Multiplex MinION sequencing suggests enteric adenovirus F41 genetic diversity comparable to pre-COVID-19 era.

Human adenovirus F41 causes acute gastroenteritis in children, and has recently been associated with an apparent increase in paediatric hepatitis of unknown aetiology in the UK, with further cases reported in multiple countries. Relatively little is known about the genetic diversity of adenovirus F41 in UK children; and it is unclear what, if any, impact the COVID-19 pandemic has had on viral diversity in the UK. Methods that allow F41 to be sequenced from clinical samples without the need for viral culture are required to provide the genomic data to address these questions. Therefore, we evaluated an overlapping-amplicon method of sequencing adenovirus genomes from clinical samples using Oxford Nanopore technology. We applied this method to a small sample of adenovirus-species-F-positive extracts collected as part of standard care in the East of England region in January-May 2022. This method produced genomes with >75 % coverage in 13/22 samples and >50 % coverage in 19/22 samples. We identified two F41 lineages present in paediatric patients in the East of England in 2022. Where F41 genomes from paediatric hepatitis cases were available (n=2), these genomes fell within the diversity of F41 from the UK and continental Europe sequenced before and after the 2020-2021 phase of the COVID-19 pandemic. Our analyses suggest that overlapping amplicon sequencing is an appropriate method for generating F41 genomic data from high-virus-load clinical samples, and currently circulating F41 viral lineages were present in the UK and Europe before the COVID-19 pandemic.

2008 financial crisis versus 2020 economic fallout: how COVID-19 might influence fertility treatment and live births.

RESEARCH QUESTION: The economic and reproductive medicine response to the coronavirus disease 2019 (COVID-19) pandemic in the USA has reduced the affordability and accessibility of fertility care. What is the impact of the 2008 financial recession and the COVID-19 recession on fertility treatments and cumulative live births? DESIGN: The study examined annual US natality, Centers for Disease Control and Prevention IVF cycle activity and live birth data from 1999 to 2018 encompassing 3,286,349 treatment cycles, to estimate the age-stratified reduction in IVF cycles undertaken after the 2008 financial recession, with forward quantitative modelling of IVF cycle activity and cumulative live births for 2020 to 2023. RESULTS: The financial recession of 2008 caused a 4-year plateau in fertility treatments with a predicted 53,026 (95% confidence interval [CI] 49,581 to 56,471) fewer IVF cycles and 16,872 (95% CI 16,713 to 17,031) fewer live births. A similar scale of economic recession would cause 67,386 (95% CI 61,686 to 73,086) fewer IVF cycles between 2020 and 2023, with women younger than 35 years overall undertaking 22,504 (95% CI 14,320 to 30,690) fewer cycles, compared with 4445 (95% CI 3144 to 5749) fewer cycles in women over the age of 40 years. This equates to overall 25,143 (95% CI 22,408 to 27,877) fewer predicted live births from IVF, of which only 490 (95% CI 381 to 601) are anticipated to occur in women over the age of 40 years. CONCLUSIONS: The COVID-19 recession could have a profound impact on US IVF live birth rates in young women, further aggravating pre-existing declines in total fertility rates.

Population implications of cessation of IVF during the COVID-19 pandemic.

RESEARCH QUESTION: Discontinuation of IVF cycles has been part of the radical transformation of healthcare provision to enable reallocation of staff and resources to deal with the COVID-19 pandemic. This study sought to estimate the impact of cessation of treatment on individual prognosis and US population live birth rates. DESIGN: Data from 271,438 ovarian stimulation UK IVF cycles was used to model the effect of age as a continuous, yet non-linear, function on cumulative live birth rate. This model was recalibrated to cumulative live birth rates reported for the 135,673 stimulation cycles undertaken in the USA in 2016, with live birth follow-up to October 2018. The effect of a 1-month, 3-month and 6-month shutdown in IVF treatment was calculated as the effect of the equivalent increase in a woman's age, stratified by age group. RESULTS: The average reduction in cumulative live birth rate would be 0.3% (95% confidence interval [CI] 0.3-0.3), 0.8% (95% CI 0.8-0.8) and 1.6% (95% CI 1.6-1.6) for 1-month, 3-month and 6-month shutdowns. This corresponds to a reduction of 369 (95% CI 360-378), 1098 (95% CI 1071-1123) and 2166 (95% CI 2116-2216) live births in the cohort, respectively. Th e greatest contribution to this reduction was from older mothers. CONCLUSIONS: The study demonstrated that the discontinuation of fertility treatment for even 1 month in the USA could result in 369 fewer women having a live birth, due to the increase in patients' age during the shutdown. As a result of reductions in cumulative live birth rate, more cycles may be required to overcome infertility at individual and population levels.