360. Evaluation of Cycle Threshold Values in Patients with Symptomatic COVID-19 Infection

Abstract Background One of the tests used to identify COVID-19 infections is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) test. There is a measure known as the cycle threshold (Ct) value, which provides an indirect measure of viral load. It has been proposed that the Ct value could help with clinical decisions regarding duration of isolation. We hypothesize that Ct values will correlate with symptom duration in a population of veterans with COVID-19 infection. Methods We reviewed the records of patients presenting to the emergency department (ED) or admitted to Audie L. Murphy VA Medical Center in San Antonio, Texas with positive SARS-CoV-2 PCR tests. We looked at patients who received multiple SARS-CoV-2 RT-qPCR tests. We compared date of onset of symptoms and cycle threshold values from their initial test to another test ordered after 7, 10, and 20 days from symptom onset. We recorded the Ct value for the N2 and E genes. Patients were classified into mild, severe and critical based on Center for Disease Control and Prevention (CDC) criteria. A Ct value of >30 as threshold for transmissible disease was used based on previously published studies. Results We identified 49 patients with more than two SARS-CoV-2 RT-qPCR tests. Patients with mild disease with tests less than or equal to ten days from symptom onset (n=10) had a mean Ct value 23.2 (±5.6) and 26.0 (±5.8) for the E and N2 genes. Patients with mild disease with tests greater than ten days from symptom onset (n=4) had mean Ct values of 26.0 (±6.5) and 27.8 (±6.8). When we stratified the patient population by disease severity, patients with severe and critical disease with tests less than ten days from symptom onset (n=24) had mean Ct values of 20.1 (±7.3) and 23.4 (±7.5). Patients with severe and critical disease greater than twenty days (n=6) had Ct values of 29.0 (±5.1) and 31.1 (±5.4). Conclusion We found that Ct values increased with longer symptom duration. We currently use the CDC criteria to discontinue isolation at ten days for mild disease and twenty days for severe and critical disease. The findings of this study suggest that our current practice for duration of isolation correlates with increasing Ct values near or above the threshold for transmissible disease. Disclosures All Authors: No reported disclosures

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SARS-CoV-2 viral persistence based on cycle threshold value and liver injury in patients with COVID-19

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab205 ◽

2021 ◽

Author(s):

Grace Lai-Hung Wong ◽

Terry Cheuk-Fung Yip ◽

Vincent Wai-Sun Wong ◽

Yee-Kit Tse ◽

David Shu-Cheong Hui ◽

...

Keyword(s):

Liver Injury ◽

Symptom Onset ◽

Viral Persistence ◽

Threshold Value ◽

Public Hospitals ◽

Angiotensin Converting Enzyme 2 ◽

Cycle Threshold ◽

Ct Value ◽

Independent Risk Factors

Abstract Background Liver injury in patients with COVID-19 is common and prognostic. Direct viral tropism of SARS-CoV-2 for angiotensin-converting enzyme 2 receptors in hepatocytes may be one of the mechanisms of liver injury. We aimed to determine the role of viral persistence of SARS-CoV-2, based on cycle threshold (Ct) value, in liver injury in COVID-19. Methods This was a territory-wide retrospective cohort study of all public hospitals in Hong Kong. Laboratory-confirmed COVID-19 were identified. Serial liver biochemistries and Ct value of SARS-CoV-2 RNA were analyzed. Results We identified 7,622 COVID-19 patients (mean age 47 years, 48.2% male) diagnosed from 24 March to 1 January 2021 who had serial liver biochemistries and Ct values. 1,363 (17.9%) COVID-19 patients had ALT/AST elevations with two temporal patterns – early (within first 14 days from symptom onset) and late (after 14 days from symptom onset). COVID-19 patients with ALT/AST elevations had a lower Ct value at admission (23 vs. 25; P<0.001), day 5 (24 vs. 26; P<0.001) and day 20 (31 vs. 32; P<0.001) after admission, compared to those without ALT/AST elevations. COVID-19 patients with ALT/AST elevations had a longer duration from first positive to first negative RT-PCR of SARS-CoV-2 (13 vs. 9 days; P<0.001). ALT/AST elevation and presence of diabetes were the independent risk factors of viral persistence. Conclusions Liver injury in COVID-19 is linked to a higher SARS-CoV-2 viral load during the early phase of infection, signifying a possible direct viral injury to liver. Prolonged viral persistence of SARS-CoV-2 is associated with liver injury.

