Severe COVID-19 outcomes by cardiovascular risk profile in England in 2020: a population-based cohort study

Background While cardiovascular disease (CVD) is a risk factor for severe COVID-19, the association between predicted cardiovascular risk and severe COVID-19 among people without diagnosed CVD is unclear. Methods We carried out historical, population-based cohort studies among adults aged 40–84 years in England using linked data from the Clinical Practice Research Datalink. Individuals were categorized into: existing CVD, raised cardiovascular risk (defined using QRISK3 score ≥10%) and low risk (QRISK3 score <10%) at 12/03/2020. We described incidence and severe outcomes of COVID-19 (deaths, intensive care unit [ICU] admissions, hospitalisations, major adverse cardiovascular events [MACE]) for each group. Among those with a COVID-19 record to 31/12/2020, we re-classified cardiovascular risk at infection and assessed the risk of severe outcomes using multivariable Cox regression with complete case analysis. We repeated analyses using hypertension to define raised cardiovascular risk. Findings Among 6,059,055 individuals, 741,913 (12.2%) had established CVD, 1,929,627 (31.8%) had a QRISK3 score ≥10% and 3,387,515 (55.9%) had a QRISK3 score <10%. Marked gradients were seen in the incidence of all severe COVID-19 outcomes by cardiovascular risk profile. Among those with COVID-19 (N = 146,760), there was a strong association between raised QRISK3 score and death: adjusted hazard ratio [aHR] 8.77 (7.62–10.10), N = 97,725, which remained present, though attenuated in age-stratified results. Risks of other outcomes were also higher among those with raised QRISK3 score: aHR 3.66 (3.18–4.21) for ICU admissions, 3.38 (3.22–3.56) for hospitalisations, 5.43 (4.44–6.64) for MACE. When raised cardiovascular risk was redefined by hypertension status, only the association with MACE remained: aHR 1.49 (1.20–1.85), N = 57,264. Interpretation Individuals without pre-existing CVD but with raised cardiovascular risk (by QRISK3 score) were more likely to experience severe COVID-19 outcomes and should be prioritised for prevention and treatment. Addressing cardiovascular risk factors could improve COVID-19 outcomes. Funding 10.13039/501100011950BMA Foundation for Medical Research/10.13039/501100000833Rosetrees Trust, 10.13039/100004440Wellcome, 10.13039/501100000274BHF.

Post-COVID-19 condition and persisting symptoms in English schoolchildren: repeated surveys to March 2022.

BACKGROUND: Both post-COVID-19 condition (long COVID) and the presence of persisting symptoms that do not meet formal definitions of post-COVID-19-condition may adversely affect quality of life and function. However, their prevalence among children and young people in England is unclear. METHODS: We used data from repeated surveys in a large cohort of English schoolchildren from the COVID-19 Schools Infection Survey (SIS) for the school year 2021/22 to describe the weighted prevalence of post-COVID-19-condition and compare persisting symptoms between individuals with a positive SARS-CoV-2 test and those with neither a positive test history nor suspected infection. RESULTS: Among 7797 children from 173 schools, 1.8% of primary school pupils (aged 4 to 11 years), 4.5% of secondary school pupils in years 7-11 (aged 11 to 16 years) and 6.9% of those in years 12-13 (aged 16 to 18 years) met a definition of post-COVID-19 condition in March 2022. Specific persisting symptoms such as anxiety or difficulty concentrating were frequently reported regardless of prior infection status and increased with age: 48.0% of primary school pupils, 52.9% of secondary school pupils in years 7-11 and 79.5% in years 12-13 reporting at least one symptom lasting more than 12 weeks. Persisting loss of smell and taste, cardiovascular and some systemic symptoms were more frequently reported by those with a previous positive test. CONCLUSIONS: We showed that ongoing symptoms were frequently reported by English schoolchildren regardless of SARS-CoV-2 test results and some specific symptoms such as loss of smell and taste were more prevalent in those with a positive test history. Our study emphasises the wide-ranging impacts of the COVID-19 pandemic on the health and wellbeing of children and young people.

Severe COVID-19 outcomes by cardiovascular risk profile in England in 2020: a population-based cohort study.

