Pragmatic randomized trial of a pre-visit intervention to improve the quality of telemedicine visits for vulnerable patients living with HIV.

INTRODUCTION: The COVID-19 pandemic has required a shift of many routine primary care visits to telemedicine, potentially widening disparities in care access among vulnerable populations. In a publicly-funded HIV clinic, we aimed to evaluate a pre-visit phone-based planning intervention to address anticipated barriers to telemedicine. METHODS: We conducted a pragmatic randomized controlled trial of patients scheduled for a phone-based HIV primary care visit at the Ward 86 HIV clinic in San Francisco from 15 April to 15 May 2020. Once reached by phone, patients were randomized to either have a structured pre-visit planning intervention to address barriers to an upcoming telemedicine visit versus a standard reminder call. The primary outcome was telemedicine visit attendance. RESULTS: Of 476 scheduled telemedicine visits, 280 patients were reached by a pre-visit call to offer enrollment. Patients were less likely to be reached if virally unsuppressed (odds ratio (OR) 0.11, 95% confidence intervals (CI) 0.03-0.48), CD4 < 200 (OR 0.24, 95% CI 0.07-0.85), or were homeless (OR 0.24, 95% CI 0.07-0.87). There was no difference between intervention and control in scheduled visit attendance (83% v. 78%, OR 1.38, 95% CI 0.67-2.81). CONCLUSIONS: A structured phone-based planning call to address barriers to telemedicine in a public HIV clinic was less likely to reach patients with poorly-controlled HIV and patients experiencing homelessness, suggesting additional interventions may be needed in this population to ensure access to telemedicine-based care. Among patients reachable by phone, telemedicine visit attendance was high and not improved with a structured pre-visit intervention, suggesting that standard reminders may be adequate in this population.

Bringing Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) to the Surface: Is There a Role for Fomites?

Understanding the contribution of routes of transmission, particularly the role of fomites in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) transmission is important in developing and implementing successful public health infection prevention and control measures. This article will look at case reports, laboratory findings, animal studies, environmental factors, the need for disinfection, and differences in settings as they relate to SARS-CoV-2 transmission.

The Impact of Vaccination on Coronavirus Disease 2019 (COVID-19) Outbreaks in the United States.

BACKGROUND: Global vaccine development efforts have been accelerated in response to the devastating coronavirus disease 2019 (COVID-19) pandemic. We evaluated the impact of a 2-dose COVID-19 vaccination campaign on reducing incidence, hospitalizations, and deaths in the United States. METHODS: We developed an agent-based model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and parameterized it with US demographics and age-specific COVID-19 outcomes. Healthcare workers and high-risk individuals were prioritized for vaccination, whereas children under 18 years of age were not vaccinated. We considered a vaccine efficacy of 95% against disease following 2 doses administered 21 days apart achieving 40% vaccine coverage of the overall population within 284 days. We varied vaccine efficacy against infection and specified 10% preexisting population immunity for the base-case scenario. The model was calibrated to an effective reproduction number of 1.2, accounting for current nonpharmaceutical interventions in the United States. RESULTS: Vaccination reduced the overall attack rate to 4.6% (95% credible interval [CrI]: 4.3%-5.0%) from 9.0% (95% CrI: 8.4%-9.4%) without vaccination, over 300 days. The highest relative reduction (54%-62%) was observed among individuals aged 65 and older. Vaccination markedly reduced adverse outcomes, with non-intensive care unit (ICU) hospitalizations, ICU hospitalizations, and deaths decreasing by 63.5% (95% CrI: 60.3%-66.7%), 65.6% (95% CrI: 62.2%-68.6%), and 69.3% (95% CrI: 65.5%-73.1%), respectively, across the same period. CONCLUSIONS: Our results indicate that vaccination can have a substantial impact on mitigating COVID-19 outbreaks, even with limited protection against infection. However, continued compliance with nonpharmaceutical interventions is essential to achieve this impact.

Virtual preoperative assessment in surgical patients: A systematic review and meta-analysis.

