COVID-19: a gray swan's impact on the adoption of novel medical technologies.

The COVID-19 pandemic offers a unique context and opportunity to investigate changes in healthcare professional perceptions towards the adoption of novel medical technologies, such as point-of-care technologies (POCTs). POCTs are a nascent technology that has experienced rapid growth as a result of COVID-19 due to their ability to increase healthcare accessibility via near-patient delivery, including at-home. We surveyed healthcare professionals before and during COVID-19 to explore whether the pandemic altered their perceptions about the usefulness of POCTs. Our network analysis method provided a structure for understanding this changing phenomenon. We uncovered that POCTs are not only useful for diagnosing COVID-19, but healthcare professionals also perceive them as increasingly important for diagnosing other diseases, such as cardiovascular, endocrine, respiratory, and metabolic diseases. Healthcare professionals also viewed POCTs as facilitating the humanization of epidemiology by improving disease management/monitoring and strengthening the clinician-patient relationship. As the accuracy and integration of these technologies into mainstream healthcare delivery improves, hurdles to their adoption dissipate, thereby encouraging healthcare professionals to rely upon them more frequently to diagnose, manage, and monitor diseases. The technological advances made in POCTs during COVID-19, combined with shifting positive perceptions of their utility by healthcare professionals, may better prepare us for the next pandemic.

Longitudinal Analysis of SARS-CoV-2 Vaccine Breakthrough Infections Reveals Limited Infectious Virus Shedding and Restricted Tissue Distribution.

Background: The global effort to vaccinate people against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during an ongoing pandemic has raised questions about how vaccine breakthrough infections compare with infections in immunologically naive individuals and the potential for vaccinated individuals to transmit the virus. Methods: We examined viral dynamics and infectious virus shedding through daily longitudinal sampling in 23 adults infected with SARS-CoV-2 at varying stages of vaccination, including 6 fully vaccinated individuals. Results: The durations of both infectious virus shedding and symptoms were significantly reduced in vaccinated individuals compared with unvaccinated individuals. We also observed that breakthrough infections are associated with strong tissue compartmentalization and are only detectable in saliva in some cases. Conclusions: Vaccination shortens the duration of time of high transmission potential, minimizes symptom duration, and may restrict tissue dissemination.

Understanding Healthcare Professionals' Perspectives on Point-of-Care Testing.

Point-of-care testing (POCT) is an emerging technology that provides crucial assistance in delivering healthcare. The COVID-19 pandemic led to the accelerated importance of POCT technology due to its in-home accessibility. While POCT use and implementation has increased, little research has been published about how healthcare professionals perceive these technologies. The objective of our study was to examine the current perspectives of healthcare professionals towards POCT. We surveyed healthcare professionals to quantify perceptions of POCT usage, adoption, benefits, and concerns between October 2020 and November 2020. Questions regarding POCT perception were assessed on a 5-point Likert Scale. We received a total of 287 survey responses. Of the respondents, 53.7% were male, 66.6% were white, and 30.7% have been in practice for over 20 years. We found that the most supported benefit was POCTs ability to improve patient management (92%) and that the most supported concern was that POCTs lead to over-testing (30%). This study provides a better understanding of healthcare workers' perspectives on POCT. To improve patient outcomes through the usage of POCT, greater research is needed to assess the needs and concerns of industry and healthcare stakeholders.

Limitations of Molecular and Antigen Test Performance for SARS-CoV-2 in Symptomatic and Asymptomatic COVID-19 Contacts.

COVID-19 has brought unprecedented attention to the crucial role of diagnostics in pandemic control. We compared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test performance by sample type and modality in close contacts of SARS-CoV-2 cases. Close contacts of SARS-CoV-2-positive individuals were enrolled after informed consent. Clinician-collected nasopharyngeal (NP) swabs in viral transport media (VTM) were tested with a routine clinical reference nucleic acid test (NAT) and PerkinElmer real-time reverse transcription-PCR (RT-PCR) assay; positive samples were tested for infectivity using a VeroE6TMPRSS2 cell culture model. Self-collected passive drool was also tested using the PerkinElmer RT-PCR assay. For the first 4 months of study, midturbinate swabs were tested using the BD Veritor rapid antigen test. Between 17 November 2020 and 1 October 2021, 235 close contacts of SARS-CoV-2 cases were recruited, including 95 with symptoms (82% symptomatic for ≤5 days) and 140 asymptomatic individuals. Reference NATs were positive for 53 (22.6%) participants; 24/50 (48%) were culture positive. PerkinElmer testing of NP and saliva samples identified an additional 28 (11.9%) SARS-CoV-2 cases who tested negative by reference NAT. Antigen tests performed for 99 close contacts showed 83% positive percent agreement (PPA) with reference NAT among early symptomatic persons, but 18% PPA in others; antigen tests in 8 of 11 (72.7%) culture-positive participants were positive. Contacts of SARS-CoV-2 cases may be falsely negative early after contact, but more sensitive platforms may identify these cases. Repeat or serial SARS-CoV-2 testing with both antigen and molecular assays may be warranted for individuals with high pretest probability for infection.

