Mental health in the COVID-19 pandemic: A longitudinal analysis of the CLoCk cohort study.

BACKGROUND: Little is known about the long-term mental health consequences of the pandemic in children and young people (CYP), despite extremely high levels of exposure to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus and the disruption to schooling and leisure activities due to the resultant restrictions. There are mixed findings from systematic reviews of how the pandemic affected CYP's mental health, which may be due to heterogeneous methods and poor quality studies. Most, but not all, suggest deterioration in mental health but population level studies may obscure the differing experiences of subgroups. The study questions are: (i) are there subgroups of CYP with distinct mental health profiles over the course of the second year of the Coronavirus Disease 2019 (COVID-19) pandemic (between April 2021 and May 2022); and (ii) do vulnerability factors influence CYP's mental health trajectories. METHODS AND FINDINGS: A matched longitudinal cohort study of non-hospitalised test-positive and test-negative 11- to 17-year-old CYP in England were recruited from the UK Health Security Agency having undergone PCR testing for COVID-19. They completed the Strengths and Difficulties Questionnaire (SDQ) at least twice over a 12-month follow-up period. Overall, 8,518 of 17,918 (47.5%) CYP who returned their first SDQ at 3 or 6 months post-testing were included in the analytical sample. Associations between age, sex, ethnicity, socioeconomic status (SES), and an educational health and care plan (EHCP, indicating special educational needs) on SDQ score trajectories were examined separately, after adjusting for PCR test result. Findings from multilevel mixed-effects linear regression model showed that on average mental health symptoms as measured by the total SDQ score increased over time (B = 0.11 (per month), 95% CI = 0.09 to 0.12, p < 0.001) although this increase was small and not clinically significant. However, associations with time varied by age, such that older participants reported greater deterioration in mental health over time (B = 0.12 (per month), 95% CI = 0.10 to 0.14 for 15 to 17y; 0.08 (95% CI = 0.06 to 0.10) for 11 to 14y; pinteraction = 0.002) and by sex, with greater deterioration in girls. Children with an EHCP experienced less deterioration in their mental health compared to those without an EHCP. There was no evidence of differences in rate of change in total SDQ by ethnicity, SES, or physical health. Those with worse prior mental health did not appear to be disproportionately negatively affected over time. There are several limitations of the methodology including relatively low response rates in CLoCk and potential for recall bias. CONCLUSIONS: Overall, there was a statistically but not clinically significant decline in mental health during the pandemic. Sex, age, and EHCP status were important vulnerability factors that were associated with the rate of mental health decline, whereas ethnicity, SES, and prior poor physical health were not. The research highlights individual factors that could identify groups of CYP vulnerable to worsening mental health.

Prevalence and co-occurrence of cognitive impairment in children and young people up to 12-months post infection with SARS-CoV-2 (Omicron variant).

BACKGROUND: Cognitive impairment is often reported after SARS-CoV-2 infection, yet evidence gaps remain. We aimed to (i) report the prevalence and characteristics of children and young people (CYP) reporting "brain fog" (i.e., cognitive impairment) 12-months post PCR-proven SARS-CoV-2 infection and determine whether differences by infection status exist and (ii) explore the prevalence of CYP experiencing cognitive impairment over a 12-month period post-infection and investigate the relationship between cognitive impairment and poor mental health and well-being, mental fatigue and sleep problems. METHODS: The Omicron CLoCk sub-study, set up in January 2022, collected data on first-time PCR-test-positive and PCR-proven reinfected CYP at time of testing and at 3-, 6- and 12-months post-testing. We describe the prevalence of cognitive impairment at 12-months, indicating when it was first reported. We characterise CYP experiencing cognitive impairment and use chi-squared tests to determine whether cognitive impairment prevalence varied by infection status. We explore the relationship between cognitive impairment and poor mental health and well-being, mental fatigue and trouble sleeping using validated scales. We examine associations at 3-, 6- and 12-months post-testing by infection status using Mann-Whitney U and chi-square tests. RESULTS: At 12-months post-testing, 7.0 % (24/345) of first-positives and 7.5 % (27/360) of reinfected CYP experienced cognitive impairment with no difference between infection-status groups (p = 0.78). The majority of these CYP experienced cognitive impairment for the first time at either time of testing or 3-months post-test (no difference between the infection-status groups; p = 0.60). 70.8 % of first-positives experiencing cognitive impairment at 12-months, were 15-to-17-years-old as were 33.3 % of reinfected CYP experiencing cognitive impairment (p < 0.01). Consistently at all time points post-testing, CYP experiencing cognitive impairment were more likely to score higher on all Strengths and Difficulties Questionnaire subscales, higher on the Chalder Fatigue sub-scale for mental fatigue, lower on the Short Warwick-Edinburgh Mental Wellbeing Scale and report more trouble sleeping. CONCLUSIONS: CYP have a fluctuating experience of cognitive impairment by 12-months post SARS-CoV-2-infection. Cognitive impairment is consistently correlated with poorer sleep, behavioural and emotional functioning over a 12-month period. Clinicians should be aware of cognitive impairment post-infection and its co-occurring nature with poorer sleep, behavioural and mental health symptoms.

