Recommendations from the Centers for Disease Control and Prevention (CDC) for duration of transmission-based precautions or “isolation” for hospitalized patients with coronavirus disease 2019 (COVID-19) are based on observational data evaluating time since symptom onset and recovery of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in viral culture as a marker for infectiousness. 1 These include a minimum 10 days of precautions without repeat testing for patients with mild-to-moderate illness (or asymptomatic), and longer durations for critically ill and immunosuppressed patients, further guided by repeated SARS-CoV-2 testing. Due to persistent viral detection in the absence of culturable virus, broad use of SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR) testing in healthcare facilities may identify individuals with a positive SARS-CoV-2 result but who are no longer infectious, contributing to prolonged isolation and delays in care and throughput. Reference O’Reilly, Mitchell and Mitra2–Reference Alsuhaibani, Kobayashi and Trannel4
Based on correlation between SARS-CoV-2 antigen test positivity and presence of potentially infectious virus, Reference Korenkov, Poopalasingam and Madler5–Reference Kirby, Riedel and Dutta7 we implemented and evaluated a SARS-CoV-2 antigen-test–based strategy to discontinue transmission-based precautions for hospitalized patients with COVID-19. We hypothesized that the antigen-test–based strategy would be associated with a significantly shorter duration of precautions than a time or an RT-PCR–based strategy.
Methods
Strategies to determine the duration of isolation
At our 800-bed, tertiary-care, academic medical center in Baltimore, Maryland, hospitalized patients with a positive SARS-CoV-2 diagnostic test and no previous positive in the preceding 12 weeks are assigned a COVID-19 banner in the electronic health record (EHR), and they receive care using transmission-based precautions per CDC guidance. Prior to February 15, 2022, we used 2 strategies to determine the duration of these precautions: (1) a time-based strategy for asymptomatic or mild-to-moderate illness requiring at least 10 days from symptom onset (or diagnosis if asymptomatic), (2) a time and test (RT-PCR)–based strategy for critically ill and severely immunosuppressed patients (Supplementary Table online).
Beginning February 15, 2022, we implemented a SARS-CoV-2 antigen-test–based strategy to facilitate discontinuation of precautions using separate algorithms (Supplementary Fig. 1 online) for patients with (1) asymptomatic or mild-to-moderate disease, (2) critical illness, and (3) severe immunosuppression. Test eligibility was established by clinical improvement and ≥5 days from symptom onset for mild-to-moderate or critical illness and ≥14 days for severely immunosuppressed patients. For asymptomatic patients without a known COVID-19 exposure, antigen testing could begin immediately. Two consecutive negative tests ≥24 hours apart were required to discontinue precautions. The antigen-test–based strategy was ordered optionally at the discretion of clinical teams. Testing was performed using FDA-authorized point-of-care SARS-CoV-2 antigen test kits (CareStart COVID-19 Antigen) by trained registered nurses on weekdays only. Infection preventionists resolved the COVID-19 banner for patients meeting criteria for discontinuation of precautions. During this period, SARS-CoV-2 antigen testing was not utilized for any other indication in hospitalized patients.
Fig. 1. Sequential point-of-care SARS-CoV-2 antigen test results during hospitalization with COVID-19.
Cohort selection
We included all patients aged ≥2 years with positive SARS-CoV-2 tests hospitalized from February 15 to September 1, 2022. During this time, all patients underwent routine SARS-CoV-2 PCR testing upon hospital admission, regardless of symptoms. Patients with duration of stay <48 hours and patients with COVID-19 banner present for <12 hours (ie, determined to be remote infection with residual PCR positivity based on history) were excluded.
Data collection
From the EHR, we obtained patient demographics, admission and discharge dates and times, location of care at admission, presence of COVID-19 symptoms, date and time of onset and resolution of the COVID-19 banner, and if performed, dates and times of antigen testing and test results.
