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).

Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant.

BACKGROUND: The B.1.617.2 (delta) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), has contributed to a surge in cases in India and has now been detected across the globe, including a notable increase in cases in the United Kingdom. The effectiveness of the BNT162b2 and ChAdOx1 nCoV-19 vaccines against this variant has been unclear. METHODS: We used a test-negative case-control design to estimate the effectiveness of vaccination against symptomatic disease caused by the delta variant or the predominant strain (B.1.1.7, or alpha variant) over the period that the delta variant began circulating. Variants were identified with the use of sequencing and on the basis of the spike (S) gene status. Data on all symptomatic sequenced cases of Covid-19 in England were used to estimate the proportion of cases with either variant according to the patients' vaccination status. RESULTS: Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) was notably lower among persons with the delta variant (30.7%; 95% confidence interval [CI], 25.2 to 35.7) than among those with the alpha variant (48.7%; 95% CI, 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among persons with the alpha variant and 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among persons with the alpha variant and 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. CONCLUSIONS: Only modest differences in vaccine effectiveness were noted with the delta variant as compared with the alpha variant after the receipt of two vaccine doses. Absolute differences in vaccine effectiveness were more marked after the receipt of the first dose. This finding would support efforts to maximize vaccine uptake with two doses among vulnerable populations. (Funded by Public Health England.).

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.

A cross-sectional study of the health of emerging young adults in England following a COVID-19 infection

Purpose This study describes long COVID symptomatology in a national sample of 18–20-year-olds with PCR-confirmed SARS-CoV-2 and matched test-negative controls in England. Symptoms in 18-20-year-olds were compared to younger adolescents (aged 11-17 years) and all adults (18+). Methods A national database was used to identify SARS-CoV-2 PCR-positive 18–20-year-olds and test-negative controls matched by time of test, age, gender and geographical region. Participants were invited to complete a questionnaire about their health retrospectively at time of test and also when completing the questionnaire. Comparison cohorts included Children and Young People with Long COVID and Real-time Assessment of Community Transmission studies. Results Of 14,986 people invited, 1,001 were included in the analysis (562 test-positive;440 test-negative). At testing, 46.5% of test-positives and 16.4% of test-negatives reported at least one symptom. At the time of questionnaire completion (median 7 months post-testing), 61.5% of test-positives and 47.5% of test-negatives reported one or more symptoms. The most common symptoms were similar amongst test-positives and test-negatives and included tiredness (44.0%;35.7%), shortness of breath (28.8%;16.3%) and headaches (13.7%;12.0%). Prevalence rates were similar to those reported by 11-17-year-olds (66.5%) and higher than those reported in all adults (37.7%). For 18-20-year-olds, there was no significant difference in health-related quality of life and wellbeing (p>0.05). However, test-positives reported being significantly more tired than test-negatives (p=0.04). Conclusions Seven months after PCR test, a high proportion of test-positive and test-negative 18-20-year-olds reported similar symptoms to each other and to those experienced by younger and older counterparts.

A Cross-Sectional Study of the Health of Emerging Young Adults in England Following a COVID-19 Infection.

PURPOSE: This study describes long COVID symptomatology in a national sample of 18- to 20-year-olds with Polymerase Chain Reaction (PCR)-confirmed Severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) and matched test-negative controls in England. Symptoms in 18- to 20-year-olds were compared to symptoms in younger adolescents (aged 11-17 years) and all adults (18+). METHODS: A national database was used to identify SARS-CoV-2 PCR-positive 18- to 20-year-olds and test-negative controls matched by time of test, age, gender, and geographical region. Participants were invited to complete a questionnaire about their health retrospectively at time of test and also when completing the questionnaire. Comparison cohorts included children and young people with long COVID and REal-time Assessment of Community Transmission studies. RESULTS: Of 14,986 people invited, 1,001 were included in the analysis (562 test-positive; 440 test-negative). At testing, 46.5% of test-positives and 16.4% of test-negatives reported at least one symptom. At the time of questionnaire completion (median 7 months post-testing), 61.5% of test-positives and 47.5% of test-negatives reported one or more symptoms. The most common symptoms were similar amongst test-positives and test-negatives and included tiredness (44.0%; 35.7%), shortness of breath (28.8%; 16.3%), and headaches (13.7%; 12.0%). Prevalence rates were similar to those reported by 11-17-year-olds (66.5%) and higher than those reported in all adults (37.7%). For 18- to 20-year-olds, there was no significant difference in health-related quality of life and well-being (p > .05). However, test-positives reported being significantly more tired than test-negatives (p = .04). DISCUSSION: Seven months after PCR test, a high proportion of test-positive and test-negative 18- to 20-year-olds reported similar symptoms to each other and to those experienced by younger and older counterparts.