Background: While cardiovascular disease (CVD) is a risk factor for severe COVID-19, the association between predicted cardiovascular risk and severe COVID-19 among people without diagnosed CVD is unclear. Methods: We carried out historical, population-based cohort studies among adults aged 40-84 years in England using linked data from the Clinical Practice Research Datalink. Individuals were categorized into: existing CVD, raised cardiovascular risk (defined using QRISK3 score ≥10%) and low risk (QRISK3 score <10%) at 12/03/2020. We described incidence and severe outcomes of COVID-19 (deaths, intensive care unit [ICU] admissions, hospitalisations, major adverse cardiovascular events [MACE]) for each group. Among those with a COVID-19 record to 31/12/2020, we re-classified cardiovascular risk at infection and assessed the risk of severe outcomes using multivariable Cox regression with complete case analysis. We repeated analyses using hypertension to define raised cardiovascular risk. Findings: Among 6,059,055 individuals, 741,913 (12.2%) had established CVD, 1,929,627 (31.8%) had a QRISK3 score ≥10% and 3,387,515 (55.9%) had a QRISK3 score <10%. Marked gradients were seen in the incidence of all severe COVID-19 outcomes by cardiovascular risk profile. Among those with COVID-19 (N = 146,760), there was a strong association between raised QRISK3 score and death: adjusted hazard ratio [aHR] 8.77 (7.62-10.10), N = 97,725, which remained present, though attenuated in age-stratified results. Risks of other outcomes were also higher among those with raised QRISK3 score: aHR 3.66 (3.18-4.21) for ICU admissions, 3.38 (3.22-3.56) for hospitalisations, 5.43 (4.44-6.64) for MACE. When raised cardiovascular risk was redefined by hypertension status, only the association with MACE remained: aHR 1.49 (1.20-1.85), N = 57,264. Interpretation: Individuals without pre-existing CVD but with raised cardiovascular risk (by QRISK3 score) were more likely to experience severe COVID-19 outcomes and should be prioritised for prevention and treatment. Addressing cardiovascular risk factors could improve COVID-19 outcomes. Funding: BMA Foundation for Medical Research/Rosetrees Trust, Wellcome, BHF.

Risk factors for SARS-CoV-2 infection in primary and secondary school students and staff in England in the 2020/2021 school year: a longitudinal study.

OBJECTIVES: Investigate risk factors for SARS-CoV-2 infections in school students and staff. METHODS: In the 2020/2021 school year, we administered polymerase chain reaction, antibody tests, and questionnaires to a sample of primary and secondary school students and staff, with data linkage to COVID-19 surveillance. We fitted logistic regression models to identify the factors associated with infection. RESULTS: We included 6799 students and 5090 staff in the autumn and 11,952 students and 4569 staff in the spring/summer terms. Infections in students in autumn 2020 were related to the percentage of students eligible for free school meals. We found no statistical association between infection risk in primary and secondary schools and reported contact patterns between students and staff in either period in our study. Using public transports was associated with increased risk in autumn in students (adjusted odds ratio = 1.72; 95% confidence interval 1.31-2.25) and staff. One or more infections in the same household during either period was the strongest risk factor for infection in students and more so among staff. CONCLUSION: Deprivation, community, and household factors were more strongly associated with infection than contacts patterns at school; this suggests that the additional school-based mitigation measures in England in 2020/2021 likely helped reduce transmission risk in schools.

Epidemiology of SARS-CoV-2 infection among staff and students in a cohort of English primary and secondary schools during 2020-2021.

Background: There remains uncertainty about the epidemiology of SARS-CoV-2 among school students and staff and the extent to which non-pharmaceutical-interventions reduce the risk of school settings. Methods: We conducted an open cohort study in a sample of 59 primary and 97 secondary schools in 15 English local authority areas that were implementing government guidance to schools open during the pandemic. We estimated SARS-CoV-2 infection prevalence among those attending school, antibody prevalence, and antibody negative to positive conversion rates in staff and students over the school year (November 2020-July 2021). Findings: 22,585 staff and students participated. SARS-CoV-2 infection prevalence among those attending school was highest during the first two rounds of testing in the autumn term, ranging from 0.7% (95% CI 0.2, 1.2) among primary staff in November 2020 to 1.6% (95% CI 0.9, 2.3) among secondary staff in December 2020. Antibody conversion rates were highest in the autumn term. Infection patterns were similar between staff and students, and between primary and secondary schools. The prevalence of nucleoprotein antibodies increased over the year and was lower among students than staff. SARS-CoV-2 infection prevalence in the North-West region was lower among secondary students attending school on normal school days than the regional estimate for secondary school-age children. Interpretation: SARS-CoV-2 infection prevalence in staff and students attending school varied with local community infection rates. Non-pharmaceutical interventions intended to prevent infected individuals attending school may have partially reduced the prevalence of infection among those on the school site. Funding: UK Department of Health and Social Care.

