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1.
Lancet Reg Health Eur ; 19: 100429, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1926750

ABSTRACT

Background: We aimed to explore the effectiveness of one-dose BNT162b2 vaccination upon SARS-CoV-2 infection, its effect on COVID-19 presentation, and post-vaccination symptoms in children and adolescents (CA) in the UK during periods of Delta and Omicron variant predominance. Methods: In this prospective longitudinal cohort study, we analysed data from 115,775 CA aged 12-17 years, proxy-reported through the Covid Symptom Study (CSS) smartphone application. We calculated post-vaccination infection risk after one dose of BNT162b2, and described the illness profile of CA with post-vaccination SARS-CoV-2 infection, compared to unvaccinated CA, and post-vaccination side-effects. Findings: Between August 5, 2021 and February 14, 2022, 25,971 UK CA aged 12-17 years received one dose of BNT162b2 vaccine. The probability of testing positive for infection diverged soon after vaccination, and was lower in CA with prior SARS-CoV-2 infection. Vaccination reduced proxy-reported infection risk (-80·4% (95% CI -0·82 -0·78) and -53·7% (95% CI -0·62 -0·43) at 14-30 days with Delta and Omicron variants respectively, and -61·5% (95% CI -0·74 -0·44) and -63·7% (95% CI -0·68 -0.59) after 61-90 days). Vaccinated CA who contracted SARS-CoV-2 during the Delta period had milder disease than unvaccinated CA; during the Omicron period this was only evident in children aged 12-15 years. Overall disease profile was similar in both vaccinated and unvaccinated CA. Post-vaccination local side-effects were common, systemic side-effects were uncommon, and both resolved within few days (3 days in most cases). Interpretation: One dose of BNT162b2 vaccine reduced risk of SARS-CoV-2 infection for at least 90 days in CA aged 12-17 years. Vaccine protection varied for SARS-CoV-2 variant type (lower for Omicron than Delta variant), and was enhanced by pre-vaccination SARS-CoV-2 infection. Severity of COVID-19 presentation after vaccination was generally milder, although unvaccinated CA also had generally mild disease. Overall, vaccination was well-tolerated. Funding: UK Government Department of Health and Social Care, Chronic Disease Research Foundation, The 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 and Alzheimer's Society, and ZOE Limited.

2.
Sci Rep ; 12(1): 10904, 2022 Jun 28.
Article in English | MEDLINE | ID: covidwho-1908282

ABSTRACT

The Delta (B.1.617.2) variant was the predominant UK circulating SARS-CoV-2 strain between May and December 2021. How Delta infection compares with previous variants is unknown. 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 the 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) the 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. 3581 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 versus Alpha infection (including fever, sore throat, and headache) and some vice versa (dyspnoea). Symptom burden in the first week was higher with Delta versus 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 versus Alpha infection, though unchanged in unvaccinated individuals. Hospitalisation for COVID-19 was unchanged. The Delta variant appeared more (1.49) transmissible than Alpha. Re-infections were low in all UK regions. Vaccination markedly reduced the risk of Delta infection (by 69-84%). We conclude that COVID-19 from Delta or Alpha infections is similar. The Delta variant is more transmissible than Alpha; however, current vaccines showed good efficacy against disease. This research framework can be useful for future comparisons with new emerging variants.


Subject(s)
COVID-19 , Hepatitis D , Adult , COVID-19/epidemiology , Humans , Prospective Studies , Reinfection , SARS-CoV-2/genetics
3.
Lancet ; 399(10335): 1618-1624, 2022 04 23.
Article in English | MEDLINE | ID: covidwho-1867912