International Care programs for Pediatric Post-COVID Condition (Long COVID) and the way forward.

BACKGROUND: Pediatric Post-COVID-Condition (PPCC) clinics treat children despite limited scientific substantiation. By exploring real-life management of children diagnosed with PPCC, the International Post-COVID-Condition in Children Collaboration (IP4C) aimed to provide guidance for future PPCC care. METHODS: We performed a cross-sectional international, multicenter study on used PPCC definitions; the organization of PPCC care programs and patients characteristics. We compared aggregated data from PPCC cohorts and identified priorities to improve PPCC care. RESULTS: Ten PPCC care programs and six COVID-19 follow-up research cohorts participated. Aggregated data from 584 PPCC patients was analyzed. The most common symptoms included fatigue (71%), headache (55%), concentration difficulties (53%), and brain fog (48%). Severe limitations in daily life were reported in 31% of patients. Most PPCC care programs organized in-person visits with multidisciplinary teams. Diagnostic testing for respiratory and cardiac morbidity was most frequently performed and seldom abnormal. Treatment was often limited to physical therapy and psychological support. CONCLUSIONS: We found substantial heterogeneity in both the diagnostics and management of PPCC, possibly explained by scarce scientific evidence and lack of standardized care. We present a list of components which future guidelines should address, and outline priorities concerning PPCC care pathways, research and international collaboration. IMPACT: Pediatric Post-COVID Condition (PPCC) Care programs have been initiated in many countries. Children with PPCC in different countries are affected by similar symptoms, limiting many to participate in daily life. There is substantial heterogeneity in diagnostic testing. Access to specific diagnostic tests is required to identify some long-term COVID-19 sequelae. Treatments provided were limited to physical therapy and psychological support. This study emphasizes the need for evidence-based diagnostics and treatment of PPCC. The International Post-COVID Collaboration for Children (IP4C) provides guidance for guideline development and introduces a framework of priorities for PPCC care and research, to improve PPCC outcomes.

Developing survey weights to ensure representativeness in a national, matched cohort study: results from the children and young people with Long Covid (CLoCk) study.

BACKGROUND: Findings from studies assessing Long Covid in children and young people (CYP) need to be assessed in light of their methodological limitations. For example, if non-response and/or attrition over time systematically differ by sub-groups of CYP, findings could be biased and any generalisation limited. The present study aimed to (i) construct survey weights for the Children and young people with Long Covid (CLoCk) study, and (ii) apply them to published CLoCk findings showing the prevalence of shortness of breath and tiredness increased over time from baseline to 12-months post-baseline in both SARS-CoV-2 Positive and Negative CYP. METHODS: Logistic regression models were fitted to compute the probability of (i) Responding given envisioned to take part, (ii) Responding timely given responded, and (iii) (Re)infection given timely response. Response, timely response and (re)infection weights were generated as the reciprocal of the corresponding probability, with an overall 'envisioned population' survey weight derived as the product of these weights. Survey weights were trimmed, and an interactive tool developed to re-calibrate target population survey weights to the general population using data from the 2021 UK Census. RESULTS: Flexible survey weights for the CLoCk study were successfully developed. In the illustrative example, re-weighted results (when accounting for selection in response, attrition, and (re)infection) were consistent with published findings. CONCLUSIONS: Flexible survey weights to address potential bias and selection issues were created for and used in the CLoCk study. Previously reported prospective findings from CLoCk are generalisable to the wider population of CYP in England. This study highlights the importance of considering selection into a sample and attrition over time when considering generalisability of findings.

