Population testing for COVID-19: an approach for infection prevention

BackgroundPopulation screening with highly sensitive diagnostic tools, such as nucleic acid amplification testing (NAAT), can enable early identification and isolation of cases and reduce transmission of SARS-CoV-2.ObjectiveTo describe the results of a rigorous, large-scale COVID-19 testing and monitoring program with confirmatory processes and adjudication of positive results.DesignDescriptive Epidemiology StudySetting32 U.S. National Football League (NFL) Clubs during the 2020 seasonParticipantsNFL players and staffMethodsThe NFL/NFL Players Association instituted a COVID-19 Testing and Surveillance Program for the 2020 Season, which included daily testing for players and staff, full medical follow-up and adjudication of cases. Clinical adjudication was based on subsequent daily testing, symptoms, and clinical history;persons remained in isolation during adjudication.ResultsBetween August 1 and November 14, 2020, a total of 632,370 RT-PCR tests were administered to 11,668 individuals;270 (2.4%) confirmed cases were observed. PPVs of the initial positive result ranged from 73–82% across RT-PCR platforms. Initial positive results were positive on re-processing 61–79% of the time. PPV increased when both results were positive to >95%;however, initial positives that were negative on confirmatory processing resulted in true cases a portion of the time, depending on machine and population prevalence. High Ct values (33 to 37) could indicate onset of infection. Infected individuals were identified and isolated early in infection, preventing spread.InterventionsDaily or frequent testing using three NAAT platforms, rapid point-of-care testing, and symptom monitoring.Main Outcome MeasurementsCOVID-19 infection.ConclusionRoutine RT-PCR testing allowed early detection of infection. Cycle threshold values provided a useful guidepost for understanding results. Confirmatory processing of initial positive values significantly improved PPV. Antigen POC testing was unable to reliably rule out COVID-19 early in infection. Adjudication processes were able to confirm or rule out SARS-CoV-2.

Optimizing SARS-CoV-2 Surveillance in the United States: Insights From the National Football League Occupational Health Program.

BACKGROUND: Evidence to understand effective strategies for surveillance and early detection of SARS-CoV-2 is limited. OBJECTIVE: To describe the results of a rigorous, large-scale COVID-19 testing and monitoring program. DESIGN: The U.S. National Football League (NFL) and the NFL Players Association (NFLPA) instituted a large-scale COVID-19 monitoring program involving daily testing using 2 reverse transcription polymerase chain reaction (RT-PCR) platforms (Roche cobas and Thermo Fisher QuantStudio), a transcription-mediated amplification platform (Hologic Panther), and an antigen point-of-care (aPOC) test (Quidel Sofia). SETTING: 32 NFL clubs in 24 states during the 2020 NFL season. PARTICIPANTS: NFL players and staff. MEASUREMENTS: SARS-CoV-2 test results were described in the context of medically adjudicated status. Cycle threshold (Ct) values are reported when available. RESULTS: A total of 632 370 tests administered across 11 668 persons identified 270 (2.4%) COVID-19 cases from 1 August to 14 November 2020. Positive predictive values ranged from 73.0% to 82.0% across the RT-PCR platforms. High Ct values (33 to 37) often indicated early infection. For the first positive result, the median Ct value was 32.77 (interquartile range, 30.02 to 34.72) and 22% of Ct values were above 35. Among adjudicated COVID-19 cases tested with aPOC, 42.3% had a negative result. Positive concordance between aPOC test result and adjudicated case status increased as viral load increased. LIMITATIONS: Platforms varied by laboratory, and test variability may reflect procedural differences. CONCLUSION: Routine RT-PCR testing allowed early detection of infection. Cycle threshold values provided a useful guidepost for understanding results, with high values often indicating early infection. Antigen POC testing was unable to reliably rule out COVID-19 early in infection. PRIMARY FUNDING SOURCE: The NFL and the NFLPA.