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.

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.

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).

Protective effect of a first SARS-CoV-2 infection from reinfection: a matched retrospective cohort study using PCR testing data in England.

The duration of immunity after first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the extent to which prior immunity prevents reinfection is uncertain and remains an important question within the context of new variants. This is a retrospective population-based matched observational study where we identified the first polymerase chain reaction (PCR) positive of primary SARS-CoV-2 infection case tests between 1 March 2020 and 30 September 2020. Each case was matched by age, sex, upper tier local authority of residence and testing route to one individual testing negative in the same week (controls) by PCR. After a 90-day pre-follow-up period for cases and controls, any subsequent positive tests up to 31 December 2020 and deaths within 28 days of testing positive were identified, this encompassed an essentially vaccine-free period. We used a conditional logistic regression to analyse the results. There were 517 870 individuals in the matched cohort with 2815 reinfection cases and 12 098 first infections. The protective effect of a prior SARS-CoV-2 PCR-positive episode was 78% (odds ratio (OR) 0.22, 0.21-0.23). Protection rose to 82% (OR 0.18, 0.17-0.19) after a sensitivity analysis excluded 933 individuals with a first test between March and May and a subsequent positive test between June and September 2020. Amongst individuals testing positive by PCR during follow-up, reinfection cases had 77% lower odds of symptoms at the second episode (adjusted OR 0.23, 0.20-0.26) and 45% lower odds of dying in the 28 days after reinfection (adjusted OR 0.55, 0.42-0.71). Prior SARS-CoV-2 infection offered protection against reinfection in this population. There was some evidence that reinfections increased with the alpha variant compared to the wild-type SARS-CoV-2 variant highlighting the importance of continued monitoring as new variants emerge.

Prevalence of hepatitis B immunity and infection in home self-sampling HIV service users.

OBJECTIVES: Although hepatitis B virus (HBV) vaccination for high-risk groups including gay, bisexual and other men who have sex with men (MSM) is recommended in the UK, data on HBV immunisation coverage are limited. This study aimed to understand the prevalence of HBV infection, susceptibility and immunity due to immunisation among a high-risk population of MSM and heterosexuals who are less likely to attend sexual health services. METHODS: Residual HIV-negative serology samples archived from a national HIV self-sampling service in 2016 were tested for HBV markers using an unlinked anonymous approach. Prevalence of HBV infection, evidence of immunisation and susceptibility were calculated and stratified by individuals' characteristics. Multinomial logistic regression was used to estimate relative risk ratios (RRRs) associated with covariates. RESULTS: Of 2172 samples tested, 1497 (68.9%) were from MSM and 657 (30.2%) were from heterosexuals. Susceptibility to HBV infection was 66.1% among MSM and 77.0% among heterosexuals. Only 29.9% of MSM and 17.4% of heterosexuals had serological evidence of immunisation. Current infection was 1.1% in heterosexuals and 0.2% in MSM. Adjusted analysis showed evidence of immunisation was lower among heterosexuals (RRR 0.66, 95% CI 0.50 to 0.86) and those with no previous HIV test (RRR 0.41, 95% CI 0.31 to 0.54), and higher in those of other white or other ethnicity. CONCLUSIONS: Among MSM and heterosexual users of a self-sampling HIV service, evidence of immunisation to HBV infection was low and susceptibility to infection was comparatively high, suggesting suboptimal delivery of HBV immunisation in sexual health services.

Risk of SARS-CoV-2 reinfections in children: a prospective national surveillance study between January, 2020, and July, 2021, in England.