Long COVID in Children and Young after Infection or Reinfection with the Omicron Variant: A Prospective Observational Study.

To describe the prevalence of long COVID in children infected for the first time (n = 332) or reinfected (n = 243) with Omicron compared with test-negative children (n = 311). Overall, 12%-16% of those infected with Omicron met the research definition of long COVID at 3 and 6 months after infection, with no evidence of difference between cases of first positive and reinfected (Pχ2 = 0.17).

Predictive model for long COVID in children 3 months after a SARS-CoV-2 PCR test.

BACKGROUND: To update and internally validate a model to predict children and young people (CYP) most likely to experience long COVID (i.e. at least one impairing symptom) 3 months after SARS-CoV-2 PCR testing and to determine whether the impact of predictors differed by SARS-CoV-2 status. METHODS: Data from a nationally matched cohort of SARS-CoV-2 test-positive and test-negative CYP aged 11-17 years was used. The main outcome measure, long COVID, was defined as one or more impairing symptoms 3 months after PCR testing. Potential pre-specified predictors included SARS-CoV-2 status, sex, age, ethnicity, deprivation, quality of life/functioning (five EQ-5D-Y items), physical and mental health and loneliness (prior to testing) and number of symptoms at testing. The model was developed using logistic regression; performance was assessed using calibration and discrimination measures; internal validation was performed via bootstrapping and the final model was adjusted for overfitting. RESULTS: A total of 7139 (3246 test-positives, 3893 test-negatives) completing a questionnaire 3 months post-test were included. 25.2% (817/3246) of SARS-CoV-2 PCR-positives and 18.5% (719/3893) of SARS-CoV-2 PCR-negatives had one or more impairing symptoms 3 months post-test. The final model contained SARS-CoV-2 status, number of symptoms at testing, sex, age, ethnicity, physical and mental health, loneliness and four EQ-5D-Y items before testing. Internal validation showed minimal overfitting with excellent calibration and discrimination measures (optimism-adjusted calibration slope: 0.96575; C-statistic: 0.83130). CONCLUSIONS: We updated a risk prediction equation to identify those most at risk of long COVID 3 months after a SARS-CoV-2 PCR test which could serve as a useful triage and management tool for CYP during the ongoing pandemic. External validation is required before large-scale implementation.

Associations between attainment of incentivized primary care indicators and incident sight-threatening diabetic retinopathy in England: A population-based historical cohort study.

AIM: To examine the impact of attainment of primary care diabetes clinical indicators on progression to sight-threatening diabetic retinopathy (STDR) among those with mild non-proliferative diabetic retinopathy (NPDR). MATERIALS AND METHODS: An historical cohort study of 18,978 adults (43.63% female) diagnosed with type 2 diabetes before 1 April 2010 and mild NPDR before 1 April 2011 was conducted. The data were obtained from the UK Clinical Practice Research Datalink during 2010-2017, provided by 330 primary care practices in England. Exposures included attainment of the Quality and Outcomes Framework HbA1c (≤59 mmol/mol [≤7.5%]), blood pressure (≤140/80 mmHg) and cholesterol (≤5 mmol/L) indicators in the financial year 2010-2011, as well as the number of National Diabetes Audit processes completed in 2010-2011. The outcome was time to incident STDR. Nearest neighbour propensity score matching was undertaken, and univariable and multivariable Cox proportional hazards models were then fitted using the matched samples. Concordance statistics were calculated for each model. RESULTS: A total of 1037 (5.5%) STDR diagnoses were observed over a mean follow-up of 3.6 (SD 2.0) years. HbA1c, blood pressure and cholesterol indicator attainment were associated with lower rates of STDR (adjusted hazard ratios [95% CI] 0.64 [0.55-0.74; p < .001], 0.83 [0.72-0.94; p = .005] and 0.80 [0.66-0.96; p = .015], respectively). CONCLUSIONS: Our findings provide support for meeting appropriate indicators for the management of type 2 diabetes in primary care to bring a range of benefits, including improved health outcomes-such as a reduction in the risk of STDR-for people with type 2 diabetes.

Rapidly Increasing Trend of Recorded Alcohol Consumption Since the End of the Armed Conflict in Sri Lanka.