STUDY OBJECTIVE: Preoperative assessment is a standard evaluation, traditionally done in-person in a preanesthesia clinic, for patients who will be undergoing a procedure involving anesthesia. Given the increased adoption of virtual care during the coronavirus disease 2019 (COVID-19) pandemic, the purpose of this systematic review and meta-analysis is to review the effectiveness of virtual preoperative assessment for the evaluation of surgical patients. DESIGN: Systematic review and meta-analysis. SETTING: MEDLINE (Ovid), MEDLINE InProcess/ePubs, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov were searched from the initial coverage of the respective database to May 2021. A manual citation search of Google Scholar and PubMed was conducted to identify missed articles. Continued literature surveillance was done through July 2021. PATIENTS: Patients aged 18 years and older undergoing virtual preoperative anesthesia assessment. INTERVENTIONS: Virtual preoperative assessment. MEASUREMENTS: Surgery cancellation rates, patient experience, resources saved, staff experience, success in using the data collected to diagnose and manage patients. MAIN RESULTS: Fifteen studies (n = 31,496 patients) were included in this review. The average age of patients was 58 ± 15 years, and 47% were male. Virtual preoperative assessment resulted in similar surgery cancellation rates compared to in-person evaluation, with a pooled cancellation rate of 2% (95% confidence interval [CI]: 1-3%). Most studies reported a positive patient experience, with a pooled estimate of 90% (95% CI, 81-95%). There was a high success rate in using the information collected with virtual care, in the range of 92-100%, to diagnose and manage patients resulting in time and cost savings in the range of 24-137 min and $60-67 per patient. CONCLUSIONS: This systematic review and meta-analysis demonstrates the utility of virtual care for preoperative assessment of surgical patients. Virtual preanesthesia evaluation had similar surgery cancellation rates, high patient satisfaction, and reduced costs compared to in-person evaluation.

Electrophysiological and Proarrhythmic Effects of Hydroxychloroquine Challenge in Guinea-Pig Hearts.

Hydroxychloroquine (HCQ), clinically established in antimalarial and autoimmune therapy, recently raised cardiac arrhythmogenic concerns when used alone or with azithromycin (HCQ+AZM) in Covid-19. We report complementary, experimental, studies of its electrophysiological effects. In patch clamped HEK293 cells expressing human cardiac ion channels, HCQ inhibited IKr and IK1 at a therapeutic concentrations (IC50s: 10 ± 0.6 and 34 ± 5.0 µM). INa and ICaL showed higher IC50s; Ito and IKs were unaffected. AZM slightly inhibited INa, ICaL, IKs, and IKr, sparing IK1 and Ito. (HCQ+AZM) inhibited IKr and IK1 (IC50s: 7.7 ± 0.8 and 30.4 ± 3.0 µM), sparing INa, ICaL, and Ito. Molecular induced-fit docking modeling confirmed potential HCQ-hERG but weak AZM-hERG binding. Effects of µM-HCQ were studied in isolated perfused guinea-pig hearts by multielectrode, optical RH237 voltage, and Rhod-2 mapping. These revealed reversibly reduced left atrial and ventricular action potential (AP) conduction velocities increasing their heterogeneities, increased AP durations (APDs), and increased durations and dispersions of intracellular [Ca2+] transients, respectively. Hearts also became bradycardic with increased electrocardiographic PR and QRS durations. The (HCQ+AZM) combination accentuated these effects. Contrastingly, (HCQ+AZM) and not HCQ alone disrupted AP propagation, inducing alternans and torsadogenic-like episodes on voltage mapping during forced pacing. O'Hara-Rudy modeling showed that the observed IKr and IK1 effects explained the APD alterations and the consequently prolonged Ca2+ transients. The latter might then downregulate INa, reducing AP conduction velocity through recently reported INa downregulation by cytosolic [Ca2+] in a novel scheme for drug action. The findings may thus prompt future investigations of HCQ's cardiac safety under particular, chronic and acute, clinical situations.

Rapid disappearance of influenza following the implementation of COVID-19 mitigation measures in Hamilton, Ontario.

