The role of ion dissolution in metal and metal oxide surface inactivation of SARS-CoV-2 (preprint)

Antiviral surface coatings are under development to prevent viral fomite transmission from high-traffic touch surfaces in public spaces. Copper's antiviral properties have been widely documented; but the antiviral mechanism of copper surfaces is not fully understood. We screened a series of metal and metal oxide surfaces for antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19). Copper and copper oxide surfaces exhibited superior anti-SARS-CoV-2 activity; however, level of antiviral activity was dependent upon the composition of the carrier solution used to deliver virus inoculum. We demonstrate that copper ions released into solution from test surfaces can mediate virus inactivation, indicating a copper ion dissolution-dependent antiviral mechanism. Level of antiviral activity is, however, not dependent on the amount of copper ions released into solution per se. Instead, our findings suggest that degree of virus inactivation is dependent upon copper ion complexation with other biomolecules (e.g., proteins/metabolites) in the virus carrier solution that compete with viral components. Although using tissue culture-derived virus inoculum is experimentally convenient to evaluate the antiviral activity of copper-derived test surfaces, we propose that the high organic content of tissue culture medium reduces the availability of "uncomplexed" copper ions to interact with the virus, negatively affecting virus inactivation and hence surface antiviral performance. We propose that laboratory antiviral surface testing should include virus delivered in a physiologically relevant carrier solution (saliva or nasal secretions when testing respiratory viruses) to accurately predict real-life surface antiviral performance when deployed in public spaces.

NK CELLS ARE CRITICAL FOR IN VIVO CONTROL OF SARS-CoV-2 REPLICATION AND DISEASE

Background: Natural killer (NK) cells play a critical role in control of viral infections. However, empirical evidence thus far has been unclear on the role of NK cells in pathogenesis and control of SARS-CoV-2 infection with some research suggesting NK cell accumulation as beneficial while others indicate it as deleterious. To address this crucial deficit in understanding, we employed a non-human primate infection model with a validated experimental NK cell depletion technique. Method(s): A total of 12 experimentally naive (75% female) cynomolgus macaques (CM) of Cambodian origin were used in this study. Six CM were NK cell-depleted using an anti-IL-15 neutralizing antibody, while six controls received placebo, prior to intranasal and intratracheal challenge with the SARS-CoV-2 Delta variant at a TCID50 of 1X105. The cohort was monitored for five weeks with scheduled blood, colorectal (CR) biopsies, and lymph node (LN) collections. Total envelope and sub-genomic viral loads (VL) were measured in the nasal cavity, throat, and bronchoalveolar lavage (BAL). 23-color flow cytometry, pathology, and 27-plex inflammatory analyte Luminex analyses were conducted. Statistical tests used were Mann-Whitney U and Spearman's Correlation. Result(s): Control CM exhibited an increase in the frequency of circulating NK cells, reaching a peak at 10 days post-infection (DPI) and returning to baseline by 22DPI. Simultaneously, NK cells expressing activation and tissue retention marker, CD69, also significantly increased. Cytotoxic NK cells were positively associated with VL (r=0.66;p=0.02), suggestive of a virus-induced mobilization. Total experimental NK cell ablation was verified in blood, CR, and LN of NK celldepleted CM, which had higher VL compared to controls in all tissues evaluated, reaching significance at 10DPI (p=0.01) and demonstrated a longer duration of viremia. Although Luminex measures were similar in plasma, BAL samples from NK cell-depleted CM had universally higher concentrations of inflammatory mediators, most notably a 25-fold higher concentration of IFN-alpha compared to controls. Lung pathology scores were also higher in NK cell-depleted CM with increased evidence of fibrosis, syncytia, pneumocyte hyperplasia, and endothelialitis. Conclusion(s): Overall, we find significant and conclusive evidence for NK cell-mediated control of SARS-CoV-2 virus replication and disease pathology. These data suggest adjunct therapies for infection could largely benefit from NK cell-targeted approaches.

Surface-Functionalized Metal-Organic Frameworks for Binding Coronavirus Proteins.

Since the outbreak of SARS-CoV-2, a multitude of strategies have been explored for the means of protection and shielding against virus particles: filtration equipment (PPE) has been widely used in daily life. In this work, we explore another approach in the form of deactivating coronavirus particles through selective binding onto the surface of metal-organic frameworks (MOFs) to further the fight against the transmission of respiratory viruses. MOFs are attractive materials in this regard, as their rich pore and surface chemistry can easily be modified on demand. The surfaces of three MOFs, UiO-66(Zr), UiO-66-NH2(Zr), and UiO-66-NO2(Zr), have been functionalized with repurposed antiviral agents, namely, folic acid, nystatin, and tenofovir, to enable specific interactions with the external spike protein of the SARS virus. Protein binding studies revealed that this surface modification significantly improved the binding affinity toward glycosylated and non-glycosylated proteins for all three MOFs. Additionally, the pores for the surface-functionalized MOFs can adsorb water, making them suitable for locally dehydrating microbial aerosols. Our findings highlight the immense potential of MOFs in deactivating respiratory coronaviruses to be better equipped to fight future pandemics.