ABSTRACT

BACKGROUND: The SARS-CoV-2 variant of concern, omicron, appears to be less severe than delta. We aim to quantify the differences in symptom prevalence, risk of hospital admission, and symptom duration among the vaccinated population. METHODS: In this prospective longitudinal observational study, we collected data from participants who were self-reporting test results and symptoms in the ZOE COVID app (previously known as the COVID Symptoms Study App). Eligible participants were aged 16-99 years, based in the UK, with a body-mass index between 15 and 55 kg/m2, had received at least two doses of any SARS-CoV-2 vaccine, were symptomatic, and logged a positive symptomatic PCR or lateral flow result for SARS-CoV-2 during the study period. The primary outcome was the likelihood of developing a given symptom (of the 32 monitored in the app) or hospital admission within 7 days before or after the positive test in participants infected during omicron prevalence compared with those infected during delta prevalence. FINDINGS: Between June 1, 2021, and Jan 17, 2022, we identified 63 002 participants who tested positive for SARS-CoV-2 and reported symptoms in the ZOE app. These patients were matched 1:1 for age, sex, and vaccination dose, across two periods (June 1 to Nov 27, 2021, delta prevalent at >70%; n=4990, and Dec 20, 2021, to Jan 17, 2022, omicron prevalent at >70%; n=4990). Loss of smell was less common in participants infected during omicron prevalence than during delta prevalence (16·7% vs 52·7%, odds ratio [OR] 0·17; 95% CI 0·16-0·19, p<0·001). Sore throat was more common during omicron prevalence than during delta prevalence (70·5% vs 60·8%, 1·55; 1·43-1·69, p<0·001). There was a lower rate of hospital admission during omicron prevalence than during delta prevalence (1·9% vs 2·6%, OR 0·75; 95% CI 0·57-0·98, p=0·03). INTERPRETATION: The prevalence of symptoms that characterise an omicron infection differs from those of the delta SARS-CoV-2 variant, apparently with less involvement of the lower respiratory tract and reduced probability of hospital admission. Our data indicate a shorter period of illness and potentially of infectiousness which should impact work-health policies and public health advice. FUNDING: Wellcome Trust, ZOE, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, and Medical Research Council.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , COVID-19 Vaccines , Hospitals , Humans , Prevalence , Prospective Studies , SARS-CoV-2/genetics
5.
Children (Basel) ; 9(5)2022 May 03.
Article in English | MEDLINE | ID: covidwho-1820186

ABSTRACT

BACKGROUND: The Delta (B.1.617.2) SARS-CoV-2 variant was the predominant UK circulating strain between May and November 2021. We investigated whether COVID-19 from Delta infection differed from infection with previous variants in children. METHODS: Through the prospective COVID Symptom Study, 109,626 UK school-aged children were proxy-reported between 28 December 2020 and 8 July 2021. We selected all symptomatic children who tested positive for SARS-CoV-2 and were proxy-reported at least weekly, within two timeframes: 28 December 2020 to 6 May 2021 (Alpha (B.1.1.7), the main UK circulating variant) and 26 May to 8 July 2021 (Delta, the main UK circulating variant), with all children unvaccinated (as per national policy at the time). 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. RESULTS: 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) symptoms with Alpha, 4 (IQR 2-7) with Delta; in older children, 5 (IQR 3-8) symptoms with Alpha, 6 (IQR 3-9) with Delta infection ). The odds of presenting 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. CONCLUSIONS: COVID-19 in UK school-aged children due to SARS-CoV-2 Delta strain B.1.617.2 resembles illness due to the Alpha variant B.1.1.7., with short duration and similar symptom burden.

