Patient characteristics associated with clinically coded long COVID: an OpenSAFELY study using electronic health records (preprint)

Despite reports of post-COVID-19 syndromes (long COVID) are rising, clinically coded long COVID cases are incomplete in electronic health records. It is unclear how patient characteristics may be associated with clinically coded long COVID. With the approval of NHS England, we undertook a cohort study using electronic health records within the OpenSAFELY-TPP platform in England, to study patient characteristics associated with clinically coded long COVID from 29 January 2020 to 31 March 2022. We estimated age-sex adjusted hazard ratios and fully adjusted hazard ratios for coded long COVID. Patient characteristics included demographic factors, and health behavioural and clinical factors. Among 17,986,419 adults, 36,886 (0.21%) were clinically coded with long COVID. Patient characteristics associated with coded long COVID included female sex, younger age (under 60 years), obesity, living in less deprived areas, ever smoking, greater consultation frequency, and history of diagnosed asthma, mental health conditions, pre-pandemic post-viral fatigue, or psoriasis. The strength of these associations was attenuated following two-dose vaccination compared to before vaccination. The incidence of coded long COVID was higher after hospitalised than non-hospitalised COVID-19. These results should be interpreted with caution given that long COVID was likely under-recorded in electronic health records.

Home working and its association with social and mental wellbeing at different stages of the COVID-19 pandemic: Evidence from seven UK longitudinal population surveys. (preprint)

Background: Home working rates have increased since the COVID-19 pandemic's onset, but the health implications of this transformation are unclear. We assessed the association between home working and social and mental wellbeing through harmonised analyses of seven UK longitudinal studies. Methods: We estimated associations between home working and measures of psychological distress, low life satisfaction, poor self-rated health, low social contact, and loneliness across three different stages of the COVID-19 pandemic (T1= Apr-Jun 2020 - first lockdown, T2=Jul-Oct 2020 - eased restrictions, T3=Nov 2020-Mar 2021 - second lockdown), in seven population-based cohort studies using modified Poisson regression and meta-analyses to pool results across studies. Findings: Among 34,131 observations spread over three time points, we found higher rates of home working at T1 and T3 compared with T2, reflecting lockdown periods. Home working was not associated with psychological distress at T1 (RR=0.92, 95%CI=0.79-1.08) or T2 (RR=0.99, 95%CI=0.88-1.11), but a detrimental association was found with psychological distress at T3 (RR=1.17, 95%CI=1.05-1.30). Poorer psychological distress associated with home working was observed for those educated to below degree level at T2 and T3. Men working from home reported poorer self-reported health at T2. Interpretation: No clear evidence of an association between home working and mental wellbeing was found, apart from greater risk of psychological distress associated with home working during the second lockdown, but differences across sub-groups may exist. Longer term shifts to home working might not have adverse impacts on population wellbeing in the absence of pandemic restrictions but further monitoring of health inequalities is required.

Metabolomic and gut microbiome profiles across the spectrum of community-based COVID and non-COVID disease: A COVID-19 Biobank study (preprint)

Whilst many with SARS-CoV-2 infection have mild disease, managed in the community, individuals with cardiovascular risk factors experienced often more severe acute disease, requiring hospitalisation. Increasing concern has also developed over long symptom duration in many individuals, including the majority who managed acutely in the community. Risk factors for long symptom duration, including biological variables, are still poorly defined. We examine post-illness metabolomic and gut-microbiome profiles, in community-dwelling participants with SARS-CoV-2, ranging from asymptomatic illness to Post-COVID Syndrome, and participants with prolonged non-COVID-19 illnesses. We also assess a pre-established metabolomic biomarker score for its association with illness duration. We found an atherogenic-dyslipidaemic metabolic profile, and greater biomarker scores, associated with longer illness, both in individuals with and without SARS-CoV-2 infection. We found no association between illness duration and gut microbiome in convalescence. Findings: highlight the potential role of cardiometabolic dysfunction to the experience of long illness duration, including after COVID-19.