AIM: To evaluate temporal changes in recorded alcohol consumption in Sri Lanka during and after the armed conflict 1998-2013. METHODS: District level alcohol sales, and mid-year population data for the whole study period (1998-2013) were consistently available from the Department of Excise and the Department of Census and Statistics for 18 of 25 districts. These data were used to estimate the recorded per capita consumption for the areas that were not directly exposed to the armed conflict. An interrupted time series design was employed to estimate the impact of the end of the armed conflict on recorded adult per capita alcohol consumption of population lived in the 18 districts. RESULTS: Adult per capita recorded alcohol consumption among Sri Lankans living in the 18 districts was 1.59 l of pure alcohol in 1998. This increased up to 2.07 l in 2009 and 2.55 l in 2013. Prior to the end of the conflict in 2009 adult per capita recorded consumption increased by 0.051 l of pure alcohol per year (95% CI: 0.029-0.074, P < 0.001); after 2009 this was 0.166 l per year (95% CI: 0.095-0.236, P < 0.001). Beer consumption showed the highest per capita growth compared with other beverages. CONCLUSIONS: Adult per capita recorded alcohol consumption among Sri Lankans living in areas that were not directly exposed to the conflict increased markedly after the end of the conflict. Rapid socio-economic development, alcohol industry penetration and lack of alcohol control strategies during the post-conflict period may have driven this increase. SHORT SUMMARY: Adult per capita recorded alcohol consumption among Sri Lankans living in 18 districts that were not directly exposed to the armed conflict increased markedly after the end of the conflict in 2009, with a dramatic acceleration in the trend of per capita beer consumption.

Measuring Alcohol Consumption in Population Surveys: A Review of International Guidelines and Comparison with Surveys in England.

AIMS: To review the international guidelines and recommendations on survey instruments for measurement of alcohol consumption in population surveys and to examine how national surveys in England meet the core recommendations. METHODS: A systematic search for international guidelines for measuring alcohol consumption in population surveys was undertaken. The common core recommendations for alcohol consumption measures and survey instruments were identified. Alcohol consumption questions in national surveys in England were compared with these recommendations for specific years and over time since 2000. RESULTS: Four sets of international guidelines and three core alcohol consumption measures (alcohol consumption status, average volume of consumption, frequency and volume of heavy episodic drinking) with another optional measure (drinking context) were identified. English national surveys have been inconsistent over time in including questions that provide information on average volume of consumption but have not included questions on another essential alcohol consumption measure, frequency of heavy episodic drinking. Instead, they have used questions that focus only on maximum volume of alcohol consumed on any day in the previous week. CONCLUSIONS: International guidelines provide consistent recommendations for measuring alcohol consumption in population surveys. These recommendations have not been consistently applied in English national surveys, and this has contributed to the inadequacy of survey measurements for monitoring vital aspects of alcohol consumption in England over recent years.

What are the main sources of smoking cessation support used by adolescent smokers in England? A cross-sectional study.

BACKGROUND: Adolescent smoking is a worldwide public health concern. Whilst various support measures are available to help young smokers quit, their utilization of cessation support remains unknown. METHODS: A cross-sectional study was conducted using data from the 2012 Smoking, Drinking and Drug Use among Young People survey to quantify the use of seven different types of cessation support by adolescents aged 11-16 in England who reported current smoking and having tried to quit, or ex-smoking. Logistic regression was used to calculate odds ratios and 95% confidence intervals for the associations between participant characteristics and reported use of cessation support. RESULTS: Amongst 617 current and ex-smokers, 67.3% (95% CI 63.0-71.2) reported use of at least one cessation support measure. Not spending time with friends who smoke was the most commonly-used measure, reported by 45.4% of participants (95% CI 41.1-49.8), followed by seeking smoking cessation advice from family or friends (27.4%, 95% CI 23.7-31.5) and using nicotine products (15.4%, 95% CI 12.6-18.7). Support services provided by the National Health Service (NHS) were infrequently utilized. Having received lessons on smoking was significantly associated with reported use of cessation support (adjusted OR 1.55, 95% CI 1.02-2.34) and not spending time with friends who smoked (adjusted OR 1.98, 95% CI 1.33-2.95). Students with family members who smoked were more likely to report asking family or friends for help to quit (adjusted OR 1.74, 95% CI 1.07-2.81). Respondents who smoked fewer cigarettes per week were generally less likely to report use of cessation support measures. CONCLUSION: The majority of young smokers reported supported attempts to quit, though the support they used tended to be informal rather than formal. Evidence is needed to quantify the effectiveness of cessation support mechanisms which are acceptable to and used by young smokers.

