Reports of “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 analysed data from 4182 incident cases of COVID-19 who logged their symptoms prospectively in the COVID Symptom Study app. 558 (13.3%) had symptoms lasting >=28 days, 189 (4.5%) for >=8 weeks and 95 (2.3%) for >=12 weeks. Long-COVID was characterised by symptoms of fatigue, headache, dyspnoea and anosmia and was more likely with increasing age, BMI and female sex. Experiencing more than five symptoms during the first week of illness was associated with Long-COVID, OR=3.53 [2.76;4.50]. A simple model to distinguish between short and long-COVID at 7 days, which gained a ROC-AUC of 76%, was replicated in an independent sample of 2472 antibody positive individuals. This model could be used to identify individuals for clinical trials to reduce long-term symptoms and target education and rehabilitation services.

Objectives Dietary supplements may ameliorate SARS-CoV-2 infection, although scientific evidence to support such a role is lacking. We investigated whether users of the COVID-19 Symptom Study app who regularly took dietary supplements were less likely to test positive for SARS-CoV-2 infection. Design App-based community survey. Setting 445 850 subscribers of an app that was launched to enable self-reported information related to SARS-CoV-2 infection for use in the general population in the UK (n=372 720), the USA (n=45 757) and Sweden (n=27 373). Main exposure Self-reported regular dietary supplement usage (constant use during previous 3 months) in the first waves of the pandemic up to 31 July 2020. Main outcome measures SARS-CoV-2 infection confirmed by viral RNA reverse transcriptase PCR test or serology test before 31 July 2020. Results In 372 720 UK participants (175 652 supplement users and 197 068 non-users), those taking probiotics, omega-3 fatty acids, multivitamins or vitamin D had a lower risk of SARS-CoV-2 infection by 14% (95% CI (8% to 19%)), 12% (95% CI (8% to 16%)), 13% (95% CI (10% to 16%)) and 9% (95% CI (6% to 12%)), respectively, after adjusting for potential confounders. No effect was observed for those taking vitamin C, zinc or garlic supplements. On stratification by sex, age and body mass index (BMI), the protective associations in individuals taking probiotics, omega-3 fatty acids, multivitamins and vitamin D were observed in females across all ages and BMI groups, but were not seen in men. The same overall pattern of association was observed in both the US and Swedish cohorts. Conclusion In women, we observed a modest but significant association between use of probiotics, omega-3 fatty acid, multivitamin or vitamin D supplements and lower risk of testing positive for SARS-CoV-2. We found no clear benefits for men nor any effect of vitamin C, garlic or zinc. Randomised controlled trials are required to confirm these observational findings before any therapeutic recommendations can be made.

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 (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.

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.

The assessment of the quality of synthesised/pseudo Computed Tomography (pCT) images is commonly measured by an intensity-wise similarity between the ground truth CT and the pCT. However, when using the pCT as an attenuation map (μ-map) for PET reconstruction in Positron Emission Tomography Magnetic Resonance Imaging (PET/MRI) minimising the error between pCT and CT neglects the main objective of predicting a pCT that when used as μ-map reconstructs a pseudo PET (pPET) which is as similar as possible to the gold standard CT-derived PET reconstruction. This observation motivated us to propose a novel multi-hypothesis deep learning framework explicitly aimed at PET reconstruction application. A convolutional neural network (CNN) synthesises pCTs by minimising a combination of the pixel-wise error between pCT and CT and a novel metric-loss that itself is defined by a CNN and aims to minimise consequent PET residuals. Training is performed on a database of twenty 3D MR/CT/PET brain image pairs. Quantitative results on a fully independent dataset of twenty-three 3D MR/CT/PET image pairs show that the network is able to synthesise more accurate pCTs. The Mean Absolute Error on the pCT (110.98 HU ± 19.22 HU) compared to a baseline CNN (172.12 HU ± 19.61 HU) and a multi-atlas propagation approach (153.40 HU ± 18.68 HU), and subsequently lead to a significant improvement in the PET reconstruction error (4.74% ± 1.52% compared to baseline 13.72% ± 2.48% and multi-atlas propagation 6.68% ± 2.06%).

Background Multiple participatory surveillance platforms were developed across the world in response to the COVID-19 pandemic, providing a real-time understanding of community-wide COVID-19 epidemiology. During this time, testing criteria broadened and healthcare policies matured. We sought to test whether there were consistent associations of symptoms with SARS-CoV-2 test status across three national surveillance platforms, during periods of testing and policy changes, and whether inconsistencies could better inform our understanding and future studies as the COVID-19 pandemic progresses. Methods Four months (1st April 2020 to 31st July 2020) of observation through three volunteer COVID-19 digital surveillance platforms targeting communities in three countries (Israel, United Kingdom, and United States). Logistic regression of self-reported symptom on self-reported SARS-CoV-2 test status (or test access), adjusted for age and sex, in each of the study cohorts. Odds ratios over time were compared to known changes in testing policies and fluctuations in COVID-19 incidence. Findings Anosmia/ageusia was the strongest, most consistent symptom associated with a positive COVID-19 test, based on 658,325 tests (5% positive) from over 10 million respondents in three digital surveillance platforms using longitudinal and cross-sectional survey methodologies. During higher-incidence periods with broader testing criteria, core COVID-19 symptoms were more strongly associated with test status. Lower incidence periods had, overall, larger confidence intervals. Interpretation The strong association of anosmia/ageusia with self-reported SARS-CoV-2 test positivity is omnipresent, supporting its validity as a reliable COVID-19 signal, regardless of the participatory surveillance platform or testing policy. This analysis highlights that precise effect estimates, as well as an understanding of test access patterns to interpret differences, are best done only when incidence is high. These findings strongly support the need for testing access to be as open as possible both for real-time epidemiologic investigation and public health utility. Funding NIH, NIHR, Alzheimer’s Society, Wellcome Trust Evidence before this study As the COVID-19 pandemic has evolved, testing capacity expanded and governmental guidelines adapted, generally encouraging testing with a broader set of symptoms, not just fever with respiratory symptoms. In parallel, multiple large-scale citizen science digital surveillance platforms launched to complement knowledge from laboratory and somewhat smaller clinical studies. Symptoms such as loss of sense of smell have been identified as strongly predictive of COVID-19 infection in both clinical and syndromic surveillance analyses, and have therefore been used to inform these testing policy changes and access expansion. Added value of this study This study identifies symptoms that are or are not consistently associated with SARS-CoV-2 test positivity over time and across three country-based COVID-19 surveillance platforms in the United States, United Kingdom and Israel. These platforms are website and smartphone based, as well as cross-sectional and longitudinal. The study period of 4 months covers fluctuating COVID-19 prevalence during the fall of the first wave and, in some areas, rise of the second wave. In addition, the study period overlaps expansion of test access and test seeking. Importantly, these analyses track and highlight the value of individual symptoms to predict SARS-CoV-2 test positivity under a range of conditions. Implications of all the available evidence Despite differences in surveillance methodology, access to SARS-CoV-2 testing and disease prevalence, loss of sense of smell or taste was consistently the strongest predictor of COVID-19 infection across all platforms over time. As access to testing broadened, the relevance of COVID-like symptoms and consistency of their predictive ability became apparent. However, confidence bounds generally widened with a fall in COVID-19 incidence. Therefore, for the most robust symptom-based COVID-19 prediction models should consider surveillance data during periods of higher incidence and improved test access, and effect estimates that replicate across different epidemiologic conditions and platforms.