Daily longitudinal sampling of SARS-CoV-2 infection reveals substantial heterogeneity in infectiousness.

The dynamics of SARS-CoV-2 replication and shedding in humans remain poorly understood. We captured the dynamics of infectious virus and viral RNA shedding during acute infection through daily longitudinal sampling of 60 individuals for up to 14 days. By fitting mechanistic models, we directly estimated viral expansion and clearance rates and overall infectiousness for each individual. Significant person-to-person variation in infectious virus shedding suggests that individual-level heterogeneity in viral dynamics contributes to 'superspreading'. Viral genome loads often peaked days earlier in saliva than in nasal swabs, indicating strong tissue compartmentalization and suggesting that saliva may serve as a superior sampling site for early detection of infection. Viral loads and clearance kinetics of Alpha (B.1.1.7) and previously circulating non-variant-of-concern viruses were mostly indistinguishable, indicating that the enhanced transmissibility of this variant cannot be explained simply by higher viral loads or delayed clearance. These results provide a high-resolution portrait of SARS-CoV-2 infection dynamics and implicate individual-level heterogeneity in infectiousness in superspreading.

ReducinG stroke by screening for UndiAgnosed atRial fibrillation in elderly inDividuals (GUARD-AF): Rationale and design of the GUARD-AF randomized trial of screening for atrial fibrillation with a 14-day patch-based continuous ECG monitor.

BACKGROUND: Screening for atrial fibrillation (AF) is attractive because AF independently raises the risk of ischemic stroke, this risk is largely reversible by long-term oral anticoagulant therapy (OAC), and many patients with AF remain undiagnosed and untreated. Recent trials of one-time brief screening for AF have not produced a significant increase in the proportion of patients diagnosed with AF. Trials of longer-term screening have demonstrated an increase in AF diagnoses, primarily paroxysmal AF. To date, however, no trials have demonstrated that screening for AF results in lower rates of stroke. Clinical practice guidelines conflict in their level of support for screening for AF. METHODS: The GUARD-AF individually randomized trial is designed to test whether screening for AF in individuals age 70 years or greater using a 2-week single-lead electrocardiographic patch monitor can identify patients with undiagnosed AF and lead to treatment with OAC, resulting in a reduced rate of stroke in the screened population. The trial's efficacy end point is hospitalization for stroke (either ischemic or hemorrhagic) and the trial's safety end point is hospitalization for a bleeding event. End points will be ascertained via Medicare claims or electronic health records at 2.5 years after study start. Enrollment is based in primary care practices and the OAC decision for screen-detected cases is left to the patient and their physician. The initial planned target sample size was 52,000, with 26,000 allocated to either screening or to usual care. RESULTS: Trial enrollment was severely hampered by the novel coronavirus disease 2019 (COVID-19) pandemic and stopped at a total enrollment of 11,931 participants. Of 5,965 randomized to the screening arm, 5,713 patients (96%) returned monitors with analyzable results. Incidence of screen-detected and clinically detected AF and associated stroke and bleeding outcomes will be ascertained. CONCLUSIONS: GUARD-AF is the largest AF screening randomized trial using a longer-term patch-based continuous electrocardiographic monitor. The results will contribute important information on the yield of patch-based AF screening, the "burden" of AF detected (percent time in AF, longest episode), and physicians' OAC decisions as a function of AF burden. GUARD-AF's stroke and bleed results will contribute to pooled trial analyses of AF screening, thereby informing future studies and guidelines.

NExUS-Heart: Novel examinations using smart technologies for heart health-Data sharing from commercial wearable devices and telehealth engagement in participants with or at risk of atrial fibrillation.

