Reducing Unnecessary Respiratory Viral Testing to Promote High-Value Care

BACKGROUND AND OBJECTIVES: Viral respiratory infections are common in children, and practice guidelines do not recommend routine testing for typical viral illnesses. Despite results often not impacting care, nasopharyngeal swabs for viral testing are frequently performed and are an uncomfortable procedure. The aim of this initiative was to decrease unnecessary respiratory viral testing (RVT) in the emergency department (ED) and the pediatric medicine wards (PMWs) by 50% and 25%, respectively, over 36 months. METHODS: An expert panel reviewed published guidelines and appropriate evidence to formulate an RVT pathway using plan-do-study-act cycles. A multifaceted improvement strategy was developed that included implementing 2 newer, more effective tests when testing was deemed necessary; electronic order modifications with force functions; audit and feedback; and education. By using statistical process control charts, the outcomes analyzed were the percentage of RVT ordered in the ED and the rate of RVT ordered on the PMWs. Balancing measures included return visits leading to admission and inpatient viral nosocomial outbreaks. RESULTS: The RVT rate decreased from a mean of 3.0% to 0.5% of ED visits and from 44.3 to 30.1 per 1000 patient days on the PMWs and was sustained throughout the study. Even when accounting for the new rapid influenza test available in the ED, a 50% decrease in overall ED RVT was still achieved without any significant impact on return visits leading to admission or inpatient nosocomial infections. CONCLUSIONS: Through implementation of a standardized, electronically integrated RVT pathway, a decrease in unnecessary RVT was successfully achieved. Audit and feedback, reminders, and biannual education all supported long-term sustainability of this initiative.

Translational Modeling of Chloroquine and Hydroxychloroquine Dosimetry in Human Airways for Treating Viral Respiratory Infections

Purpose Chloroquine and hydroxychloroquine are effective against respiratory viruses in vitro. However, they lack antiviral efficacy upon oral administration. Translation of in vitro to in vivo exposure is necessary for understanding the disconnect between the two to develop effective therapeutic strategies. Methods We employed an in vitro ion-trapping kinetic model to predict the changes in the cytosolic and lysosomal concentrations of chloroquine and hydroxychloroquine in cell lines and primary human airway cultures. A physiologically based pharmacokinetic model with detailed respiratory physiology was used to predict regional airway exposure and optimize dosing regimens. Results At their reported in vitro effective concentrations in cell lines, chloroquine and hydroxychloroquine cause a significant increase in their cytosolic and lysosomal concentrations by altering the lysosomal pH. Higher concentrations of the compounds are required to achieve similar levels of cytosolic and lysosomal changes in primary human airway cells in vitro. The predicted cellular and lysosomal concentrations in the respiratory tract for in vivo oral doses are lower than the in vitro effective levels. Pulmonary administration of aerosolized chloroquine or hydroxychloroquine is predicted to achieve high bound in vitro-effective concentrations in the respiratory tract, with low systemic exposure. Achieving effective cytosolic concentrations for activating immunomodulatory effects and adequate lysosomal levels for inhibiting viral replication could be key drivers for treating viral respiratory infections. Conclusion Our analysis provides a framework for extrapolating in vitro effective concentrations of chloroquine and hydroxychloroquine to in vivo dosing regimens for treating viral respiratory infections. Graphical abstract