BACKGROUND: Public health measures, such as physical distancing and closure of schools and non-essential services, were rapidly implemented in Canada to interrupt the spread of the coronavirus disease 2019 (COVID-19). We sought to investigate the impact of mitigation measures during the spring wave of COVID-19 on the incidence of other laboratory-confirmed respiratory viruses in Hamilton, Ontario. METHODS: All nasopharyngeal swab specimens (n=57,503) submitted for routine respiratory virus testing at a regional laboratory serving all acute-care hospitals in Hamilton between January 2010 and June 2020 were reviewed. Testing for influenza A and B, respiratory syncytial virus, human metapneumovirus, parainfluenza I-III, adenovirus, and rhinovirus/enterovirus was done routinely using a laboratory-developed polymerase chain reaction multiplex respiratory viral panel. A Bayesian linear regression model was used to determine the trend of positivity rates of all influenza samples for the first 26 weeks of each year from 2010 to 2019. The mean positivity rate of Bayesian inference was compared with the weekly reported positivity rate of influenza samples in 2020. RESULTS: The positivity rate of influenza in 2020 diminished sharply following the population-wide implementation of COVID-19 interventions. Weeks 12-26 reported 0% positivity for influenza, with the exception of 0.1% reported in week 13. CONCLUSION: Public health measures implemented during the COVID-19 pandemic were associated with a reduced incidence of other respiratory viruses and should be considered to mitigate severe seasonal influenza and other respiratory virus pandemics.

Simulated Identification of Silent COVID-19 Infections Among Children and Estimated Future Infection Rates With Vaccination.

Importance: A significant proportion of COVID-19 transmission occurs silently during the presymptomatic and asymptomatic stages of infection. Children, although important drivers of silent transmission, are not included in the current COVID-19 vaccination campaigns. Objective: To estimate the benefits of identifying silent infections among children as a proxy for their vaccination. Design, Setting, and Participants: This study used an age-structured disease transmission model, parameterized with census data and estimates from published literature, to simulate the estimated synergistic effect of interventions in reducing attack rates during the course of 1 year among a synthetic population representative of the US demographic composition. The population included 6 age groups of 0 to 4, 5 to 10, 11 to 18, 19 to 49, 50 to 64, and 65 years or older based on US census data. Data were analyzed from December 12, 2020, to February 26, 2021. Exposures: In addition to the isolation of symptomatic cases within 24 hours of symptom onset, vaccination of adults was implemented to reach a 40% to 60% coverage during 1 year with an efficacy of 95% against symptomatic and severe COVID-19. Main Outcomes and Measures: The combinations of proportion and speed for detecting silent infections among children that would suppress future attack rates to less than 5%. Results: In the base-case scenarios with an effective reproduction number Re = 1.2, a targeted approach that identifies 11% of silent infections among children within 2 days and 14% within 3 days after infection would bring attack rates to less than 5% with 40% vaccination coverage of adults. If silent infections among children remained undetected, achieving the same attack rates would require an unrealistically high vaccination coverage (≥81%) of this age group, in addition to 40% vaccination coverage of adults. The estimated effect of identifying silent infections was robust in sensitivity analyses with respect to vaccine efficacy against infection and reduced susceptibility of children to infection. Conclusions and Relevance: In this simulation modeling study of a synthetic US population, in the absence of vaccine availability for children, a targeted approach to rapidly identify silent COVID-19 infections in this age group was estimated to significantly mitigate disease burden. These findings suggest that without measures to interrupt transmission chains from silent infections, vaccination of adults is unlikely to contain the outbreaks in the near term.

Evaluation of COVID-19 vaccination strategies with a delayed second dose.

