Publications by authors named "Claire J Steves"

77 Publications

Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study.

Lancet Infect Dis 2021 Apr 27. Epub 2021 Apr 27.

Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.

Background: The Pfizer-BioNTech (BNT162b2) and the Oxford-AstraZeneca (ChAdOx1 nCoV-19) COVID-19 vaccines have shown excellent safety and efficacy in phase 3 trials. We aimed to investigate the safety and effectiveness of these vaccines in a UK community setting.

Methods: In this prospective observational study, we examined the proportion and probability of self-reported systemic and local side-effects within 8 days of vaccination in individuals using the COVID Symptom Study app who received one or two doses of the BNT162b2 vaccine or one dose of the ChAdOx1 nCoV-19 vaccine. We also compared infection rates in a subset of vaccinated individuals subsequently tested for SARS-CoV-2 with PCR or lateral flow tests with infection rates in unvaccinated controls. All analyses were adjusted by age (≤55 years vs >55 years), sex, health-care worker status (binary variable), obesity (BMI <30 kg/mvs ≥30 kg/m), and comorbidities (binary variable, with or without comorbidities).

Findings: Between Dec 8, and March 10, 2021, 627 383 individuals reported being vaccinated with 655 590 doses: 282 103 received one dose of BNT162b2, of whom 28 207 received a second dose, and 345 280 received one dose of ChAdOx1 nCoV-19. Systemic side-effects were reported by 13·5% (38 155 of 282 103) of individuals after the first dose of BNT162b2, by 22·0% (6216 of 28 207) after the second dose of BNT162b2, and by 33·7% (116 473 of 345 280) after the first dose of ChAdOx1 nCoV-19. Local side-effects were reported by 71·9% (150 023 of 208 767) of individuals after the first dose of BNT162b2, by 68·5% (9025 of 13 179) after the second dose of BNT162b2, and by 58·7% (104 282 of 177 655) after the first dose of ChAdOx1 nCoV-19. Systemic side-effects were more common (1·6 times after the first dose of ChAdOx1 nCoV-19 and 2·9 times after the first dose of BNT162b2) among individuals with previous SARS-CoV-2 infection than among those without known past infection. Local effects were similarly higher in individuals previously infected than in those without known past infection (1·4 times after the first dose of ChAdOx1 nCoV-19 and 1·2 times after the first dose of BNT162b2). 3106 of 103 622 vaccinated individuals and 50 340 of 464 356 unvaccinated controls tested positive for SARS-CoV-2 infection. Significant reductions in infection risk were seen starting at 12 days after the first dose, reaching 60% (95% CI 49-68) for ChAdOx1 nCoV-19 and 69% (66-72) for BNT162b2 at 21-44 days and 72% (63-79) for BNT162b2 after 45-59 days.

Interpretation: Systemic and local side-effects after BNT162b2 and ChAdOx1 nCoV-19 vaccination occur at frequencies lower than reported in phase 3 trials. Both vaccines decrease the risk of SARS-CoV-2 infection after 12 days.

Funding: ZOE Global, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, UK Medical Research Council, Wellcome Trust, UK Research and Innovation, American Gastroenterological Association.
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http://dx.doi.org/10.1016/S1473-3099(21)00224-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078878PMC
April 2021

Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study.

Lancet Public Health 2021 05 12;6(5):e335-e345. Epub 2021 Apr 12.

School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK.

Background: The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility.

Methods: We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, R, for the two incidence estimates.

Findings: From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6-0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56-0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38-0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the R of B.1.1.7 by a factor of 1·35 (95% CI 1·02-1·69) relative to pre-existing variants. However, R fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant.

Interpretation: The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant.

Funding: Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society.
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http://dx.doi.org/10.1016/S2468-2667(21)00055-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041365PMC
May 2021

Integrating Comprehensive Geriatric Assessment for people with COPD and frailty starting pulmonary rehabilitation: the Breathe Plus feasibility trial protocol.

ERJ Open Res 2021 Jan 29;7(1). Epub 2021 Mar 29.

King's College London, Cicely Saunders Institute of Palliative Care, Policy and Rehabilitation, London, UK.

One in five people with COPD also lives with frailty. People living with both COPD and frailty are at increased risk of poorer health and outcomes, and face challenges to completing pulmonary rehabilitation. Integrated approaches that are adapted to the additional context of frailty are required. The aim of the present study is to determine the feasibility of conducting a randomised controlled trial of an integrated Comprehensive Geriatric Assessment for people with COPD and frailty starting pulmonary rehabilitation. This is a multicentre, mixed-methods, assessor-blinded, randomised, parallel group, controlled feasibility trial ("Breathe Plus"; ISRCTN13051922). We aim to recruit 60 people aged ≥50 with both COPD and frailty referred for pulmonary rehabilitation. Participants will be randomised 1:1 to receive usual pulmonary rehabilitation, or pulmonary rehabilitation with an additional Comprehensive Geriatric Assessment. Outcomes (physical, psycho-social and service use) will be measured at baseline, 90 days and 180 days. We will also collect service and trial process data, and conduct qualitative interviews with a sub-group of participants and staff. We will undertake descriptive analysis of quantitative feasibility outcomes (recruitment, retention, missing data, blinding, contamination, fidelity), and framework analysis of qualitative feasibility outcomes (intervention acceptability and theory, outcome acceptability). Recommendations on progression to a full trial will comprise integration of quantitative and qualitative data, with input from relevant stakeholders. This study has been approved by a UK Research Ethics Committee (ref.: 19/LO/1402). This protocol describes the first study testing the feasibility of integrating a Comprehensive Geriatric Assessment alongside pulmonary rehabilitation, and testing this intervention within a mixed-methods randomised controlled trial.
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http://dx.doi.org/10.1183/23120541.00717-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005693PMC
January 2021

Symptoms and syndromes associated with SARS-CoV-2 infection and severity in pregnant women from two community cohorts.

Sci Rep 2021 03 25;11(1):6928. Epub 2021 Mar 25.