BACKGROUND: Reinfection after primary SARS-CoV-2 infection is uncommon in adults, but little is known about the risks, characteristics, severity, or outcomes of reinfection in children. We aimed to assess the risk of SARS-CoV-2 reinfection in children and compare this with the risk in adults, by analysis of national testing data for England. METHODS: In our prospective, national surveillance study to assess reinfection of SARS-CoV-2 in children in England, we used national SARS-CoV-2 testing data to estimate the risk of reinfection at least 90 days after primary infection from Jan 27, 2020, to July, 31, 2021, which encompassed the alpha (B.1.1.7) and delta (B.1.617.2) variant waves in England. Data from children up to age 16 years who met the criteria for reinfection were included. Disease severity was assessed by linking reinfection cases to national hospital admission data, intensive care admission, and death registration datasets. FINDINGS: Reinfection rates closely followed community infection rates, with a small peak during the alpha wave and a larger peak during the delta wave. In children aged 16 years and younger, 688 418 primary infections and 2343 reinfections were identified. The overall reinfection rate was 66·88 per 100 000 population, which was higher in adults (72·53 per 100 000) than children (21·53 per 100 000). The reinfection rate after primary infection was 0·68% overall, 0·73% in adults compared with 0·18% in children age younger than 5 years, 0·24% in those aged 5-11 years, and 0·49% in those aged 12-16 years. Of the 109 children admitted to hospital with reinfection, 78 (72%) had comorbidities. Hospital admission rates were similar for the first (64 [2·7%] of 2343) and second episode (57 [2·4%] of 2343) and intensive care admissions were rare (seven children for the first episode and four for reinfections). There were 44 deaths within 28 days after primary infection (0·01%) and none after reinfection. INTERPRETATION: The risk of SARS-CoV-2 reinfection is strongly related to exposure due to community infection rates, especially during the delta variant wave. Children had a lower risk of reinfection than did adults, but reinfections were not associated with more severe disease or fatal outcomes. FUNDING: UK Health Security Agency.

Effects of COVID-19 Pandemic Response on Service Provision for Sexually Transmitted Infections, HIV, and Viral Hepatitis, England.

Since the coronavirus disease pandemic response began in March 2020, tests, vaccinations, diagnoses, and treatment initiations for sexual health, HIV, and viral hepatitis in England have declined. The shift towards online and outreach services happened rapidly during 2020 and highlights the need to evaluate the effects of these strategies on health inequalities.

Disease severity during SARS-COV-2 reinfection: a nationwide study.

OBJECTIVE: We aimed to look at the burden of disease caused by SARS-COV-2 reinfections and identified potential risk factors for disease severity. METHODS: We used national surveillance data to collect information on all SARS-CoV-2 primary infection and suspected reinfection cases between January 2020 until early May 2021. Reinfection cases were positive COVID-19 PCR or antigen test, 90 days after their first COVID-19 positive test. We collected information on case demographics, hospital and ICU admission, immunisation status and if individuals were at risk of complication for COVID-19. RESULTS: Deaths reported within 28 days of testing positive were 61% (95% confidence interval: 56% to 65%) lower in suspected COVID-19 reinfection than primary infection cases. In the unvaccinated cohort, reinfections were associated with 49% (37% to 58%) lower odds of hospital admission in cases aged 50 to 65 years in the population not identified at risk of complication for COVID-19, and 34% (17% to 48%) in those at risk. ICU admission at reinfection compared to primary infection decreased 76% (55% to 87%). Individuals at risk and those aged below 50 years, who received at least 1 dose of vaccine against COVID-19, were 62% (39% to 74%) and 58% (24% to 77%) less likely to get admitted to hospital at reinfection, respectively. CONCLUSION: Prior SARS-CoV-2 infection was associated with lower odds of dying, and both prior infection and immunisation showed a protective effect against severe disease in selected populations. Older age, sex and underlying comorbidities appeared as principal risk factors for illness severity at reinfection. FUNDING: PHE/UKHSA.

Physical and mental health 3 months after SARS-CoV-2 infection (long COVID) among adolescents in England (CLoCk): a national matched cohort study.