Two of the Coronavirus Disease 2019 (COVID-19) vaccines currently approved in the United States require 2 doses, administered 3 to 4 weeks apart. Constraints in vaccine supply and distribution capacity, together with a deadly wave of COVID-19 from November 2020 to January 2021 and the emergence of highly contagious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants, sparked a policy debate on whether to vaccinate more individuals with the first dose of available vaccines and delay the second dose or to continue with the recommended 2-dose series as tested in clinical trials. We developed an agent-based model of COVID-19 transmission to compare the impact of these 2 vaccination strategies, while varying the temporal waning of vaccine efficacy following the first dose and the level of preexisting immunity in the population. Our results show that for Moderna vaccines, a delay of at least 9 weeks could maximize vaccination program effectiveness and avert at least an additional 17.3 (95% credible interval [CrI]: 7.8-29.7) infections, 0.69 (95% CrI: 0.52-0.97) hospitalizations, and 0.34 (95% CrI: 0.25-0.44) deaths per 10,000 population compared to the recommended 4-week interval between the 2 doses. Pfizer-BioNTech vaccines also averted an additional 0.60 (95% CrI: 0.37-0.89) hospitalizations and 0.32 (95% CrI: 0.23-0.45) deaths per 10,000 population in a 9-week delayed second dose (DSD) strategy compared to the 3-week recommended schedule between doses. However, there was no clear advantage of delaying the second dose with Pfizer-BioNTech vaccines in reducing infections, unless the efficacy of the first dose did not wane over time. Our findings underscore the importance of quantifying the characteristics and durability of vaccine-induced protection after the first dose in order to determine the optimal time interval between the 2 doses.

Multifaceted strategies for the control of COVID-19 outbreaks in long-term care facilities in Ontario, Canada.

The novel coronavirus disease 2019 (COVID-19) has caused severe outbreaks in Canadian long-term care facilities (LTCFs). In Canada, over 80% of COVID-19 deaths during the first pandemic wave occurred in LTCFs. We sought to evaluate the effect of mitigation measures in LTCFs including frequent testing of staff, and vaccination of staff and residents. We developed an agent-based transmission model and parameterized it with disease-specific estimates, temporal sensitivity of nasopharyngeal and saliva testing, results of vaccine efficacy trials, and data from initial COVID-19 outbreaks in LTCFs in Ontario, Canada. Characteristics of staff and residents, including contact patterns, were integrated into the model with age-dependent risk of hospitalization and death. Estimates of infection and outcomes were obtained and 95% credible intervals were generated using a bias-corrected and accelerated bootstrap method. Weekly routine testing of staff with 2-day turnaround time reduced infections among residents by at least 25.9% (95% CrI: 23.3%-28.3%), compared to baseline measures of mask-wearing, symptom screening, and staff cohorting alone. A similar reduction of hospitalizations and deaths was achieved in residents. Vaccination averted 2-4 times more infections in both staff and residents as compared to routine testing, and markedly reduced hospitalizations and deaths among residents by 95.9% (95% CrI: 95.4%-96.3%) and 95.8% (95% CrI: 95.5%-96.1%), respectively, over 200 days from the start of vaccination. Vaccination could have a substantial impact on mitigating disease burden among residents, but may not eliminate the need for other measures before population-level control of COVID-19 is achieved.

Fomite Transmission, Physicochemical Origin of Virus-Surface Interactions, and Disinfection Strategies for Enveloped Viruses with Applications to SARS-CoV-2.

Inanimate objects or surfaces contaminated with infectious agents, referred to as fomites, play an important role in the spread of viruses, including SARS-CoV-2, the virus responsible for the COVID-19 pandemic. The long persistence of viruses (hours to days) on surfaces calls for an urgent need for effective surface disinfection strategies to intercept virus transmission and the spread of diseases. Elucidating the physicochemical processes and surface science underlying the adsorption and transfer of virus between surfaces, as well as their inactivation, is important for understanding how diseases are transmitted and for developing effective intervention strategies. This review summarizes the current knowledge and underlying physicochemical processes of virus transmission, in particular via fomites, and common disinfection approaches. Gaps in knowledge and the areas in need of further research are also identified. The review focuses on SARS-CoV-2, but discussion of related viruses is included to provide a more comprehensive review given that much remains unknown about SARS-CoV-2. Our aim is that this review will provide a broad survey of the issues involved in fomite transmission and intervention to a wide range of readers to better enable them to take on the open research challenges.

Projecting the impact of a two-dose COVID-19 vaccination campaign in Ontario, Canada.

