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1.
Preprint in English | bioRxiv | ID: ppbiorxiv-443253

ABSTRACT

The SARS-CoV-2 B.1.617.2 (Delta) variant was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha). In vitro, B.1.617.2 is 6-fold less sensitive to serum neutralising antibodies from recovered individuals, and 8-fold less sensitive to vaccine-elicited antibodies as compared to wild type Wuhan-1 bearing D614G. Serum neutralising titres against B.1.617.2 were lower in ChAdOx-1 versus BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies against the receptor binding domain (RBD) and N-terminal domain (NTD), in particular to the clinically approved bamlavinimab and imdevimab monoclonal antibodies. B.1.617.2 demonstrated higher replication efficiency in both airway organoid and human airway epithelial systems as compared to B.1.1.7, associated with B.1.617.2 spike being in a predominantly cleaved state compared to B.1.1.7. Additionally we observed that B.1.617.2 had higher replication and spike mediated entry as compared to B.1.617.1, potentially explaining B.1.617.2 dominance. In an analysis of over 130 SARS-CoV-2 infected healthcare workers across three centres in India during a period of mixed lineage circulation, we observed substantially reduced ChAdOx-1 vaccine efficacy against B.1.617.2 relative to non-B.1.617.2. Compromised vaccine efficacy against the highly fit and immune evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.

2.
Preprint in English | medRxiv | ID: ppmedrxiv-21252512

ABSTRACT

BackgroundEngland has experienced high rates of SARS-CoV-2 infection during the COVID-19 pandemic, affecting in particular minority ethnic groups and more deprived communities. A vaccination programme began in England in December 2020, with priority given to administering the first dose to the largest number of older individuals, healthcare and care home workers. MethodsA cross-sectional community survey in England undertaken between 26 January and 8 February 2021 as the fifth round of the REal-time Assessment of Community Transmission-2 (REACT-2) programme. Participants completed questionnaires, including demographic details and clinical and COVID-19 vaccination histories, and self-administered a lateral flow immunoassay (LFIA) test to detect IgG against SARS-CoV-2 spike protein. There were sufficient numbers of participants to analyse antibody positivity after 21 days from vaccination with the PfizerBioNTech but not the AstraZeneca/Oxford vaccine which was introduced slightly later. ResultsThe survey comprised 172,099 people, with valid IgG antibody results from 155,172. The overall prevalence of antibodies (weighted to be representative of the population of England and adjusted for test sensitivity and specificity) in England was 13.9% (95% CI 13.7, 14.1) overall, 37.9% (37.2, 38.7) in vaccinated and 9.8% (9.6, 10.0) in unvaccinated people. The prevalence of antibodies (weighted) in unvaccinated people was highest in London at 16.9% (16.3, 17.5), and higher in people of Black (22.4%, 20.8, 24.1) and Asian (20.0%, 19.0, 21.0) ethnicity compared to white (8.5%, 8.3, 8.7) people. The uptake of vaccination by age was highest in those aged 80 years or older (93.5%). Vaccine confidence was high with 92.0% (91.9, 92.1) of people saying that they had accepted or intended to accept the offer. Vaccine confidence varied by age and ethnicity, with lower confidence in young people and those of Black ethnicity. Particular concerns were identified around pregnancy, fertility and allergies. In 971 individuals who received two doses of the Pfizer-BioNTech vaccine, the proportion testing positive was high across all age groups. Following a single dose of Pfizer-BioNTech vaccine after 21 days or more, 84.1% (82.2, 85.9) of people under 60 years tested positive (unadjusted) with a decreasing trend with increasing age, but high responses to a single dose in those with confirmed or suspected prior COVID at 90.1% (87.2, 92.4) across all age groups. ConclusionsThere is uneven distribution of SARS-CoV-2 antibodies in the population with a higher burden in key workers and some minority ethnic groups, similar to the pattern in the first wave. Confidence in the vaccine programme is high overall although it was lower in some of the higher prevalence groups which suggests the need for improved communication about specific perceived risks. Two doses of Pfizer-BioNTech vaccine, or a single dose following previous infection, confers high levels of antibody positivity across all ages. Further work is needed to understand the relationship between antibody positivity, clinical outcomes such as hospitalisation, and transmission.

3.
Preprint in English | medRxiv | ID: ppmedrxiv-21251419

ABSTRACT

ObjectivesTo investigate whether the antimicrobial emollient Dermol 500 and its active components, benzalkonium chloride (BAK) and chlorhexidine dihydrochloride (CD), exhibit virucidal activity thus informing whether Dermol 500 is a suitable soap substitute for use during the COVID19 pandemic, to combat the increased incidence of work-related contact dermatitis in clinical settings that we report here. MethodsInactivation of influenza A virus and SARS-CoV-2 by Dermol 500 and the independent and combined virucidal activity of the Dermol 500 components BAK and CD was assessed by influenza A virus and SARS-CoV-2 infectivity assays. Viruses were treated with concentrations of BAK and CD comparable to Dermol 500, and lower, and infectivity of the viruses assessed by titration. ResultsDermol 500 exhibits comparable virucidal activity to alcohol-based sanitisers against influenza A virus and SARS-CoV-2. In addition, the Dermol 500 components BAK and CD exhibit independent and synergistic virucidal activity against influenza A virus and SARS-CoV-2, the causative agent of COVID19. ConclusionsThe synergistic virucidal activity of the Dermol 500 components BAK and CD makes Dermol 500 suitable as a soap substitute to treat and prevent work-related contact dermatitis in healthcare settings. KEY MESSAGESO_LIWhat is already known about this subject? O_LIWork-related contact dermatitis is a prominent issue among healthcare workers, and likely exacerbated by the enhanced hand hygiene and personal protective equipment required to control infection during the COVID19 pandemic. C_LIO_LIThe antimicrobial lotion Dermol 500 is frequently prescribed as an emollient and soap substitute to help prevent and treat dermatitis, but its use during the COVID19 pandemic was not advised as its capacity to inactivate viruses was unknown. C_LI C_LIO_LIWhat are the new findings? O_LIIncreased incidence of irritant contact dermatitis was recorded amongst healthcare workers at Kings College Hospital NHS Foundation Trust in 2020 compared to 2019. C_LIO_LIDermol 500 lotion and its antimicrobial components, benzalkonium chloride (BAK) and chlorhexidine dihydrochloride (CD), exhibit virucidal activity against influenza A virus and SARS-CoV-2, the virus responsible for COVID19 pandemic. C_LI C_LIO_LIHow might this impact policy or clinical practice in the foreseeable future? O_LIOur results demonstrate that Dermol 500 can be safely used as a soap substitute to treat work-related contact dermatitis in clinical care settings during the COVID19 pandemic. C_LIO_LIEmployers can meet their obligations under COSHH to eliminate workplace exposure to a harmful substance and substitute with an alternative product for hand hygiene. C_LI C_LI

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