for constructing mobile phone exposure histories within COSMOS. We evaluated and compared the performance of four regression calibration (RC) methods (simple, direct, inverse, and generalized additive model for location, shape, and scale), complete-case (CC) analysis and multiple imputation (MI) in a simulation study with a binary health outcome. We used self-reported and operator-recorded mobile phone call data collected at baseline (2007-2012) from participants in Denmark, Finland, the Netherlands, Sweden, and the UK. Parameter estimates obtained using simple, direct, and inverse RC methods were associated with less bias and lower mean squared error than those obtained with CC analysis or MI. We showed that RC methods resulted in more accurate estimation of the relation between mobile phone use and health outcomes, by combining self-reported data with objective operator-recorded data available for a subset of participants.
RESUMO
BACKGROUND: Each new generation of mobile phone technology has triggered discussions about potential carcinogenicity from exposure to radiofrequency electromagnetic fields (RF-EMF). Available evidence has been insufficient to conclude about long-term and heavy mobile phone use, limited by differential recall and selection bias, or crude exposure assessment. The Cohort Study on Mobile Phones and Health (COSMOS) was specifically designed to overcome these shortcomings. METHODS: We recruited participants in Denmark, Finland, the Netherlands, Sweden, and the UK 2007-2012. The baseline questionnaire assessed lifetime history of mobile phone use. Participants were followed through population-based cancer registers to identify glioma, meningioma, and acoustic neuroma cases during follow-up. Non-differential exposure misclassification was reduced by adjusting estimates of mobile phone call-time through regression calibration methods based on self-reported data and objective operator-recorded information at baseline. Hazard ratios (HR) and 95% confidence intervals (CI) for glioma, meningioma, and acoustic neuroma in relation to lifetime history of mobile phone use were estimated with Cox regression models with attained age as the underlying time-scale, adjusted for country, sex, educational level, and marital status. RESULTS: 264,574 participants accrued 1,836,479 person-years. During a median follow-up of 7.12 years, 149 glioma, 89 meningioma, and 29 incident cases of acoustic neuroma were diagnosed. The adjusted HR per 100 regression-calibrated cumulative hours of mobile phone call-time was 1.00 (95 % CI 0.98-1.02) for glioma, 1.01 (95 % CI 0.96-1.06) for meningioma, and 1.02 (95 % CI 0.99-1.06) for acoustic neuroma. For glioma, the HR for ≥ 1908 regression-calibrated cumulative hours (90th percentile cut-point) was 1.07 (95 % CI 0.62-1.86). Over 15 years of mobile phone use was not associated with an increased tumour risk; for glioma the HR was 0.97 (95 % CI 0.62-1.52). CONCLUSIONS: Our findings suggest that the cumulative amount of mobile phone use is not associated with the risk of developing glioma, meningioma, or acoustic neuroma.
Assuntos
Neoplasias Encefálicas , Uso do Telefone Celular , Telefone Celular , Glioma , Neoplasias Meníngeas , Meningioma , Neuroma Acústico , Humanos , Meningioma/epidemiologia , Meningioma/etiologia , Estudos de Coortes , Neuroma Acústico/epidemiologia , Neuroma Acústico/etiologia , Estudos Prospectivos , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/etiologia , Glioma/epidemiologia , Glioma/etiologia , Campos Eletromagnéticos , Inquéritos e Questionários , Estudos de Casos e ControlesRESUMO
INTRODUCTION: The Dementias Platform UK (DPUK) Data Portal is a data repository bringing together a wide range of cohorts. Neurodegenerative dementias are a group of diseases with highly heterogeneous pathology and an overlapping genetic component that is poorly understood. The DPUK collection of independent cohorts can facilitate research in neurodegeneration by combining their genetic and phenotypic data. METHODS: For genetic data processing, pipelines were generated to perform quality control analysis, genetic imputation, and polygenic risk score (PRS) derivation with six genome-wide association studies of neurodegenerative diseases. Pipelines were applied to five cohorts. DISCUSSION: The data processing pipelines, research-ready imputed genetic data, and PRS scores are now available on the DPUK platform and can be accessed upon request though the DPUK application process. Harmonizing genome-wide data for multiple datasets increases scientific opportunity and allows the wider research community to access and process data at scale and pace.
Assuntos
Demência , Estudo de Associação Genômica Ampla , Herança Multifatorial , Humanos , Demência/genética , Reino Unido , Herança Multifatorial/genética , Predisposição Genética para Doença , Estudos de Coortes , Bases de Dados GenéticasRESUMO
BACKGROUND: The SSaSS (Salt Substitute and Stroke Study) has shown that use of a potassium-enriched salt lowers the risk of stroke, total cardiovascular events, and premature death. The effects on cause-specific cardiac outcomes are reported here. METHODS: SSaSS was an unblinded, cluster-randomised trial assessing the effects of potassium-enriched salt compared with regular salt among 20 995 Chinese adults with established stroke and older age and uncontrolled hypertension. Post hoc efficacy analyses were performed using an intention-to-treat method and a hierarchical Poisson regression model adjusting for clustering to obtain rate ratios and 95% CIs. We assessed acute coronary syndrome, heart failure, arrhythmia, and sudden death. RESULTS: Over a mean 4.74 years follow-up, there were 695 acute coronary syndrome events, 454 heart failure events, 230 arrhythmia events, and 1133 sudden deaths recorded. The rates of events were lower in potassium-enriched salt group for all outcomes but CIs were wide for most: acute coronary syndrome (6.32 versus 7.65 events per 1000 person-years; rate ratio, 0.80 [95% CI, 0.65-0.99]); heart failure (9.14 versus 11.32 events per 1000 person-years; rate ratio, 0.88 [95% CI, 0.60-1.28]); arrhythmia (4.43 versus 6.20 events per 1000 person-years; rate ratio, 0.59 [95% CI, 0.35-0.98]); and sudden death (11.01 versus 11.76 events per 1000 person-years; rate ratio, 0.94 [95% CI, 0.82-1.07]; all P>0.05 with adjustment for multiple comparisons). CONCLUSIONS: These results suggest that use of potassium-enriched salt is more likely to prevent than cause cardiac disease but the post hoc nature of these analyses precludes definitive conclusions. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02092090.
