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.

Bovine viral diarrhoea virus (BVDV) is an economically significant disease affecting the Australian cattle industry, with losses stemming from decreased production and reproductive performance and control costs. However, these losses can be difficult to appreciate, particularly in endemic regions. Overall, there is a variable but high herd‐level seroprevalence in Australia. Despite a potentially high financial burden of the disease, the onus for control ultimately falls on producers and strategies employed will vary between regions. A cross‐sectional study, using a postal survey, was conducted in 2013 to evaluate the BVDV knowledge, attitudes and management practices utilised by Australian cattle producers. A total of 192 producers participated in the study, and results indicate that knowledge and attitudes towards disease risk are variable and can be improved. Producer knowledge of how persistently infected (PI) animals are produced was higher than that of disease outcomes or transmission pathways. Implementation of biosecurity practices was limited, with approximately half of respondents employing quarantine procedures for introduced stock and only 2% indicating they would antigen test introduced stock for BVDV. Approximately a third (36%) of producers reported engaging in BVDV control, with the majority of these using vaccination strategies over deliberate exposure to a PI. Knowledge of and engagement with BVDV control was positively influenced by the producer relationships with veterinarians. Findings from this study suggest that building on education and delivering a consistent message among stakeholders would likely improve producer awareness and understanding in relation to BVDV and support decision making in BVDV management.

Routine Bovine Viral Diarrhoea Virus (BVDV) monitoring of a commercial beef herd in southern New South Wales over a 10-year period provided an opportunity to assess the impact of the introduction of BVDV on that herd. BVDV antibody testing provided strong evidence that the herd was initially free of BVDV (2009-2011). Testing from 2012 suggested BVDV had been introduced into the herd and this was confirmed in 2015 with the identification of persistently infected (PI) animals. Having become established in the herd, the owners then set out to eliminate BVDV from the herd. Antigen testing aimed at identifying PI animals revealed BVDV was already absent from the herd. Subsequent antibody testing confirmed that the herd was now free from BVDV. Despite the incursion of BVDV in this herd, there was little measurable impact on reproductive performance (pregnancy rates), although suspected increased calf losses from birth to calf marking were reported. This is the first time such self-clearance has been documented as part of a longitudinal study under Australian conditions.