BACKGROUND: We describe post-COVID symptomatology in a non-hospitalised, national sample of adolescents aged 11-17 years with PCR-confirmed SARS-CoV-2 infection compared with matched adolescents with negative PCR status. METHODS: In this national cohort study, adolescents aged 11-17 years from the Public Health England database who tested positive for SARS-CoV-2 between January and March, 2021, were matched by month of test, age, sex, and geographical region to adolescents who tested negative. 3 months after testing, a subsample of adolescents were contacted to complete a detailed questionnaire, which collected data on demographics and their physical and mental health at the time of PCR testing (retrospectively) and at the time of completing the questionnaire (prospectively). We compared symptoms between the test-postive and test-negative groups, and used latent class analysis to assess whether and how physical symptoms at baseline and at 3 months clustered among participants. This study is registered with the ISRCTN registry (ISRCTN 34804192). FINDINGS: 23 048 adolescents who tested positive and 27 798 adolescents who tested negative between Jan 1, 2021, and March 31, 2021, were contacted, and 6804 adolescents (3065 who tested positive and 3739 who tested negative) completed the questionnaire (response rate 13·4%). At PCR testing, 1084 (35·4%) who tested positive and 309 (8·3%) who tested negative were symptomatic and 936 (30·5%) from the test-positive group and 231 (6·2%) from the test-negative group had three or more symptoms. 3 months after testing, 2038 (66·5%) who tested positive and 1993 (53·3%) who tested negative had any symptoms, and 928 (30·3%) from the test-positive group and 603 (16·2%) from the test-negative group had three or more symptoms. At 3 months after testing, the most common symptoms among the test-positive group were tiredness (1196 [39·0%]), headache (710 [23·2%]), and shortness of breath (717 [23·4%]), and among the test-negative group were tiredness (911 [24·4%]), headache (530 [14·2%]), and other (unspecified; 590 [15·8%]). Latent class analysis identified two classes, characterised by few or multiple symptoms. The estimated probability of being in the multiple symptom class was 29·6% (95% CI 27·4-31·7) for the test-positive group and 19·3% (17·7-21·0) for the test-negative group (risk ratio 1·53; 95% CI 1·35-1·70). The multiple symptoms class was more frequent among those with positive PCR results than negative results, in girls than boys, in adolescents aged 15-17 years than those aged 11-14 years, and in those with lower pretest physical and mental health. INTERPRETATION: Adolescents who tested positive for SARS-CoV-2 had similar symptoms to those who tested negative, but had a higher prevalence of single and, particularly, multiple symptoms at the time of PCR testing and 3 months later. Clinicians should consider multiple symptoms that affect functioning and recognise different clusters of symptoms. The multiple and varied symptoms show that a multicomponent intervention will be required, and that mental and physical health symptoms occur concurrently, reflecting their close relationship. FUNDING: UK Department of Health and Social Care, in their capacity as the National Institute for Health Research, and UK Research and Innovation.

Real-world data on immune responses following heterologous prime-boost COVID-19 vaccination schedule with Pfizer and AstraZeneca vaccines in England.

BACKGROUND: There are limited data on immune responses to heterologous COVID-19 immunisation schedules, especially following an extended ≥12-week interval between doses. METHODS: SARS-CoV-2 infection-naïve and previously-infected adults receiving ChAd-BNT (ChAdOx1 nCoV-19, AstraZeneca followed by BNT162b2, Pfizer-BioNTech) or BNT-ChAd as part of the UK national immunisation programme provided blood samples at 30 days and 12 weeks after their second dose. Geometric mean concentrations (GMC) of anti-SARS-CoV-2 spike (S-antibody) and nucleoprotein (N-antibody) IgG antibodies and geometric mean ratios (GMR) were compared with a contemporaneous cohort receiving homologous ChAd-ChAd or BNT-BNT. RESULTS: During March-October 2021, 75,827 individuals were identified as having received heterologous vaccination, 9,489 invited to participate, 1,836 responded (19.3%) and 656 were eligible. In previously-uninfected adults, S-antibody GMC at 30 days post-second dose were lowest for ChAd-ChAd (862 [95% CI, 694 - 1069]) and significantly higher for ChAd-BNT (6233 [5522-7035]; GMR 6.29; [5.04-7.85]; p<0.001), BNT-ChAd (4776 [4066-5610]; GMR 4.55 [3.56-5.81]; p<0.001) and BNT-BNT (5377 [4596-6289]; GMR 5.66 [4.49-7.15]; p<0.001). By 12 weeks after dose two, S-antibody GMC had declined in all groups and remained significantly lower for ChAd-ChAd compared to ChAd-BNT (GMR 5.12 [3.79-6.92]; p<0.001), BNT-ChAd (GMR 4.1 [2.96-5.69]; p<0.001) and BNT-BNT (GMR 6.06 [4.32-8.50]; p<0.001). Previously infected adults had higher S-antibody GMC compared to infection-naïve adults at all time-points and with all vaccine schedules. CONCLUSIONS: These real-world findings demonstrate heterologous schedules with adenoviral-vector and mRNA vaccines are highly immunogenic and may be recommended after a serious adverse reaction to one vaccine product, or to increase programmatic flexibility where vaccine supplies are constrained.

Duration of Protection against Mild and Severe Disease by Covid-19 Vaccines.