BACKGROUND: A number of highly effective COVID-19 vaccines have been developed and approved for mass vaccination. We evaluated the impact of vaccination on COVID-19 outbreak and disease outcomes in Ontario, Canada. METHODS: We used an agent-based transmission model and parameterized it with COVID-19 characteristics, demographics of Ontario, and age-specific clinical outcomes. We implemented a two-dose vaccination program according to tested schedules in clinical trials for Pfizer-BioNTech and Moderna vaccines, prioritizing healthcare workers, individuals with comorbidities, and those aged 65 and older. Daily vaccination rate was parameterized based on vaccine administration data. Using estimates of vaccine efficacy, we projected the impact of vaccination on the overall attack rate, hospitalizations, and deaths. We further investigated the effect of increased daily contacts at different stages during vaccination campaigns on outbreak control. RESULTS: Maintaining non-pharmaceutical interventions (NPIs) with an average of 74% reduction in daily contacts, vaccination with Pfizer-BioNTech and Moderna vaccines was projected to reduce hospitalizations by 27.3% (95% CrI: 22.3% - 32.4%) and 27.0% (95% CrI: 21.9% - 32.6%), respectively, over a one-year time horizon. The largest benefits of vaccination were observed in preventing deaths with reductions of 31.5% (95% CrI: 22.5% - 39.7%) and 31.9% (95% CrI: 22.0% - 41.4%) for Pfizer-BioNTech and Moderna vaccines, respectively, compared to no vaccination. We found that an increase of only 10% in daily contacts at the end of lockdown, when vaccination coverage with only one dose was 6%, would trigger a surge in the outbreak. Early relaxation of population-wide measures could lead to a substantial increase in the number of infections, potentially reaching levels observed during the peak of the second wave in Ontario. CONCLUSIONS: Vaccination can substantially mitigate ongoing COVID-19 outbreaks. Sustaining population-wide NPIs, to allow for a sufficient increase in population-level immunity through vaccination, is essential to prevent future outbreaks.

Routine saliva testing for the identification of silent coronavirus disease 2019 (COVID-19) in healthcare workers.

OBJECTIVE: Current COVID-19 guidelines recommend symptom-based screening and regular nasopharyngeal (NP) testing for healthcare personnel in high-risk settings. We sought to estimate case detection percentages with various routine NP and saliva testing frequencies. DESIGN: Simulation modeling study. METHODS: We constructed a sensitivity function based on the average infectiousness profile of symptomatic coronavirus disease 2019 (COVID-19) cases to determine the probability of being identified at the time of testing. This function was fitted to reported data on the percent positivity of symptomatic COVID-19 patients using NP testing. We then simulated a routine testing program with different NP and saliva testing frequencies to determine case detection percentages during the infectious period, as well as the presymptomatic stage. RESULTS: Routine biweekly NP testing, once every 2 weeks, identified an average of 90.7% (SD, 0.18) of cases during the infectious period and 19.7% (SD, 0.98) during the presymptomatic stage. With a weekly NP testing frequency, the corresponding case detection percentages were 95.9% (SD, 0.18) and 32.9% (SD, 1.23), respectively. A 5-day saliva testing schedule had a similar case detection percentage as weekly NP testing during the infectious period, but identified ~10% more cases (mean, 42.5%; SD, 1.10) during the presymptomatic stage. CONCLUSION: Our findings highlight the utility of routine noninvasive saliva testing for frontline healthcare workers to protect vulnerable patient populations. A 5-day saliva testing schedule should be considered to help identify silent infections and prevent outbreaks in nursing homes and healthcare facilities.

Routine saliva testing for the identification of silent COVID-19 infections in healthcare workers.