Environmental Factors Influencing COVID-19 Incidence and Severity

Emerging evidence supports a link between environmental factors—including air pollution and chemical exposures, climate, and the built environment—and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and coronavirus disease 2019 (COVID-19) susceptibility and severity. Climate, air pollution, and the built environment have long been recognized to influence viral respiratory infections, and studies have established similar associations with COVID-19 outcomes. More limited evidence links chemical exposures to COVID-19. Environmental factors were found to influence COVID-19 through four major interlinking mechanisms: increased risk of preexisting conditions associated with disease severity; immune system impairment; viral survival and transport; and behaviors that increase viral exposure. Both data and methodologic issues complicate the investigation of these relationships, including reliance on coarse COVID-19 surveillance data; gaps in mechanistic studies; and the predominance of ecological designs. We evaluate the strength of evidence for environment–COVID-19 relationships and discuss environmental actions that might simultaneously address the COVID-19 pandemic, environmental determinants of health, and health disparities. Expected final online publication date for the Annual Review of Public Health, Volume 43 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Characterization of the Role of Extracellular Vesicles Released from Chicken Tracheal Cells in the Antiviral Responses against Avian Influenza Virus

During viral respiratory infections, the innate antiviral response engages a complex network of cells and coordinates the secretion of key antiviral factors, such as cytokines, which requires high levels of regulation and communication. Extracellular vesicles (EVs) are particles released from cells that contain an array of biomolecules, including lipids, proteins, and RNAs. The contents of EVs can be influenced by viral infections and may play a role in the regulation of antiviral responses. We hypothesized that the contents of EVs released from chicken tracheal cells are influenced by viral infection and that these EVs regulate the function of other immune cells, such as macrophages. To this end, we characterized the protein profile of EVs during avian influenza virus (AIV) infection and evaluated the impact of EV stimulation on chicken macrophage functions. A total of 140 differentially expressed proteins were identified upon stimulation with various stimuli. These proteins were shown to be involved in immune responses and cell signaling pathways. In addition, we demonstrated that EVs can activate macrophages. These results suggest that EVs play a role in the induction and modulation of antiviral responses during viral respiratory infections in chickens.

Respiratory Syncytial Virus Resurgence in Italy: The Need to Protect All Neonates and Young Infants

Respiratory syncytial virus (RSV) is the most prevalent cause of viral respiratory infections in children up to the age of 2 years and causes a wide range of clinical manifestations [...]

Application of recommended preventive measures against COVID-19 could help mitigate the risk of SARS-CoV-2 infection during dental practice: Results from a follow-up survey of French dentists

Background During the first-wave of the COVID-19 pandemic, dentists were considered at high-risk of infection. In France, to stop the spread of SARS-CoV-2, a nationwide lockdown was enforced, during which dentists suspended their routine clinical activities, working solely on dental emergencies. This measure has had an indisputable mitigating effect on the pandemic. To continue protecting dentists after suspension of nationwide lockdown, implementation of preventive measures was recommended, including adequate personal protective equipment (PPE) and room aeration between patients. No study has explored whether implementation of such preventive measures since the end of the first-wave has had an impact on the contamination of dentists. Methods An online survey was conducted within a French dentist population between July and September 2020. To explore risk factors associated with COVID-19, univariate and multivariate logistic regression analyses were performed. Results The results showed that COVID-19 prevalence among the 3497 respondents was 3.6%. Wearing surgical masks during non-aerosol generating procedures was a risk factor of COVID-19, whereas reducing the number of patients was a protective factor. Conclusions Considering the similar COVID-19 prevalence between dentists and the general population, such data suggest that dentists are not overexposed in their work environment when adequate preventive measures are applied. Impact Dentists should wear specific PPE (FFP2, FFP3 or (K)N95 masks) including during non-aerosol generating procedures and reduce the number of patients to allow proper implementation of disinfection and aeration procedures. Considering the similarities between COVID-19 and other viral respiratory infections, such preventive measures may also be of interest to limit emerging variants spread as well as seasonal viral outbreaks.

