Diet quality and risk and severity of COVID-19: a prospective cohort study.

OBJECTIVE: Poor metabolic health and unhealthy lifestyle factors have been associated with risk and severity of COVID-19, but data for diet are lacking. We aimed to investigate the association of diet quality with risk and severity of COVID-19 and its interaction with socioeconomic deprivation. DESIGN: We used data from 592 571 participants of the smartphone-based COVID-19 Symptom Study. Diet information was collected for the prepandemic period using a short food frequency questionnaire, and diet quality was assessed using a healthful Plant-Based Diet Score, which emphasises healthy plant foods such as fruits or vegetables. Multivariable Cox models were fitted to calculate HRs and 95% CIs for COVID-19 risk and severity defined using a validated symptom-based algorithm or hospitalisation with oxygen support, respectively. RESULTS: Over 3 886 274 person-months of follow-up, 31 815 COVID-19 cases were documented. Compared with individuals in the lowest quartile of the diet score, high diet quality was associated with lower risk of COVID-19 (HR 0.91; 95% CI 0.88 to 0.94) and severe COVID-19 (HR 0.59; 95% CI 0.47 to 0.74). The joint association of low diet quality and increased deprivation on COVID-19 risk was higher than the sum of the risk associated with each factor alone (Pinteraction=0.005). The corresponding absolute excess rate per 10 000 person/months for lowest vs highest quartile of diet score was 22.5 (95% CI 18.8 to 26.3) among persons living in areas with low deprivation and 40.8 (95% CI 31.7 to 49.8) among persons living in areas with high deprivation. CONCLUSIONS: A diet characterised by healthy plant-based foods was associated with lower risk and severity of COVID-19. This association may be particularly evident among individuals living in areas with higher socioeconomic deprivation.

Anxiety and depression symptoms after COVID-19 infection: results from the COVID Symptom Study app.

BACKGROUND: Mental health issues have been reported after SARS-CoV-2 infection. However, comparison to prevalence in uninfected individuals and contribution from common risk factors (eg, obesity and comorbidities) have not been examined. We identified how COVID-19 relates to mental health in the large community-based COVID Symptom Study. METHODS: We assessed anxiety and depression symptoms using two validated questionnaires in 413148 individuals between February and April 2021; 26998 had tested positive for SARS-CoV-2. We adjusted for physical and mental prepandemic comorbidities, body mass index (BMI), age and sex. FINDINGS: Overall, 26.4% of participants met screening criteria for general anxiety and depression. Anxiety and depression were slightly more prevalent in previously SARS-CoV-2-positive (30.4%) vs SARS-CoV-2-negative (26.1%) individuals. This association was small compared with the effect of an unhealthy BMI and the presence of other comorbidities, and not evident in younger participants (≤40 years). Findings were robust to multiple sensitivity analyses. Association between SARS-CoV-2 infection and anxiety and depression was stronger in individuals with recent (<30 days) versus more distant (>120 days) infection, suggesting a short-term effect. INTERPRETATION: A small association was identified between SARS-CoV-2 infection and anxiety and depression symptoms. The proportion meeting criteria for self-reported anxiety and depression disorders is only slightly higher than prepandemic.

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.

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.

DISEASE CLASSIFICATION OF MACULAR OPTICAL COHERENCE TOMOGRAPHY SCANS USING DEEP LEARNING SOFTWARE: Validation on Independent, Multicenter Data.

PURPOSE: To evaluate Pegasus optical coherence tomography (OCT), a clinical decision support software for the identification of features of retinal disease from macula OCT scans, across heterogenous populations involving varying patient demographics, device manufacturers, acquisition sites, and operators. METHODS: Five thousand five hundred and eighty-eight normal and anomalous macular OCT volumes (162,721 B-scans), acquired at independent centers in five countries, were processed using the software. Results were evaluated against ground truth provided by the data set owners. RESULTS: Pegasus-OCT performed with areas under the curve of the receiver operating characteristic of at least 98% for all data sets in the detection of general macular anomalies. For scans of sufficient quality, the areas under the curve of the receiver operating characteristic for general age-related macular degeneration and diabetic macular edema detection were found to be at least 99% and 98%, respectively. CONCLUSION: The ability of a clinical decision support system to cater for different populations is key to its adoption. Pegasus-OCT was shown to be able to detect age-related macular degeneration, diabetic macular edema, and general anomalies in OCT volumes acquired across multiple independent sites with high performance. Its use thus offers substantial promise, with the potential to alleviate the burden of growing demand in eye care services caused by retinal disease.

