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.

Understanding drivers of population change is critical for effective species conservation. In the northeast Atlantic Ocean, recent changes amongst seabird communities are linked to human and climate change impacts on food webs. Many species have declined severely, with food shortages, and increased predation reducing productivity. Arctic skua Stercorarius parasiticus, a kleptoparasite of other seabirds, is one such species. The aim of the study was to determine relative effects of bottom-up and top-down pressures on Arctic skuas across multiple colonies in a rapidly declining national population. Long-term monitoring data were used to quantify changes in population size and productivity of Arctic skuas, their hosts (black-legged kittiwake Rissa tridactyla, common guillemot Uria aalge, Atlantic puffin Fratercula arctica, Arctic tern Sterna paradisaea) and an apex predator (great skua Stercorarius skua) over 24 years (1992-2015) in Scotland. We used digital mapping and statistical models to determine relative effects of bottom-up (host productivity) and top-down (great skua density) pressures on Arctic skuas across 33 colonies, and assess variation between three colony types classified by host abundance. Arctic skuas declined by 81% and their hosts by 42%-92%, whereas at most colonies great skuas increased. Annual productivity declined in Arctic skuas and their hosts, and reduced Arctic skua breeding success was a driver of the species' population decline. Arctic skua productivity was positively associated with annual breeding success of hosts and negatively with great skua density. Intercolony variation suggested Arctic skua trends and productivity were most sensitive to top-down pressures at smaller colonies of host species where great skuas had increased most, whereas bottom-up pressures dominated at large colonies of host species. Scotland's Arctic skua population is declining rapidly, with bottom-up and top-down pressures simultaneously reducing breeding success to unsustainably low levels. Marine food web alterations, strongly influenced by fisheries management and climate change, are driving the decline, and this study demonstrates severe vulnerability of seabirds to rapid change in human-modified ecosystems. Potential but untested conservation solutions for Arctic skuas include marine protected areas, supplementary feeding within colonies and management of great skuas.