Summary SARS-CoV-2 Spike protein is critical for virus infection via engagement of ACE2 1 , and is a major antibody target. Here we report chronic SARS-CoV-2 with reduced sensitivity to neutralising antibodies in an immune suppressed individual treated with convalescent plasma, generating whole genome ultradeep sequences over 23 time points spanning 101 days. Little change was observed in the overall viral population structure following two courses of remdesivir over the first 57 days. However, following convalescent plasma therapy we observed large, dynamic virus population shifts, with the emergence of a dominant viral strain bearing D796H in S2 and ΔH69/ΔV70 in the S1 N-terminal domain NTD of the Spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype diminished in frequency, before returning during a final, unsuccessful course of convalescent plasma. In vitro , the Spike escape double mutant bearing ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, whilst maintaining infectivity similar to wild type. D796H appeared to be the main contributor to decreased susceptibility but incurred an infectivity defect. The ΔH69/ΔV70 single mutant had two-fold higher infectivity compared to wild type, possibly compensating for the reduced infectivity of D796H. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy associated with emergence of viral variants with evidence of reduced susceptibility to neutralising antibodies.

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Background Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, which are typically transmitted via respiratory droplets, are leading causes of invasive diseases, including bacteraemic pneumonia and meningitis, and of secondary infections subsequent to post-viral respiratory disease. The aim of this study was to investigate the incidence of invasive disease due to these pathogens during the early months of the COVID-19 pandemic. MethodsIn this prospective analysis of surveillance data, laboratories in 26 countries and territories across six continents submitted data on cases of invasive disease due to S pneumoniae, H influenzae, and N meningitidis from Jan 1, 2018, to May, 31, 2020, as part of the Invasive Respiratory Infection Surveillance (IRIS) Initiative. Numbers of weekly cases in 2020 were compared with corresponding data for 2018 and 2019. Data for invasive disease due to Streptococcus agalactiae, a non-respiratory pathogen, were collected from nine laboratories for comparison. The stringency of COVID-19 containment measures was quantified using the Oxford COVID-19 Government Response Tracker. Changes in population movements were assessed using Google COVID-19 Community Mobility Reports. Interrupted time-series modelling quantified changes in the incidence of invasive disease due to S pneumoniae, H influenzae, and N meningitidis in 2020 relative to when containment measures were imposed. Findings 27 laboratories from 26 countries and territories submitted data to the IRIS Initiative for S pneumoniae (62 434 total cases), 24 laboratories from 24 countries submitted data for H influenzae (7796 total cases), and 21 laboratories from 21 countries submitted data for N meningitidis (5877 total cases). All countries and territories had experienced a significant and sustained reduction in invasive diseases due to S pneumoniae, H influenzae, and N meningitidis in early 2020 (Jan 1 to May 31, 2020), coinciding with the introduction of COVID-19 containment measures in each country. By contrast, no significant changes in the incidence of invasive S agalactiae infections were observed. Similar trends were observed across most countries and territories despite differing stringency in COVID-19 control policies. The incidence of reported S pneumoniae infections decreased by 68% at 4 weeks (incidence rate ratio 0•32 [95% CI 0•27-0•37]) and 82% at 8 weeks (0•18 [0•14-0•23]) following the week in which significant changes in population movements were recorded. Interpretation The introduction of COVID-19 containment policies and public information campaigns likely reduced transmission of S pneumoniae, H influenzae, and N meningitidis, leading to a significant reduction in life-threatening invasive diseases in many countries worldwide.

The COVID-19 pandemic has highlighted existing health inequalities for ethnic minority groups and those living in more socioeconomically deprived areas in the UK. With higher levels of severe outcomes in these groups, equitable vaccination coverage should be prioritised. The aim of this study was to identify inequalities in coverage of COVID-19 vaccination in Wales, UK and to highlight areas which may benefit from routine enhanced surveillance and targeted interventions. Records within the Wales Immunisation System (WIS) population register were linked to the Welsh Demographic Service Dataset (WDSD) and central list of shielding patients, held within the Secure Anonymised Information Linkage (SAIL) Databank. Ethnic group was derived from the 2011 census and over 20 administrative electronic health record (EHR) data sources. Uptake of first dose of any COVID-19 vaccine was analysed over time, with the odds of being vaccinated as at 25 th April 2021 by sex, health board of residence, rural/urban classification, deprivation quintile and ethnic group presented. Using logistic regression models, analyses were adjusted for age group, care home resident status, health and social care worker status and shielding status. This study included 1,256,412 individuals aged 50 years and over. Vaccine coverage increased steadily from 8 th December 2020 until mid-April 2021. Overall uptake of first dose of COVID-19 vaccine in this group was 92.1%. After adjustment the odds of being vaccinated were lower for individuals who were male, resident in the most deprived areas, resident in an urban area and an ethnic group other than White. The largest inequality was seen between ethnic groups, with the odds of being vaccinated 0.22 (95%CI 0.21-0.24) if in any Black ethnic group compared to any White ethnic group. Ongoing monitoring of inequity in uptake of vaccinations is required, with better targeted interventions and engagement with deprived and ethnic communities to improve vaccination uptake.