Viral dynamics of acute SARS-CoV-2 infection and applications to diagnostic and public health strategies.

SARS-CoV-2 infections are characterized by viral proliferation and clearance phases and can be followed by low-level persistent viral RNA shedding. The dynamics of viral RNA concentration, particularly in the early stages of infection, can inform clinical measures and interventions such as test-based screening. We used prospective longitudinal quantitative reverse transcription PCR testing to measure the viral RNA trajectories for 68 individuals during the resumption of the 2019-2020 National Basketball Association season. For 46 individuals with acute infections, we inferred the peak viral concentration and the duration of the viral proliferation and clearance phases. According to our mathematical model, we found that viral RNA concentrations peaked an average of 3.3 days (95% credible interval [CI] 2.5, 4.2) after first possible detectability at a cycle threshold value of 22.3 (95% CI 20.5, 23.9). The viral clearance phase lasted longer for symptomatic individuals (10.9 days [95% CI 7.9, 14.4]) than for asymptomatic individuals (7.8 days [95% CI 6.1, 9.7]). A second test within 2 days after an initial positive PCR test substantially improves certainty about a patient's infection stage. The effective sensitivity of a test intended to identify infectious individuals declines substantially with test turnaround time. These findings indicate that SARS-CoV-2 viral concentrations peak rapidly regardless of symptoms. Sequential tests can help reveal a patient's progress through infection stages. Frequent, rapid-turnaround testing is needed to effectively screen individuals before they become infectious.

SARS-CoV-2 Transmission Risk Among National Basketball Association Players, Staff, and Vendors Exposed to Individuals With Positive Test Results After COVID-19 Recovery During the 2020 Regular and Postseason.

Importance: Clinical data are lacking regarding the risk of viral transmission from individuals who have positive reverse-transcription-polymerase chain reaction (RT-PCR) SARS-CoV-2 test results after recovery from COVID-19. Objective: To describe case characteristics, including viral dynamics and transmission of infection, for individuals who have clinically recovered from SARS-CoV-2 infection but continued to have positive test results following discontinuation of isolation precautions. Design, Setting, and Participants: This retrospective cohort study used data collected from June 11, 2020, to October 19, 2020, as part of the National Basketball Association (NBA) closed campus occupational health program in Orlando, Florida, which required daily RT-PCR testing and ad hoc serological testing for SARS-CoV-2 IgG antibodies. Nearly 4000 NBA players, staff, and vendors participated in the NBA's regular and postseason occupational health program in Orlando. Persistent positive cases were those who recovered from a documented SARS-CoV-2 infection, satisfied US Centers for Disease Control and Prevention criteria for discontinuation of isolation precautions, and had at least 1 postinfection positive RT-PCR test(s) result. Exposures: Person-days of participation in indoor, unmasked activities that involved direct exposure between persistent positive cases and noninfected individuals. Main Outcomes and Measures: Transmission of SARS-CoV-2 following interaction with persistent positive individuals, as measured by the number of new COVID-19 cases in the Orlando campus program. Results: Among 3648 individuals who participated, 36 (1%) were persistent positive cases, most of whom were younger than 30 years (24 [67%]) and male (34 [94%]). Antibodies were detected in 33 individuals (91.7%); all remained asymptomatic following the index persistent positive RT-PCR result. Cycle threshold values for persistent positive RT-PCR test results were typically above the Roche cobas SARS-CoV-2 limit of detection. Cases were monitored for up to 100 days (mean [SD], 51 [23.9] days), during which there were at least 1480 person-days of direct exposure activities, with no transmission events or secondary infections of SARS-CoV-2 detected (0 new cases). Conclusions and Relevance: In this retrospective cohort study of the 2020 NBA closed campus occupational health program, recovered individuals who continued to test positive for SARS-CoV-2 following discontinuation of isolation were not infectious to others. These findings support time-based US Centers of Disease Control and Prevention recommendations for ending isolation.