Assuntos
Síndrome Coronariana Aguda , Insuficiência Cardíaca , Acidente Vascular Cerebral , Adulto , Humanos , Arritmias Cardíacas , Morte Súbita , Potássio , Acidente Vascular Cerebral/prevenção & controleRESUMO
BACKGROUND: Caffeine is one of the most utilized drugs in the world, yet its clinical effects are not fully understood. Circulating caffeine levels are influenced by the interplay between consumption behaviour and metabolism. This study aimed to investigate the effects of circulating caffeine levels by considering genetically predicted variation in caffeine metabolism. METHODS: Leveraging genetic variants related to caffeine metabolism that affect its circulating levels, we investigated the clinical effects of plasma caffeine in a phenome-wide association study (PheWAS). We validated novel findings using a two-sample Mendelian randomization framework and explored the potential mechanisms underlying these effects in proteome-wide and metabolome-wide Mendelian randomization. RESULTS: Higher levels of genetically predicted circulating caffeine among caffeine consumers were associated with a lower risk of obesity (odds ratio (OR) per standard deviation increase in caffeine = 0.97, 95% confidence interval (CI) CI: 0.95-0.98, p = 2.47 × 10-4), osteoarthrosis (OR = 0.97, 95% CI: 0.96-0.98, P=1.10 × 10-8) and osteoarthritis (OR: 0.97, 95% CI: 0.96 to 0.98, P = 1.09 × 10-6). Approximately one third of the protective effect of plasma caffeine on osteoarthritis risk was estimated to be mediated through lower bodyweight. Proteomic and metabolomic perturbations indicated lower chronic inflammation, improved lipid profiles, and altered protein and glycogen metabolism as potential biological mechanisms underlying these effects. CONCLUSIONS: We report novel evidence suggesting that long-term increases in circulating caffeine may reduce bodyweight and the risk of osteoarthrosis and osteoarthritis. We confirm prior genetic evidence of a protective effect of plasma caffeine on risk of overweight and obesity. Further clinical study is warranted to understand the translational relevance of these findings before clinical practice or lifestyle interventions related to caffeine consumption are introduced.
Assuntos
Cafeína , Osteoartrite , Humanos , Proteoma/genética , Análise da Randomização Mendeliana , Proteômica , Obesidade/epidemiologia , Obesidade/genética , Metaboloma/genética , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Cognitive symptoms after coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are well-recognized. Whether objectively measurable cognitive deficits exist and how long they persist are unclear. METHODS: We invited 800,000 adults in a study in England to complete an online assessment of cognitive function. We estimated a global cognitive score across eight tasks. We hypothesized that participants with persistent symptoms (lasting ≥12 weeks) after infection onset would have objectively measurable global cognitive deficits and that impairments in executive functioning and memory would be observed in such participants, especially in those who reported recent poor memory or difficulty thinking or concentrating ("brain fog"). RESULTS: Of the 141,583 participants who started the online cognitive assessment, 112,964 completed it. In a multiple regression analysis, participants who had recovered from Covid-19 in whom symptoms had resolved in less than 4 weeks or at least 12 weeks had similar small deficits in global cognition as compared with those in the no-Covid-19 group, who had not been infected with SARS-CoV-2 or had unconfirmed infection (-0.23 SD [95% confidence interval {CI}, -0.33 to -0.13] and -0.24 SD [95% CI, -0.36 to -0.12], respectively); larger deficits as compared with the no-Covid-19 group were seen in participants with unresolved persistent symptoms (-0.42 SD; 95% CI, -0.53 to -0.31). Larger deficits were seen in participants who had SARS-CoV-2 infection during periods in which the original virus or the B.1.1.7 variant was predominant than in those infected with later variants (e.g., -0.17 SD for the B.1.1.7 variant vs. the B.1.1.529 variant; 95% CI, -0.20 to -0.13) and in participants who had been hospitalized than in those who had not been hospitalized (e.g., intensive care unit admission, -0.35 SD; 95% CI, -0.49 to -0.20). Results of the analyses were similar to those of propensity-score-matching analyses. In a comparison of the group that had unresolved persistent symptoms with the no-Covid-19 group, memory, reasoning, and executive function tasks were associated with the largest deficits (-0.33 to -0.20 SD); these tasks correlated weakly with recent symptoms, including poor memory and brain fog. No adverse events were reported. CONCLUSIONS: Participants with resolved persistent symptoms after Covid-19 had objectively measured cognitive function similar to that in participants with shorter-duration symptoms, although short-duration Covid-19 was still associated with small cognitive deficits after recovery. Longer-term persistence of cognitive deficits and any clinical implications remain uncertain. (Funded by the National Institute for Health and Care Research and others.).