School of Biomedical Engineering and Imaging Sciences, King's College London, 9th floor, Becket House, 1 Lambeth Palace Road, London, SE1 7EU, UK.

We tested whether pregnant and non-pregnant women differ in COVID-19 symptom profile and severity, and we extended previous investigations on hospitalized pregnant women to those who did not require hospitalization. Two female community-based cohorts (18-44 years) provided longitudinal (smartphone application, N = 1,170,315, n = 79 pregnant tested positive) and cross-sectional (web-based survey, N = 1,344,966, n = 134 pregnant tested positive) data, prospectively collected through self-participatory citizen surveillance in UK, Sweden and USA. Pregnant and non-pregnant were compared for frequencies of events, including SARS-CoV-2 testing, symptoms and hospitalization rates. Multivariable regression was used to investigate symptoms severity and comorbidity effects. Pregnant and non-pregnant women positive for SARS-CoV-2 infection were not different in syndromic severity, except for gastrointestinal symptoms. Pregnant were more likely to have received testing, despite reporting fewer symptoms. Pre-existing lung disease was most closely associated with syndromic severity in pregnant hospitalized. Heart and kidney diseases and diabetes increased risk. The most frequent symptoms among non-hospitalized women were anosmia [63% pregnant, 92% non-pregnant] and headache [72%, 62%]. Cardiopulmonary symptoms, including persistent cough [80%] and chest pain [73%], were more frequent among pregnant who were hospitalized. Consistent with observations in non-pregnant populations, lung disease and diabetes were associated with increased risk of more severe SARS-CoV-2 infection during pregnancy.
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http://dx.doi.org/10.1038/s41598-021-86452-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994587PMC
March 2021

Symptom clusters in COVID-19: A potential clinical prediction tool from the COVID Symptom Study app.

Sci Adv 2021 03 19;7(12). Epub 2021 Mar 19.

Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, MA, USA.

As no one symptom can predict disease severity or the need for dedicated medical support in coronavirus disease 2019 (COVID-19), we asked whether documenting symptom time series over the first few days informs outcome. Unsupervised time series clustering over symptom presentation was performed on data collected from a training dataset of completed cases enlisted early from the COVID Symptom Study Smartphone application, yielding six distinct symptom presentations. Clustering was validated on an independent replication dataset between 1 and 28 May 2020. Using the first 5 days of symptom logging, the ROC-AUC (receiver operating characteristic - area under the curve) of need for respiratory support was 78.8%, substantially outperforming personal characteristics alone (ROC-AUC 69.5%). Such an approach could be used to monitor at-risk patients and predict medical resource requirements days before they are required.
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http://dx.doi.org/10.1126/sciadv.abd4177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978420PMC
March 2021

Attributes and predictors of long COVID.

Nat Med 2021 04 10;27(4):626-631. Epub 2021 Mar 10.

Zoe Global, London, UK.

Reports of long-lasting coronavirus disease 2019 (COVID-19) symptoms, the so-called 'long COVID', are rising but little is known about prevalence, risk factors or whether it is possible to predict a protracted course early in the disease. We analyzed data from 4,182 incident cases of COVID-19 in which individuals self-reported their symptoms prospectively in the COVID Symptom Study app. A total of 558 (13.3%) participants reported symptoms lasting ≥28 days, 189 (4.5%) for ≥8 weeks and 95 (2.3%) for ≥12 weeks. Long COVID was characterized by symptoms of fatigue, headache, dyspnea and anosmia and was more likely with increasing age and body mass index and female sex. Experiencing more than five symptoms during the first week of illness was associated with long COVID (odds ratio = 3.53 (2.76-4.50)). A simple model to distinguish between short COVID and long COVID at 7 days (total sample size, n = 2,149) showed an area under the curve of the receiver operating characteristic curve of 76%, with replication in an independent sample of 2,472 individuals who were positive for severe acute respiratory syndrome coronavirus 2. This model could be used to identify individuals at risk of long COVID for trials of prevention or treatment and to plan education and rehabilitation services.
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http://dx.doi.org/10.1038/s41591-021-01292-yDOI Listing
April 2021

Racial and ethnic differences in COVID-19 vaccine hesitancy and uptake.

medRxiv 2021 Feb 28. Epub 2021 Feb 28.

Background: Racial and ethnic minorities have been disproportionately impacted by COVID-19. In the initial phase of population-based vaccination in the United States (U.S.) and United Kingdom (U.K.), vaccine hesitancy and limited access may result in disparities in uptake.

Methods: We performed a cohort study among U.S. and U.K. participants in the smartphone-based COVID Symptom Study (March 24, 2020-February 16, 2021). We used logistic regression to estimate odds ratios (ORs) of COVID-19 vaccine hesitancy (unsure/not willing) and receipt.

Results: In the U.S. ( =87,388), compared to White non-Hispanic participants, the multivariable ORs of vaccine hesitancy were 3.15 (95% CI: 2.86 to 3.47) for Black participants, 1.42 (1.28 to 1.58) for Hispanic participants, 1.34 (1.18 to 1.52) for Asian participants, and 2.02 (1.70 to 2.39) for participants reporting more than one race/other. In the U.K. ( =1,254,294), racial and ethnic minorities had similarly elevated hesitancy: compared to White participants, their corresponding ORs were 2.84 (95% CI: 2.69 to 2.99) for Black participants, 1.66 (1.57 to 1.76) for South Asian participants, 1.84 (1.70 to 1.98) for Middle East/East Asian participants, and 1.48 (1.39 to 1.57) for participants reporting more than one race/other. Among U.S. participants, the OR of vaccine receipt was 0.71 (0.64 to 0.79) for Black participants, a disparity that persisted among individuals who specifically endorsed a willingness to obtain a vaccine. In contrast, disparities in uptake were not observed in the U.K.

Conclusions: COVID-19 vaccine hesitancy was greater among racial and ethnic minorities, and Black participants living in the U.S. were less likely to receive a vaccine than White participants. Lower uptake among Black participants in the U.S. during the initial vaccine rollout is attributable to both hesitancy and disparities in access.
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http://dx.doi.org/10.1101/2021.02.25.21252402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924296PMC
February 2021

The composition of the gut microbiome differs among community dwelling older people with good and poor appetite.

