Advances in molecular infectious diseases testing in the time of COVID-19.

The Coronavirus Disease of 2019 (COVID-19) pandemic has been a challenging event for laboratory medicine and diagnostics manufacturers. We have had to confront numerous unique and previously unthinkable issues on a daily basis in order to continue offering diagnostic testing for not only Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), but other testing that was significantly impacted by supply chain and staffing disruptions related to COVID-19. Out of this tremendously stressful and, at times, chaotic environment, decades of innovations and advances in testing methodologies and instrumentation became essential to handle the overwhelming volume of samples with clinically appropriate turn-around-time. Additionally, a number of novel testing approaches and technological innovations emerged to address laboratory and public health needs for widespread testing. In this review we consider both technological advances in infectious diseases testing and other innovations in sample collection, processing, automation, workflow, and testing that have embodied the laboratory response to the COVID-19 pandemic.

Longitudinal Assessment of SARS-CoV-2 Antinucleocapsid and Antispike-1-RBD Antibody Testing Following PCR-Detected SARS-CoV-2 Infection.

BACKGROUND: SARS-CoV-2 serologic assays are becoming increasingly available and may serve as a diagnostic aid in a multitude of settings relating to past infection status. However, there is limited literature detailing the longitudinal performance of EUA-cleared serologic assays in US populations, particularly in cohorts with a remote history of PCR-confirmed SARS-CoV-2 infection (e.g., >2 months). METHODS: We evaluated the diagnostic sensitivities and specificities of the Elecsys® Anti-SARS-CoV-2 (anti-N) and Elecsys Anti-SARS-CoV-2 S (anti-S1-RBD) assays, using 174 residual clinical samples up to 267 days post-PCR diagnosis of SARS-CoV-2 infection (n = 154) and a subset of samples obtained prior to the COVID-19 pandemic as negative controls (n = 20). RESULTS: The calculated diagnostic sensitivities for the anti-N and anti-S1-RBD assays were 89% and 93%, respectively. Of the 154 samples in the SARS-CoV-2-positive cohort, there were 6 discrepant results between the anti-N and anti-S1-RBD assays, 5 of which were specimens collected ≥200 days post-PCR positivity and only had detectable levels of anti-S1-RBD antibodies. When only considering specimens collected ≥100 days post-PCR positivity (n = 41), the sensitivities for the anti-N and anti-S1-RBD assays were 85% and 98%, respectively. CONCLUSIONS: The anti-S1-RBD assay demonstrated superior sensitivity at time points more remote to the PCR detection date, with 6 more specimens from the SARS-CoV-2-positive cohort detected, 5 of which were collected more than 200 days post-PCR positivity. While analytical differences and reagent lot-to-lot variability are possible, this may indicate that, in some instances, anti-S1-RBD antibodies may persist longer in vivo and may be a better target for detecting remote SARS-CoV-2 infection.

Clinical characteristics and outcomes for 7,995 patients with SARS-CoV-2 infection.

OBJECTIVE: Severe acute respiratory syndrome virus (SARS-CoV-2) has infected millions of people worldwide. Our goal was to identify risk factors associated with admission and disease severity in patients with SARS-CoV-2. DESIGN: This was an observational, retrospective study based on real-world data for 7,995 patients with SARS-CoV-2 from a clinical data repository. SETTING: Yale New Haven Health (YNHH) is a five-hospital academic health system serving a diverse patient population with community and teaching facilities in both urban and suburban areas. POPULATIONS: The study included adult patients who had SARS-CoV-2 testing at YNHH between March 1 and April 30, 2020. MAIN OUTCOME AND PERFORMANCE MEASURES: Primary outcomes were admission and in-hospital mortality for patients with SARS-CoV-2 infection as determined by RT-PCR testing. We also assessed features associated with the need for respiratory support. RESULTS: Of the 28605 patients tested for SARS-CoV-2, 7995 patients (27.9%) had an infection (median age 52.3 years) and 2154 (26.9%) of these had an associated admission (median age 66.2 years). Of admitted patients, 2152 (99.9%) had a discharge disposition at the end of the study period. Of these, 329 (15.3%) required invasive mechanical ventilation and 305 (14.2%) expired. Increased age and male sex were positively associated with admission and in-hospital mortality (median age 80.7 years), while comorbidities had a much weaker association with the risk of admission or mortality. Black race (OR 1.43, 95%CI 1.14-1.78) and Hispanic ethnicity (OR 1.81, 95%CI 1.50-2.18) were identified as risk factors for admission, but, among discharged patients, age-adjusted in-hospital mortality was not significantly different among racial and ethnic groups. CONCLUSIONS: This observational study identified, among people testing positive for SARS-CoV-2 infection, older age and male sex as the most strongly associated risks for admission and in-hospital mortality in patients with SARS-CoV-2 infection. While minority racial and ethnic groups had increased burden of disease and risk of admission, age-adjusted in-hospital mortality for discharged patients was not significantly different among racial and ethnic groups. Ongoing studies will be needed to continue to evaluate these risks, particularly in the setting of evolving treatment guidelines.

Agile Health Care Analytics: Enabling Real-Time Disease Surveillance With a Computational Health Platform.

The ongoing coronavirus disease outbreak demonstrates the need for novel applications of real-time data to produce timely information about incident cases. Using health information technology (HIT) and real-world data, we sought to produce an interface that could, in near real time, identify patients presenting with suspected respiratory tract infection and enable monitoring of test results related to specific pathogens, including severe acute respiratory syndrome coronavirus 2. This tool was built upon our computational health platform, which provides access to near real-time data from disparate HIT sources across our health system. This combination of technology allowed us to rapidly prototype, iterate, and deploy a platform to support a cohesive organizational response to a rapidly evolving outbreak. Platforms that allow for agile analytics are needed to keep pace with evolving needs within the health care system.

Impact of COVID-19 Pandemic on Laboratory Utilization.

BACKGROUND: Coronavirus disease 2019 (COVID-19) was formally characterized as a pandemic on March 11, 2020. Since that time, the COVID-19 pandemic has led to unprecedented demand for healthcare resources. The purpose of this study was to identify changes in laboratory test utilization in the setting of increasing local incidence of COVID-19. METHODS: We performed a retrospective assessment of laboratory test order and specimen container utilization at a single, urban tertiary care medical center. Data were extracted from the laboratory information system database over a 10-week period, spanning the primordial inflection of COVID-19 incidence in our region. Total testing volumes were calculated during the first 2 and last 2 weeks of the observation period and used as reference points to examine the absolute and relative differences in test order volume between the prepandemic and COVID-19 surge periods. RESULTS: Between February 2, 2020, and April 11, 2020, there were 873 397 tests ordered and final verified. The in-house SARS-CoV-2 PCR positivity rate for admitted patients in the last week of the observation period was 30.8%. Significant increases in workload were observed in the send-out laboratory section and for COVID-19 diagnosis (PCR) and management-related testing. Otherwise, there was a net decrease in overall demand across nearly all laboratory sections. Increases in testing were noted for tests related to COVID-19 management. Viral transport media and citrated blue top containers demonstrated increases in utilization. CONCLUSION: Increasing local incidence of COVID-19 had a profound impact on laboratory operations. While volume increases were seen for laboratory tests related to COVID-19 diagnostics and management, including some with limited evidence to support their use, overall testing volumes decreased substantially. During events such as COVID-19, monitoring of such patterns can help inform laboratory management, staffing, and test stewardship recommendations for managing resource and supply availability.