Outcomes and analysis
We summarized patient characteristics for the overall cohort and separately for patients who underwent antigen testing and those who did not. For patients who underwent antigen testing, we calculated time from admission and time from COVID-19 banner onset to first antigen test, and the proportion of positive antigen test results for each sequential test performed. The primary outcome was duration of COVID-19 transmission-based precautions estimated using time from assignment of a COVID-19 banner to resolution. Bivariate analyses were conducted to compare patients who underwent antigen testing with those who did not and to compare patients who tested positive versus negative on initial antigen testing. We used the χ2, Wilcoxon ranked-sum, or Student t test as appropriate. Data analysis was conducted using SAS version 9.4 software (SAS Institute, Cary, NC). This study was determined to be exempt from approval by the University of Maryland, Baltimore Institutional Review Board.
Results
We included 623 unique hospital admissions with positive SARS-CoV-2 tests; 171 patients (27%) underwent SARS-CoV-2 antigen testing to facilitate discontinuation of precautions. Patients who underwent SARS-COV-2 antigen testing were older and had a higher proportion of admissions to intermediate level of care (Table 1).
Table 1. Characteristics and COVID-19 Banner Duration for Patients Hospitalized With COVID-19
a Data are no. (%) unless otherwise specified.
Of 171 admitted patients who underwent SARS-COV-2 antigen testing, 50 (29%) had COVID-19 symptoms, and 128 (75%) received at least 2 antigen tests (range, 1–6). The median times to first antigen test from admission and from COVID-19 banner assignment were 121 hours (interquartile range [IQR], 72–181) and 113 hours (IQR, 62–154), respectively. These times were not different between symptomatic and asymptomatic patients. The first antigen test was negative in 116 cases (68%). A positive test was more frequent in symptomatic (22 of 50, 44%) compared to asymptomatic patients (33 of 121, 27%; P = .04). Of 128 patients who underwent a second SARS-COV-2 antigen test, 90 (70%) had 2 negative tests, 17 (13%) had a negative second test after an initial positive result, 16 (13%) had 2 positive tests, and 5 (4%) had a positive second test after an initial negative result (Fig. 1).
The median duration of COVID-19 banner was significantly shorter for patients who underwent SARS-COV-2 antigen testing compared to those who did not, a difference of 144 hours (∼6 days). In a subset of 383 patients for whom the COVID-19 banner resolved prior to discharge, the duration of isolation was 93 hours shorter with antigen testing (Table 1).
Discussion
In this analysis of a SARS-CoV-2 antigen-test–based strategy to facilitate the discontinuation of transmission-based precautions for hospitalized patients with COVID-19, patients who underwent antigen testing had a significantly shorter duration of COVID-19 banner (by ∼6 days on average) than those not tested.
Most patients were negative on their first antigen testing, which occurred at a median of 5 days from admission; symptomatic patients were more likely to have a positive initial antigen test. In a very small proportion of patients, a positive antigen test followed an initial negative result, underscoring the recommendation to use antigen testing serially over 24–48 hours. 8
This study had several limitations. We did not systematically study SARS-CoV-2 transmission following discontinuation of precautions; however, we did not observe any transmission to patients or staff on routine infection prevention surveillance. We did not directly measure days of isolation, but at our hospital, duration of COVID-19 banners and duration of isolation are intimately linked. Other limitations included the single-center observational design and lack of data on comorbidities and vaccination status, which may have varied between patients selected for antigen testing and those that were not and could account for some differences in duration of precautions. The study was limited to a 6-month period when SARS-CoV-2 omicron subvariants were predominant. Lastly, the limited availability of antigen testing to weekdays likely affected the use and timeliness of testing, potentially leading to the underestimation of the impact of this strategy. Our hospital has since transitioned antigen testing from bedside point of care to the laboratory to increase testing capacity.
In conclusion, in the absence of new data on the duration of SARS-CoV-2 infectiousness, an antigen-test–based strategy could be considered to reduce time in contact precautions (ie, isolation) for hospitalized COVID-19 patients.
Supplementary material
The supplementary material for this article can be found at https://doi.org/10.1017/ice.2023.164
Acknowledgements
The authors extend gratitude to Maureen Archibald and the University of Maryland Medical Center Office of Clinical Practice & Professional Development for their assistance with the education and training of staff and the Mobile Health Mobile Practitioner Team for the performance of the point-of-care SARS-COV-2 antigen test.
Financial support
No financial support was provided relevant to this article.
Conflicts of interest
All authors report no conflicts of interest relevant to this article.