J Cachexia Sarcopenia Muscle 2021 Apr 13;12(2):368-377. Epub 2021 Feb 13.

Department of Twins Research and Genetic Epidemiology, Kings College London, St Thomas' Hospital, London, UK.

Background: Anorexia of ageing is common and important in the development of sarcopenia in older individuals. Links have been proposed between the gut microbiota and sarcopenia. Disordered gut function is also recognized in anorexia of ageing, but how this may relate to resident gut microbiota is unexplored. Understanding this relationship may provide a basis for novel interventions for anorexia of ageing and sarcopenia. This study explores compositional differences of the gut microbiota between community dwelling healthy older adults with good or poor appetite, and associated differences in sarcopenia.

Methods: We assessed appetite by the Simplified Nutritional Appetite Questionnaire (SNAQ) in members of the TwinsUK cohort aged ≥65 years. Using a pool of 776 individuals with existing microbiome data estimated from 16S rRNA sequencing data, we identified 102 cases (SNAQ score < 14) (95% female, mean age 68 years) matched to controls (SNAQ > 14) on body mass index, gender, age, diet, calorie consumption, frailty, antibiotic use, socio-economic status, and technical variables to minimize confounding microbiota associations. Species abundance and diversity, compositional differences, and paired differences in taxa abundance were compared between cases and controls. Additionally, we compared case and controls for sarcopenia as measured by muscle mass (appendicular lean mass/height ) and strength (chair stand time in seconds).

Results: Cases with poor appetite had reduced species richness and diversity of their gut microbiome (adjusted OBSERVED: beta = -0.2, P < 0.001; adjusted SHANNON: beta = -0.17, P = 0.0135), significant compositional differences (adjusted non-parametric multivariate analysis of variance, P = 0.0095), and significant differences in taxa abundance including reduction of genus Lachnospira (logFC = -1.015, q = 0.023). In all-female subgroup analysis, cases with poor appetite demonstrated reduction in muscle strength (11.03 s vs. 9.26 s, P = 0.02).

Conclusions: This study is the first to observe differences in the composition of gut microbiota between healthy community dwelling older individuals with good and poor appetite. We found female individuals with reduced muscle strength had poor appetite compared with those with normal strength. These associations require further examination to understand causality and mechanisms of interaction, to inform potential strategies targeting the gut microbiota as a novel intervention for anorexia of ageing and sarcopenia.
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http://dx.doi.org/10.1002/jcsm.12683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061352PMC
April 2021

Self-Reported Symptoms of COVID-19, Including Symptoms Most Predictive of SARS-CoV-2 Infection, Are Heritable.

Twin Res Hum Genet 2020 12;23(6):316-321

Department of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King's College London, London, UK.

Susceptibility to infection such as SARS-CoV-2 may be influenced by host genotype. TwinsUK volunteers (n = 3261) completing the C-19 COVID-19 symptom tracker app allowed classical twin studies of COVID-19 symptoms, including predicted COVID-19, a symptom-based algorithm to predict true infection, derived from app users tested for SARS-CoV-2. We found heritability of 49% (32-64%) for delirium; 34% (20-47%) for diarrhea; 31% (8-52%) for fatigue; 19% (0-38%) for anosmia; 46% (31-60%) for skipped meals and 31% (11-48%) for predicted COVID-19. Heritability estimates were not affected by cohabiting or by social deprivation. The results suggest the importance of host genetics in the risk of clinical manifestations of COVID-19 and provide grounds for planning genome-wide association studies to establish specific genes involved in viral infectivity and the host immune response.
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http://dx.doi.org/10.1017/thg.2020.85DOI Listing
December 2020

Effects of Environmental Factors on Severity and Mortality of COVID-19.

Front Med (Lausanne) 2020 20;7:607786. Epub 2021 Jan 20.

Central Clinical Hospital of Ministry of the Interior and Administration, Warsaw, Poland.

Most respiratory viruses show pronounced seasonality, but for SARS-CoV-2, this still needs to be documented. We examined the disease progression of COVID-19 in 6,914 patients admitted to hospitals in Europe and China. In addition, we evaluated progress of disease symptoms in 37,187 individuals reporting symptoms into the COVID Symptom Study application. Meta-analysis of the mortality risk in seven European hospitals estimated odds ratios per 1-day increase in the admission date to be 0.981 (0.973-0.988, < 0.001) and per increase in ambient temperature of 1°C to be 0.854 (0.773-0.944, = 0.007). Statistically significant decreases of comparable magnitude in median hospital stay, probability of transfer to the intensive care unit, and need for mechanical ventilation were also observed in most, but not all hospitals. The analysis of individually reported symptoms of 37,187 individuals in the UK also showed the decrease in symptom duration and disease severity with time. Severity of COVID-19 in Europe decreased significantly between March and May and the seasonality of COVID-19 is the most likely explanation.
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http://dx.doi.org/10.3389/fmed.2020.607786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855590PMC
January 2021

Tackling immunosenescence to improve COVID-19 outcomes and vaccine response in older adults.

Lancet Healthy Longev 2020 Nov 9;1(2):e55-e57. Epub 2020 Nov 9.

AGE Research Group, NIHR Newcastle Biomedical Research Centre, Newcastle University, Newcastle upon Tyne Hospitals NHS Foundation Trust.

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http://dx.doi.org/10.1016/S2666-7568(20)30011-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834195PMC
November 2020

Large-scale association analyses identify host factors influencing human gut microbiome composition.

Nat Genet 2021 02 18;53(2):156-165. Epub 2021 Jan 18.

Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.

To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 × 10) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 × 10), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 10 < P < 5 × 10) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
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http://dx.doi.org/10.1038/s41588-020-00763-1DOI Listing
February 2021

Current smoking and COVID-19 risk: results from a population symptom app in over 2.4 million people.

Thorax 2021 Jan 5. Epub 2021 Jan 5.

The Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.