The association between vitamin D status and COVID-19 in England: A cohort study using UK Biobank.

BACKGROUND: Recent studies indicate that vitamin D supplementation may decrease respiratory tract infections, but the association between vitamin D and COVID-19 is still unclear. OBJECTIVE: To explore the association between vitamin D status and infections, hospitalisation, and mortality due to COVID-19. METHODS: We used UK Biobank, a nationwide cohort of 500,000 individuals aged between 40 and 69 years at recruitment between 2006 and 2010. We included people with at least one serum vitamin D test, living in England with linked primary care and inpatient records. The primary exposure was serum vitamin D status measured at recruitment, defined as deficiency at <25 nmol/L, insufficiency at 25-49 nmol/L and sufficiency at ≥ 50 nmol/L. Secondary exposures were self-reported or prescribed vitamin D supplements. The primary outcome was laboratory-confirmed or clinically diagnosed SARS-CoV-2 infections. The secondary outcomes included hospitalisation and mortality due to COVID-19. We used multivariable Cox regression models stratified by summertime months and non-summertime months, adjusting for demographic factors and underlying comorbidities. RESULTS: We included 307,512 participants (54.9% female, 55.9% over 70 years old) in our analysis. During summertime months, weak evidence existed that the vitamin D deficiency group had a lower hazard of being diagnosed with COVID-19 (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.77-0.95). During non-summertime, the vitamin D deficiency group had a higher hazard of COVID-19 compared with the vitamin D sufficient group (HR = 1.14, 95% CI = 1.01-1.30). No evidence was found that vitamin D deficiency or insufficiency was associated with either hospitalisation or mortality due to COVID-19 in any time strata. CONCLUSION: We found no evidence of an association between historical vitamin D status and hospitalisation or mortality due to COVID-19, along with inconsistent results for any association between vitamin D and diagnosis of COVID-19. However, studies using more recent vitamin D measurements and systematic COVID-19 testing are needed.

Indirect acute effects of the COVID-19 pandemic on physical and mental health in the UK: a population-based study.

BACKGROUND: There are concerns that the response to the COVID-19 pandemic in the UK might have worsened physical and mental health, and reduced use of health services. However, the scale of the problem is unquantified, impeding development of effective mitigations. We aimed to ascertain what has happened to general practice contacts for acute physical and mental health outcomes during the pandemic. METHODS: Using de-identified electronic health records from the Clinical Research Practice Datalink (CPRD) Aurum (covering 13% of the UK population), between 2017 and 2020, we calculated weekly primary care contacts for selected acute physical and mental health conditions: anxiety, depression, self-harm (fatal and non-fatal), severe mental illness, eating disorder, obsessive-compulsive disorder, acute alcohol-related events, asthma exacerbation, chronic obstructive pulmonary disease exacerbation, acute cardiovascular events (cerebrovascular accident, heart failure, myocardial infarction, transient ischaemic attacks, unstable angina, and venous thromboembolism), and diabetic emergency. Primary care contacts included remote and face-to-face consultations, diagnoses from hospital discharge letters, and secondary care referrals, and conditions were identified through primary care records for diagnoses, symptoms, and prescribing. Our overall study population included individuals aged 11 years or older who had at least 1 year of registration with practices contributing to CPRD Aurum in the specified period, but denominator populations varied depending on the condition being analysed. We used an interrupted time-series analysis to formally quantify changes in conditions after the introduction of population-wide restrictions (defined as March 29, 2020) compared with the period before their introduction (defined as Jan 1, 2017 to March 7, 2020), with data excluded for an adjustment-to-restrictions period (March 8-28). FINDINGS: The overall population included 9 863 903 individuals on Jan 1, 2017, and increased to 10 226 939 by Jan 1, 2020. Primary care contacts for almost all conditions dropped considerably after the introduction of population-wide restrictions. The largest reductions were observed for contacts for diabetic emergencies (odds ratio 0·35 [95% CI 0·25-0·50]), depression (0·53 [0·52-0·53]), and self-harm (0·56 [0·54-0·58]). In the interrupted time-series analysis, with the exception of acute alcohol-related events (0·98 [0·89-1·10]), there was evidence of a reduction in contacts for all conditions (anxiety 0·67 [0·66-0·67], eating disorders 0·62 [0·59-0·66], obsessive-compulsive disorder [0·69 [0·64-0·74]], self-harm 0·56 [0·54-0·58], severe mental illness 0·80 [0·78-0·83], stroke 0·59 [0·56-0·62], transient ischaemic attack 0·63 [0·58-0·67], heart failure 0·62 [0·60-0·64], myocardial infarction 0·72 [0·68-0·77], unstable angina 0·72 [0·60-0·87], venous thromboembolism 0·94 [0·90-0·99], and asthma exacerbation 0·88 [0·86-0·90]). By July, 2020, except for unstable angina and acute alcohol-related events, contacts for all conditions had not recovered to pre-lockdown levels. INTERPRETATION: There were substantial reductions in primary care contacts for acute physical and mental conditions following the introduction of restrictions, with limited recovery by July, 2020. Further research is needed to ascertain whether these reductions reflect changes in disease frequency or missed opportunities for care. Maintaining health-care access should be a key priority in future public health planning, including further restrictions. The conditions we studied are sufficiently severe that any unmet need will have substantial ramifications for the people with the conditions as well as health-care provision. FUNDING: Wellcome Trust Senior Fellowship, Health Data Research UK.