A supervised learning approach for diffusion MRI quality control with minimal training data.

Quality control (QC) is a fundamental component of any study. Diffusion MRI has unique challenges that make manual QC particularly difficult, including a greater number of artefacts than other MR modalities and a greater volume of data. The gold standard is manual inspection of the data, but this process is time-consuming and subjective. Recently supervised learning approaches based on convolutional neural networks have been shown to be competitive with manual inspection. A drawback of these approaches is they still require a manually labelled dataset for training, which is itself time-consuming to produce and still introduces an element of subjectivity. In this work we demonstrate the need for manual labelling can be greatly reduced by training on simulated data, and using a small amount of labelled data for a final calibration step. We demonstrate its potential for the detection of severe movement artefacts, and compare performance to a classifier trained on manually-labelled real data.

Susceptibility-induced distortion that varies due to motion: Correction in diffusion MR without acquiring additional data.

Because of their low bandwidth in the phase-encode (PE) direction, the susceptibility-induced off-resonance field causes distortions in echo planar imaging (EPI) images. It is therefore crucial to correct for susceptibility-induced distortions when performing diffusion studies using EPI. The susceptibility-induced field is caused by the object (head) disrupting the field and it is typically assumed that it remains constant within a framework defined by the object, (i.e. it follows the object as it moves in the scanner). However, this is only approximately true. When a non-spherical object rotates around an axis other than that parallel with the magnetic flux (the z-axis) it changes the way it disrupts the field, leading to different distortions. Hence, if using a single field to correct for distortions there will be residual distortions in the volumes where the object orientation is substantially different to that when the field was measured. In this paper we present a post-processing method for estimating the field as it changes with motion during the course of an experiment. It only requires a single measured field and knowledge of the orientation of the subject when that field was acquired. The volume-to-volume changes of the field as a consequence of subject movement are estimated directly from the diffusion data without the need for any additional or special acquisitions. It uses a generative model that predicts how each volume would look predicated on field change and inverts that model to yield an estimate of the field changes. It has been validated on both simulations and experimental data. The results show that we are able to track the field with high accuracy and that we are able to correct the data for the adverse effects of the changing field.

Towards a comprehensive framework for movement and distortion correction of diffusion MR images: Within volume movement.

Most motion correction methods work by aligning a set of volumes together, or to a volume that represents a reference location. These are based on an implicit assumption that the subject remains motionless during the several seconds it takes to acquire all slices in a volume, and that any movement occurs in the brief moment between acquiring the last slice of one volume and the first slice of the next. This is clearly an approximation that can be more or less good depending on how long it takes to acquire one volume and in how rapidly the subject moves. In this paper we present a method that increases the temporal resolution of the motion correction by modelling movement as a piecewise continous function over time. This intra-volume movement correction is implemented within a previously presented framework that simultaneously estimates distortions, movement and movement-induced signal dropout. We validate the method on highly realistic simulated data containing all of these effects. It is demonstrated that we can estimate the true movement with high accuracy, and that scalar parameters derived from the data, such as fractional anisotropy, are estimated with greater fidelity when data has been corrected for intra-volume movement. Importantly, we also show that the difference in fidelity between data affected by different amounts of movement is much reduced when taking intra-volume movement into account. Additional validation was performed on data from a healthy volunteer scanned when lying still and when performing deliberate movements. We show an increased correspondence between the "still" and the "movement" data when the latter is corrected for intra-volume movement. Finally we demonstrate a big reduction in the telltale signs of intra-volume movement in data acquired on elderly subjects.

Realistic simulation of artefacts in diffusion MRI for validating post-processing correction techniques.

