ENDO-LYSOSOME-TARGETED NANOPARTICLE DELIVERY OF ANTIVIRAL THERAPY FOR CORONAVIRUS INFECTIONS (preprint)

SARS-CoV-2 can infect cells through endocytic uptake, a process which can be targeted by inhibition of lysosomal proteases. However, clinically this approach fared poorly with an oral regimen of hydroxychloroquine that was accompanied by significant toxicity due to off-target effects. We rationalized that an organelle-targeted approach will avoid toxicity while increasing the concentration of the drug at the target. Here we describe a lysosome-targeted, mefloquine-loaded poly(glycerol monostearate-co-{varepsilon}-caprolactone) nanoparticle (MFQ-NP) for pulmonary delivery via inhalation. Mefloquine is a more effective inhibitor of viral endocytosis than hydroxychloroquine in cellular models of COVID-19. MFQ-NPs are less toxic than molecular mefloquine, 100-150 nm in diameter, and possess a negative surface charge which facilitates uptake via endocytosis allowing inhibition of lysosomal proteases. MFQ-NPs inhibit coronavirus infection in mouse MHV-A59 and human OC43 coronavirus model systems and inhibit SARS-CoV-2-WA1 and its Omicron variant in a human lung epithelium model. This study demonstrates that organelle-targeted delivery is an effective means to inhibit viral infection.

Restaurant Cleaning Practices During COVID-19 Pandemic: An Analysis of Microbial Persistence on High Contact Surface Areas

The relationship between cleaning practices and the persistence of microbes on the surfaces in public settings, such as restaurants, is not clear. It has been shown that enteric Gramnegative bacteria and the SARS-CoV-2 can persist on inanimate objects and can potentially cause life-threatening diseases in humans. During the COVID-19 pandemic, the authors questioned the presence of potentially infectious microbes on high contact restaurant surfaces with intention to demonstrate the prevalence. Lake Erie College of Osteopathic Medicine students swabbed the following surfaces at seven restaurants: tabletop (n=7), menu (n4), chair (n=7), condiment bottle (n=5), and bathroom handle (n=7). Bacteria were identified biochemically. SARS-CoV-2 was detected by RT-PCR. Restaurant managers completed a questionnaire about cleaning practices at their facilities. No IRB approval was necessary. Ewingella americana and Escherichia vulneris were among the identified enteric organisms. Average total colonies per surface 6 SEM included;tabletop - 1363.0 (n6), chair - 8.262.2 (n6), bathroom handle - 9.464.3 (n=5), condiment bottle - 23621.03 (n=3), menu - 1364 (n=2). Total number of isolated colonies was lowest in the restaurants with higher cleaning frequencies. To date, no SARS-CoV-2 has been detected. Although this study had limited numbers of samples, early results show low probability of contracting COVID from restaurant surface areas. The effort to identify a relationship between restaurant cleaning practices and potential pathogens is still in progress, we propose that cleaning all high contact surfaces employing standardized methods may reduce potential sources of infection and thus improve public health.

Bridging the technological divide: Stigmas and challenges with technology in clinical studies of older adults. (preprint)

The COVID-19 pandemic has increased adoption of remote assessments in clinical research. However, longstanding stereotypes persist regarding older adults’ technology familiarity and their willingness to participate in technology-enabled remote studies. We examined the validity of these stereotypes using a novel technology familiarity assessment (n = 342) and with a critical evaluation of participation factors from an intensive smartphone study of cognition in older adults (n = 445). The technology assessment revealed that older age was strongly associated with less technology familiarity, less frequent engagement with technology, and higher difficulty ratings. Despite this, the majority (86.5%) of older adults elected to participate in the smartphone study and showed exceptional adherence (85.7%). Furthermore, among those enrolled, neither technology familiarity, knowledge, perceived difficulty, nor gender, race, or education were associated with adherence. These results suggest that while older adults remain significantly less familiar with technology than younger generations, with thoughtful study planning that emphasizes participant support and user-centered design, they are willing and capable participants in technology-enabled studies. And once enrolled, they are remarkably adherent.

Effectiveness of the BNT162b2 (Pfizer-BioNTech) and the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccines for reducing susceptibility to infection with the Delta variant(B.1.617.2) of SARS-CoV-2 (preprint)

Background From January to May 2021 the alpha variant (B.1.1.7) of SARS-CoV-2 was the most commonly detected variant in the UK, but since then the Delta variant (B.1.617.2), first detected in India, has become the predominant variant. The UK COVID-19 vaccination programme started on 8thDecember 2020. Most vaccine effectiveness studies to date have focused on the alpha variant. We therefore aimed to estimate the effectiveness of the BNT162b2 (Pfizer-BioNTech) and the ChAdOx1nCoV-19 (Oxford-AstraZeneca) vaccines in preventing infection with respect to the Delta variant in a UK setting. Methods We used anonymised public health record data linked to infection data (PCR) using the Combined Intelligence for Population Health Action resource. We then constructed an SIR epidemic model to explain SARS-CoV-2 infection data across the Cheshire and Merseyside region of the UK. Results We determined that the effectiveness of the Oxford-AstraZeneca vaccine in reducing susceptibility to infection is 39% (95% credible interval [34,43]) and 64% (95% credible interval [61,67]) for a single dose and a double dose respectively. For the Pfizer-BioNTech vaccine, the effectiveness is 20% (95% credible interval [10,28]) and 84% (95% credible interval [82,86]) for a single-dose and a double dose respectively. Conclusion Vaccine effectiveness for reducing susceptibility to SARS-CoV-2 infection shows noticeable improvement after receiving two doses of either vaccine. Findings also suggest that a full course of the Pfizer-BioNTech provides the optimal protection against infection with the Delta variant. This would advocate for completing the full course programme to maximise individual protection and reduce transmission.