Background: The association between current tobacco smoking, the risk of developing symptomatic COVID-19 and the severity of illness is an important information gap.

Methods: UK users of the Zoe COVID-19 Symptom Study app provided baseline data including demographics, anthropometrics, smoking status and medical conditions, and were asked to log their condition daily. Participants who reported that they did not feel physically normal were then asked by the app to complete a series of questions, including 14 potential COVID-19 symptoms and about hospital attendance. The main study outcome was the development of 'classic' symptoms of COVID-19 during the pandemic defined as fever, new persistent cough and breathlessness and their association with current smoking. The number of concurrent COVID-19 symptoms was used as a proxy for severity and the pattern of association between symptoms was also compared between smokers and non-smokers.

Results: Between 24 March 2020 and 23 April 2020, data were available on 2 401 982 participants, mean (SD) age 43.6 (15.1) years, 63.3% female, overall smoking prevalence 11.0%. 834 437 (35%) participants reported being unwell and entered one or more symptoms. Current smokers were more likely to report symptoms suggesting a diagnosis of COVID-19; classic symptoms adjusted OR (95% CI) 1.14 (1.10 to 1.18); >5 symptoms 1.29 (1.26 to 1.31); >10 symptoms 1.50 (1.42 to 1.58). The pattern of association between reported symptoms did not vary between smokers and non-smokers.

Interpretation: These data are consistent with people who smoke being at an increased risk of developing symptomatic COVID-19.
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http://dx.doi.org/10.1136/thoraxjnl-2020-216422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789201PMC
January 2021

Geo-social gradients in predicted COVID-19 prevalence in Great Britain: results from 1 960 242 users of the COVID-19 Symptoms Study app.

Thorax 2020 Dec 29. Epub 2020 Dec 29.

Twin Research, King's College London, London, UK

Understanding the geographical distribution of COVID-19 through the general population is key to the provision of adequate healthcare services. Using self-reported data from 1 960 242 unique users in Great Britain (GB) of the we estimated that, concurrent to the GB government sanctioning lockdown, COVID-19 was distributed across GB, with evidence of 'urban hotspots'. We found a geo-social gradient associated with predicted disease prevalence suggesting urban areas and areas of higher deprivation are most affected. Our results demonstrate use of self-reported symptoms data to provide focus on geographical areas with identified risk factors.
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http://dx.doi.org/10.1136/thoraxjnl-2020-215119DOI Listing
December 2020

Associations between gut microbiota and genetic risk for rheumatoid arthritis in the absence of disease: a cross-sectional study.

Lancet Rheumatol 2020 Jul 25;2(7):e418-e427. Epub 2020 Jun 25.

Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.

Background: Rheumatoid arthritis is a chronic inflammatory autoimmune disease that is associated with reduced life expectancy. The disease is heritable and an extensive repertoire of genetic variants have been identified. The gut microbiota might represent an environmental risk factor for rheumatoid arthritis. We aimed to assess whether known rheumatoid arthritis risk alleles were associated with the gut microbiota in a large population who do not have rheumatoid arthritis.

Methods: In this cross-sectional study done in the UK and Switzerland, we used genotyping and microbiota data from previous studies of the TwinsUK cohort, excluding participants who had ever had a diagnosis of rheumatoid arthritis, as well as their unaffected co-twins. We used blood samples for genotyping and stool samples for the assessment of the gut microbiota. We generated a polygenic risk score (PRS) for rheumatoid arthritis in 1650 TwinsUK participants without the disease, based on 233 GWAS-identified single nucleotide polymorphisms associated with rheumatoid arthritis. We validated the PRS using logistic regression against rheumatoid arthritis diagnosis in 2686 UK Biobank individuals with a confirmed diagnosis of rheumatoid arthritis. Amplicon sequence variants (ASVs) were generated from 16S rRNA gene sequencing of stool samples and assessed for association with the PRS for rheumatoid arthritis. We validated the findings in an independent sample comprised of first-degree relatives of patients with rheumatoid arthritis from the SCREEN-RA cohort. Differential abundance of ASVs present in more than 5% of samples, grouped by ASV taxon annotation, against the rheumatoid arthritis PRS as a continuous variable was assessed using fixed-effects covariates. To account for multiple testing, the false discovery rate calculation was applied to all p values to generate q values, with a significance threshold of 0·05 determined a priori.

Findings: We found that presence of spp were positively associated with the rheumatoid arthritis PRS in TwinsUK participants (q<1 × 10). This finding was validated in SCREEN-RA participants (n=133) carrying established shared epitope risk alleles (q=0·0011). We also found an association between spp and presence of preclinical rheumatoid arthritis phases (q=0·021).

Interpretation: spp in the gut microbiota are associated with the rheumatoid arthritis genotype in the absence of rheumatoid arthritis, including in individuals at high risk of developing rheumatoid arthritis. Our findings suggest that host genotype is associated with microbiota profile before disease onset.

Funding: Versus Arthritis.
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http://dx.doi.org/10.1016/S2665-9913(20)30064-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729822PMC
July 2020

An association between chronic widespread pain and the gut microbiome.

Rheumatology (Oxford) 2020 Dec 17. Epub 2020 Dec 17.

Department of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King's College London, London, United Kingdom.

Objectives: Chronic widespread musculoskeletal pain (CWP) is a characteristic symptom of fibromyalgia, which has been shown to be associated with an altered gut microbiome. Microbiome studies to date have not examined the milder CWP phenotype specifically nor have they explored the role of raised BMI. The aim of this study was to investigate whether the microbiome is abnormal in CWP.

Methods: CWP was assessed using a standardized screening questionnaire in female volunteers from the TwinsUK cohort including 113 CWP cases and 1623 controls. The stool microbiome was characterised using 16S rRNA amplicon sequencing and amplicon sequence variants (ASVs), and associations with CWP examined using linear mixed-effects models adjusting for BMI, age, diet, family relatedness and technical factors.