Mental health outcomes following COVID-19 infection: Evidence from 11 UK longitudinal population studies (preprint)

Background Evidence on associations between COVID-19 illness and mental health is mixed. We examined longitudinal associations between COVID-19 and mental health while considering: 1) pre-pandemic mental health, 2) time since infection; 3) subgroup differences; and 4) confirmation of infection via self-reported test, and serology data. Methods Using data from 11 UK longitudinal studies, involving 54,442 participants, with 2 to 8 repeated measures of mental health and COVID-19 between April 2020 and April 2021, we standardised continuous mental health scales within each study across time. We investigated associations between COVID-19 (self-report, test-confirmed, serology-confirmed) and mental health using multilevel generalised estimating equations. We examined whether associations varied by age, sex, ethnicity, education and pre-pandemic mental health. Effect-sizes were pooled in random-effects meta-analyses. Outcomes Pooled estimates of the standardized difference in outcome between those with and without self-reported COVID-19 suggested associations with subsequent psychological distress (0.10 [95%CI: 0.06; 0.13], I 2 =42.8%), depression (0.08 [0.05; 0.10], I 2 =20.8%), anxiety (0.08 [0.05; 0.10], I 2 =0%), and lower life satisfaction (−0.06 [-0.08; -0.04], I 2 =29.2%). Associations did not vary by time since infection until 3+ months and were present in all age groups, with some evidence of stronger effects in those aged 50+. Self-reported COVID-19, whether suspected or test-confirmed and irrespective of serology status, was associated with poorer mental health. Interpretation Self-reporting COVID-19 was longitudinally associated with deterioration in mental health and life satisfaction. Our findings have important implications for mental health service provision, given the substantial prevalence of COVID-19 in the UK and worldwide. Funding MRC and NIHR

COVID-19 due to the B.1.617.2 (Delta) variant compared to B.1.1.7 (Alpha) variant of SARS-CoV-2: two prospective observational cohort studies (preprint)

Background The Delta (B.1.617.2) variant became the predominant UK circulating SARS-CoV-2 strain in May 2021. How Delta infection compares with previous variants is unknown. Methods This prospective observational cohort study assessed symptomatic adults participating in the app-based COVID Symptom Study who tested positive for SARS-CoV-2 from May 26 to July 1, 2021 (Delta overwhelmingly predominant circulating UK variant), compared (1:1, age- and sex-matched) with individuals presenting from December 28, 2020 to May 6, 2021 (Alpha (B.1.1.7) predominant variant). We assessed illness (symptoms, duration, presentation to hospital) during Alpha- and Delta-predominant timeframes; and transmission, reinfection, and vaccine effectiveness during the Delta-predominant period. Findings 3,581 individuals (aged 18 to 100 years) from each timeframe were assessed. The seven most frequent symptoms were common to both variants. Within the first 28 days of illness, some symptoms were more common with Delta vs. Alpha infection (including fever, sore throat and headache) and vice versa (dyspnoea). Symptom burden in the first week was higher with Delta vs. Alpha infection; however, the odds of any given symptom lasting [≥]7 days was either lower or unchanged. Illness duration [≥]28 days was lower with Delta vs. Alpha infection, though unchanged in unvaccinated individuals. Hospitalisation for COVID-19 was unchanged. The Delta variant appeared more (1.47) transmissible than Alpha. Re-infections were low in all UK regions. Vaccination markedly (69-84%) reduced risk of Delta infection. Interpretation COVID-19 from Delta or Alpha infections is clinically similar. The Delta variant is more transmissible than Alpha; however, current vaccines show good efficacy against disease. Funding UK Government Department of Health and Social Care, Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging & Artificial Intelligence Centre for Value Based Healthcare, UK National Institute for Health Research, UK Medical Research Council, British Heart Foundation, Alzheimer's Society, and ZOE Limited.

Illness characteristics of COVID-19 in children infected with the SARS-CoV-2 Delta variant (preprint)

Background The Delta (B.1.617.2) SARSCoV2 variant became the predominant UK circulating strain in May 2021. Whether COVID19 from Delta infection differs to infection with other variants in children is unknown. Methods Through the prospective COVID Symptom Study, 109,626 UK school-aged children were proxy-reported between December 28, 2020 and July 8, 2021. We selected all symptomatic children who tested positive for SARS-CoV-2 and were proxy-reported at least weekly, within two timeframes: December 28, 2020 to May 6, 2021 (Alpha (B.1.1.7) the main UK circulating variant); and May 26 to July 8, 2021 (Delta the main UK circulating variant). We assessed illness profiles (symptom prevalence, duration, and burden), hospital presentation, and presence of long (>28 day) illness; and calculated odds ratios for symptoms presenting within the first 28 days of illness. Findings 694 (276 younger [5 11 years], 418 older [12 17 years]) symptomatic children tested positive for SARS-CoV-2 with Alpha infection and 706 (227 younger and 479 older) children with Delta infection. Median illness duration was short with either variant (overall cohort: 5 days (IQR 2 9.75) with Alpha, 5 days (IQR 2 9) with Delta). The seven most prevalent symptoms were common to both variants. Symptom burden over the first 28 days was slightly greater with Delta compared with Alpha infection (in younger children, 3 (IQR 2 5) with Alpha, 4 (IQR 2 7) with Delta; in older children 5 (IQR 3 8) with Alpha and 6 (IQR 3 9) with Delta infection in older children). The odds of several symptoms were higher with Delta than Alpha infection, including headache and fever. Few children presented to hospital, and long illness duration was uncommon, with either variant. Interpretation COVID-19 in UK school-aged children due to SARSCoV2 Delta strain B.1.617.2 resembles illness due to the Alpha variant B.1.1.7., with short duration and similar symptom burden.