Effect of Relative Humidity in Air on the Transmission of Respiratory Viruses

Viral respiratory infections have plagued mankind over its known history. Unfortunately, there has been a lack of meaningful progress in preventing the spread of viral respiratory infections globally. The central dogma appears to be that viruses are the villains. This framing focuses on a viral load balance (VLB) in the air. It follows that physical dilution through various means have been the primary focus of attempts to reduce the spread of infections. The problem of obesity provides a good example of how paradigm blindness can slow down progress in a field. Obesity has been framed as an energy balance disorder that blames overeating and lack of exercise for weight gain. Reframing obesity as a disorder of fat metabolism and storage caused by the quantity and quality of carbohydrates in the diet, referred to as the carbohydrate-insulin model (CIM), opened an alternative line of questioning with a testable hypothesis. Similarly, we postulate an alternative way to frame the spread of viral respiratory infections that would lead to new insights and potentially new ways to prevent infections. It has long been recognized that viral respiratory infections show a pronounced seasonal variation, referred to as seasonal forging, such that they increase in the winter but decrease or virtually disappear in the summer. In temperate regions, people spend over 90% of their time indoors. This is, therefore, where most respiratory infections are expected to occur. Evidence has been accumulating for decades on the strong correlation between variations in indoor relative humidity (RH) and variations in infection rates. Within a RH Goldilocks zone of 40%-60%, encapsulated viruses like influenza and SARS are optimally inactivated outside the infected host. Below 40% and above 80%, viruses can survive for extended periods in the air or on surfaces. This may explain in part the seasonality of infections as the indoor level of RH in winter is typically about 20% and above 40% in summer in temperate regions. However, the mechanism for the inactivation at midrange RH (in summer) is not well understood. This paper offers a hypothesis that could explain these observations. We have demonstrated that H2O2 and other reactive oxygen species (ROS) are formed spontaneously at the water-air interface of pure water microdroplets. Using only water and a nebulizing gas in the presence of oxygen, we have demonstrated the significant disinfectant potential of pure water microdroplets caused by the activity of H2O2 and other ROS. We postulate that spontaneous H2O2 and ROS formation in viruses containing exhaled microdroplets have a similar virucidal effect at mid-range RH. The droplet evaporation rate is sufficient to concentrate the solutes and provide enough time for reactions to occur at significantly higher rates than in bulk solutions. The concentration of H2O2 has also been shown to be positively correlated to RH. In addition, several other ROS/RNS may be present or formed through interactions with H2O2 that may act as even more effective virucide disinfectants to inactivate the virus. Below RH 40% evaporation happens too rapidly for these reactions to make an impact before the droplet is desiccated, and above RH 80% the solutes remain too diluted. Rapid inactivation of viruses at midrange RH may therefore play a greater role in preventing infections than physical dilution of virus load in the air through excessive mechanical ventilation. Similar to obesity, we suggest that a new paradigm that considers virus infectivity outside the host rather than the virus load balance in the air alone could greatly contribute to our understanding of respiratory infections. The proposed new “Relative Humidity Infectivity” RHI paradigm could explain the causal mechanisms underlying seasonal respiratory infections. This can point to better prevention strategies that avoid further distortion of our indoor environment and create conditions within which humans can thrive and be optimally protected. We need more focus on testing the various hypotheses and more data to determine which of the two paradigms will lead us in the right direction or how to use the best of both in an optimal combination. The stakes cannot be higher, and the potential for eradicating future viral respiratory pandemics with nature-based solutions may be right under our noses, literally.

Requirements and study designs for US regulatory approval of influenza home tests

Home testing for infectious disease has come to the forefront during the COVID-19 pandemic. There is now considerable commercial interest in developing complete home tests for a variety of viral and bacterial pathogens. However, the regulatory science around home infectious disease test approval, and procedures test manufacturers and laboratory professionals will need to follow, have not yet been formalized by US FDA, with the exception of EUA guidance for COVID-19 tests. We describe the state of home-based testing for influenza with a focus on sample-to-result home tests, discuss the various regulatory pathways by which these products can reach populations, and provide recommendations for study designs, patient samples, and other important features necessary to gain market access. These recommendations have potential application for home use tests being developed for other viral respiratory infections, such as COVID-19, as guidance moves from EUA designation into 510(k) requirements.