In this paper we demonstrate a simulation framework that enables the direct and quantitative comparison of post-processing methods for diffusion weighted magnetic resonance (DW-MR) images. DW-MR datasets are employed in a range of techniques that enable estimates of local microstructure and global connectivity in the brain. These techniques require full alignment of images across the dataset, but this is rarely the case. Artefacts such as eddy-current (EC) distortion and motion lead to misalignment between images, which compromise the quality of the microstructural measures obtained from them. Numerous methods and software packages exist to correct these artefacts, some of which have become de-facto standards, but none have been subject to rigorous validation. In the literature, improved alignment is assessed using either qualitative visual measures or quantitative surrogate metrics. Here we introduce a simulation framework that allows for the direct, quantitative assessment of techniques, enabling objective comparisons of existing and future methods. DW-MR datasets are generated using a process that is based on the physics of MRI acquisition, which allows for the salient features of the images and their artefacts to be reproduced. We apply this framework in three ways. Firstly we assess the most commonly used method for artefact correction, FSL's eddy_correct, and compare it to a recently proposed alternative, eddy. We demonstrate quantitatively that using eddy_correct leads to significant errors in the corrected data, whilst eddy is able to provide much improved correction. Secondly we investigate the datasets required to achieve good correction with eddy, by looking at the minimum number of directions required and comparing the recommended full-sphere acquisitions to equivalent half-sphere protocols. Finally, we investigate the impact of correction quality by examining the fits from microstructure models to real and simulated data.

Incorporating outlier detection and replacement into a non-parametric framework for movement and distortion correction of diffusion MR images.

Despite its great potential in studying brain anatomy and structure, diffusion magnetic resonance imaging (dMRI) is marred by artefacts more than any other commonly used MRI technique. In this paper we present a non-parametric framework for detecting and correcting dMRI outliers (signal loss) caused by subject motion. Signal loss (dropout) affecting a whole slice, or a large connected region of a slice, is frequently observed in diffusion weighted images, leading to a set of unusable measurements. This is caused by bulk (subject or physiological) motion during the diffusion encoding part of the imaging sequence. We suggest a method to detect slices affected by signal loss and replace them by a non-parametric prediction, in order to minimise their impact on subsequent analysis. The outlier detection and replacement, as well as correction of other dMRI distortions (susceptibility-induced distortions, eddy currents (EC) and subject motion) are performed within a single framework, allowing the use of an integrated approach for distortion correction. Highly realistic simulations have been used to evaluate the method with respect to its ability to detect outliers (types 1 and 2 errors), the impact of outliers on retrospective correction of movement and distortion and the impact on estimation of commonly used diffusion tensor metrics, such as fractional anisotropy (FA) and mean diffusivity (MD). Data from a large imaging project studying older adults (the Whitehall Imaging sub-study) was used to demonstrate the utility of the method when applied to datasets with severe subject movement. The results indicate high sensitivity and specificity for detecting outliers and that their deleterious effects on FA and MD can be almost completely corrected.

Latent Transformer Models for out-of-distribution detection.

Any clinically-deployed image-processing pipeline must be robust to the full range of inputs it may be presented with. One popular approach to this challenge is to develop predictive models that can provide a measure of their uncertainty. Another approach is to use generative modelling to quantify the likelihood of inputs. Inputs with a low enough likelihood are deemed to be out-of-distribution and are not presented to the downstream predictive model. In this work, we evaluate several approaches to segmentation with uncertainty for the task of segmenting bleeds in 3D CT of the head. We show that these models can fail catastrophically when operating in the far out-of-distribution domain, often providing predictions that are both highly confident and wrong. We propose to instead perform out-of-distribution detection using the Latent Transformer Model: a VQ-GAN is used to provide a highly compressed latent representation of the input volume, and a transformer is then used to estimate the likelihood of this compressed representation of the input. We demonstrate this approach can identify images that are both far- and near- out-of-distribution, as well as provide spatial maps that highlight the regions considered to be out-of-distribution. Furthermore, we find a strong relationship between an image's likelihood and the quality of a model's segmentation on it, demonstrating that this approach is viable for filtering out unsuitable images.

Self-reported COVID-19 vaccine hesitancy and uptake among participants from different racial and ethnic groups in the United States and United Kingdom.

