Evaluation of cycle threshold to assist with safe return to work for healthcare workers with coronavirus disease 2019 (COVID-19)

The coronavirus disease 2019 (COVID-19) pandemic has resulted in critical staffing shortages in healthcare facilities due to many ill healthcare workers (HCWs), and this has been particularly evident with the emergence of the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) ο (omicron) variant in late 2021. ^1,2 In response to an escalating critical staffing deficiency, the University of Nebraska Medical Center instituted a return-to-work testing program through the employee health department to evaluate cycle threshold (Ct) values in HCWs in critical hospital roles. The goal of this program was to aid in establishing the appropriate duration of isolation and to facilitate a safe return to work to mitigate significant staffing shortages that would adversely affect patient care.

The detection of COVID-19 via RT-PCR does not necessarily equate to infectiousness; patients can have positive PCR tests in the absence of culturable virus. ³ Although currently available SARS-CoV-2 RT-PCR testing is not a true quantitative measure, published literature has demonstrated that SARS-CoV-2 can most consistently be grown in viral culture when the Ct is <30. ^3–6 Other studies have shown that it is possible to culture viable virus in patients with Ct values in the 30–35 range; however, the yield is low. ⁴

Starting on January 1, 2022, HCWs with mild or asymptomatic COVID-19 with resolving symptoms were tested with RT-PCR via nasopharyngeal swab 5–7 days after symptom onset or initial positive SARS-CoV-2 test, whichever was earlier. If employees tested negative or tested positive with a Ct ≥ 32, they were deemed to be less of a transmission risk and were allowed to return to work. Employees with a Ct ≤ 31 were considered potentially still infectious and were excluded from work until day 10. A Ct of 32 was chosen as a conservative cutoff based on a review of previous studies, which demonstrated that culture of viable SARS-CoV-2 is generally possible when the Ct is <30 but is much less likely with higher Ct values. ^4–6 This program was paused from January 5, 2022, through February 14, 2022, due to the implementation of crisis standards of care, in which all employees returned to work after 7 days due to critical staffing shortages. Employees tested prior to the January 2022 pause were tested using the Roche Cobas 6800 system (Roche Diagnostics, Indianapolis, IN) with the SARS-CoV-2 and influenza A/B tests (E gene and orf1a gene SARS-CoV-2 targets); thereafter, they were tested using the Cepheid GeneXpert Infinity system (Cepheid, Sunnyvale, CA) using the Xpert Xpress SARS-CoV-2/Flu/RSV assay (E gene and N2 gene SARS-CoV-2 targets).

Overall, 57 employees deemed essential to the clinical operations of the organization and ineligible to work from home completed the testing program. Among them, 56 employees completed their primary COVID-19 vaccine series with mRNA vaccines and 1 had the J&J/Janssen vaccine. All but 4 of these employees had received an mRNA booster >2 weeks prior to testing positive for SARS-CoV-2.

Testing for early return to work ranged from 5 to 8 days from initial symptoms or positive SARS-CoV-2 test. Of the 57 HCWs, 2 tested negative and 55 tested positive. One of the HCWs who tested negative was symptomatic at the time of original positive test and the other was not. Of the positive SARS-CoV-2 tests, the average Ct was 26. We did not detect a difference in the average Ct values of the 48 HCWs who reported symptoms at time of positive test versus the 7 HCWs who were asymptomatic. Among these 55 HCWs, 6 had a Ct ≥ 32 (Table 1).

Table 1. Cycle Thresholds (Ct) of COVID-19 RT-PCR Test on Early Return to Work Testing (n = 57)

Note. RT-PCR, reverse-transcription polymerase chain reaction.

Using the Ct cutoff of ≥32 as a conservative threshold, our program allowed 14.0% of tested HCWs to return to work early and 86% were required to complete the full isolation period of 10 days. Notably, if a Ct criterion of ≥30 had been utilized, only 21.0% of tested HCWs would have qualified to return to work early.

Numerous nosocomial outbreaks of COVID-19 have been reported since the start of the pandemic. ^7,8 A systematic literature review of 35 hospital outbreaks revealed that 40% of the primary cases were HCWs. ⁷ Based on this, identifying HCWs who remain potentially infectious could decrease the risk of nosocomial COVID-19 cases in coworkers, patients, visitors, and others in the healthcare environment. Our data suggest that HCWs with asymptomatic or mild COVID-19 can potentially present a risk of infection to others if returning to work prior to day 10 of illness.

This study had several limitations. We used a modest sample size, and the study was conducted at a single center. During the study, 2 different testing platforms were used. Studies correlating Ct value with culture of viable virus were also published prior to the emergence of newer SARS-CoV-2 variants. Despite these limitations, our data resulted in a modification of our institutional return-to-work policy to allow those with a Ct ≥ 30 to return to work early. We suggest that outside crisis standards of care, healthcare systems should consider a 10-day return-to-work policy or implement test-based strategies, such as the one described here, for early return to work for HCWs with COVID-19.