Results: Alpha diversity was significantly lower in CWP cases than controls (Mann-Whitney test, p-values 2.3e-04 and 1.2e-02, respectively). The species Coprococcus comes was significantly depleted in CWP cases (p.adj = 3.04e-03). A genome-wide association study (GWAS) performed for C. comes in TwinsUK followed by meta-analysis with three Dutch cohorts (total n = 3521) resulted in nine suggestive regions, with the most convincing on chromosome 4 near the TRAM1L1 gene (rs76957229, p= 7.4e-8). A Mendelian randomisation study based on the results of the GWAS did not support a causal role for C. comes on the development of CWP.

Conclusions: We have demonstrated reduced diversity in the microbiome in CWP, indicating an involvement of the gut microbiota in CWP; prospectively the microbiome may offer therapeutic opportunities for this condition.
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http://dx.doi.org/10.1093/rheumatology/keaa847DOI Listing
December 2020

Detecting COVID-19 infection hotspots in England using large-scale self-reported data from a mobile application: a prospective, observational study.

Lancet Public Health 2021 01 3;6(1):e21-e29. Epub 2020 Dec 3.

School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK.

Background: As many countries seek to slow the spread of COVID-19 without reimposing national restrictions, it has become important to track the disease at a local level to identify areas in need of targeted intervention.

Methods: In this prospective, observational study, we did modelling using longitudinal, self-reported data from users of the COVID Symptom Study app in England between March 24, and Sept 29, 2020. Beginning on April 28, in England, the Department of Health and Social Care allocated RT-PCR tests for COVID-19 to app users who logged themselves as healthy at least once in 9 days and then reported any symptom. We calculated incidence of COVID-19 using the invited swab (RT-PCR) tests reported in the app, and we estimated prevalence using a symptom-based method (using logistic regression) and a method based on both symptoms and swab test results. We used incidence rates to estimate the effective reproduction number, R(t), modelling the system as a Poisson process and using Markov Chain Monte-Carlo. We used three datasets to validate our models: the Office for National Statistics (ONS) Community Infection Survey, the Real-time Assessment of Community Transmission (REACT-1) study, and UK Government testing data. We used geographically granular estimates to highlight regions with rapidly increasing case numbers, or hotspots.

Findings: From March 24 to Sept 29, 2020, a total of 2 873 726 users living in England signed up to use the app, of whom 2 842 732 (98·9%) provided valid age information and daily assessments. These users provided a total of 120 192 306 daily reports of their symptoms, and recorded the results of 169 682 invited swab tests. On a national level, our estimates of incidence and prevalence showed a similar sensitivity to changes to those reported in the ONS and REACT-1 studies. On Sept 28, 2020, we estimated an incidence of 15 841 (95% CI 14 023-17 885) daily cases, a prevalence of 0·53% (0·45-0·60), and R(t) of 1·17 (1·15-1·19) in England. On a geographically granular level, on Sept 28, 2020, we detected 15 (75%) of the 20 regions with highest incidence according to government test data.

Interpretation: Our method could help to detect rapid case increases in regions where government testing provision is lower. Self-reported data from mobile applications can provide an agile resource to inform policy makers during a quickly moving pandemic, serving as a complementary resource to more traditional instruments for disease surveillance.

Funding: Zoe Global, UK Government Department of Health and Social Care, Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK National Institute for Health Research, UK Medical Research Council and British Heart Foundation, Alzheimer's Society, Chronic Disease Research Foundation.
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http://dx.doi.org/10.1016/S2468-2667(20)30269-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785969PMC
January 2021

Association of social distancing and masking with risk of COVID-19.

medRxiv 2020 Nov 13. Epub 2020 Nov 13.

Given the continued burden of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) disease (COVID-19) across the U.S., there is a high unmet need for data to inform decision-making regarding social distancing and universal masking. We examined the association of community-level social distancing measures and individual masking with risk of predicted COVID-19 in a large prospective U.S. cohort study of 198,077 participants. Individuals living in communities with the greatest social distancing had a 31% lower risk of predicted COVID-19 compared with those living in communities with poor social distancing. Self-reported masking was associated with a 63% reduced risk of predicted COVID-19 even among individuals living in a community with poor social distancing. These findings provide support for the efficacy of mask-wearing even in settings of poor social distancing in reducing COVID-19 transmission. In the current environment of relaxed social distancing mandates and practices, universal masking may be particularly important in mitigating risk of infection.
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http://dx.doi.org/10.1101/2020.11.11.20229500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668763PMC
November 2020

Widespread smell testing for COVID-19 has limited application - Authors' reply.

Lancet 2020 11 3;396(10263):1630-1631. Epub 2020 Nov 3.

Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(20)32316-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832202PMC
November 2020

Detecting COVID-19 infection hotspots in England using large-scale self-reported data from a mobile application.

medRxiv 2020 Oct 27. Epub 2020 Oct 27.

School of Biomedical Engineering & Imaging Sciences, King's College London, London, UK.

Background: As many countries seek to slow the spread of COVID-19 without reimposing national restrictions, it has become important to track the disease at a local level to identify areas in need of targeted intervention.

Methods: We performed modelling on longitudinal, self-reported data from users of the COVID Symptom Study app in England between 24 March and 29 September, 2020. Combining a symptom-based predictive model for COVID-19 positivity and RT-PCR tests provided by the Department of Health we were able to estimate disease incidence, prevalence and effective reproduction number. Geographically granular estimates were used to highlight regions with rapidly increasing case numbers, or hotspots.

Findings: More than 2.6 million app users in England provided 115 million daily reports of their symptoms, and recorded the results of 170,000 PCR tests. On a national level our estimates of incidence and prevalence showed similar sensitivity to changes as two national community surveys: the ONS and REACT studies. On a geographically granular level, our estimates were able to highlight regions before they were subject to local government lockdowns. Between 12 May and 29 September we were able to flag between 35-80% of regions appearing in the Government's hotspot list.

Interpretation: Self-reported data from mobile applications can provide a cost-effective and agile resource to inform a fast-moving pandemic, serving as an independent and complementary resource to more traditional instruments for disease surveillance.

Funding: Zoe Global Limited, Department of Health, Wellcome Trust, EPSRC, NIHR, MRC, Alzheimer's Society.

