Neutralising antibodies in Spike mediated SARS-CoV-2 adaptation.

SARS-CoV-2 Spike protein is critical for virus infection via engagement of ACE2, and amino acid variation in Spike is increasingly appreciated. Given both vaccines and therapeutics are designed around Wuhan-1 Spike, this raises the theoretical possibility of virus escape, particularly in immunocompromised individuals where prolonged viral replication occurs. 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 by both short and long read technologies over 23 time points spanning 101 days. Although little change was observed in the overall viral population structure following two courses of remdesivir over the first 57 days, N501Y in Spike was transiently detected at day 55 and V157L in RdRp emerged. However, following convalescent plasma 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 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 and appeared to compensate for the reduced infectivity of D796H. Consistent with the observed mutations being outside the RBD, monoclonal antibodies targeting the RBD were not impacted by either or both mutations, but a non RBD binding monoclonal antibody was less potent against ΔH69/ΔV70 and the double mutant. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy associated with emergence of viral variants with reduced susceptibility to neutralising antibodies.

Syphilitic cervical lymphadenopathy: return of an old foe.

We present the case of a 38-year-old man who presented to the ENT clinic with cervical lymphadenopathy, oral ulceration, and generalized rash. He was diagnosed with syphilis after serologic testing. After years of decline, the incidence of syphilis is now increasing. It is unusual for patients to present to the otolaryngologist, but the recent marked increase in the incidence of syphilis in the UK is likely to translate into a greater incidence of pathology in the head and neck region. Knowledge of the condition, along with its head and neck manifestations, remains central to the diagnosis of this treatable infection. This article provides a summary of syphilis in the head and neck, for the latest generation of otorhinolaryngologist.

Topical imiquimod cream 5% for resistant perianal warts in a renal transplant patient.

Renal transplant recipients represent a patient subgroup for whom the effective treatment of genital warts poses a significant problem in genitourinary medicine. This case demonstrates the safe and effective treatment of resistant perianal warts in a male renal transplant recipient using imiquimod.

Topical imiquimod cream 5% for resistant perianal warts in a renal transplant patient.

Renal transplant recipients represent a patient subgroup for whom the effective treatment of genital warts poses a significant problem in genitourinary medicine. This case demonstrates the safe and effective treatment of resistant perianal warts in a male renal transplant recipient using imiquimod.

Influence of age, sex and body weight on the dapsone acetylation phenotype.

The acetylation of dapsone (DDS) was determined by estimation of the ratio of monoacetyldapsone (MADDS) to DDS concentrations in plasma following a single dose of DDS in 337 white British subjects (193 female; 144 male). The percentage of slow DDS acetylators in the whole group was 60.3%. There was no statistically significant difference in this proportion between 191 elderly subjects (age greater than 65 years) and 143 young subjects (age less than 30 years). Although there was a small (66.3%) but significant (P = 0.033) preponderance of slow acetylators in the young male group there was no difference in the distribution of acetylator phenotypes between the sexes among either the elderly group or in the whole population studied. No correlation was found between absolute body weight and MADDS/DDS ratios.

Geomapping of chlamydia and gonorrhoea in Birmingham.

OBJECTIVE: To investigate if the core population hypothesis is applicable to patients with genital chlamydia infections. DESIGN: Retrospective cross sectional study. SETTING: Two genitourinary medicine (GUM) clinics in the city of Birmingham and eight adjacent clinics. SUBJECTS: All patients with chlamydia (n = 665) or gonorrhoea (n = 584) attending between 1 October 1995 and 30 September 1996 with a postcode within the Birmingham health district. Controls were 727 patients seen in the same period with no infection. METHODS: Postcodes were used to calculate population prevalence rates per 100,000 aged 15-65 in the 39 wards of the city and to estimate the socioeconomic status using the Super Profile (SP). Ethnic specific rates were also calculated. Data were obtained on gonorrhoea and chlamydia isolation from all the major laboratories of the city over the same time period. RESULTS: GUM clinic attenders accounted for 67.6% and 82.5% of all chlamydia and gonorrhoea isolates reported by the laboratories and that were available for our epidemiological analysis. Both infections were more common in men and in black ethnic groups. However, patients with gonorrhoea only infection were more likely to be of black ethnicity than those with chlamydia only infection (p = 0.0001) and to have different SP distribution (p = 0.0001). On logistic regression age < 20 years, male sex, black ethnicity, and living in neighbourhoods with SP J ("have nots") were predictive of both infections compared with controls. Overall chlamydia and gonorrhoea prevalence rates were 129 and 98.4 per 10(5) respectively. Corresponding rates for whites was 64.7 and 37.2 and for black ethnic groups 1105 and 1183 per 10(5) of each ethnic group. Eight adjacent wards accounted for 41% of the chlamydia and 66.5% of the gonorrhoea. CONCLUSION: In a large urban setting patients attending GUM clinics with chlamydia belong to core population groups with similar, but not identical, sociodemographic characteristics to patients with gonorrhoea infection.