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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This is a PDF file of a peer-reviewed paper that has been accepted for publication. Although unedited, the content has been subjected to preliminary formatting. Nature is providing this early version of the typeset paper as a service to our authors and readers. The text and figures will undergo copyediting and a proof review before the paper is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.
Abstract. A coupled regional-to-local modelling system comprising a regional chemistry-climate model with 5 km horizontal resolution (EMEP4UK) and an urban dispersion and chemistry model with explicit road source emissions (ADMS-Urban) has been used to simulate air quality in 2012 across London. The study makes use of emission factors for NO x and NO 2 and non-exhaust emission rates of PM 10 and PM 2.5 which have been adjusted compared to standard factors to reflect real-world emissions, with increases in total emissions of around 30 % for these species. The performance of the coupled model and each of the two component models is assessed against measurements from background and near-road sites in London using a range of metrics concerning annual averages, high hourly average concentrations and diurnal cycles. The regional model shows good performance compared to measurements for background sites for these metrics, but under-predicts concentrations of all pollutants except O 3 at near-road sites due to the low resolution of input emissions and calculations. The coupled model shows good performance at both background and near-road sites, which is broadly comparable with that of the urban model that uses measured concentrations as regional background, except for PM 2.5 where the under-prediction of the regional model causes the coupled model to also under-predict concentrations. Using the coupled model, it is estimated that 13 % of the area of London exceeded the EU limit value of 40 µg m −3 for annual average NO 2 in 2012, whilst areas of exceedances of the annual average limit values of 40 and 25 µg m −3 for PM 10 and PM 2.5 respectively were negligible.
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