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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Objective To create an aerosol containment mask (ACM) for common otolaryngologic endoscopic procedures that also provides nanoparticle-level protection to patients. Study Design Prospective feasibility study . Setting In-person testing with a novel ACM. Methods The mask was designed in Solidworks and 3D printed. Measurements were made on 10 healthy volunteers who wore the ACM while reading the Rainbow Passage repeatedly and performing a forced cough or sneeze at 5-second intervals over 1 minute with an endoscope in place. Results There was a large variation in the number of aerosol particles generated among the volunteers. Only the sneeze task showed a significant increase compared with normal breathing in the 0.3-µm particle size when compared with a 1-tailed t test ( P = .013). Both the 0.5-µm and 2.5-µm particle sizes showed significant increases for all tasks, while the 2 largest particle sizes, 5 and 10 µm, showed no significant increase (both P < .01). With the suction off, 3 of 30 events (2 sneeze events and 1 cough event) had increases in particle counts, both inside and outside the mask. With the suction on, 2 of 30 events had an increase in particle counts outside the mask without a corresponding increase in particle counts inside the mask. Therefore, these fluctuations in particle counts were determined to be due to random fluctuation in room particle levels. Conclusion ACM will accommodate rigid and flexible endoscopes plus instruments and may prevent the leakage of patient-generated aerosols, thus avoiding contamination of the room and protecting health care workers from airborne contagions. Level of evidence 2

Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness of travellers being required to quarantine for 14-days on return to England in Summer 2020. We identified 4,207 travel-related SARS-CoV-2 cases and their contacts, and identified 827 associated SARS-CoV-2 genomes. Overall, quarantine was associated with a lower rate of contacts, and the impact of quarantine was greatest in the 16–20 age-group. 186 SARS-CoV-2 genomes were sufficiently unique to identify travel-related clusters. Fewer genomically-linked cases were observed for index cases who returned from countries with quarantine requirement compared to countries with no quarantine requirement. This difference was explained by fewer importation events per identified genome for these cases, as opposed to fewer onward contacts per case. Overall, our study demonstrates that a 14-day quarantine period reduces, but does not completely eliminate, the onward transmission of imported cases, mainly by dissuading travel to countries with a quarantine requirement.

In the version of this article initially published, the surname of a member of The COVID-19 Genomics UK (COG-UK) Consortium was misspelt as Gramatopoulos. The correct spelling is Dimitris Grammatopoulos. The name has been corrected in the HTML and PDF versions of the article.

Objective: To compare the effect of virtual and in-person head and neck physical examination training events on medical student confidence in performing examination maneuvers and seeking mentorship from otolaryngology faculty and residents. Methods: Training events were held with first-year medical student volunteers in 2020 (in-person) and 2021 (virtual). Participants in both cohorts were given didactics on head and neck cancer, trained to perform a head and neck physical examination, and demonstrated their clinical skills to otolaryngology faculty and residents. Pre- and post-training surveys were utilized to assess the following outcomes: participant head and neck cancer knowledge, confidence in performing examination maneuvers, and confidence in seeking mentorship in otolaryngology. Differences in outcomes between training settings were assessed by comparing participant survey responses pre- and post- training. Results: Both in-person and virtual training modalities improved participant confidence in performing the physical examination. There was no significant difference in the degree of improvement between training types. In-person training significantly increased participant confidence in seeking mentorship from otolaryngology faculty and residents ( P = .003), while virtual training did not ( P = .194). Conclusion: Virtual training modalities are feasible methods of teaching the head and neck physical examination. Instruction through a video conferencing platform has the potential to be incorporated into traditional in-person medical education in a permanent fashion. This pilot study can inform future studies directly comparing in-person and virtual physical examination training modalities.

Objective To understand the effect of age on health‐related quality of life (HRQoL) in patients with hearing loss and determine how primary language mediates this relationship. Study Design Cross‐sectional study. Setting General otolaryngology clinic in Los Angeles. Methods Demographics, medical records, and HRQoL data of adult patients presenting with otology symptoms were reviewed. HRQoL was measured using the Short‐Form 6‐Dimension utility index. All patients underwent audiological testing. A path analysis was performed to generate a moderated path analysis with HRQoL as the primary outcome. Results This study included 255 patients (mean age = 54 years; 55% female; 27.8% did not speak English as a primary language). Age had a positive direct association with HRQoL (p < .001). However, the direction of this association was reversed by hearing loss. Older patients exhibited significantly worse hearing (p < .001), which was negatively associated with HRQoL (p < .05). Primary language moderated the relationship between age and hearing loss. Specifically, patients who did not speak English as a primary language had significantly worse hearing (p < .001) and therefore worse HRQoL (p < .01) than patients who spoke English as a primary language with hearing loss. Increasing age was associated with bilateral hearing loss compared to unilateral hearing loss (p < .001) and subsequently lower HRQoL (p < .001). Polypharmacy (p < .01) and female gender (p < .01) were significantly associated with lower HRQoL. Conclusion Among otolaryngology patients with otology symptoms, older age and not speaking English as a primary language were associated with worse hearing and subsequently lower HRQoL.

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