Post-Covid-19 condition (Long Covid) in children and young people 12 months after infection or reinfection with the Omicron variant: a prospective observational study.

Our previous study in children and young people (CYP) at 3- and 6-months post-infection showed that 12-16% of those infected with the Omicron (B.1.1.529) variant of SARS-CoV-2 met the research definition of Long Covid, with no differences between first-positive and reinfected CYP. The primary objective of the current study is to explore the impact of the Omicron variant of SARS-CoV-2 infection on young people 12 months post infection. 345 CYP aged 11-17 years with a first laboratory-confirmed infection with the Omicron variant and 360 CYP reinfected with the Omicron variant completed an online questionnaire assessing demographics, symptoms, and their impact shortly after testing and again at 3-, 6-and 12-months post-testing. Vaccination status was determined from information held at UKHSA. Comparisons between groups were made using chi-squared, Mann-Whitney U, and Kruskal-Wallis tests. The most common symptoms in first-positive and reinfected CYP 12-months post-testing were tiredness (35.7 and 33.6% respectively) and sleeping difficulties (27.5 and 28.3% respectively). Symptom profiles, severity and impact were similar in the two infection status groups. Overall, by 12-months, 17.4% of first-positives and 21.9% of reinfected CYP fulfilled the research consensus Long Covid definition (p = 0.13). 12-months post Omicron infection, there is little difference between first-positive and reinfected CYP with respect to symptom profiles and impact. Clinicians may not therefore need to consider number of infections and type of variant when developing treatment plans. Further studies are needed to assess causality of reported symptoms up to 12-months after SARS-CoV-2 infection.

Post-COVID-19 condition at 6 months and COVID-19 vaccination in non-hospitalised children and young people.

OBJECTIVES: To describe the physical and mental health of children and young people (CYP) 6 months after infection with SARS-CoV-2 and explore whether this varies by COVID-19 vaccination. DESIGN: A non-hospitalised, national cohort of people aged 11-17 years old with PCR-confirmed SARS-CoV-2 infection and PCR negatives matched at study invitation, by age, sex, region and date of testing who completed questionnaires 6 months after PCR testing. The questionnaire included 21 symptoms and standardised scales (eg, EQ-5D-Y and Chalder Fatigue Scale). RESULTS: 6407 test-positive and 6542 test-negative CYP completed the 6-month questionnaire: 60.9% of test-positive vs 43.2% of test-negative CYP reported at least one symptom 6 months post-test; 27.6% of test-positive vs 15.9% of test-negative CYP reported 3+ symptoms. Common symptoms at 6 months were tiredness and shortness of breath among both test-positive and test-negative CYP; however, the prevalence of both was higher in test-positive (38.4% and 22.8%, respectively) compared with test-negative CYP (26.7% and 10.9%, respectively). 24.5% test-positive vs 17.8% test-negative CYP met the Delphi research definition of long COVID. Mental health, well-being, fatigue and health-related quality of life scores were similar among test-positive and test-negative CYP 6 months post-test. Similarly, symptomatology was similar among COVID-19-vaccinated and COVID-19-unvaccinated test-positive and test-negative CYP. CONCLUSIONS: Six-months post-PCR testing, CYP who tested positive for SARS-CoV-2 had similar symptoms to those who tested negative, but test-positive CYP had higher symptom prevalence. Mental health, well-being, fatigue and health-related quality of life were similar among test-positive and test-negative CYP, and symptoms at 6 months were similar in COVID-19 vaccinated and unvaccinated. TRIAL REGISTRATION NUMBER: ISRCTN 34804192.

Long COVID-six months of prospective follow-up of changes in symptom profiles of non-hospitalised children and young people after SARS-CoV-2 testing: A national matched cohort study (The CLoCk) study.