Global, regional, and national estimates of the population at increased risk of severe COVID-19 due to underlying health conditions in 2020: a modelling study.

BACKGROUND: The risk of severe COVID-19 if an individual becomes infected is known to be higher in older individuals and those with underlying health conditions. Understanding the number of individuals at increased risk of severe COVID-19 and how this varies between countries should inform the design of possible strategies to shield or vaccinate those at highest risk. METHODS: We estimated the number of individuals at increased risk of severe disease (defined as those with at least one condition listed as "at increased risk of severe COVID-19" in current guidelines) by age (5-year age groups), sex, and country for 188 countries using prevalence data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 and UN population estimates for 2020. The list of underlying conditions relevant to COVID-19 was determined by mapping the conditions listed in GBD 2017 to those listed in guidelines published by WHO and public health agencies in the UK and the USA. We analysed data from two large multimorbidity studies to determine appropriate adjustment factors for clustering and multimorbidity. To help interpretation of the degree of risk among those at increased risk, we also estimated the number of individuals at high risk (defined as those that would require hospital admission if infected) using age-specific infection-hospitalisation ratios for COVID-19 estimated for mainland China and making adjustments to reflect country-specific differences in the prevalence of underlying conditions and frailty. We assumed males were twice at likely as females to be at high risk. We also calculated the number of individuals without an underlying condition that could be considered at increased risk because of their age, using minimum ages from 50 to 70 years. We generated uncertainty intervals (UIs) for our estimates by running low and high scenarios using the lower and upper 95% confidence limits for country population size, disease prevalences, multimorbidity fractions, and infection-hospitalisation ratios, and plausible low and high estimates for the degree of clustering, informed by multimorbidity studies. FINDINGS: We estimated that 1·7 billion (UI 1·0-2·4) people, comprising 22% (UI 15-28) of the global population, have at least one underlying condition that puts them at increased risk of severe COVID-19 if infected (ranging from <5% of those younger than 20 years to >66% of those aged 70 years or older). We estimated that 349 million (186-787) people (4% [3-9] of the global population) are at high risk of severe COVID-19 and would require hospital admission if infected (ranging from <1% of those younger than 20 years to approximately 20% of those aged 70 years or older). We estimated 6% (3-12) of males to be at high risk compared with 3% (2-7) of females. The share of the population at increased risk was highest in countries with older populations, African countries with high HIV/AIDS prevalence, and small island nations with high diabetes prevalence. Estimates of the number of individuals at increased risk were most sensitive to the prevalence of chronic kidney disease, diabetes, cardiovascular disease, and chronic respiratory disease. INTERPRETATION: About one in five individuals worldwide could be at increased risk of severe COVID-19, should they become infected, due to underlying health conditions, but this risk varies considerably by age. Our estimates are uncertain, and focus on underlying conditions rather than other risk factors such as ethnicity, socioeconomic deprivation, and obesity, but provide a starting point for considering the number of individuals that might need to be shielded or vaccinated as the global pandemic unfolds. FUNDING: UK Department for International Development, Wellcome Trust, Health Data Research UK, Medical Research Council, and National Institute for Health Research.