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Broadly neutralizing antibodies are an important treatment for individuals with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Antibody-based therapeutics are also essential for pandemic preparedness against future Sarbecovirus outbreaks. Camelid-derived single domain antibodies (VHHs) exhibit potent antimicrobial activity and are being developed as SARS-CoV-2–neutralizing antibody-like therapeutics. Here, we identified VHHs that neutralize both SARS-CoV-1 and SARS-CoV-2, including now circulating variants. We observed that the VHHs bound to a highly conserved epitope in the receptor binding domain of the viral spike protein that is difficult to access for human antibodies. Structure-guided molecular modeling, combined with rapid yeast-based prototyping, resulted in an affinity enhanced VHH-human immunoglobulin G1 Fc fusion molecule with subnanomolar neutralizing activity. This VHH-Fc fusion protein, produced in and purified from cultured Chinese hamster ovary cells, controlled SARS-CoV-2 replication in prophylactic and therapeutic settings in mice expressing human angiotensin converting enzyme 2 and in hamsters infected with SARS-CoV-2. These data led to affinity-enhanced selection of the VHH, XVR011, a stable anti–COVID-19 biologic that is now being evaluated in the clinic. ispartof: SCIENCE TRANSLATIONAL MEDICINE vol:13 issue:621 ispartof: location:United States status: published

Introduction Delivering timely cancer care during the COVID-19 pandemic was a major challenge. We analysed our success in addressing this. Method A key factor was the proximity of a private hospital (GN) to the primary trust. GN acted as a ‘clean site’. From 6th April 2020, two robots and dedicated staff were relocated to day surgery theatres with direct access to GN. Procedures and post-operative recovery happened in GN. National surgical guidelines were followed related to Covid-19. All theatre staff were swabbed weekly. Patients were risk stratified prior to admittance. Results We reviewed operations performed and cancer pathway data from March to June 2020 and compared it to data collected from August to November 2019. From March until June 2020 we performed 369 cancer operations; 120 robotic, 138 endoscopic and 7 open cases. From August to November 2019 we performed 407 cancer operations; 116 robotic, 175 endoscopic and 7 open cases. No elective patient developed symptomatic COVID-19 secondary to admission. Conclusions This study demonstrates that with rapid development of separate ‘clean’ and ‘COVID’ sites, we successfully delivered a comparable, safe and effective cancer service. As we potentially face a second wave we share our success to see if these changes can be replicated elsewhere.

The tumor suppressor protein p16 plays a fundamental role in cell cycle regulation and exerts a protective effect against tumor growth. Two different polymorphisms at positions 540 and 580 at the 3'UTR of exon 3 of p16 gene are implicated in several types of cancer, while their role in cervical cancer development remains rather vague. In the present study, we investigated for the impact of p16 genotypes/haplotypes on patients' vulnerability to cervical disease and examined whether these factors can be used as progression markers in the Greek population. A total of 96 HPV16 positive samples and histologically confirmed as LSIL (42 samples), HSIL (44 samples), and cervical cancer cases (10 samples) along with 50 control cases were tested. The identification of p16 polymorphisms was performed by PCR-RFLP methodology. The present analysis revealed that women with p16 540 CG/GG genotype are at a 2.7-fold higher risk of developing HPV16-associated HSIL (OR = 2.7, 95%CI: 1.01-6.6, P = 0.028). The G allele can be regarded as a risk factor of developing HSIL in the Greek population (OR = 2.7, 95%CI: 1.2-5.9, P = 0.012). Moreover, p16 polymorphism C580T is not associated with the growth of cervical lesion in Greek patients, while 540G/580C haplotype can be regarded as a risk haplotype of developing HSIL (OR = 3.67, 95%CI: 1.56-8.6, P = 0.0019). Our results demonstrated that p16 C540G polymorphism influence patients' susceptibility to more severe dysplasia and consequently this polymorphism could potentially emerge as a valuable biomarker for HSIL development in the Greek population.