BACKGROUND: Little is known about the prevalence and natural trajectory of post-COVID symptoms in young people, despite very high numbers of young people having acute COVID. To date, there has been no prospective follow-up to establish the pattern of symptoms over a 6-month time period. METHODS: A non-hospitalised, national sample of 3,395 (1,737 SARS-COV-2 Negative;1,658 SARS-COV-2 Positive at baseline) children and young people (CYP) aged 11-17 completed questionnaires 3 and 6 months after PCR-confirmed SARS-CoV-2 infection between January and March 2021 and were compared with age, sex and geographically-matched test-negative CYP. RESULTS: Three months after a positive SARS-CoV-2 PCR test, 11 of the 21 most common symptoms reported by >10% of CYP had reduced. There was a further decline at 6 months. By 3 and 6 months the prevalence of chills, fever, myalgia, cough and sore throat of CYP who tested positive for SARS-CoV-2 reduced from 10-25% at testing to <3%. The prevalence of loss of smell declined from 21% to 5% at 3 months and 4% at 6 months. Prevalence of shortness of breath and tiredness also declined, but at a lower rate. Among test-negatives, the same common symptoms and trends were observed at lower prevalence's. Importantly, in some instances (shortness of breath, tiredness) the overall prevalence of specific individual symptoms at 3 and 6 months was higher than at PCR-testing because these symptoms were reported in new cohorts of CYP who had not reported the specific individual symptom previously. CONCLUSIONS: In CYP, the prevalence of specific symptoms reported at time of PCR-testing declined with time. Similar patterns were observed among test-positives and test-negatives and new symptoms were reported six months post-test for both groups suggesting that symptoms are unlikely to exclusively be a specific consequence of SARS-COV-2 infection. Many CYP experienced unwanted symptoms that warrant investigation and potential intervention.

Children and Young People with Long COVID-Comparing Those Seen in Post-COVID Services with a Non-Hospitalised National Cohort: A Descriptive Study.

BACKGROUND: Post-COVID services have been set up in England to treat children with ongoing symptoms of Long COVID. To date, the characteristics of children seeking treatment from these services has not been described. PURPOSE: (1) to describe the characteristics of children aged 11-17 referred to the Pan-London Post-COVID service and (2) to compare characteristics of these children with those taking part in the United Kingdom's largest research study of Long COVID in children (CLoCk). DESIGN: Data from 95 children seeking treatment from the Post-COVID service between May 2021 and August 2022 were included in the study. Their demographic characteristics, symptom burden and the impact of infection are described and compared to children from CLoCk. RESULTS: A high proportion of children from the Post-COVID service and CLoCk reported experiencing health problems prior to the pandemic. Almost all Post-COVID service children met the research Delphi definition of Long COVID (94.6%), having multiple symptoms that impacted their lives. Symptoms were notably more severe than the participants in CLoCk. CONCLUSIONS: This study describes the characteristics of children seeking treatment for Long COVID compared to those identified in the largest longitudinal observational study to date. Post-COVID service children have more symptoms and are more severely affected by their symptoms following infection with COVID-19 than children in the CLoCk study. Research to understand predisposing factors for severity and prognostic indicators is essential to prevent this debilitating condition. Evaluation of short- and long-term outcomes of interventions by clinical services can help direct future therapy for this group.

The CLoCk study: A retrospective exploration of loneliness in children and young people during the COVID-19 pandemic, in England.

BACKGROUND: During the COVID-19 pandemic children and young people (CYP) were socially restricted during a stage of life crucial to development, potentially putting an already vulnerable population at higher risk of loneliness, social isolation, and poorer wellbeing. The objectives of this study are to conduct an exploratory analysis into loneliness before and during the pandemic, and determine which self-reported factors are associated with loneliness. METHODS AND FINDINGS: Participants from The Children with Long COVID (CLoCk) national study were invited to take part via an online survey, with a total of 31,017 participants taking part, 31,016 of which reported on their experience of loneliness. Participants retrospectively answered questions on demographics, lifestyle, physical health and mental health and loneliness before the pandemic and at the time of answering the survey. Before the pandemic 6.5% (2,006/31,016) of participants reported experiencing loneliness "Often/Always" and at the time of survey completion 17.4% (5,395/31,016) reported feeling lonelier. There was an association between meeting the research definition of long COVID and loneliness [3.49 OR, 95%CI 3.28-3.72]. CYP who reported feeling lonelier at the time of the survey than before the pandemic were assigned female at birth, older CYP, those from Black/African/Caribbean/Black British or other ethnicity groups, those that had 3-4 siblings and lived in more deprived areas. CONCLUSIONS: We demonstrate associations between multiple factors and experiences of loneliness during the pandemic. There is a need for a multi-faceted integrated approach when developing interventions targeted at loneliness. It is important to follow up the CYP involved at regular intervals to investigate the progression of their experience of loneliness over time.