Worldwide, racial and ethnic minorities have been disproportionately impacted by COVID-19 with increased risk of infection, its related complications, and death. In the initial phase of population-based vaccination in the United States (U.S.) and United Kingdom (U.K.), vaccine hesitancy may result in differences in uptake. We performed a cohort study among U.S. and U.K. participants who volunteered to take part in the smartphone-based COVID Symptom Study (March 2020-February 2021) and used logistic regression to estimate odds ratios of vaccine hesitancy and uptake. In the U.S. (n = 87,388), compared to white participants, vaccine hesitancy was greater for Black and Hispanic participants and those reporting more than one or other race. In the U.K. (n = 1,254,294), racial and ethnic minority participants showed similar levels of vaccine hesitancy to the U.S. However, associations between participant race and ethnicity and levels of vaccine uptake were observed to be different in the U.S. and the U.K. studies. Among U.S. participants, vaccine uptake was significantly lower among Black participants, which persisted among participants that self-reported being vaccine-willing. In contrast, statistically significant racial and ethnic disparities in vaccine uptake were not observed in the U.K sample. In this study of self-reported vaccine hesitancy and uptake, lower levels of vaccine uptake in Black participants in the U.S. during the initial vaccine rollout may be attributable to both hesitancy and disparities in access.

Knowledge barriers in a national symptomatic-COVID-19 testing programme.

Symptomatic testing programmes are crucial to the COVID-19 pandemic response. We sought to examine United Kingdom (UK) testing rates amongst individuals with test-qualifying symptoms, and factors associated with not testing. We analysed a cohort of untested symptomatic app users (N = 1,237), nested in the Zoe COVID Symptom Study (Zoe, N = 4,394,948); and symptomatic respondents who wanted, but did not have a test (N = 1,956), drawn from a University of Maryland survey administered to Facebook users (The Global COVID-19 Trends and Impact Survey [CTIS], N = 775,746). The proportion tested among individuals with incident test-qualifying symptoms rose from ~20% to ~75% from April to December 2020 in Zoe. Testing was lower with one vs more symptoms (72.9% vs 84.6% p<0.001), or short vs long symptom duration (69.9% vs 85.4% p<0.001). 40.4% of survey respondents did not identify all three test-qualifying symptoms. Symptom identification decreased for every decade older (OR = 0.908 [95% CI 0.883-0.933]). Amongst symptomatic UMD-CTIS respondents who wanted but did not have a test, not knowing where to go was the most cited factor (32.4%); this increased for each decade older (OR = 1.207 [1.129-1.292]) and for every 4-years fewer in education (OR = 0.685 [0.599-0.783]). Despite current UK messaging on COVID-19 testing, there is a knowledge gap about when and where to test, and this may be contributing to the ~25% testing gap. Risk factors, including older age and less education, highlight potential opportunities to tailor public health messages. The testing gap may be ever larger in countries that do not have extensive, free testing, as the UK does.

App-based COVID-19 syndromic surveillance and prediction of hospital admissions in COVID Symptom Study Sweden.

The app-based COVID Symptom Study was launched in Sweden in April 2020 to contribute to real-time COVID-19 surveillance. We enrolled 143,531 study participants (≥18 years) who contributed 10.6 million daily symptom reports between April 29, 2020 and February 10, 2021. Here, we include data from 19,161 self-reported PCR tests to create a symptom-based model to estimate the individual probability of symptomatic COVID-19, with an AUC of 0.78 (95% CI 0.74-0.83) in an external dataset. These individual probabilities are employed to estimate daily regional COVID-19 prevalence, which are in turn used together with current hospital data to predict next week COVID-19 hospital admissions. We show that this hospital prediction model demonstrates a lower median absolute percentage error (MdAPE: 25.9%) across the five most populated regions in Sweden during the first pandemic wave than a model based on case notifications (MdAPE: 30.3%). During the second wave, the error rates are similar. When we apply the same model to an English dataset, not including local COVID-19 test data, we observe MdAPEs of 22.3% and 19.0% during the first and second pandemic waves, respectively, highlighting the transferability of the prediction model.

Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: a prospective, community-based, nested, case-control study.