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Epidemiological Correlates of Polymerase Chain Reaction Cycle Threshold Values in the Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1469 ◽

2020 ◽

Cited By ~ 2

Author(s):

Phillip P Salvatore ◽

Patrick Dawson ◽

Ashutosh Wadhwa ◽

Elizabeth M Rabold ◽

Sean Buono ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

Severe Acute Respiratory Syndrome ◽

Symptom Onset ◽

Temporal Trends ◽

Viral Rna ◽

Chain Reaction ◽

Cycle Threshold ◽

Ct Value ◽

Polymerase Chain ◽

Epidemiological Characteristics

Abstract Background Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has principally been performed through the use of real-time reverse-transcription polymerase chain reaction testing. Results of such tests can be reported as cycle threshold (Ct) values, which may provide semi-quantitative or indirect measurements of viral load. Previous reports have examined temporal trends in Ct values over the course of a SARS-CoV-2 infection. Methods Using testing data collected during a prospective household transmission investigation of outpatient and mild coronavirus disease 2019 cases, we examined the relationships between Ct values of the viral RNA N1 target and demographic, clinical, and epidemiological characteristics collected through participant interviews and daily symptom diaries. Results We found that Ct values are lowest (corresponding to a higher viral RNA concentration) soon after symptom onset and are significantly correlated with the time elapsed since onset (P < .001); within 7 days after symptom onset, the median Ct value was 26.5, compared with a median Ct value of 35.0 occurring 21 days after onset. Ct values were significantly lower among participants under 18 years of age (P = .01) and those reporting upper respiratory symptoms at the time of sample collection (P = .001), and were higher among participants reporting no symptoms (P = .05). Conclusions These results emphasize the importance of early testing for SARS-CoV-2 among individuals with symptoms of respiratory illness, and allow cases to be identified and isolated when their viral shedding may be highest.

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Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19, England, January to May 2020

Eurosurveillance ◽

10.2807/1560-7917.es.2020.25.32.2001483 ◽

2020 ◽

Vol 25 (32) ◽

Cited By ~ 43

Author(s):

Anika Singanayagam ◽

Monika Patel ◽

Andre Charlett ◽

Jamie Lopez Bernal ◽

Vanessa Saliba ◽

...

Keyword(s):

Viral Load ◽

Severe Acute Respiratory Syndrome ◽

Respiratory Tract ◽

Symptom Onset ◽

Infectious Virus ◽

Upper Respiratory Tract ◽

Threshold Values ◽

Rt Pcr ◽

Cycle Threshold ◽

Upper Respiratory

Severe acute respiratory syndrome coronavirus 2 viral load in the upper respiratory tract peaks around symptom onset and infectious virus persists for 10 days in mild-to-moderate coronavirus disease (n = 324 samples analysed). RT-PCR cycle threshold (Ct) values correlate strongly with cultivable virus. Probability of culturing virus declines to 8% in samples with Ct > 35 and to 6% 10 days after onset; it is similar in asymptomatic and symptomatic persons. Asymptomatic persons represent a source of transmissible virus.

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496. Higher SARS-CoV-2 RT-PCR Cycle Threshold (Ct) Values Associated with Longer Symptom Duration Among Patients Hospitalized with COVID-19

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.689 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S314-S314

Author(s):

Lillian B Brown ◽

Lisa Gail Winston ◽

Barbara Haller ◽

Phong Pham ◽

Beatrice Marcelo ◽

...

Keyword(s):

Viral Load ◽

San Francisco ◽

Symptom Onset ◽

Diagnostic Testing ◽

Symptom Duration ◽

Rt Pcr ◽

Duration Of Symptoms ◽

Cycle Threshold ◽

Asymptomatic Patients

Abstract Background Most diagnostic tests for SARS-CoV-2, the causative agent of COVID-19, are RT-PCR based. This method is sensitive but cannot distinguish replicating from non-replicating virus. RT-PCR cycle threshold (Ct) values are inversely correlated with viral load, and higher Ct values have been correlated with lower in vitro viral infectivity. However, relatively few data exist on the association between Ct values and patients’ duration of symptoms remains unclear. We thus evaluated Ct values and symptom duration in a cohort of patients hospitalized with COVID-19. Methods We assessed all patients admitted to San Francisco General Hospital between April 1 and May 18, 2020 with confirmed COVID-19 infection based on RT-PCR testing (Abbott m2000 platform). We included patients having diagnostic testing for suspected COVID-19 and patients having asymptomatic testing per hospital policy. For symptomatic patients, date of symptom onset was abstracted from hospital records, and time from symptom onset to test date was calculated. RT-PCR Ct values were manually extracted. Median Ct and IQR were calculated for patients with < 10 days of symptoms, ≥10 days of symptoms, and asymptomatic disease. Between-group comparisons were performed using the Kruskal-Wallis test. Results Among 61 patients with positive RT-PCR tests, 40 patients reported < 10 days of symptoms at the time of testing, 15 reported ≥10 days of symptoms, and 6 were asymptomatic. The median Ct value was 14.2 cycles (IQR, 10.2, 18.3) among patients reporting < 10 days of symptoms, 19.7 cycles (IQR, 15.3, 23.9) among patients reporting ≥10 days of symptoms, and 26.3 (IQR, 25.0, 29.1) among asymptomatic patients. Ct values were significantly lower among patients with < 10 days of symptoms compared to patients with >=10 days of symptoms (p=0.01) and when compared to asymptomatic patients (p=0.0002) [Figure]. Cycle threshold (Ct) by days of symptoms at time of testing Conclusion SARS-CoV-2 RT-PCR cycle threshold values were higher (indicating lower viral load) in patients with longer symptom duration and were highest in asymptomatic patients. These results add to emerging data suggesting that strategies for optimal isolation of patients in both community and hospital settings could be informed by a combination of symptom duration and RT-PCR Ct values. Disclosures All Authors: No reported disclosures

