Risk of severe outcomes among Omicron sub-lineages BA.4.6, BA.2.75, and BQ.1 compared to BA.5 in England.

Since the emergence of Omicron variant of SARS-CoV-2 in late 2021, a number of sub-lineages have arisen and circulated internationally. Little is known about the relative severity of Omicron sub-lineages BA.2.75, BA.4.6, and BQ.1. We undertook a case-control analysis to determine the clinical severity of these lineages relative to BA.5, using whole genome sequenced, PCR-confirmed infections, between 1 August 2022 and 27 November 2022, among those who presented to emergency care in England 14 days after and up to one day prior to the positive specimen. A total of 10,375 episodes were included in the analysis; of which, 5,207 (50.2%) were admitted to the hospital or died. Multivariable conditional regression analyses found no evidence of greater odds of hospital admission or death among those with BA.2.75 (odds ratio (OR) = 0.96, 95% confidence interval (CI): 0.84-1.09) and BA.4.6 (OR = 1.02, 95% CI: 0.88- 1.17) or BQ.1 (OR = 1.03, 95% CI: 0.94-1.13) compared to BA.5. Future lineages may not follow the same trend and there remains a need for continued surveillance of COVID-19 variants and their clinical outcomes to inform the public health response.

COVID-19 deaths in children and young people in England, March 2020 to December 2021: An active prospective national surveillance study.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) deaths are rare in children and young people (CYP). The high rates of asymptomatic and mild infections complicate assessment of cause of death in CYP. We assessed the cause of death in all CYP with a positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) test since the start of the pandemic in England. METHODS AND FINDINGS: CYP aged <20 years who died within 100 days of laboratory-confirmed SARS-CoV-2 infection between 01 March 2020 and 31 December 2021 in England were followed up in detail, using national databases, surveillance questionnaires, post-mortem reports, and clinician interviews. There were 185 deaths during the 22-month follow-up and 81 (43.8%) were due to COVID-19. Compared to non-COVID-19 deaths in CYP with a positive SARS-CoV-2 test, death due to COVID-19 was independently associated with older age (aOR 1.06 95% confidence interval (CI) 1.01 to 1.11, p = 0.02) and underlying comorbidities (aOR 2.52 95% CI 1.27 to 5.01, p = 0.008), after adjusting for age, sex, ethnicity group, and underlying conditions, with a shorter interval between SARS-CoV-2 testing and death. Half the COVID-19 deaths (41/81, 50.6%) occurred within 7 days of confirmation of SARS-CoV-2 infection and 91% (74/81) within 30 days. Of the COVID-19 deaths, 61 (75.3%) had an underlying condition, especially severe neurodisability (n = 27) and immunocompromising conditions (n = 12). Over the 22-month surveillance period, SARS-CoV-2 was responsible for 1.2% (81/6,790) of all deaths in CYP aged <20 years, with an infection fatality rate of 0.70/100,000 SARS-CoV-2 infections in this age group estimated through real-time, nowcasting modelling, and a mortality rate of 0.61/100,000. Limitations include possible under-ascertainment of deaths in CYP who were not tested for SARS-CoV-2 and lack of direct access to clinical data for hospitalised CYP. CONCLUSIONS: COVID-19 deaths remain extremely rare in CYP, with most fatalities occurring within 30 days of infection and in children with specific underlying conditions.

Concussion and long-term cognitive function among rugby players-The BRAIN Study.

OBJECTIVE: The BRAIN Study was established to assess the associations between self-reported concussions and cognitive function among retired rugby players. METHODS: Former elite-level male rugby union players (50+ years) in England were recruited. Exposure to rugby-related concussion was collected using the BRAIN-Q tool. The primary outcome measure was the Preclinical Alzheimer Cognitive Composite (PACC). Linear regressions were conducted for the association between concussion and PACC score, adjusting for confounders. RESULTS: A total of 146 participants were recruited. The mean (standard deviation) length of playing career was 15.8 (5.4) years. A total of 79.5% reported rugby-related concussion(s). No association was found between concussion and PACC (ß -0.03 [95% confidence interval (CI): -1.31, 0.26]). However, participants aged 80+ years reporting 3+ concussions had worse cognitive function than those without concussion (ß -1.04 [95% CI: -1.62, -0.47]). CONCLUSIONS: Overall there was no association between concussion and cognitive function; however, a significant interaction with age revealed an association in older participants.

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.

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.

Feasibility study of assessing the Preclinical Alzheimer Cognitive Composite (PACC) score via videoconferencing.

BACKGROUND: The Preclinical Alzheimer Cognitive Composite (PACC) is a composite score which can detect the first signs of cognitive impairment, which can be of importance for research and clinical practice. It is designed to be administered in person; however, in-person assessments are costly, and are difficult during the current COVID-19 pandemic. OBJECTIVE: To assess the feasibility of performing the PACC assessment with videoconferencing, and to compare the validity of this remote PACC with the in-person PACC obtained previously. METHODS: Participants from the HEalth and Ageing Data IN the Game of football (HEADING) Study who had already undergone an in-person assessment were re-contacted and re-assessed remotely. The correlation between the two PACC scores was estimated. The difference between the two PACC scores was calculated and used in multiple linear regression to assess which variables were associated with a difference in PACC scores. FINDINGS: Of the 43 participants who were invited to this external study, 28 were re-assessed. The median duration in days between the in-person and the remote assessments was 236.5 days (7.9 months) (IQR 62.5). There was a strong positive correlation between the two assessments for the PACC score, with a Pearson correlation coefficient of 0·82 (95% CI 0·66, 0·98). The multiple linear regression found that the only predictor of the PACC difference was the time between assessments. INTERPRETATION: This study provides evidence on the feasibility of performing cognitive tests online, with the PACC tests being successfully administered through videoconferencing. This is relevant, especially during times when face-to-face assessments cannot be performed.

The BRAIN-Q, a tool for assessing self-reported sport-related concussions for epidemiological studies.

OBJECTIVES: The BRAIN-Q is a tool aimed at maximising the accuracy and minimising measurement error for retrospectively assessing concussions. This paper reports the agreement of the BRAIN-Q tool when compared to extant questionnaire questions, and its reproducibility when compared with its telephonic version (tBRAIN-Q). METHODS: The BRAIN-Q entails a 3-stage process: defining a concussion, creating a visual timeline with life events, and establishing detailed characteristics for each reported concussion. It was designed to be administered in-person by trained personnel, and was used in the BRAIN study. Its performance was compared with the MSK study, which previously collected a few questions in a broader self-administered questionnaire, and with the tBRAIN-Q Recall, its telephonic version. RESULTS: In total, 101 participants were included, of whom 9 were re-assessed with the tBRAIN-Q. The agreement of the BRAIN-Q with the muscle skeletal-questionnaire for rugby-related concussion was 86.7% (κ=0.6). Rugby-related concussion with loss of consciousness showed lower agreement (82.0%; κ=0.6). The comparison between the BRAIN-Q and the tBRAIN-Q showed good reproducibility. CONCLUSIONS: The BRAIN-Q is a relatively easy tool to administer in face-to-face assessments, and it showed optimal reproducibility. It includes a well-established definition of concussion, and is used to collect detailed information on each concussion, allowing for a number of subgroup analyses (e.g., by severity, age, or context). The BRAIN-Q is easily adaptable to other sporting settings.