Association between household exposure and cycle threshold in COVID-19 infected health care workers.

OBJECTIVE: Household SARS-COV-2 contact constitutes a high-risk exposure for health care workers (HCWs). Cycle threshold (Ct) of reverse transcriptase-polymerase chain reaction testing provides an estimate of COVID-19 viral load, which can inform clinical and workplace management. We assessed whether Ct values differed between HCWs with COVID-19 with and without household exposure. METHODS: We analyzed HCW COVID-19 cases whose Ct data could be compared. We defined low Ct at a cut-point approximating a viral load of 4.6 × 106 copies per ml. Logistic regression tested the association of household exposure and symptoms at diagnosis with a low Ct value. RESULTS: Of 77 HCWs with COVID-19, 20 were household exposures cases and 34 were symptomatic at testing (7 were both household-exposed and symptomatic at testing). Among household exposures, 9 of 20 (45%) manifested lower Ct values compared to 14 of 57 (25%) for all others. In a bivariate model, household exposure was not statistically associated with lower Ct (Odds Ratio [OR] 1.20; 95% Confidence Interval [CI] 0.97-1.51). In multivariable modelling both household exposure (OR] 1.3; 95% CI 1.03-1.6) and symptoms at diagnosis (OR 1.4; 95% CI 1.15-1.7) were associated with a low Ct value. DISCUSSION: Household exposure in HCWs with newly diagnosed COVID-19 was associated with lower Ct values, consistent with a higher viral load, supporting the hypothesis that contracting COVID-19 in that manner leads to a greater viral inoculum.

Saliva as a testing specimen with or without pooling for SARS-CoV-2 detection by multiplex RT-PCR test.

BACKGROUND: Sensitive and high throughput molecular detection assays are essential during the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The vast majority of the SARS-CoV-2 molecular assays use nasopharyngeal swab (NPS) or oropharyngeal swab (OPS) specimens collected from suspected individuals. However, using NPS or OPS as specimens has apparent drawbacks, e.g. the collection procedures for NPS or OPS specimens can be uncomfortable to some people and may cause sneezing and coughing which in turn generate droplets and/or aerosol particles that are of risk to healthcare workers, requiring heavy use of personal protective equipment. There have been recent studies indicating that self-collected saliva specimens can be used for molecular detection of SARS-CoV-2 and provides more comfort and ease of use for the patients. Here we report the performance of QuantiVirus™ SARS-CoV-2 test using saliva as the testing specimens with or without pooling. METHODS: Development and validation studies were conducted following FDA-EUA and molecular assay validation guidelines. Using SeraCare Accuplex SARS-CoV-2 reference panel, the limit of detection (LOD) and clinical performance studies were performed with the QuantiVirus™ SARS-CoV-2 test. For clinical evaluation, 85 known positive and 90 known negative clinical NPS samples were tested. Additionally, twenty paired NPS and saliva samples collected from recovering COVID-19 patients were tested and the results were further compared to that of the Abbott m2000 SARS-CoV-2 PCR assay. Results of community collected 389 saliva samples for COVID-19 screening by QuantiVirus™ SARS-CoV-2 test were also obtained and analyzed. Additionally, testing of pooled saliva samples was evaluated. RESULTS: The LOD for the QuantiVirus™ SARS-CoV-2 test was confirmed to be 100-200 copies/mL. The clinical performance studies using contrived saliva samples indicated that the positive percentage agreement (PPA) of the QuantiVirus™ SARS-CoV-2 test is 100% at 1xLOD, 1.5xLOD and 2.5xLOD. No cross-reactivity was observed for the QuantiVirus™ SARS-CoV-2 test with common respiratory pathogens. Testing of clinical samples showed a positive percentage agreement (PPA) of 100% (95% CI: 94.6% to 100%) and a negative percentage agreement (NPA) of 98.9% (95% CI: 93.1% to 99.9%). QuantiVirus™ SARS CoV-2 test had 80% concordance rate and no significant difference (p = 0.13) between paired saliva and NPS specimens by Wilcoxon matched pairs signed rank test. Positive test rate was 1.79% for 389 saliva specimens collected from local communities for COVID-19 screening. Preliminary data showed that saliva sample pooling up to 6 samples (1:6 pooling) for SARS-CoV-2 detection is feasible (sensitivity 94.8% and specificity 100%). CONCLUSION: The studies demonstrated that the QuantiVirus™ SARS-CoV-2 test has a LOD of 200 copies/mL in contrived saliva samples. The clinical performance of saliva-based testing is comparable to that of NPS-based testing. Pooling of saliva specimens for SARS-CoV-2 detection is feasible. Saliva based and high-throughput QuantiVirus™ SARS-CoV-2 test offers a highly desirable testing platform during the ongoing COVID-19 pandemic.

Cycle Threshold to Test Positivity in COVID-19 for Return to Work Clearance in Health Care Workers.

OBJECTIVE: To ascertain whether reverse transcriptase polymerase chain reaction (RT-PCR) cycle amplifications until detection, the cycle threshold (Ct), could help inform return to work (RTW) strategies for health care workers (HCWs) recovering from COVID-19 infection. METHODS: Sequential Ct data from COVID-19 nasal pharyngeal (NP) RT-PCR testing in all COVID-19 positive HCWs at a single institution. Analysis of Ct in relation to time until negative testing for RTW clearance. RESULTS: Data for 12 employees showed that time elapsed until RT-PCR test-based RTW clearance ranged from 7 to 57 days (median, 34.5 days). Lower initial Ct correlated with the total time elapsed until clearance (r = -0.80; P = 0.002). CONCLUSION: Considering the RT-PCR Ct, which correlates with the estimated viral load, may help inform RTW planning and decision making beyond solely relying on dichotomized positive/negative results.