BACKGROUND: COVID-19 vaccines show excellent efficacy in clinical trials and effectiveness in real-world data, but some people still become infected with SARS-CoV-2 after vaccination. This study aimed to identify risk factors for post-vaccination SARS-CoV-2 infection and describe the characteristics of post-vaccination illness. METHODS: This prospective, community-based, nested, case-control study used self-reported data (eg, on demographics, geographical location, health risk factors, and COVID-19 test results, symptoms, and vaccinations) from UK-based, adult (≥18 years) users of the COVID Symptom Study mobile phone app. For the risk factor analysis, cases had received a first or second dose of a COVID-19 vaccine between Dec 8, 2020, and July 4, 2021; had either a positive COVID-19 test at least 14 days after their first vaccination (but before their second; cases 1) or a positive test at least 7 days after their second vaccination (cases 2); and had no positive test before vaccination. Two control groups were selected (who also had not tested positive for SARS-CoV-2 before vaccination): users reporting a negative test at least 14 days after their first vaccination but before their second (controls 1) and users reporting a negative test at least 7 days after their second vaccination (controls 2). Controls 1 and controls 2 were matched (1:1) with cases 1 and cases 2, respectively, by the date of the post-vaccination test, health-care worker status, and sex. In the disease profile analysis, we sub-selected participants from cases 1 and cases 2 who had used the app for at least 14 consecutive days after testing positive for SARS-CoV-2 (cases 3 and cases 4, respectively). Controls 3 and controls 4 were unvaccinated participants reporting a positive SARS-CoV-2 test who had used the app for at least 14 consecutive days after the test, and were matched (1:1) with cases 3 and 4, respectively, by the date of the positive test, health-care worker status, sex, body-mass index (BMI), and age. We used univariate logistic regression models (adjusted for age, BMI, and sex) to analyse the associations between risk factors and post-vaccination infection, and the associations of individual symptoms, overall disease duration, and disease severity with vaccination status. FINDINGS: Between Dec 8, 2020, and July 4, 2021, 1 240 009 COVID Symptom Study app users reported a first vaccine dose, of whom 6030 (0·5%) subsequently tested positive for SARS-CoV-2 (cases 1), and 971 504 reported a second dose, of whom 2370 (0·2%) subsequently tested positive for SARS-CoV-2 (cases 2). In the risk factor analysis, frailty was associated with post-vaccination infection in older adults (≥60 years) after their first vaccine dose (odds ratio [OR] 1·93, 95% CI 1·50-2·48; p<0·0001), and individuals living in highly deprived areas had increased odds of post-vaccination infection following their first vaccine dose (OR 1·11, 95% CI 1·01-1·23; p=0·039). Individuals without obesity (BMI <30 kg/m2) had lower odds of infection following their first vaccine dose (OR 0·84, 95% CI 0·75-0·94; p=0·0030). For the disease profile analysis, 3825 users from cases 1 were included in cases 3 and 906 users from cases 2 were included in cases 4. Vaccination (compared with no vaccination) was associated with reduced odds of hospitalisation or having more than five symptoms in the first week of illness following the first or second dose, and long-duration (≥28 days) symptoms following the second dose. Almost all symptoms were reported less frequently in infected vaccinated individuals than in infected unvaccinated individuals, and vaccinated participants were more likely to be completely asymptomatic, especially if they were 60 years or older. INTERPRETATION: To minimise SARS-CoV-2 infection, at-risk populations must be targeted in efforts to boost vaccine effectiveness and infection control measures. Our findings might support caution around relaxing physical distancing and other personal protective measures in the post-vaccination era, particularly around frail older adults and individuals living in more deprived areas, even if these individuals are vaccinated, and might have implications for strategies such as booster vaccinations. FUNDING: ZOE, the UK Government Department of Health and Social Care, the Wellcome Trust, the UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging and Artificial Intelligence Centre for Value Based Healthcare, the UK National Institute for Health Research, the UK Medical Research Council, the British Heart Foundation, and the Alzheimer's Society.

The mental health burden of racial and ethnic minorities during the COVID-19 pandemic.

