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.

The impact of socioeconomic status on access to cancer clinical trials.

Cancer clinical trials enable the development of novel agents for the potential benefit of cancer patients. Enrolment in a trial offers patients the chance of superior efficacy coupled to the risk of unanticipated toxicity. For trial results to be generalisable, the data need to be collected in patients' representative of the general cancer population. Socioeconomic deprivation is associated with poor cancer outcomes. In the developed world, the gap between the most and least deprived is widening. This mini-review explores the evidence regarding socioeconomics and access to cancer trials, highlighting the underrepresentation of deprived patients, and exploring reasons for this disparity.

Missed opportunities for identifying primary HIV within genitourinary medical/HIV services.

To assess the ability of three genitourinary medical centres to clinically identify primary HIV infection (PHI). Cases of recently acquired HIV infection, identified using the Health Protection Agency (HPA) avidity assay on all HIV diagnoses from January to August 2009, were investigated by case-note review. Sixty-four individuals were identified as PHI using the HPA avidity assay. Of 64 individuals, 31 (48%) were identified clinically. Imperial College identified 8/26 (31%), Guys and St Thomas' 15/27 (56%) and Brighton 8/11 (73%). Clinical suspicion of PHI was associated with reported unprotected anal intercourse (P = 0.017), seroconversion symptoms (P = 0.0004), a negative HIV test within six months (P = 0.024) and avidity assay result availability (P = 0.0169). Seventy percent of PHI cases missed had a documented risk factor. Thirty-five percent of those clinically identified with PHI were documented as informed of the associated enhanced infectivity. Suspicion of PHI was low despite documented risk factors and recent HIV-negative antibody tests. Counselling to prevent onward transmission was suboptimal.