6.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330263

ABSTRACT

Background We aimed to explore the effectiveness of one-dose BNT162b2 vaccination upon SARS-CoV-2 infection, its effect on COVID-19 presentation, and post-vaccination symptoms in children and young people (CYP) in the UK during periods of Delta and Omicron variant predominance. Methods In this prospective longitudinal cohort study, we analysed data from 115,775 CYP aged 12-17 years, proxy-reported through the Covid Symptom Study (CSS) smartphone application. We calculated post-vaccination infection risk after one dose of BNT162b2, and described the illness profile of CYP with post-vaccination SARS- CoV-2 infection, compared to unvaccinated CYP, and post-vaccination side-effects. Findings Between August 5, 2021 and February 14, 2022, 25,971 UK CYP aged 12-17 years received one dose of BNT162b2 vaccine. Vaccination reduced (proxy-reported) infection risk (-80·4% and -53·7% at 14–30 days with Delta and Omicron variants respectively, and -61·5% and -63·7% after 61–90 days). The probability of remaining infection-free diverged soon after vaccination, and was greater in CYP with prior SARS-CoV-2 infection. Vaccinated CYP who contracted SARS-CoV-2 during the Delta period had milder disease than unvaccinated CYP;during the Omicron period this was only evident in children aged 12-15 years. Overall disease profile was similar in both vaccinated and unvaccinated CYP. Post-vaccination local side-effects were common, systemic side-effects were uncommon, and both resolved quickly. Interpretation One dose of BNT162b2 vaccine reduced risk of SARS-CoV-2 infection for at least 90 days in CYP aged 12-17 years. Vaccine protection varied for SARS-CoV-2 variant type (lower for Omicron than Delta variant), and was enhanced by pre-vaccination SARS-CoV-2 infection. Severity of COVID-19 presentation after vaccination was generally milder, although unvaccinated CYP also had generally mild disease. Overall, vaccination was well-tolerated. Funding UK Government Department of Health and Social Care, Chronic Disease Research Foundation, The 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 and Alzheimer’s Society, and ZOE Limited. Research in context Evidence before this study: We searched PubMed database for peer-reviewed articles and medRxiv for preprint papers, published between January 1, 2021 and February 15, 2022 using keywords (“SARS-CoV-2” OR “COVID-19”) AND (child* OR p?ediatric* OR teenager*) AND (“vaccin*” OR “immunization campaign”) AND (“efficacy” OR “effectiveness” OR “symptoms”) AND (“delta” or “omicron” OR “B.1.617.2” OR “B.1.1.529”). The PubMed search retrieved 36 studies, of which fewer than 30% specifically investigated individuals <18 years. Eleven studies explored SARS-CoV-2 viral transmission: seroprevalence in children (n=4), including age-dependency of susceptibility to SARS-CoV-2 infection (n=1), SARS-CoV-2 transmission in schools (n=5), and the effect of school closure on viral transmission (n=1). Eighteen documents reported clinical aspects, including manifestation of infection (n=13), symptomatology, disease duration, and severity in children. Other studies estimated emergency department visits, hospitalization, need for intensive care, and/or deaths in children (n=4), and explored prognostic factors (n=1). Thirteen studies explored vaccination-related aspects, including vaccination of children within specific paediatric co-morbidity groups (e.g., children with Down syndrome, inflammatory bowel disease, and cancer survivors, n=4), mRNA vaccine efficacy in children and adolescents from the general population (n=7), and the relation between vaccination and severity of disease and hospitalization cases (n=2). Four clinical trials were conducted using mRNA vaccines in minors, also xploring side effects. Sixty percent of children were found to have side effects after BNT162b2 vaccination, and especially after the second dose;however, most symptoms were mild and transient apart from rare uncomplicated skin ulcers. Two studies focused on severe adverse effects and safety of SARS-CoV-2 vaccines in children, reporting on myocarditis episodes and two cases of Guillain-Barrè syndrome. All other studies were beyond the scope of our research. Added value of this study: We assessed multiple components of the UK vaccination campaign in a cohort of children and young people (CYP) aged 12-17 years drawn from a large UK community-based citizen-science study, who received a first dose of BNT162b2 vaccine. We describe a variant-dependent protective effect of the first dose against both Delta and Omicron, with additional protective effect of pre-vaccination SARS- CoV-2 infection on post-vaccination re-infection. We compare the illness profile in CYP infected post-vaccination with that of unvaccinated CYP, demonstrating overall milder disease with fewer symptoms for vaccinated CYP. We describe local and systemic side-effects during the first week following first-dose vaccination, confirming that local symptoms are common, systemic symptoms uncommon, and both usually transient. Implications of all the available evidence: Our data confirm that first dose BNT162b2 vaccination in CYP reduces risk of infection by SARS-CoV-2 variants, with generally local and brief side-effects. If infected after vaccination, COVID-19 is milder, if manifest at all. The study aims to contribute quantitative evidence to the risk-benefit evaluation of vaccination in CYP to inform discussion regarding rationale for their vaccination and the designing of national immunisation campaigns for this age group;and applies citizen-science approaches in the conduct of epidemiological surveillance and data collection in the UK community. Importantly, this study was conducted during Delta and Omicron predominance in UK;specificity of vaccine efficacy to variants is also illustrated;and results may not be generalizable to future SARS-CoV-2 strains.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-317604

