key: cord-0755271-mfqas8ay
authors: Long, Sallie M; Chern, Alexander; Cooley, Victoria; Chung, Sei; Feit, Noah Z.; Craney, Arryn; Simon, Matthew S.; Tassler, Andrew B.
title: Temporal Dynamics of Nasopharyngeal and Tracheal SARS-CoV-2 Cycle Thresholds in COVID-19 Patients with Tracheostomy
date: 2022-04-20
journal: Clin Infect Dis
DOI: 10.1093/cid/ciac316
sha: 59cfbf758f87f78751d97a98617114821cc85eeb
doc_id: 755271
cord_uid: mfqas8ay

In this study of 45 patients with COVID-19 undergoing tracheostomy, nasopharyngeal and tracheal cycle threshold (Ct) values were analyzed. Ct values rose to 37.9 by the time of tracheostomy and remained >35 postoperatively, demonstrating that persistent test positivity may not be associated with persistent transmissible virus in this population.

The COVID-19 pandemic resulted in a dramatic rise in tracheostomies worldwide for patients with 2 ventilator dependency. Particularly at the start of the pandemic, much discussion surrounded the optimal 3 technique for performing airway surgery and how to minimize transmission risk as much as possible for 4 healthcare workers performing these aerosol-generating procedures (AGPs). Many studies have since 5 been published on outcomes following tracheostomy in patients with COVID-19 and have supported not 6 only its utility but also its safety for those involved in the surgery. 1-3 It is known that polymerase chain 7 reaction (PCR) positivity after infection with SARS-CoV-2 can persist for several weeks following an 8 initial positive test. 4 Others have studied the degree of viral aerosolization from tracheostomy and related 9 tracheostomy care, however, the dynamics of SARS-CoV-2 viral shedding in the lower respiratory tract in 10 a clinical setting remain poorly understood. 5 

The objectives of this pilot study are to 1) demonstrate the pattern of test positivity over time in both 12 nasopharyngeal and tracheal aspirates in patients with COVID-19 undergoing tracheostomy and 2) 13 determine the cycle threshold (Ct) values over time in this patient population. We hypothesized that the 14 Ct values (a known proxy for viral load) 6 by the time of tracheostomy and during tracheostomy care 15 postoperatively increase over time following initial diagnosis, rendering these patients unlikely to remain 16 infectious at the time of tracheostomy. 17

This analysis utilized a prospective database of COVID-19 patients admitted to our institution between 19

March and April 2020. Each patient's diagnosis was confirmed by nasopharyngeal swab RT-PCR. All 20 included patients had respiratory failure secondary to COVID-19 and had met criteria to undergo 21 tracheostomy as determined by an institutional protocol, as previously published. 1 To collect information 22 on COVID-19 laboratory results, including date of test, positive or negative result, and specimen source, 23 the electronic medical record (Eclipsys Allscripts Enterprise, Allscripts Healthcare Solutions, Inc., 24

Chicago, IL) was queried. Ct values were retroactively determined from the existing qualitative positive 1 PCR tests for a subset of the total prospective cohort for whom specimens remained available. PCR tests 2 from tracheal aspirates were performed using various platforms detecting ORF1a, N2, and E genes. The 3

length of viral shedding was determined by the difference from the date of last positive test 4 (nasopharyngeal or tracheal) and the date of the first positive test (nasopharyngeal). This study was 5 approved by the Weill Cornell Medicine Institutional Review Board. 6

A linear mixed effects model with a random subject intercept adjusting for first Ct measurement and time 8 from tracheostomy date was utilized to analyze differences in Ct by location (tracheal compared to 9 nasopharyngeal). Ninety-five percent confidence intervals were generated for all predictor estimates and 10 statistical significance was evaluated at the 0.05 alpha level. All analyses were performed in R for 11

Windows (version 4.0.3, 2019, Vienna, Austria). 12

Our dataset included forty-five patients with available Ct values, including 13 females (29%) and 32 14 males (71%) with a median age of 67 years (IQR 56, 74). The majority of patients identified as 15

White/Caucasian (n=22, 49%) or Other (n=13, 29%). Included patients underwent tracheostomy between 16

April and May 2020 after a median of 23 days intubated (IQR 20, 27) and at a median of 24 days 17 following admission (IQR 21, 31.5). 18

All patients were presumed positive for COVID-19 at the time of tracheostomy based on perioperative 19

testing. The first available Ct value was obtained at a median of 25 days prior to tracheostomy (IQR -32, -20 20 days) and was 24 (IQR 19, 29). At the time of tracheostomy (+/-three days), the median 21 nasopharyngeal Ct value was 37.9 (IQR 33.6, 41.4). This difference between first Ct value and Ct value at individually compared by Wilcoxon rank-sum tests, the tracheal Ct values were significantly lower at 10 weeks two and three following tracheostomy (p<0.0001), but not at week one following tracheostomy 11 (p=0.12). However, this analysis should be interpreted with caution due to the small sample size and 12 potential for confounders. 13

Ct values for nasopharyngeal and tracheal aspirates in patients with COVID-19 undergoing tracheostomy 15

have not been previously well-studied. Results from our pilot study show that patients may test 16 persistently positive in both upper and lower respiratory tract specimens for greater than one month, 17 which is slightly longer than the average time noted in a recent meta-analysis. 7 However, our viral 18 shedding time may be longer than others since all of our patients were inpatients with critical COVID-19 19 illness and therefore represented the severest of cases. Although other variables (i.e., time from symptom 20 onset) may account for risk of COVID-19 transmission, a Ct value >30 is generally thought to be 21 associated with a low risk of transmission. 8 variable tracheal Ct values may also have been related to random variation due to the small sample size of 2 patients with tracheal aspirates. A larger sample of tracheal aspirate data would allow for more robust 3 comparison with that from the nasopharynx. 4

It should be noted that a limitation to this study is the use of Ct values as a surrogate for viral load. 

Percutaneous and Open Tracheostomy in Patients With COVID-2 19: The Weill Cornell Experience in New York City

Comparison and Outcomes of an Institutional Series

Patients: A Systematic Review and Meta-analysis of Weaning, Decannulation, and Survival

Persistent viral RNA shedding in COVID-19: Caution, not fear

Quantifying Viral Particle Aerosolization Risk During 13

IDSA and AMP joint statement on the use of SARS-CoV-2 PCR cycle threshold (Ct) values for 16 clinical decision-making

Characteristics of Viral Shedding Time in SARS-CoV