Disentangling post-vaccination symptoms from early COVID-19 (preprint)

Background Identifying and testing individuals likely to have SARS-CoV-2 is critical for infection control, including post-vaccination. Vaccination is a major public health strategy to reduce SARS-CoV-2 infection globally. Some individuals experience systemic symptoms post-vaccination, which overlap with COVID-19 symptoms. This study compared early post-vaccination symptoms in individuals who subsequently tested positive or negative for SARS-CoV-2, using data from the COVID Symptom Study (CSS) app. Design We conducted a prospective observational study in UK CSS participants who were asymptomatic when vaccinated with Pfizer-BioNTech mRNA vaccine (BNT162b2) or Oxford-AstraZeneca adenovirus-vectored vaccine (ChAdOx1 nCoV-19) between 8 December 2020 and 17 May 2021, who subsequently reported symptoms within seven days (other than local symptoms at injection site) and were tested for SARS-CoV-2, aiming to differentiate vaccination side-effects per se from superimposed SARS-CoV-2 infection. The post-vaccination symptoms and SARS-CoV-2 test results were contemporaneously logged by participants. Demographic and clinical information (including comorbidities) were also recorded. Symptom profiles in individuals testing positive were compared with a 1:1 matched population testing negative, including using machine learning and multiple models including UK testing criteria. Findings Differentiating post-vaccination side-effects alone from early COVID-19 was challenging, with a sensitivity in identification of individuals testing positive of 0.6 at best. A majority of these individuals did not have fever, persistent cough, or anosmia/dysosmia, requisite symptoms for accessing UK testing; and many only had systemic symptoms commonly seen post-vaccination in individuals negative for SARS-CoV-2 (headache, myalgia, and fatigue). Interpretation Post-vaccination side-effects per se cannot be differentiated from COVID-19 with clinical robustness, either using symptom profiles or machine-derived models. Individuals presenting with systemic symptoms post-vaccination should be tested for SARS-CoV-2, to prevent community spread. Funding Zoe Limited, 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, Massachusetts Consortium on Pathogen Readiness (MassCPR). Research in context Evidence before this study There are now multiple surveillance platforms internationally interrogating COVID-19 and/or post-vaccination side-effects. We designed a study to examine for differences between vaccination side-effects and early symptoms of COVID-19. We searched PubMed for peer-reviewed articles published between 1 January 2020 and 21 June 2021, using keywords: “COVID-19” AND “Vaccination” AND (“mobile application” OR “web tool” OR “digital survey” OR “early detection” OR “Self-reported symptoms” OR “side-effects”). Of 185 results, 25 studies attempted to differentiate symptoms of COVID-19 vs. post-vaccination side-effects; however, none used artificial intelligence (AI) technologies (“machine learning”) coupled with real-time data collection that also included comprehensive and systematic symptom assessment. Additionally, none of these studies attempt to discriminate the early signs of infection from side-effects of vaccination (specifically here: Pfizer-BioNTech mRNA vaccine (BNT162b2) and Oxford-AstraZeneca adenovirus-vectored vaccine (ChAdOx1 nCoV-19)). Further, none of these studies sought to provide comparisons with current testing criteria used by healthcare services. Added value of this study This study, in a uniquely large community-based cohort, uses prospective data capture in a novel effort to identify individuals with COVID-19 in the immediate post-vaccination period. Our results show that early symptoms of SARS-CoV-2 cannot be differentiated from vaccination side-effects robustly. Thus, post-vaccination systemic symptoms should not be ignored, and testing should be considered to prevent COVID-19 dissemination by vaccinated individuals. Implications of all the available evidence Our study demonstrates the critical importance of testing symptomatic individuals - even if vaccinated – to ensure early detection of SARS-CoV-2 infection, helping to prevent future pandemic waves in the UK and elsewhere.