Natural course of health and well-being in non-hospitalised children and young people after testing for SARS-CoV-2: a prospective follow-up study over 12 months.

Background: Despite high numbers of children and young people (CYP) having acute COVID, there has been no prospective follow-up of CYP to establish the pattern of health and well-being over a year following infection. Methods: A non-hospitalised, national sample of 5086 (2909 SARS-COV-2 Positive; 2177 SARS-COV-2 Negative at baseline) CYP aged 11-17 completed questionnaires 6- and 12-months after PCR-tests between October 2020 and March 2021 confirming SARS-CoV-2 infection (excluding CYP with subsequent (re)infections). SARS-COV-2 Positive CYP was compared to age, sex and geographically-matched test-negative CYP. Findings: Ten of 21 symptoms had a prevalence less than 10% at baseline, 6- and 12-months post-test in both test-positives and test-negatives. Of the other 11 symptoms, in test-positives who had these at baseline, the prevalence of all symptoms declined greatly by 12-months. For CYP first describing one of these at 6-months, there was a decline in prevalence by 12-months. The overall prevalence of 9 of 11 symptoms declined by 12-months. As many CYP first described shortness of breath and tiredness at either 6- or 12-months, the overall prevalence of these two symptoms in test-positives appeared to increase by 6-months and increase further by 12-months. However, within-individual examination demonstrated that the prevalence of shortness of breath and tiredness actually declined in those first describing these two symptoms at either baseline or 6-months. This pattern was also evident for these two symptoms in test-negatives. Similar patterns were observed for validated measures of poor quality of life, emotional and behavioural difficulties, poor well-being and fatigue. Moreover, broadly similar patterns and results were noted for the sub-sample (N = 1808) that had data at baseline, 3-, 6- and 12-months post-test. Interpretation: In CYP, the prevalence of adverse symptoms reported at the time of a positive PCR-test declined over 12-months. Some test-positives and test-negatives reported adverse symptoms for the first time at six- and 12-months post-test, particularly tiredness, shortness of breath, poor quality of life, poor well-being and fatigue suggesting they are likely to be caused by multiple factors. Funding: NIHR/UKRI (ref: COVLT0022).

Symptom Profiles of Children and Young People 12 Months after SARS-CoV-2 Testing: A National Matched Cohort Study (The CLoCk Study).

BACKGROUND: Although 99% of children and young people have been exposed to SARS-CoV-2, the long-term prevalence of post-COVID-19 symptoms in young people is unclear. The aim of this study is to describe symptom profiles 12 months after SARS-CoV-2 testing. METHOD: A matched cohort study of a national sample of 20,202 children and young people who took a SARS-CoV-2 PCR test between September 2020 and March 2021. RESULTS: 12 months post-index-test, there was a difference in the number of symptoms reported by initial negatives who never tested positive (NN) compared to the other three groups who had at least one positive test (p < 0.001). Similarly, 10.2% of the NN group described five-plus symptoms at 12 months compared to 15.9-24.0% in the other three groups who had at least one positive test. The most common symptoms were tiredness, sleeping difficulties, shortness of breath, and headaches for all four groups. For all these symptoms, the initial test positives with subsequent reports of re-infection had higher prevalences than other positive groups (p < 0.001). Symptom profiles, mental health, well-being, fatigue, and quality of life did not vary by vaccination status. CONCLUSIONS: Following the pandemic, many young people, particularly those that have had multiple SARS-CoV-2 positive tests, experience a range of symptoms that warrant consideration and potential investigation and intervention.

Development and validation of predictive risk models for sight threatening diabetic retinopathy in patients with type 2 diabetes to be applied as triage tools in resource limited settings.