DEVELOPMENT OF A NASAL SPRAY CONTAINING A NOVEL HUMAN RECOMBINANT ANTIBODY FOR SARS-COV-2 THERAPY

A novel human recombinant antibody for prophylactic treatment against SARS-CoV-2 was formulated in a nasal solution comprising chitosan as mucoadhesive polymer. Two levels of protein concentration have been assessed and formulations loaded into Aptar VP3 nasal pump. The formulations produced showed values of pH (6.2- 6.3) and osmolality (414 and 421 mosm/kg) suitable to prevent precipitation of the antibody in the final solution and for nasal administration. Assay of the protein after formulation manufacturing showed a lower dimeric fraction than the reference standard and hydrodynamic diameter of the final formulations was also comparable to the unprocessed antibody solution (10 nm). Zeta-potential values were higher than 25mV, indicating colloidal stability against aggregation due to charge stabilization for the formulations obtained. Spray performance did not evidence any difference between protein levels in the final formulations when combined with VP3 nasal pump. Particularly, droplet size distribution (mean volume diameter of 55.13 lm for the low dose formulation and 57.21 lm for the high dose), spray pattern and plume geometry resulted to be applicable for nasal delivery. Finally, for both solutions sprayed antibody content was within 75-125% of the target delivered dose with a very low variability on ten consecutive shots (5%). Future studies will assess the formulations stability under refrigerated and ambient storage conditions of the combination product and of the antibody comprised in the formulation,whereas in vivo studieswill define pharmacokinetics and pharmacodynamics profile of these final formulations. Key Message: The possibility to deliver to the nose a novel human antibody for prophylactic treatment against SARS-CoV-2 employing Aptar VP3 pump was assessed. Spray performance of the formulations manufactured was characterized and no protein agglomeration was observed in the formulations and after spraying, indicating favourable results in applying this system for delivery of antibodies to the nose.

Occupational changes during the COVID-19 lockdown in Jordan.

BACKGROUND: Measures to limit the spread of COVID-19 have disrupted the lives of countless millions of individuals worldwide. OBJECTIVE: To explore the experiences of occupational disruption and changing social roles among Jordanians during COVID-19 lockdown in 2020. The specific aim was to explore the changing occupations, routines, roles and coping strategies. MATERIAL AND METHODS: This qualitative study used a digital ethnographic approach. Data collection included online observations of Jordanian's posts of comments, photos and videos on six public Facebook pages during the COVID-19 lockdown for the initial 3-week period. In addition, 150 Jordanians participated in an online interview answering four open-ended questions to achieve triangulation. Qualitative analyses included open coding of the photos, videos and text as well as the interviews independently and blindly by the research team. RESULTS: Four themes were identified: changing daily occupations; changing family roles; missing pre-lockdown life and coping strategies under lockdown. CONCLUSION: The COVID-19 lockdown restrictions caused direct, significant and immediate changes to Jordanians' occupations, routines and roles; enforcing new obligatory occupations and eliminating desired ones. SIGNIFICANCE: Knowledge from this study highlight the kinds of strategies and supports during and after lockdowns that need to be considered in future planning of occupational therapy practice in Jordan.

Outpatient clinical pharmacy practice in the face of COVID-19 at a cancer center in New York City.

PURPOSE: With the rapid spread of COVID-19 in New York City since early March 2020, innovative measures were needed for clinical pharmacy specialists to provide direct clinical care safely to cancer patients. Allocating the workforce was necessary to meet the surging needs of the inpatient services due to the COVID-19 outbreak, which had the potential to compromise outpatient services. We present here our approach of restructuring clinical pharmacy services and providing direct patient care in outpatient clinics during the pandemic. DATA SOURCES: We conducted a retrospective review of electronic clinical documentation involving clinical pharmacy specialist patient encounters in 9 outpatient clinics from March 1, 2020 to May 31, 2020. The analysis of the clinical pharmacy specialist interventions and the impact of the interventions was descriptive. DATA SUMMARY: As hospital services were modified to handle the surge due to COVID-19, select clinical pharmacy specialists were redeployed from the outpatient clinics or research blocks to COVID-19 inpatient teams. During these 3 months, clinical pharmacy specialists were involved in 2535 patient visits from 9 outpatient clinics and contributed a total of 4022 interventions, the majority of which utilized telemedicine. The interventions provided critical clinical pharmacy care during the pandemic and omitted 199 in-person visits for medical care. CONCLUSION: The swift transition to telemedicine allowed the provision of direct clinical pharmacy services to patients with cancer during the COVID-19 pandemic.