Diet quality and risk and severity of COVID-19: a prospective cohort study (preprint)

Objective: Poor metabolic health and certain lifestyle factors have been associated with risk and severity of coronavirus disease 2019 (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 intersection with socioeconomic deprivation. Design: We used data from 592,571 participants of the smartphone-based COVID Symptom Study. Diet quality was assessed using a healthful plant-based diet score, which emphasizes healthy plant foods such as fruits or vegetables. Multivariable Cox models were fitted to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for COVID-19 risk and severity defined using a validated symptom-based algorithm or hospitalization 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, 0.88-0.94) and severe COVID-19 (HR, 0.59; 95% CI, 0.47-0.74). 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 for lowest vs highest quartile of diet score was 22.5 (95% CI, 18.8-26.3) and 40.8 (95% CI, 31.7-49.8; 10,000 person-months) among persons living in areas with low and high deprivation, respectively. Conclusions: A dietary pattern characterized by healthy plant-based foods was associated with lower risk and severity of COVID-19. These association may be particularly evident among individuals living in areas with higher socioeconomic deprivation.

Predicting Hospital Outpatient Attendance Using Random Forest Classifiers (preprint)

Background: Patient non-attendance of outpatient appointments is a major concern for healthcare providers. These non-attendances are detrimental to the patient's health and a major cost to the provider. However, non-targeted interventions may cost more in administrative resources than the missed appointments themselves. Methods: In this work, a random forest classification algorithm was trained to predict whether an appointment will be missed for patients of all ages and appointments with all specialties at a major London hospital. Findings: The model achieves an AUROC score of 0.76 and accuracy of 73\% on test data which contained only appointments from patients who did not appear in the training data. Further, the model achieves an AUROC score of 0.75 in a second test set which contains only patients from the year 2020. Interpretation: Our model is strongly predictive of whether a hospital outpatient appointment will be attended. Its performance on both patients who did not appear in the training data and appointments from a different time period which covers the Covid-19 pandemic indicate it generalized well and could be used to target resources towards those patients who are likely to miss an appointment. Funding: This study was partially funded by STFC DiRAC innovation fellowships which funded the work of Jonathan Holdship and Harpreet Dhanoa.Declaration of Interests: The authors declare that there is no conflict of interest regarding the publication of this article.Ethics Approval Statement: The Trust Quality Improvement & Audit Committee at Guy’s & St Thomas NHS Foundation Trust approved audit/service evaluation number 116298 registered on the trust database.

Aspirin and NSAID use and the risk of COVID-19 (preprint)

Early reports raised concern that use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19). Users of the COVID Symptom Study smartphone application reported use of aspirin and other NSAIDs between March 24 and May 8, 2020. Users were queried daily about symptoms, COVID-19 testing, and healthcare seeking behavior. Cox proportional hazards regression was used to determine the risk of COVID-19 among according to aspirin or non-aspirin NSAID users. Among 2,736,091 individuals in the U.S., U.K., and Sweden, we documented 8,966 incident reports of a positive COVID-19 test over 60,817,043 person-days of follow-up. Compared to non-users and after stratifying by age, sex, country, day of study entry, and race/ethnicity, non-aspirin NSAID use was associated with a modest risk for testing COVID-19 positive (HR 1.23 [1.09, 1.32]), but no significant association was observed among aspirin users (HR 1.13 [0.92, 1.38]). After adjustment for lifestyle factors, comorbidities and baseline symptoms, any NSAID use was not associated with risk (HR 1.02 [0.94, 1.10]). Results were similar for those seeking healthcare for COVID-19 and were not substantially different according to lifestyle and sociodemographic factors or after accounting for propensity to receive testing. Our results do not support an association of NSAID use, including aspirin, with COVID-19 infection. Previous reports of a potential association may be due to higher rates of comorbidities or use of NSAIDs to treat symptoms associated with COVID-19. One Sentence Summary NSAID use is not associated with COVID-19 risk.