Research In Context: To identify instances of the use of digital tools to perform COVID-19 surveillance, we searched PubMed for peer-reviewed articles between 1 January and 14 October 2020, using the keywords COVID-19 AND ((mobile application) OR (web tool) OR (digital survey)). Of the 382 results, we found eight that utilised user-reported data to ascertain a user's COVID-19 status. Of these, none sought to provide disease surveillance on a national level, or to compare these predictions to other tools to ascertain their accuracy. Furthermore, none of these papers sought to use their data to highlight geographical areas of concern. To our knowledge, we provide the first demonstration of mobile technology to provide national-level disease surveillance. Using over 115 million reports from more than 2.6 million users across England, we estimate incidence, prevalence, and the effective reproduction number. We compare these estimates to those from national community surveys to understand the effectiveness of these digital tools. Furthermore, we demonstrate the large number of users can be used to provide disease surveillance with high geographical granularity, potentially providing a valuable source of information for policymakers seeking to understand the spread of the disease. Our findings suggest that mobile technology can be used to provide real-time data on the national and local state of the pandemic, enabling policymakers to make informed decisions in a fast-moving pandemic.
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http://dx.doi.org/10.1101/2020.10.26.20219659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605586PMC
October 2020

Detecting SARS-CoV-2 at point of care: preliminary data comparing loop-mediated isothermal amplification (LAMP) to polymerase chain reaction (PCR).

BMC Infect Dis 2020 Oct 20;20(1):783. Epub 2020 Oct 20.

Department of Ageing & Health, Guy's and St Thomas' NHS Foundation Trust, London, UK.

Background: A cost effective and efficient diagnostic tool for COVID-19 as near to the point of care (PoC) as possible would be a game changer in the current pandemic. We tested reverse transcription loop mediated isothermal amplification (RT-LAMP), a method which can produce results in under 30 min, alongside standard methods in a real-life clinical setting.

Methods: This prospective service improvement project piloted an RT-LAMP method on nasal and pharyngeal swabs on 21 residents of a high dependency care home, with two index COVID-19 cases, and compared it to multiplex tandem reverse transcription polymerase chain reaction (RT-PCR). We recorded vital signs of patients to correlate clinical and laboratory information and calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of a single swab using RT-LAMP compared with the current standard, RT-PCR, as per Standards for Reporting Diagnostic Accuracy Studies (STARD) guidelines.

Results: The novel method accurately detected 8/10 RT-PCR positive cases and identified a further 3 positive cases. Eight further cases were negative using both methods. Using repeated RT-PCR as a "gold standard", the sensitivity and specificity of a single novel test were 80 and 73% respectively. PPV was 73% and NPV was 83%. Incorporating retesting of low signal RT-LAMP positives improved the specificity to 100%. We also speculate that hypothermia may be a significant early clinical sign of COVID-19.

Conclusions: RT-LAMP testing for SARS-CoV-2 was found to be promising, fast and to work equivalently to RT-PCR methods. RT-LAMP has the potential to transform COVID-19 detection, bringing rapid and accurate testing to the PoC. RT-LAMP could be deployed in mobile community testing units, care homes and hospitals to detect disease early and prevent spread.
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http://dx.doi.org/10.1186/s12879-020-05484-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574392PMC
October 2020

Estimates of the rate of infection and asymptomatic COVID-19 disease in a population sample from SE England.

J Infect 2020 12 15;81(6):931-936. Epub 2020 Oct 15.

Department of Twin Research, King's College London, St Thomas' Hospital, London SE1 7EH, UK.

Background: Understanding of the true asymptomatic rate of infection of SARS-CoV-2 is currently limited, as is understanding of the population-based seroprevalence after the first wave of COVID-19 within the UK. The majority of data thus far come from hospitalised patients, with little focus on general population cases, or their symptoms.

Methods: We undertook enzyme linked immunosorbent assay characterisation of IgM and IgG responses against SARS-CoV-2 spike glycoprotein and nucleocapsid protein of 431 unselected general-population participants of the TwinsUK cohort from South-East England, aged 19-86 (median age 48; 85% female). 382 participants completed prospective logging of 14 COVID-19 related symptoms via the COVID Symptom Study App, allowing consideration of serology alongside individual symptoms, and a predictive algorithm for estimated COVID-19 previously modelled on PCR positive individuals from a dataset of over 2 million.

Findings: We demonstrated a seroprevalence of 12% (51 participants of 431). Of 48 seropositive individuals with full symptom data, nine (19%) were fully asymptomatic, and 16 (27%) were asymptomatic for core COVID-19 symptoms: fever, cough or anosmia. Specificity of anosmia for seropositivity was 95%, compared to 88% for fever cough and anosmia combined. 34 individuals in the cohort were predicted to be Covid-19 positive using the App algorithm, and of those, 18 (52%) were seropositive.

Interpretation: Seroprevalence amongst adults from London and South-East England was 12%, and 19% of seropositive individuals with prospective symptom logging were fully asymptomatic throughout the study. Anosmia demonstrated the highest symptom specificity for SARS-CoV-2 antibody response.

Funding: NIHR BRC, CDRF, ZOE global LTD, RST-UKRI/MRC.
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http://dx.doi.org/10.1016/j.jinf.2020.10.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557299PMC
December 2020

Probable delirium is a presenting symptom of COVID-19 in frail, older adults: a cohort study of 322 hospitalised and 535 community-based older adults.

Age Ageing 2021 01;50(1):40-48

Department of Twin Research and Genetic Epidemiology, King's College London, St Thomas' Hospital, London, SE1 7EH, UK.

Background: Frailty, increased vulnerability to physiological stressors, is associated with adverse outcomes. COVID-19 exhibits a more severe disease course in older, comorbid adults. Awareness of atypical presentations is critical to facilitate early identification.

Objective: To assess how frailty affects presenting COVID-19 symptoms in older adults.

Design: Observational cohort study of hospitalised older patients and self-report data for community-based older adults.

