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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Summary Drug reaction with eosinophilia and systemic symptoms (DRESS) describes a severe medication-induced adverse reaction, which has cutaneous, haematological and solid-organ features. It is one of the triad of life-threatening drug hypersensitivity dermatoses, along with acute generalized exanthematous pustulosis (AGEP) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). In this article, we discuss several controversies that surround DRESS, including problems with nomenclature and the lack of consensus in diagnostic criteria.

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Our series is the first in which a detailed dermatological assessment has been made of consecutive patients presenting with DRESS, and the largest U.K. series to date. Our results suggest a possible prognostic role of the cutaneous and dermatopathic findings in DRESS in predicting the severity of visceral involvement in this syndrome. What's already known about this topic? • Drug reaction with eosinophilia and systemic symptoms (DRESS) has a heterogeneous clinical presentation, with a skin eruption of variable morphology. • DRESS carries considerable morbidity and mortality, usually hepatic in origin, although renal, pulmonary and pericardial involvement can be seen. What does this study add? •   The cutaneous phenotype in DRESS can be categorized as an urticated papular exanthem, a morbilliform erythema, exfoliative erythroderma or erythema multiforme-like (EM-like). •   An EM-like eruption DRESS may be prognostic of more severe hepatic involvement.