Pre-pandemic mental health and disruptions to healthcare, economic, and housing outcomes during COVID –19: evidence from 12 UK longitudinal studies (preprint)

Background The COVID-19 pandemic and associated virus suppression measures have disrupted lives and livelihoods and people already experiencing mental ill-health may have been especially vulnerable. Aim To quantify mental health inequalities in disruptions to healthcare, economic activity and housing. Method 59,482 participants in 12 UK longitudinal adult population studies with data collected prior to and during the COVID-19 pandemic. Within each study we estimated the association between psychological distress assessed pre-pandemic and disruptions since the start of the pandemic to three domains: healthcare (medication access, procedures, or appointments); economic activity (employment, income, or working hours); and housing (change of address or household composition). Meta-analyses were used to pool estimates across studies. Results Across the analysed datasets, one to two-thirds of participants experienced at least one disruption, with 2.3-33.2% experiencing disruptions in two or more domains. One standard deviation higher pre-pandemic psychological distress was associated with: (i) increased odds of any healthcare disruptions (OR=1.30; [95% CI:1.20–1.40]) with fully adjusted ORs ranging from 1.24 [1.09–1.41] for disruption to procedures and 1.33 [1.20– 1.49] for disruptions to prescriptions or medication access; (ii) loss of employment (OR=1.13 [1.06–1.21]) and income (OR=1.12 [1.06 –1.19]) and reductions in working hours/furlough (OR=1.05 [1.00–1.09]); (iii) no associations with housing disruptions (OR=1.00 [0.97–1.03]); and (iv) increased likelihood of experiencing a disruption in at least two domains (OR=1.25 [1.18–1.32]) or in one domain (OR=1.11 [1.07–1.16]) relative to no disruption. Conclusion People experiencing psychological distress pre-pandemic have been more likely to experience healthcare and economic disruptions, and clusters of disruptions across multiple domains during the pandemic. Failing to address these disruptions risks further widening the existing inequalities in mental health.

Knowledge barriers in the symptomatic-COVID-19 testing programme in the UK: an observational study (preprint)

Background 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. Methods 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 survey respondents who wanted, but did not have a test (N=1,956), drawn from the University of Maryland-Facebook Covid-19 Symptom Survey (UMD-Facebook, N=775,746). Findings 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 (73.0% vs 85.0%), or short vs long symptom duration (72.6% vs 87.8%). 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-Facebook 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]). Interpretation 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.

Vaccine after Effects and Post-Vaccine Infection in a Real World Setting: Results from the COVID Symptom Study App (preprint)

Background: The Pfizer-BioNTech (BNT162b2) and the Oxford/AstraZeneca (ChAdOx1 nCoV-19) COVID-19 vaccines have shown excellent safety and efficacy in Phase III trials. Here we report results from a real world setting on the two most administered vaccines in the UK.Methods: We investigated self-reported systemic and local effects within eight days of vaccination in 387,471 individuals from the COVID Symptom Study app who received one (n=209,251) or two (n=13,478) doses of the BNT162b2 vaccine, or one dose of ChAdOx1 nCoV-19 vaccine (n=178,220) between December 8 and February 15 2021. A subset of individuals subsequently tested for SARS-CoV-2 were studied for infection rates from PCR or lateral flow test results post-vaccination (59,639 vaccinated vs 277,599 controls).Findings: Systemic side effects were reported in 11.8% of participants after the first BNT162b2 dose, 20.3% after the second BNT162b2 dose, and 29.4% after the first ChAdOx1 nCoV-19 dose. Systemic effects were more prevalent among individuals with pre-existing COVID-19 infection (BNT162b2:34.1%; ChAdOx1 nCoV-19:51.6%) than among individuals without known prior infection (BNT162b2:10.6%; ChAdOx1 nCoV-19:28.6%) and among those aged <55 years (BNT162b2:19.9%; ChAdOx1 nCoV-19:45.3%) compared to those aged >55 years (BNT162b2:9.2%, ChAdOx1 nCoV-19: 26.9%). We observed significant reduction in infection risk 12-21 days after the first dose (BNT162b2:-57% [-71%, -38%], ChAdOx1 nCoV-19:-42% [-71%, -17%]). Interpretation: This phase IV-type study assessing both BNT162b2 and ChAdOx1 nCoV-19 vaccines identifies mild systemic side effects affecting 11-30% of individuals post-vaccination, lower than in published Phase III trials. Our data on infection post-vaccine were also reassuring.Funding: Zoe, NIHR, CDRF, NIH, MRCDeclaration of Interests: TDS and AMV are consultants to Zoe Global Ltd (“Zoe”). JW, AM, LP and JC are employees of Zoe Global Limited. ALG is a regional PI on the COV002 trial and the Novavax COVID-19 vaccine trial and as such her organisation has received grants from Novavax. Other authors have no conflict of interest to declare.Ethics Approval Statement: Ethical approval for use of the app for research purposes in the UK was obtained from King’s College London Ethics Committee (review reference LRS-19/20-18210), and all users provided consent for non-commercial use.