BACKGROUND: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), have been used since December 2020 in the United Kingdom. Real-world data have shown the vaccines to be highly effective against Covid-19 and related severe disease and death. Vaccine effectiveness may wane over time since the receipt of the second dose of the ChAdOx1-S (ChAdOx1 nCoV-19) and BNT162b2 vaccines. METHODS: We used a test-negative case-control design to estimate vaccine effectiveness against symptomatic Covid-19 and related hospitalization and death in England. Effectiveness of the ChAdOx1-S and BNT162b2 vaccines was assessed according to participant age and status with regard to coexisting conditions and over time since receipt of the second vaccine dose to investigate waning of effectiveness separately for the B.1.1.7 (alpha) and B.1.617.2 (delta) variants. RESULTS: Vaccine effectiveness against symptomatic Covid-19 with the delta variant peaked in the early weeks after receipt of the second dose and then decreased by 20 weeks to 44.3% (95% confidence interval [CI], 43.2 to 45.4) with the ChAdOx1-S vaccine and to 66.3% (95% CI, 65.7 to 66.9) with the BNT162b2 vaccine. Waning of vaccine effectiveness was greater in persons 65 years of age or older than in those 40 to 64 years of age. At 20 weeks or more after vaccination, vaccine effectiveness decreased less against both hospitalization, to 80.0% (95% CI, 76.8 to 82.7) with the ChAdOx1-S vaccine and 91.7% (95% CI, 90.2 to 93.0) with the BNT162b2 vaccine, and death, to 84.8% (95% CI, 76.2 to 90.3) and 91.9% (95% CI, 88.5 to 94.3), respectively. Greater waning in vaccine effectiveness against hospitalization was observed in persons 65 years of age or older in a clinically extremely vulnerable group and in persons 40 to 64 years of age with underlying medical conditions than in healthy adults. CONCLUSIONS: We observed limited waning in vaccine effectiveness against Covid-19-related hospitalization and death at 20 weeks or more after vaccination with two doses of the ChAdOx1-S or BNT162b2 vaccine. Waning was greater in older adults and in those in a clinical risk group.

Long COVID and the mental and physical health of children and young people: national matched cohort study protocol (the CLoCk study).

INTRODUCTION: There is uncertainty surrounding the diagnosis, prevalence, phenotype, duration and treatment of Long COVID. This study aims to (A) describe the clinical phenotype of post-COVID symptomatology in children and young people (CYP) with laboratory-confirmed SARS-CoV-2 infection compared with test-negative controls, (B) produce an operational definition of Long COVID in CYP, and (C) establish its prevalence in CYP. METHODS AND ANALYSIS: A cohort study of SARS-CoV-2-positive CYP aged 11-17 years compared with age, sex and geographically matched SARS-CoV-2 test-negative CYP. CYP aged 11-17 testing positive and negative for SARS-CoV-2 infection will be identified and contacted 3, 6, 12 and 24 months after the test date. Consenting CYP will complete an online questionnaire. We initially planned to recruit 3000 test positives and 3000 test negatives but have since extended our target. Data visualisation techniques will be used to examine trajectories over time for symptoms and variables measured repeatedly, separately by original test status. Summary measures of fatigue and mental health dimensions will be generated using dimension reduction methods such as latent variables/latent class/principal component analysis methods. Cross-tabulation of collected and derived variables against test status and discriminant analysis will help operationalise preliminary definitions of Long COVID. ETHICS AND DISSEMINATION: Research Ethics Committee approval granted. Data will be stored in secure Public Health England servers or University College London's Data Safe Haven. Risks of harm will be minimised by providing information on where to seek support. Results will be published on a preprint server followed by journal publication, with reuse of articles under a CC BY licence. Data will be published with protection against identification when there are small frequencies involved. TRIAL REGISTRATION NUMBER: ISRCTN34804192; Pre-results.

Real-world data shows increased reactogenicity in adults after heterologous compared to homologous prime-boost COVID-19 vaccination, March-June 2021, England.

Adults receiving heterologous COVID-19 immunisation with mRNA (Comirnaty) or adenoviral-vector (Vaxzevria) vaccines had higher reactogenicity rates and sought medical attention more often after two doses than homologous schedules. Reactogenicity was higher among ≤ 50 than > 50 year-olds, women and those with prior symptomatic/confirmed COVID-19. Adults receiving heterologous schedules on clinical advice after severe first-dose reactions had lower reactogenicity after dose 2 following Vaxzevria/Comirnaty (93.4%; 95% confidence interval: 90.5-98.1 vs 48% (41.0-57.7) but not Comirnaty/Vaxzevria (91.7%; (77.5-98.2 vs 75.0% (57.8-87.9).

Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study.