Background: Delayed diagnosis and treatment of sight threatening diabetic retinopathy (STDR) is a common cause of visual impairment in people with Type 2 diabetes. Therefore, systematic regular retinal screening is recommended, but global coverage of such services is challenging. We aimed to develop and validate predictive models for STDR to identify 'at-risk' population for retinal screening. Methods: Models were developed using datasets obtained from general practices in inner London, United Kingdom (UK) on adults with type 2 Diabetes during the period 2007-2017. Three models were developed using Cox regression and model performance was assessed using C statistic, calibration slope and observed to expected ratio measures. Models were externally validated in cohorts from Wales, UK and India. Findings: A total of 40,334 people were included in the model development phase of which 1427 (3·54%) people developed STDR. Age, gender, diabetes duration, antidiabetic medication history, glycated haemoglobin (HbA1c), and history of retinopathy were included as predictors in the Model 1, Model 2 excluded retinopathy status, and Model 3 further excluded HbA1c. All three models attained strong discrimination performance in the model development dataset with C statistics ranging from 0·778 to 0·832, and in the external validation datasets (C statistic 0·685 - 0·823) with calibration slopes closer to 1 following re-calibration of the baseline survival. Interpretation: We have developed new risk prediction equations to identify those at risk of STDR in people with type 2 diabetes in any resource-setting so that they can be screened and treated early. Future testing, and piloting is required before implementation. Funding: This study was funded by the GCRF UKRI (MR/P207881/1) and supported by the NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology.

Long COVID (post-COVID-19 condition) in children: a modified Delphi process.

OBJECTIVE: The aim of this study was to derive a research definition for 'Long COVID (post-COVID-19 condition)' in children and young people (CYP) to allow comparisons between research studies. DESIGN: A three-phase online Delphi process was used, followed by a consensus meeting. Participants were presented with 49 statements in each phase and scored them from 1 to 9 based on how important they were for inclusion in the research definition of Long COVID in CYP. The consensus meeting was held to achieve representation across the stakeholder groups. Statements agreed at the consensus meeting were reviewed by participants in the Patient and Public Involvement (PPI) Research Advisory Group. SETTING: The study was conducted remotely using online surveys and a virtual consensus meeting. PARTICIPANTS: 120 people with relevant expertise were divided into three panels according to their area of expertise: Service Delivery, Research (or combination of research and service delivery) and Lived Experience. The PPI Research Advisory group consisted of CYP aged 11-17 years. MAIN OUTCOME MEASURES: Consensus was defined using existing guidelines. If consensus was achieved in two or more panels or was on the border between one and two panels, those statements were discussed and voted on at the consensus meeting. RESULTS: Ten statements were taken forward for discussion in the consensus meeting and five statements met threshold to be included in the research definition of Long COVID among CYP. The research definition, aligned to the clinical case definition of the WHO, is proposed as follows: Post-COVID-19 condition occurs in young people with a history of confirmed SARS-CoV-2 infection, with at least one persisting physical symptom for a minimum duration of 12 weeks after initial testing that cannot be explained by an alternative diagnosis. The symptoms have an impact on everyday functioning, may continue or develop after COVID infection, and may fluctuate or relapse over time. The positive COVID-19 test referred to in this definition can be a lateral flow antigen test, a PCR test or an antibody test. CONCLUSIONS: This is the first research definition of Long COVID (post-COVID-19 condition) in CYP and complements the clinical case definition in adults proposed by the WHO.

Ethnic Disparities in the Development of Sight-Threatening Diabetic Retinopathy in a UK Multi-Ethnic Population with Diabetes: An Observational Cohort Study.

There is little data on ethnic differences in incidence of DR and sight threatening DR (STDR) in the United Kingdom. We aimed to determine ethnic differences in the development of DR and STDR and to identify risk factors of DR and STDR in people with incident or prevalent type II diabetes (T2DM). We used electronic primary care medical records of people registered with 134 general practices in East London during the period from January 2007-January 2017. There were 58,216 people with T2DM eligible to be included in the study. Among people with newly diagnosed T2DM, Indian, Pakistani and African ethnic groups showed an increased risk of DR with Africans having highest risk of STDR compared to White ethnic groups (HR: 1.36 95% CI 1.02-1.83). Among those with prevalent T2DM, Indian, Pakistani, Bangladeshi and Caribbean ethnic groups showed increased risk of DR and STDR with Indian having the highest risk of any DR (HR: 1.24 95% CI 1.16-1.32) and STDR (HR: 1.38 95% CI 1.17-1.63) compared with Whites after adjusting for all covariates considered. It is important to optimise prevention, screening and treatment options in these ethnic minority groups to avoid health inequalities in diabetes eye care.