Setting: Admissions to St Thomas' Hospital, London with laboratory-confirmed COVID-19. Community-based data for older adults using the COVID Symptom Study mobile application.

Subjects: Hospital cohort: patients aged 65 and over (n = 322); unscheduled hospital admission between 1 March 2020 and 5 May 2020; COVID-19 confirmed by RT-PCR of nasopharyngeal swab. Community-based cohort: participants aged 65 and over enrolled in the COVID Symptom Study (n = 535); reported test-positive for COVID-19 from 24 March (application launch) to 8 May 2020.

Methods: Multivariable logistic regression analysis performed on age-matched samples from hospital and community-based cohorts to ascertain association of frailty with symptoms of confirmed COVID-19.

Results: Hospital cohort: significantly higher prevalence of probable delirium in the frail sample, with no difference in fever or cough. Community-based cohort: significantly higher prevalence of possible delirium in frailer, older adults and fatigue and shortness of breath.

Conclusions: This is the first study demonstrating higher prevalence of probable delirium as a COVID-19 symptom in older adults with frailty compared to other older adults. This emphasises need for systematic frailty assessment and screening for delirium in acutely ill older patients in hospital and community settings. Clinicians should suspect COVID-19 in frail adults with delirium.
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http://dx.doi.org/10.1093/ageing/afaa223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543251PMC
January 2021

Cancer and Risk of COVID-19 Through a General Community Survey.

Oncologist 2021 01 7;26(1). Epub 2020 Sep 7.

Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Individuals with cancer may be at high risk for coronavirus disease 2019 (COVID-19) and adverse outcomes. However, evidence from large population-based studies examining whether cancer and cancer-related therapy exacerbates the risk of COVID-19 infection is still limited. Data were collected from the COVID Symptom Study smartphone application since March 29 through May 8, 2020. Among 23,266 participants with cancer and 1,784,293 without cancer, we documented 10,404 reports of a positive COVID-19 test. Compared with participants without cancer, those living with cancer had a 60% increased risk of a positive COVID-19 test. Among patients with cancer, current treatment with chemotherapy or immunotherapy was associated with a 2.2-fold increased risk of a positive test. The association between cancer and COVID-19 infection was stronger among participants >65 years and males. Future studies are needed to identify subgroups by tumor types and treatment regimens who are particularly at risk for COVID-19 infection and adverse outcomes.
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http://dx.doi.org/10.1634/theoncologist.2020-0572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460944PMC
January 2021

Associations between UK tap water and gut microbiota composition suggest the gut microbiome as a potential mediator of health differences linked to water quality.

Sci Total Environ 2020 Oct 26;739:139697. Epub 2020 May 26.

Department of Twin Research and Genetic Epidemiology, King's College London, 3-4th Floor South Wing Block D, St Thomas' Hospital, Westminster Bridge Road, London SE1 7EH, UK; Department of Ageing and Health, St Thomas' Hospital, 9th floor, North Wing, Westminster Bridge Road, London SE1 7EH, UK. Electronic address:

Tap water composition has been widely linked to differences in human health, however the biological pathways underlying this association are less clearly defined. We provide the first investigation of the potential for the gut microbiota to mediate this association. Tap water samples and drinking habits from 85 Mono-zygotic twins with existing faecal microbiota profiles from around the UK were used to assess associations of water composition with the gut microbiome. Water composition was captured using the first 3 principle components (PCs) from multiple factor analysis of ion concentrations, additionally estimating average daily dose (ADD) of the primary three solutes contributing to its variance: chloride, sulphate and sodium. Geographic differences in water composition were assessed. We used measures of faecal microbial diversity, between-individual differences in composition and differences in taxa abundance estimated from 16S rRNA sequencing data. Differences between twin pairs were also considered. We observed significant associations of sodium ADD with microbiota diversity (Chao1), chloride, sodium and sulphate ADD with dissimilarity between samples, and significant associations for all PCs and ADD-adjusted solutes with abundances of individual microbial taxa. These results support the hypothesis that the gut microbiota could mediate the effects of tap water composition on host health, warranting further investigation into tap-water as an influencer of microbiota composition.
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http://dx.doi.org/10.1016/j.scitotenv.2020.139697DOI Listing
October 2020

Risk of COVID-19 among front-line health-care workers and the general community: a prospective cohort study.

Lancet Public Health 2020 09 31;5(9):e475-e483. Epub 2020 Jul 31.

Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.

Background: Data for front-line health-care workers and risk of COVID-19 are limited. We sought to assess risk of COVID-19 among front-line health-care workers compared with the general community and the effect of personal protective equipment (PPE) on risk.

Methods: We did a prospective, observational cohort study in the UK and the USA of the general community, including front-line health-care workers, using self-reported data from the COVID Symptom Study smartphone application (app) from March 24 (UK) and March 29 (USA) to April 23, 2020. Participants were voluntary users of the app and at first use provided information on demographic factors (including age, sex, race or ethnic background, height and weight, and occupation) and medical history, and subsequently reported any COVID-19 symptoms. We used Cox proportional hazards modelling to estimate multivariate-adjusted hazard ratios (HRs) of our primary outcome, which was a positive COVID-19 test. The COVID Symptom Study app is registered with ClinicalTrials.gov, NCT04331509.

Findings: Among 2 035 395 community individuals and 99 795 front-line health-care workers, we recorded 5545 incident reports of a positive COVID-19 test over 34 435 272 person-days. Compared with the general community, front-line health-care workers were at increased risk for reporting a positive COVID-19 test (adjusted HR 11·61, 95% CI 10·93-12·33). To account for differences in testing frequency between front-line health-care workers and the general community and possible selection bias, an inverse probability-weighted model was used to adjust for the likelihood of receiving a COVID-19 test (adjusted HR 3·40, 95% CI 3·37-3·43). Secondary and post-hoc analyses suggested adequacy of PPE, clinical setting, and ethnic background were also important factors.

Interpretation: In the UK and the USA, risk of reporting a positive test for COVID-19 was increased among front-line health-care workers. Health-care systems should ensure adequate availability of PPE and develop additional strategies to protect health-care workers from COVID-19, particularly those from Black, Asian, and minority ethnic backgrounds. Additional follow-up of these observational findings is needed.