ABSTRACT

The Covid Symptom Study, a smartphone-based surveillance study on COVID-19 symptoms in the population, is an exemplar of big data citizen science. Over 4.7 million participants and 189 million unique assessments have been logged since its introduction in March 2020. The success of the Covid Symptom Study creates technical challenges around effective data curation for two reasons. Firstly, the scale of the dataset means that it can no longer be easily processed using standard software on commodity hardware. Secondly, the size of the research group means that replicability and consistency of key analytics used across multiple publications becomes an issue. We present ExeTera, an open source data curation software designed to address scalability challenges and to enable reproducible research across an international research group for datasets such as the Covid Symptom Study dataset.

8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-316937

ABSTRACT

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.

9.
Lancet Child Adolesc Health ; 6(4): 216-217, 2022 04.
Article in English | MEDLINE | ID: covidwho-1671375
10.
Lancet Child Adolesc Health ; 6(1): e3, 2022 01.
Article in English | MEDLINE | ID: covidwho-1596118
11.
EClinicalMedicine ; 42: 101212, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1540603

ABSTRACT

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. METHODS: We conducted a prospective observational study in 1,072,313 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 (N=362,770) (other than local symptoms at injection site) and were tested for SARS-CoV-2 (N=14,842), 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 recorded. Symptom profiles in individuals testing positive were compared with a 1:1 matched population testing negative, including using machine learning and multiple models considering 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. Most 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 symptoms 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 or quarantining, to prevent community spread. FUNDING: 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, Chronic Disease Research Foundation, Zoe Limited.

12.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-292996

ABSTRACT

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.

13.
Sci Data ; 8(1): 297, 2021 11 22.
Article in English | MEDLINE | ID: covidwho-1528020

ABSTRACT

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.


Subject(s)
COVID-19/epidemiology , Citizen Science , Data Curation , Big Data , Data Science , Datasets as Topic , Epidemiological Monitoring , Humans , Mobile Applications , Smartphone , Software
14.
Lancet Child Adolesc Health ; 5(10): 708-718, 2021 10.
Article in English | MEDLINE | ID: covidwho-1510511