Background: Telemedicine and commercial wearable devices capable of detecting atrial fibrillation (AF) have revolutionized arrhythmia care during coronavirus disease 2019. However, not much is known about virtual patient-provider interactions or device sharing behaviors. Objective: The purpose of this study was to characterize how participants with or at risk of AF are engaging with their providers in the context of telemedicine and using commercially wearable devices to manage their health. Methods: We developed a survey to describe participant behaviors around telemedicine encounters and commercial wearable device use. The survey was distributed to participants diagnosed with AF or those at risk of AF (as determined by being at least 65 years old and having a CHA2DS2-VASc stroke risk score of >2) in the University of Massachusetts Memorial Health Care system. Results: The survey was distributed to 23,530 patients, and there were 1222 (5.19%) participant responses. Among the participants, 327 (26.8%) had AF and 895 (73.2%) were at risk of AF. Neither device ownership nor device type use differed by AF status. After adjusting for covariates that may influence surveyed participant communication patterns, we found that participants with AF were more likely to share their wearable device-derived data with providers (adjusted odds ratio 1.87; 95% confidence interval 1.02-3.41). Rates of sharing physical activity or sleep data were low for both groups and did not differ by AF status. Conclusion: Compared with participants at risk of developing AF, those with AF were more likely to share heart rate and rhythm data from their commercial wearable devices with providers. However, both groups had similar rates of sharing physical activity and sleep data, telemedicine engagement, and technology use and ownership.

New Opportunities and Cautionary Insights about Decentralizing and Deglobalizing Clinical Trials During the Great Lockdown.

The 2020s began with a rare coronavirus (COVID-19) disaster, which led to a pandemic-induced recession and Great Lockdown. In response, there has been a worldwide mobilization of resources to detect, treat, and cure the virus. Some policymakers are advocating for the repatriation of globally distributed healthcare know-how. Without a cure for COVID-19, the ambiguity concerning how coronavirus-related policies will impact international business remains unclear. Through a multi-method approach, our study sheds light on two key healthcare industry trends: decentralization and deglobalization of clinical trials. We offer actionable strategies to not only mitigate these challenges, but also to take advantage of their new opportunities.

Longitudinal Assessment of Diagnostic Test Performance Over the Course of Acute SARS-CoV-2 Infection.

BACKGROUND: Serial screening is critical for restricting spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by facilitating timely identification of infected individuals to interrupt transmission. Variation in sensitivity of different diagnostic tests at different stages of infection has not been well documented. METHODS: In a longitudinal study of 43 adults newly infected with SARS-CoV-2, all provided daily saliva and nasal swabs for quantitative reverse transcription polymerase chain reaction (RT-qPCR), Quidel SARS Sofia antigen fluorescent immunoassay (FIA), and live virus culture. RESULTS: Both RT-qPCR and Quidel SARS Sofia antigen FIA peaked in sensitivity during the period in which live virus was detected in nasal swabs, but sensitivity of RT-qPCR tests rose more rapidly prior to this period. We also found that serial testing multiple times per week increases the sensitivity of antigen tests. CONCLUSIONS: RT-qPCR tests are more effective than antigen tests at identifying infected individuals prior to or early during the infectious period and thus for minimizing forward transmission (given timely results reporting). All tests showed >98% sensitivity for identifying infected individuals if used at least every 3 days. Daily screening using antigen tests can achieve approximately 90% sensitivity for identifying infected individuals while they are viral culture positive.

A multi-institutional partnership catalyzing the commercialization of medical devices and biotechnology products.

The commercialization of medical devices and biotechnology products is characterized by high failure rates and long development lead times particularly among start-up enterprises. To increase the success rate of these high-risk ventures, the University of Massachusetts Lowell (UML) and University of Massachusetts Medical School (UMMS) partnered to create key academic support centers with programs to accelerate entrepreneurship and innovation in this industry. In 2008, UML and UMMS founded the Massachusetts Medical Device Development Center (M2D2), which is a business and technology incubator that provides business planning, product prototyping, laboratory services, access to clinical testing, and ecosystem networking to medical device and biotech start-up firms. M2D2 has three physical locations that encompass approximately 40,000 square feet. Recently, M2D2 leveraged these resources to expand into new areas such as health security, point of care technologies for heart, lung, blood, and sleep disorders, and rapid diagnostics to detect SARS-CoV-2. Since its inception, M2D2 has vetted approximately 260 medical device and biotech start-up companies for inclusion in its programs and provided active support to more than 80 firms. This manuscript describes how two UMass campuses leveraged institutional, state, and Federal resources to create a thriving entrepreneurial environment for medical device and biotech companies.