Objective: Current COVID-19 guidelines recommend symptom-based screening and regular nasopharyngeal (NP) testing for healthcare personnel in high-risk settings. We sought to estimate case detection percentages with various routine NP and saliva testing frequencies. Design: Simulation modelling study. Methods: We constructed a sensitivity function based on the average infectiousness profile of symptomatic COVID-19 cases to determine the probability of being identified at the time of testing. This function was fitted to reported data on the percent positivity of symptomatic COVID-19 patients using NP testing. We then simulated a routine testing program with different NP and saliva testing frequencies to determine case detection percentages during the infectious period, as well as the pre-symptomatic stage. Results: Routine bi-weekly NP testing, once every two weeks, identified an average of 90.7% (SD: 0.18) of cases during the infectious period and 19.7% (SD: 0.98) during the pre-symptomatic stage. With a weekly NP testing frequency, the corresponding case detection percentages were 95.9% (SD: 0.18) and 32.9% (SD: 1.23), respectively. A 5-day saliva testing schedule had a similar case detection percentage as weekly NP testing during the infectious period, but identified about 10% more cases (mean: 42.5%; SD: 1.10) during the pre-symptomatic stage. Conclusion: Our findings highlight the utility of routine non-invasive saliva testing for frontline healthcare workers to protect vulnerable patient populations. A 5-day saliva testing schedule should be considered to help identify silent infections and prevent outbreaks in nursing homes and healthcare facilities.

The impact of vaccination on COVID-19 outbreaks in the United States.

BACKGROUND: Global vaccine development efforts have been accelerated in response to the devastating COVID-19 pandemic. We evaluated the impact of a 2-dose COVID-19 vaccination campaign on reducing incidence, hospitalizations, and deaths in the United States (US). METHODS: We developed an agent-based model of SARS-CoV-2 transmission and parameterized it with US demographics and age-specific COVID-19 outcomes. Healthcare workers and high-risk individuals were prioritized for vaccination, while children under 18 years of age were not vaccinated. We considered a vaccine efficacy of 95% against disease following 2 doses administered 21 days apart achieving 40% vaccine coverage of the overall population within 284 days. We varied vaccine efficacy against infection, and specified 10% pre-existing population immunity for the base-case scenario. The model was calibrated to an effective reproduction number of 1.2, accounting for current non-pharmaceutical interventions in the US. RESULTS: Vaccination reduced the overall attack rate to 4.6% (95% CrI: 4.3% - 5.0%) from 9.0% (95% CrI: 8.4% - 9.4%) without vaccination, over 300 days. The highest relative reduction (54-62%) was observed among individuals aged 65 and older. Vaccination markedly reduced adverse outcomes, with non-ICU hospitalizations, ICU hospitalizations, and deaths decreasing by 63.5% (95% CrI: 60.3% - 66.7%), 65.6% (95% CrI: 62.2% - 68.6%), and 69.3% (95% CrI: 65.5% - 73.1%), respectively, across the same period. CONCLUSIONS: Our results indicate that vaccination can have a substantial impact on mitigating COVID-19 outbreaks, even with limited protection against infection. However, continued compliance with non-pharmaceutical interventions is essential to achieve this impact.

The impact of mask-wearing and shelter-in-place on COVID-19 outbreaks in the United States.

OBJECTIVES: A hasty reopening has led to a resurgence of the novel coronavirus disease 2019 (COVID-19) in the United States (US). We aimed to quantify the impact of several public health measures including non-medical mask-wearing, shelter-in-place, and detection of silent infections to help inform COVID-19 mitigation strategies. METHODS: We extended a previously established agent-based disease transmission model and parameterized it with estimates of COVID-19 characteristics and US population demographics. We implemented non-medical mask-wearing, shelter-in-place, and case isolation as control measures, and quantified their impact on reducing the attack rate and adverse clinical outcomes. RESULTS: We found that non-medical mask-wearing by 75% of the population reduced infections, hospitalizations, and deaths by 37.7% (interquartile range (IQR): 36.1-39.4%), 44.2% (IQR: 42.9-45.8%), and 47.2% (IQR: 45.5-48.7%), respectively, in the absence of a shelter-in-place strategy. Sheltering individuals aged 50 to 64 years of age was the most efficient strategy, decreasing attack rate, hospitalizations, and deaths by over 82% when combined with mask-wearing. Outbreak control was achieved in the simulated scenarios and the attack rate was reduced to below 1% when at least 33% of silent pre-symptomatic and asymptomatic infections were identified and isolated. CONCLUSIONS: Mask-wearing, even with the use of non-medical masks, has a substantial impact on outbreak control. A judicious implementation of shelter-in-place strategies remains an important public health intervention amid ongoing outbreaks.