OBJECTIVE: To estimate the real world effectiveness of the Pfizer-BioNTech BNT162b2 and Oxford-AstraZeneca ChAdOx1-S vaccines against confirmed covid-19 symptoms (including the UK variant of concern B.1.1.7), admissions to hospital, and deaths. DESIGN: Test negative case-control study. SETTING: Community testing for covid-19 in England. PARTICIPANTS: 156 930 adults aged 70 years and older who reported symptoms of covid-19 between 8 December 2020 and 19 February 2021 and were successfully linked to vaccination data in the National Immunisation Management System. INTERVENTIONS: Vaccination with BNT162b2 or ChAdOx1-S. MAIN OUTCOME MEASURES: Primary outcomes were polymerase chain reaction confirmed symptomatic SARS-CoV-2 infections, admissions to hospital for covid-19, and deaths with covid-19. RESULTS: Participants aged 80 years and older vaccinated with BNT162b2 before 4 January 2021 had a higher odds of testing positive for covid-19 in the first nine days after vaccination (odds ratio up to 1.48, 95% confidence interval 1.23 to 1.77), indicating that those initially targeted had a higher underlying risk of infection. Vaccine effectiveness was therefore compared with the baseline post-vaccination period. Vaccine effects were noted 10 to 13 days after vaccination, reaching a vaccine effectiveness of 70% (95% confidence interval 59% to 78%), then plateauing. From 14 days after the second dose a vaccination effectiveness of 89% (85% to 93%) was found compared with the increased baseline risk. Participants aged 70 years and older vaccinated from 4 January (when ChAdOx1-S delivery commenced) had a similar underlying risk of covid-19 to unvaccinated individuals. With BNT162b2, vaccine effectiveness reached 61% (51% to 69%) from 28 to 34 days after vaccination, then plateaued. With ChAdOx1-S, effects were seen from 14 to 20 days after vaccination, reaching an effectiveness of 60% (41% to 73%) from 28 to 34 days, increasing to 73% (27% to 90%) from day 35 onwards. On top of the protection against symptomatic disease, a further 43% (33% to 52%) reduced risk of emergency hospital admission and 51% (37% to 62%) reduced risk of death was observed in those who had received one dose of BNT162b2. Participants who had received one dose of ChAdOx1-S had a further 37% (3% to 59%) reduced risk of emergency hospital admission. Follow-up was insufficient to assess the effect of ChAdOx1-S on mortality. Combined with the effect against symptomatic disease, a single dose of either vaccine was about 80% effective at preventing admission to hospital with covid-19 and a single dose of BNT162b2 was 85% effective at preventing death with covid-19. CONCLUSION: Vaccination with either one dose of BNT162b2 or ChAdOx1-S was associated with a significant reduction in symptomatic covid-19 in older adults, and with further protection against severe disease. Both vaccines showed similar effects. Protection was maintained for the duration of follow-up (>6 weeks). A second dose of BNT162b2 was associated with further protection against symptomatic disease. A clear effect of the vaccines against the B.1.1.7 variant was found.

The impact of social and physical distancing measures on COVID-19 activity in England: findings from a multi-tiered surveillance system.

BackgroundA multi-tiered surveillance system based on influenza surveillance was adopted in the United Kingdom in the early stages of the coronavirus disease (COVID-19) epidemic to monitor different stages of the disease. Mandatory social and physical distancing measures (SPDM) were introduced on 23 March 2020 to attempt to limit transmission.AimTo describe the impact of SPDM on COVID-19 activity as detected through the different surveillance systems.MethodsData from national population surveys, web-based indicators, syndromic surveillance, sentinel swabbing, respiratory outbreaks, secondary care admissions and mortality indicators from the start of the epidemic to week 18 2020 were used to identify the timing of peaks in surveillance indicators relative to the introduction of SPDM. This timing was compared with median time from symptom onset to different stages of illness and levels of care or interactions with healthcare services.ResultsThe impact of SPDM was detected within 1 week through population surveys, web search indicators and sentinel swabbing reported by onset date. There were detectable impacts on syndromic surveillance indicators for difficulty breathing, influenza-like illness and COVID-19 coding at 2, 7 and 12 days respectively, hospitalisations and critical care admissions (both 12 days), laboratory positivity (14 days), deaths (17 days) and nursing home outbreaks (4 weeks).ConclusionThe impact of SPDM on COVID-19 activity was detectable within 1 week through community surveillance indicators, highlighting their importance in early detection of changes in activity. Community swabbing surveillance may be increasingly important as a specific indicator, should circulation of seasonal respiratory viruses increase.