ABSTRACT

BACKGROUND: In children, SARS-CoV-2 infection is usually asymptomatic or causes a mild illness of short duration. Persistent illness has been reported; however, its prevalence and characteristics are unclear. We aimed to determine illness duration and characteristics in symptomatic UK school-aged children tested for SARS-CoV-2 using data from the COVID Symptom Study, one of the largest UK citizen participatory epidemiological studies to date. METHODS: In this prospective cohort study, data from UK school-aged children (age 5-17 years) were reported by an adult proxy. Participants were voluntary, and used a mobile application (app) launched jointly by Zoe Limited and King's College London. Illness duration and symptom prevalence, duration, and burden were analysed for children testing positive for SARS-CoV-2 for whom illness duration could be determined, and were assessed overall and for younger (age 5-11 years) and older (age 12-17 years) groups. Children with longer than 1 week between symptomatic reports on the app were excluded from analysis. Data from symptomatic children testing negative for SARS-CoV-2, matched 1:1 for age, gender, and week of testing, were also assessed. FINDINGS: 258 790 children aged 5-17 years were reported by an adult proxy between March 24, 2020, and Feb 22, 2021, of whom 75 529 had valid test results for SARS-CoV-2. 1734 children (588 younger and 1146 older children) had a positive SARS-CoV-2 test result and calculable illness duration within the study timeframe (illness onset between Sept 1, 2020, and Jan 24, 2021). The most common symptoms were headache (1079 [62·2%] of 1734 children), and fatigue (954 [55·0%] of 1734 children). Median illness duration was 6 days (IQR 3-11) versus 3 days (2-7) in children testing negative, and was positively associated with age (Spearman's rank-order rs 0·19, p<0·0001). Median illness duration was longer for older children (7 days, IQR 3-12) than younger children (5 days, 2-9). 77 (4·4%) of 1734 children had illness duration of at least 28 days, more commonly in older than younger children (59 [5·1%] of 1146 older children vs 18 [3·1%] of 588 younger children; p=0·046). The commonest symptoms experienced by these children during the first 4 weeks of illness were fatigue (65 [84·4%] of 77), headache (60 [77·9%] of 77), and anosmia (60 [77·9%] of 77); however, after day 28 the symptom burden was low (median 2 symptoms, IQR 1-4) compared with the first week of illness (median 6 symptoms, 4-8). Only 25 (1·8%) of 1379 children experienced symptoms for at least 56 days. Few children (15 children, 0·9%) in the negatively tested cohort had symptoms for at least 28 days; however, these children experienced greater symptom burden throughout their illness (9 symptoms, IQR 7·7-11·0 vs 8, 6-9) and after day 28 (5 symptoms, IQR 1·5-6·5 vs 2, 1-4) than did children who tested positive for SARS-CoV-2. INTERPRETATION: Although COVID-19 in children is usually of short duration with low symptom burden, some children with COVID-19 experience prolonged illness duration. Reassuringly, symptom burden in these children did not increase with time, and most recovered by day 56. Some children who tested negative for SARS-CoV-2 also had persistent and burdensome illness. A holistic approach for all children with persistent illness during the pandemic is appropriate. FUNDING: Zoe Limited, UK Government Department of Health and Social Care, Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging and Artificial Intelligence Centre for Value Based Healthcare, UK National Institute for Health Research, UK Medical Research Council, British Heart Foundation, and Alzheimer's Society.


Subject(s)
COVID-19/epidemiology , COVID-19/pathology , SARS-CoV-2/isolation & purification , Adolescent , COVID-19/diagnosis , COVID-19/virology , COVID-19 Testing , Child , Child, Preschool , Citizen Science , Cohort Studies , Cost of Illness , Female , Humans , Male , Prospective Studies , SARS-CoV-2/pathogenicity , United Kingdom
15.
Lancet Infect Dis ; 22(1): 43-55, 2022 01.
Article in English | MEDLINE | ID: covidwho-1500361

ABSTRACT

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.


Subject(s)
COVID-19/epidemiology , Mobile Applications/statistics & numerical data , Vaccination/statistics & numerical data , Adult , Aged , COVID-19/prevention & control , COVID-19 Testing/statistics & numerical data , Case-Control Studies , Female , Humans , Male , Middle Aged , Prospective Studies , Risk Factors , Self Report , United Kingdom/epidemiology , Young Adult
16.
J Neurol Neurosurg Psychiatry ; 92(12): 1254-1258, 2021 12.
Article in English | MEDLINE | ID: covidwho-1443621

ABSTRACT

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.


Subject(s)
Anxiety/epidemiology , COVID-19/psychology , Depression/epidemiology , Mobile Applications , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Mental Health , Middle Aged , Prevalence , SARS-CoV-2 , Self Report , Young Adult
17.
Lancet Infect Dis ; 21(7): 939-949, 2021 07.
Article in English | MEDLINE | ID: covidwho-1433943

ABSTRACT

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/m2vs ≥30 kg/m2), 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.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , COVID-19/immunology , Drug-Related Side Effects and Adverse Reactions/immunology , SARS-CoV-2/immunology , Vaccination/adverse effects , Female , Humans , Male , Middle Aged , Prospective Studies , Safety/statistics & numerical data , Self Report/statistics & numerical data , United Kingdom
18.
Lancet Digit Health ; 3(9): e587-e598, 2021 09.
Article in English | MEDLINE | ID: covidwho-1331339

ABSTRACT

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.