Racial and ethnic differences in COVID-19 vaccine hesitancy and uptake (preprint)

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. ( n =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. ( n =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.

The effect of SARS-CoV-2 variant B.1.1.7 on symptomatology, re-infection and transmissibility (preprint)

The new SARS-CoV-2 variant B.1.1.7 was identified in December 2020 in the South-East of England, and rapidly increased in frequency and geographic spread. While there is some evidence for increased transmissibility of this variant, it is not known if the new variant presents with variation in symptoms or disease course, or if previously infected individuals may become reinfected with the new variant. Using longitudinal symptom and test reports of 36,920 users of the Covid Symptom Study app testing positive for COVID-19 between 28 September and 27 December 2020, we examined the association between the regional proportion of B.1.1.7 and reported symptoms, disease course, rates of reinfection, and transmissibility. We found no evidence for changes in reported symptoms, disease severity and disease duration associated with B.1.1.7. We found a likely reinfection rate of around 0.7% (95% CI 0.6-0.8), but no evidence that this was higher compared to older strains. We found an increase in R(t) by a factor of 1.35 (95% CI 1.02-1.69). Despite this, we found that regional and national lockdowns have reduced R(t) below 1 in regions with very high proportions of B.1.1.7.

Impact of COVID-19 on health behaviours and body weight: A prospective observational study in a cohort of 1.1 million UK and US individuals (preprint)

Evidence regarding the impact of COVID-19 on health behaviours is limited. In this prospective study including 1.1 million UK and US participants we collected diet and lifestyle data ‘pre-’ and ‘peri-’ pandemic, and computed a bi-directional health behaviour disruption index. We show that disruption was higher in the younger, female and socioeconomically deprived (p<0.001). A loss in body weight (-0.57kg) was greater in highly disrupted individuals compared to those with low disruption (0.01kg). There were large inter-individual changes observed in all 46 health and diet behaviors measured peri-pandemic versus pre-pandemic, but no mean change in the total population. Individuals most adherent to unhealthy pre-pandemic health behaviours improved their diet quality (0.93units) and weight (-0.79kg) compared with those reporting healthy pre-pandemic behaviours (0.08units and 0.04kg respectively), irrespective of relative deprivation. For a proportion of the population, the pandemic may have provided an impetus to improve health behaviours.

Anosmia and other SARS-CoV-2 positive test-associated symptoms, across three national, digital surveillance platforms as the COVID-19 pandemic and response unfolded: an observation study (preprint)

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 658325 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.

Dietary supplements during the COVID-19 pandemic: insights from 1.4M users of the COVID Symptom Study app - a longitudinal app-based community survey (preprint)

Objectives: Dietary supplements may provide nutrients of relevance to ameliorate SARS-CoV-2 infection, although scientific evidence to support a role is lacking. We investigate whether the regular use of dietary supplements can reduce the risk of testing positive for SARS-CoV-2 infection in around 1.4M users of the COVID Symptom Study App who completed a supplement use questionnaire. Design: Longitudinal app-based community survey and nested case control study. Setting: Subscribers to an app that was launched to enable self-reported information related to SARS-CoV-2 infection for use in the general population in three countries. Main Exposure: Self-reported regular dietary supplement usage since the beginning of the pandemic. Main Outcome Measures: SARS-CoV-2 infection confirmed by viral RNA polymerase chain reaction test (RT-PCR) or serology test. A secondary outcome was new-onset anosmia. Results: In an analysis including 327,720 UK participants, the use of probiotics, omega-3 fatty acids, multivitamins or vitamin D was associated with a lower risk of SARS-CoV-2 infection by 14%(95%CI: [8%,19%]), 12%(95%CI: [8%,16%]), 13%(95%CI: [10%,16%]) and 9%(95%CI: [6%,12%]), respectively, after adjusting for potential confounders. No effect was observed for vitamin C, zinc or garlic supplements. When analyses were stratified by sex, age and body mass index (BMI), the protective associations for 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. Results were further confirmed in a sub-analysis of 993,365 regular app users who were not tested for SARS-CoV-2 with cases (n= 126,556) defined as those with new onset anosmia (the strongest COVID-19 predictor). Conclusion: 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 in women. No clear benefits for men were observed nor any effect of vitamin C, garlic or zinc for men or women. Randomised controlled trials of selected supplements would be required to confirm these observational findings before any therapeutic recommendations can be made.