Racial/ethnic minorities have been disproportionately impacted by COVID-19. The effects of COVID-19 on the long-term mental health of minorities remains unclear. To evaluate differences in odds of screening positive for depression and anxiety among various racial and ethnic groups during the latter phase of the COVID-19 pandemic, we performed a cross-sectional analysis of 691,473 participants nested within the prospective smartphone-based COVID Symptom Study in the United States (U.S.) and United Kingdom (U.K). from February 23, 2021 to June 9, 2021. In the U.S. (n=57,187), compared to White participants, the multivariable odds ratios (ORs) for screening positive for depression were 1·16 (95% CI: 1·02 to 1·31) for Black, 1·23 (1·11 to 1·36) for Hispanic, and 1·15 (1·02 to 1·30) for Asian participants, and 1·34 (1·13 to 1·59) for participants reporting more than one race/other even after accounting for personal factors such as prior history of a mental health disorder, COVID-19 infection status, and surrounding lockdown stringency. Rates of screening positive for anxiety were comparable. In the U.K. (n=643,286), racial/ethnic minorities had similarly elevated rates of positive screening for depression and anxiety. These disparities were not fully explained by changes in leisure time activities. Racial/ethnic minorities bore a disproportionate mental health burden during the COVID-19 pandemic. These differences will need to be considered as health care systems transition from prioritizing infection control to mitigating long-term consequences.

Evaluation of Automated Multiclass Fluid Segmentation in Optical Coherence Tomography Images Using the Pegasus Fluid Segmentation Algorithms.

Purpose: To evaluate the performance of the Pegasus-OCT (Visulytix Ltd) multiclass automated fluid segmentation algorithms on independent spectral domain optical coherence tomography data sets. Methods: The Pegasus automated fluid segmentation algorithms were applied to three data sets with edematous pathology, comprising 750, 600, and 110 b-scans, respectively. Intraretinal fluid (IRF), sub-retinal fluid (SRF), and pigment epithelial detachment (PED) were automatically segmented by Pegasus-OCT for each b-scan where ground truth from data set owners was available. Detection performance was assessed by calculating sensitivities and specificities, while Dice coefficients were used to assess agreement between the segmentation methods. Results: For two data sets, IRF detection yielded promising sensitivities (0.98 and 0.94, respectively) and specificities (1.00 and 0.98) but less consistent agreement with the ground truth (dice coefficients 0.81 and 0.59); likewise, SRF detection showed high sensitivity (0.86 and 0.98) and specificity (0.83 and 0.89) but less consistent agreement (0.59 and 0.78). PED detection on the first data set showed moderate agreement (0.66) with high sensitivity (0.97) and specificity (0.98). IRF detection in a third data set yielded less favorable agreement (0.46-0.57) and sensitivity (0.59-0.68), attributed to image quality and ground truth grader discordance. Conclusions: The Pegasus automated fluid segmentation algorithms were able to detect IRF, SRF, and PED in SD-OCT b-scans acquired across multiple independent data sets. Dice coefficients and sensitivity and specificity values indicate the potential for application to automated detection and monitoring of retinal diseases such as age-related macular degeneration and diabetic macular edema. Translational Relevance: The potential of Pegasus-OCT for automated fluid quantification and differentiation of IRF, SRF, and PED in OCT images has application to both clinical practice and research.

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

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, Rt, 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 Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02-1·69) relative to pre-existing variants. However, Rt 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.

Anxiety and depression symptoms after COVID-19 infection: results from the COVID Symptom Study app.

BACKGROUND: Mental health issues have been reported after SARS-CoV-2 infection. However, comparison to prevalence in uninfected individuals and contribution from common risk factors (e.g., obesity, comorbidities) have not been examined. We identified how COVID-19 relates to mental health in the large community-based COVID Symptom Study. METHODS: We assessed anxiety and depression symptoms using two validated questionnaires in 413,148 individuals between February and April 2021; 26,998 had tested positive for SARS-CoV-2. We adjusted for physical and mental pre-pandemic comorbidities, BMI, age, and sex. FINDINGS: Overall, 26.4% of participants met screening criteria for general anxiety and depression. Anxiety and depression were slightly more prevalent in previously SARS-CoV-2 positive (30.4%) vs. negative (26.1%) individuals. This association was small compared to the effect of an unhealthy BMI and the presence of other comorbidities, and not evident in younger participants (≤40 years). Findings were robust to multiple sensitivity analyses. Association between SARS-CoV-2 infection and anxiety and depression was stronger in individuals with recent (<30 days) vs. more distant (>120 days) infection, suggesting a short-term effect. INTERPRETATION: A small association was identified between SARS-CoV-2 infection and anxiety and depression symptoms. The proportion meeting criteria for self-reported anxiety and depression disorders is only slightly higher than pre-pandemic. FUNDING: Zoe Limited, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, Medical Research Council UK.