Subject(s)
Artificial Intelligence , COVID-19/diagnosis , Models, Biological , Adolescent , Adult , Aged , Aged, 80 and over , Anosmia , COVID-19/complications , Chest Pain , Dyspnea , Early Diagnosis , Epidemiologic Studies , Female , Humans , Male , Middle Aged , Mobile Applications , Pandemics , Prospective Studies , SARS-CoV-2 , Self Report , Sensitivity and Specificity , United Kingdom , Young Adult
19.
Lancet Digit Health ; 3(9): e577-e586, 2021 09.
Article in English | MEDLINE | ID: covidwho-1322425

ABSTRACT

BACKGROUND: Multiple voluntary surveillance platforms were developed across the world in response to the COVID-19 pandemic, providing a real-time understanding of population-based COVID-19 epidemiology. During this time, testing criteria broadened and health-care policies matured. We aimed to test whether there were consistent associations of symptoms with SARS-CoV-2 test status across three surveillance platforms in three countries (two platforms per country), during periods of testing and policy changes. METHODS: For this observational study, we used data of observations from three volunteer COVID-19 digital surveillance platforms (Carnegie Mellon University and University of Maryland Facebook COVID-19 Symptom Survey, ZOE COVID Symptom Study app, and the Corona Israel study) targeting communities in three countries (Israel, the UK, and the USA; two platforms per country). The study population included adult respondents (age 18-100 years at baseline) who were not health-care workers. We did logistic regression of self-reported symptoms on self-reported SARS-CoV-2 test status (positive or negative), adjusted for age and sex, in each of the study cohorts. We compared odds ratios (ORs) across platforms and countries, and we did meta-analyses assuming a random effects model. We also evaluated testing policy changes, COVID-19 incidence, and time scales of duration of symptoms and symptom-to-test time. FINDINGS: Between April 1 and July 31, 2020, 514 459 tests from over 10 million respondents were recorded in the six surveillance platform datasets. Anosmia-ageusia was the strongest, most consistent symptom associated with a positive COVID-19 test (robust aggregated rank one, meta-analysed random effects OR 16·96, 95% CI 13·13-21·92). Fever (rank two, 6·45, 4·25-9·81), shortness of breath (rank three, 4·69, 3·14-7·01), and cough (rank four, 4·29, 3·13-5·88) were also highly associated with test positivity. The association of symptoms with test status varied by duration of illness, timing of the test, and broader test criteria, as well as over time, by country, and by platform. INTERPRETATION: The strong association of anosmia-ageusia with self-reported positive SARS-CoV-2 test was consistently observed, supporting its validity as a reliable COVID-19 signal, regardless of the participatory surveillance platform, country, phase of illness, or testing policy. These findings show that associations between COVID-19 symptoms and test positivity ranked similarly in a wide range of scenarios. Anosmia, fever, and respiratory symptoms consistently had the strongest effect estimates and were the most appropriate empirical signals for symptom-based public health surveillance in areas with insufficient testing or benchmarking capacity. Collaborative syndromic surveillance could enhance real-time epidemiological investigations and public health utility globally. FUNDING: National Institutes of Health, National Institute for Health Research, Alzheimer's Society, Wellcome Trust, and Massachusetts Consortium on Pathogen Readiness.


Subject(s)
Ageusia , Anosmia , COVID-19 , Cough , Dyspnea , Fever , Population Surveillance/methods , Adolescent , Adult , Aged , Aged, 80 and over , Ageusia/epidemiology , Ageusia/etiology , Anosmia/epidemiology , Anosmia/etiology , COVID-19/complications , COVID-19/epidemiology , COVID-19/virology , Cough/epidemiology , Cough/etiology , Digital Technology , Dyspnea/epidemiology , Dyspnea/etiology , Female , Fever/epidemiology , Fever/etiology , Humans , Israel/epidemiology , Male , Middle Aged , Odds Ratio , Pandemics , SARS-CoV-2 , United Kingdom/epidemiology , United States/epidemiology , Young Adult
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