Funding: Zoe Global, Wellcome Trust, Engineering and Physical Sciences Research Council, National Institutes of Health Research, UK Research and Innovation, Alzheimer's Society, National Institutes of Health, National Institute for Occupational Safety and Health, and Massachusetts Consortium on Pathogen Readiness.
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http://dx.doi.org/10.1016/S2468-2667(20)30164-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491202PMC
September 2020

The association between low birth weight, childhood recollections of parental response to illness, and irritable bowel syndrome: a twin study.

Neurogastroenterol Motil 2020 11 26;32(11):e13939. Epub 2020 Jul 26.

Department of Gastroenterology, Sandwell & West Birmingham Hospitals NHS Trust, West Bromwich, UK.

Background: The aetiology of irritable bowel syndrome (IBS) is multifactorial, including genetic and environmental factors. Previous studies have suggested that low birth weight and family environment during childhood are associated with developing IBS.

Methods: A survey was sent to all individuals in a UK twin registry. Questions included IBS diagnosed by the Rome IV criteria and if a doctor had previously diagnosed them with IBS. Subjects were categorized as having IBS by Rome IV criteria, a medical diagnosis of IBS or no IBS. Further questions included subjects' recollections of their parents' responses to illness in both the respondent as a child and in the parents themselves. Information regarding birth weight and gestational age have been collected previously.

Key Results: 4258 subjects responded to the questionnaire (51.7%), mean age of 52 (SD 14) years, of whom 98.5% were white and 89.6% female. The mean birth weight was 2.4  (0.6) kg. 5.1% satisfied the Rome IV IBS criteria, the same prevalence as the UK population. However, 14.1% had a previous medical diagnosis of IBS. There was no association found between birth weight and IBS or a medical diagnosis of IBS. On multivariable regression analysis, including parental responses to illness, subjects recalling a parent responding to the parent's bowel symptoms by excusing themselves from household chores were associated with a Rome IV diagnosis of IBS (OR 2.19 (95% CI 1.17-4.10), P = .013).

Conclusions And Inferences: There was no association between birth weight and IBS. However, observing their parents excuse themselves from household chores when they had bowel symptoms was associated with IBS in later life.
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http://dx.doi.org/10.1111/nmo.13939DOI Listing
November 2020

Risk of COVID-19 among frontline healthcare workers and the general community: a prospective cohort study.

medRxiv 2020 May 25. Epub 2020 May 25.

Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School. Boston, MA, USA.

Background: Data for frontline healthcare workers (HCWs) and risk of SARS-CoV-2 infection are limited and whether personal protective equipment (PPE) mitigates this risk is unknown. We evaluated risk for COVID-19 among frontline HCWs compared to the general community and the influence of PPE.

Methods: We performed a prospective cohort study of the general community, including frontline HCWs, who reported information through the COVID Symptom Study smartphone application beginning on March 24 (United Kingdom, U.K.) and March 29 (United States, U.S.) through April 23, 2020. We used Cox proportional hazards modeling to estimate multivariate-adjusted hazard ratios (aHRs) of a positive COVID-19 test.

Findings: Among 2,035,395 community individuals and 99,795 frontline HCWs, we documented 5,545 incident reports of a positive COVID-19 test over 34,435,272 person-days. Compared with the general community, frontline HCWs had an aHR of 11·6 (95% CI: 10·9 to 12·3) for reporting a positive test. The corresponding aHR was 3·40 (95% CI: 3·37 to 3·43) using an inverse probability weighted Cox model adjusting for the likelihood of receiving a test. A symptom-based classifier of predicted COVID-19 yielded similar risk estimates. Compared with HCWs reporting adequate PPE, the aHRs for reporting a positive test were 1·46 (95% CI: 1·21 to 1·76) for those reporting PPE reuse and 1·31 (95% CI: 1·10 to 1·56) for reporting inadequate PPE. Compared with HCWs reporting adequate PPE who did not care for COVID-19 patients, HCWs caring for patients with documented COVID-19 had aHRs for a positive test of 4·83 (95% CI: 3·99 to 5·85) if they had adequate PPE, 5·06 (95% CI: 3·90 to 6·57) for reused PPE, and 5·91 (95% CI: 4·53 to 7·71) for inadequate PPE.

Interpretation: Frontline HCWs had a significantly increased risk of COVID-19 infection, highest among HCWs who reused PPE or had inadequate access to PPE. However, adequate supplies of PPE did not completely mitigate high-risk exposures.

Funding: Zoe Global Ltd., Wellcome Trust, EPSRC, NIHR, UK Research and Innovation, Alzheimer's Society, NIH, NIOSH, Massachusetts Consortium on Pathogen Readiness.
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http://dx.doi.org/10.1101/2020.04.29.20084111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273299PMC
May 2020

Quantifying additional COVID-19 symptoms will save lives.

Lancet 2020 06 4;395(10241):e107-e108. Epub 2020 Jun 4.

Department of Twin Research and Genetic Epidemiology, King's College London, SE1 7EH London, UK. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(20)31281-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272184PMC
June 2020

Real-time tracking of self-reported symptoms to predict potential COVID-19.

Nat Med 2020 07 11;26(7):1037-1040. Epub 2020 May 11.

Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.

A total of 2,618,862 participants reported their potential symptoms of COVID-19 on a smartphone-based app. Among the 18,401 who had undergone a SARS-CoV-2 test, the proportion of participants who reported loss of smell and taste was higher in those with a positive test result (4,668 of 7,178 individuals; 65.03%) than in those with a negative test result (2,436 of 11,223 participants; 21.71%) (odds ratio = 6.74; 95% confidence interval = 6.31-7.21). A model combining symptoms to predict probable infection was applied to the data from all app users who reported symptoms (805,753) and predicted that 140,312 (17.42%) participants are likely to have COVID-19.
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http://dx.doi.org/10.1038/s41591-020-0916-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751267PMC
July 2020