Accessible data curation and analytics for international-scale citizen science datasets.

The Covid Symptom Study, a smartphone-based surveillance study on COVID-19 symptoms in the population, is an exemplar of big data citizen science. As of May 23rd, 2021, over 5 million participants have collectively logged over 360 million self-assessment reports since its introduction in March 2020. The success of the Covid Symptom Study creates significant technical challenges around effective data curation. The primary issue is scale. The size of the dataset means that it can no longer be readily processed using standard Python-based data analytics software such as Pandas on commodity hardware. Alternative technologies exist but carry a higher technical complexity and are less accessible to many researchers. We present ExeTera, a Python-based open source software package designed to provide Pandas-like data analytics on datasets that approach terabyte scales. We present its design and capabilities, and show how it is a critical component of a data curation pipeline that enables reproducible research across an international research group for the Covid Symptom Study.

Early detection of COVID-19 in the UK using self-reported symptoms: a large-scale, prospective, epidemiological surveillance study.

BACKGROUND: Self-reported symptoms during the COVID-19 pandemic have been used to train artificial intelligence models to identify possible infection foci. To date, these models have only considered the culmination or peak of symptoms, which is not suitable for the early detection of infection. We aimed to estimate the probability of an individual being infected with SARS-CoV-2 on the basis of early self-reported symptoms to enable timely self-isolation and urgent testing. METHODS: In this large-scale, prospective, epidemiological surveillance study, we used prospective, observational, longitudinal, self-reported data from participants in the UK on 19 symptoms over 3 days after symptoms onset and COVID-19 PCR test results extracted from the COVID-19 Symptom Study mobile phone app. We divided the study population into a training set (those who reported symptoms between April 29, 2020, and Oct 15, 2020) and a test set (those who reported symptoms between Oct 16, 2020, and Nov 30, 2020), and used three models to analyse the self-reported symptoms: the UK's National Health Service (NHS) algorithm, logistic regression, and the hierarchical Gaussian process model we designed to account for several important variables (eg, specific COVID-19 symptoms, comorbidities, and clinical information). Model performance to predict COVID-19 positivity was compared in terms of sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) in the test set. For the hierarchical Gaussian process model, we also evaluated the relevance of symptoms in the early detection of COVID-19 in population subgroups stratified according to occupation, sex, age, and body-mass index. FINDINGS: The training set comprised 182 991 participants and the test set comprised 15 049 participants. When trained on 3 days of self-reported symptoms, the hierarchical Gaussian process model had a higher prediction AUC (0·80 [95% CI 0·80-0·81]) than did the logistic regression model (0·74 [0·74-0·75]) and the NHS algorithm (0·67 [0·67-0·67]). AUCs for all models increased with the number of days of self-reported symptoms, but were still high for the hierarchical Gaussian process model at day 1 (0·73 [95% CI 0·73-0·74]) and day 2 (0·79 [0·78-0·79]). At day 3, the hierarchical Gaussian process model also had a significantly higher sensitivity, but a non-statistically lower specificity, than did the two other models. The hierarchical Gaussian process model also identified different sets of relevant features to detect COVID-19 between younger and older subgroups, and between health-care workers and non-health-care workers. When used during different pandemic periods, the model was robust to changes in populations. INTERPRETATION: Early detection of SARS-CoV-2 infection is feasible with our model. Such early detection is crucial to contain the spread of COVID-19 and efficiently allocate medical resources. FUNDING: ZOE, the UK Government Department of Health and Social Care, the Wellcome Trust, the UK Engineering and Physical Sciences Research Council, the UK National Institute for Health Research, the UK Medical Research Council, the British Heart Foundation, the Alzheimer's Society, the Chronic Disease Research Foundation, and the Massachusetts Consortium on Pathogen Readiness.