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.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-g and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A*01:01-restricted CD8+ ORF3a epitope FTSDYYQLY 207-215 ; due to P13L, P13S, and P13T in the B*27:05-restricted CD8+ nucleocapsid epitope QRNAP-RITF 9-17 ; and due to T362I and P365S in the A*03:01/A*11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK 361-369 . CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.

Background Community pharmacy Common Ailments Services can ease the considerable workload pressures on primary and secondary care services. However, evidence is needed to determine whether there are benefits of extending such services beyond their typically limited scope. This study therefore aimed to evaluate a new community pharmacy model of a service for patients with ear, nose and throat (ENT) and eye conditions who would otherwise have had to seek primary care appointments or emergency care. Methods People with specified ENT or eye conditions registered with General Practitioners in Staffordshire or Shropshire who presented at participating community pharmacies were offered a consultation with a pharmacist trained to provide the service. The service included provision of relevant self-care advice and, where clinically appropriate, supply of non-prescription medicines or specified prescription-only medicines (POMs), including antibiotics, under Patient Group Directions. Patients received a follow up telephone call from the pharmacist five days later. Data were collected on the characteristics of patients accessing the service, the proportion of those who were treated by the pharmacist without subsequently seeing another health professional about the same condition, and patient reported satisfaction from a questionnaire survey. Results A total of 408 patients accessed the service, of whom 61% received a POM, 15% received advice and medicine supplied under the common ailments service, 9% received advice and purchased a medicine, 10% received advice only and 5% were referred onwards. Sore throat accounted for 45% of diagnoses where a POM was supplied, 32% were diagnosed with acute otitis media and 15% were diagnosed with acute bacterial conjunctivitis. The number of patients successfully followed up was 309 (76%), of whom 264 (85%) had not seen another health professional for the same symptoms, whilst 45 (15%) had seen another health professional, usually their GP. The questionnaire was completed by 259 patients (response rate 63%) of whom 96% reported being very satisfied or satisfied with the service. Conclusions The study demonstrates that pharmacists can effectively diagnose and treat these conditions, with a high degree of patient satisfaction. Wider adoption of such service models could substantially benefit primary care and emergency care services.