Occurrence and Timing of Subsequent SARS-CoV-2 RT-PCR Positivity Among Initially Negative Patients

BackgroundSARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) testing remains the cornerstone of laboratory-based identification of patients with COVID-19. As the availability and speed of SARS-CoV-2 testing platforms improve, results are increasingly relied upon to inform critical decisions related to therapy, use of personal protective equipment, and workforce readiness. However, early reports of RT-PCR test performance have left clinicians and the public with concerns regarding the reliability of this predominant testing modality and the interpretation of negative results. In this work, two independent research teams report the frequency of discordant SARS-CoV-2 test results among initially negative, repeatedly tested patients in regions of the United States with early community transmission and access to testing. MethodsAll patients at the University of Washington (UW) and Stanford Health Care undergoing initial testing by nasopharyngeal (NP) swab between March 2nd and April 7th, 2020 were included. SARS-CoV-2 RT-PCR was performed targeting the N, RdRp, S, and E genes and ORF1ab, using a combination of Emergency Use Authorization laboratory-developed tests and commercial assays. Results through April 14th were extracted to allow for a complete 7-day observation period and an additional day for reporting. ResultsA total of 23,126 SARS-CoV-2 RT-PCR tests (10,583 UW, 12,543 Stanford) were performed in 20,912 eligible patients (8,977 UW, 11,935 Stanford) undergoing initial testing by NP swab; 626 initially test-negative patients were re-tested within 7 days. Among this group, repeat testing within 7 days yielded a positive result in 3.5% (4.3% UW, 2.8% Stanford) of cases, suggesting an initial false negative RT-PCR result; the majority (96.5%) of patients with an initial negative result who warranted reevaluation for any reason remained negative on all subsequent tests performed within this window. ConclusionsTwo independent research teams report the similar finding that, among initially negative patients subjected to repeat SARS-CoV-2 RT-PCR testing, the occurrence of a newly positive result within 7 days is uncommon. These observations suggest that false negative results at the time of initial presentation do occur, but potentially at a lower frequency than is currently believed. Although it is not possible to infer the clinical sensitivity of NP SARS-CoV-2 RT-PCR testing using these data, they may be used in combination with other reports to guide the use and interpretation of this common testing modality.

Real-time assessment of COVID-19 impact on global surgical case volumes

ImportanceThe COVID-19 pandemic has disrupted global surgical capacity. The impact of the pandemic in low and middle income countries has the potential to worsen already strained access to surgical care. Timely assessment of surgical volumes in these countries remains challenging. ObjectiveTo determine whether usage data from a globally used anesthesiology calculator mobile application can serve as a proxy for global surgical case volume and contribute to monitoring of the impact of the COVID-19 pandemic, particularly in World Bank low income countries where official data collection is not currently practical. DesignSubset of data from an ongoing observational cohort study of users of the application collected from October 1, 2018 to April 18, 2020. SettingThe mobile application is available from public sources; users download and use the application per their own clinical needs on personal mobile devices. ParticipantsNo user data was excluded from the study. Exposure(s)Events with impacts on surgical case volumes, including weekends, holidays, and the COVID-19 pandemic. Main Outcome(s) and Measure(s)It was previously noted that application usage was decreased on weekends and during winter holidays. We subsequently hypothesized that more detailed analysis would reveal impacts of country-specific or region-specific holidays on the volume of app use. Results4,300,975 data points from 92,878 unique users were analyzed. Physicians and other anesthesia providers comprised 85.8% of the study population. Application use was reduced on holidays and weekends and correlated with fluctuations in surgical volume. The COVID-19 pandemic was associated with substantial reductions in app use globally and regionally. There was strong cross correlation between COVID-19 case count and reductions in app use. By country, there was a median global reduction in app use to 58% of baseline (interquartile range, 46%-75%). Application use in low-income continues to decline but in high-income countries has stabilized. Conclusions and RelevanceApplication usage metadata provides a real-time indicator of surgical volume. This data may be used to identify impacted regions where disruptions to surgical care are disproportionate or prolonged. A dashboard for continuous visualization of these data has been deployed. Key PointsO_ST_ABSQuestionC_ST_ABSCan usage data from a globally used anesthesiology calculator mobile application contribute to monitoring of the impacts to global surgical case volume caused by the COVID-19 pandemic, particularly in resource-limited environments such as World Bank low income countries? FindingsIn this ongoing observational cohort study, application usage data from 92,878 unique users in 221 countries was found to serve well as a qualitative proxy for surgical case volume, with clear impacts to app use during weekend, holidays, and during the COVID-19 pandemic. MeaningThis proxy of surgical volume will provide insight into the impact of and recovery from the COVID-19 pandemic where official data collection is not currently practical. A real time dashboard tracking this proxy of global surgical volume is live and under continued development.