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Pre-test symptom duration and cycle threshold values for SARS-CoV-2 reverse transcription-PCR (RT-PCR) predict COVID-19 mortality

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab003 ◽

2021 ◽

Author(s):

Emily Happy Miller ◽

Jason Zucker ◽

Delivette Castor ◽

Medini K Annavajhala ◽

Jorge L Sepulveda ◽

...

Keyword(s):

Viral Load ◽

Symptom Onset ◽

Medical Center ◽

Strong Predictor ◽

Academic Medical Center ◽

Patient Characteristics ◽

Symptom Duration ◽

Rt Pcr ◽

Duration Of Symptoms ◽

The Impact

Abstract Background The relationship between SARS-CoV-2 viral load and patient symptom duration in both in- and outpatients, and the impact of these factors on patient outcomes, are currently unknown. Understanding these associations is important to clinicians caring for patients with COVID-19. Methods We conducted an observational study between March 10–May 30, 2020 at a large quaternary academic medical center in New York City. Patient characteristics, laboratory values, and clinical outcomes were abstracted from the electronic medical records. Of all patients tested for SARS-CoV-2 during this time (N=16,384), there were 5,467 patients with positive tests, of which 4,254 had available Ct values and were included in further analysis. Univariable and multivariable logistic regression models were used to test associations between Ct values, duration of symptoms prior to testing, patient characteristics and mortality. The primary outcome is defined as death or discharge to hospice. Results Lower Ct values at diagnosis (i.e. higher viral load) were associated with significantly higher mortality among both in- and out-patients. Interestingly, patients with a shorter time since the onset of symptoms to testing had a worse prognosis, with those presenting less than three days from symptom onset having 2-fold increased odds of death. After adjusting for time since symptom onset and other clinical covariates, Ct values remained a strong predictor of mortality. Conclusions SARS-CoV-2 RT-PCR Ct value and duration of symptoms are strongly associated with mortality. These two factors add useful information for clinicians to risk stratify patients presenting with COVID-19.

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Concept of cycle threshold values in SARS-CoV-2 positive patients at childbirth admission: a retrospective observational study

10.22541/au.160578736.68156883/v1 ◽

2020 ◽

Author(s):

Victoria Greenberg ◽

Olga Grechukhina ◽

Jennifer Cate ◽

Marie-Louise Landry ◽

Christian Pettker ◽

...

Keyword(s):

Symptom Onset ◽

New Haven ◽

Threshold Values ◽

Cycle Threshold ◽

Disease Characteristics ◽

Asymptomatic Patients ◽

Pregnancy And Postpartum ◽

Polymerase Chain ◽

Study Setting ◽

Asymptomatic Women

Objective To evaluate relationships between cycle threshold values and COVID-19 presentations and clinical courses in women presenting for childbirth. Cycle threshold values from polymerase chain reaction (PCR) testing are inversely proportional to viral burden and may be important predictors of disease state and infectivity risk. Design Retrospective cohort study Setting Three Yale-New Haven Health Hospitals between 4/2/2020-5/14/2020 Population Women presenting for childbirth who underwent SARS-CoV-2 PCR testing Methods Electronic health records were reviewed for socio-demographics, medical comorbidities, pregnancy and postpartum course, and COVID-19 symptoms and exposures. Records of SARS-CoV-2 positive women were reviewed for symptom onset, duration, and relation to test timing, disease course, and neonatal SARS-CoV-2 results. Main Outcome Measures SARS-CoV-2 real-time PCR cycle threshold values from positive tests were compared between asymptomatic and symptomatic women and in relation to disease severity. In women with symptomatic COVID-19, cycle threshold values were evaluated as a function of time since symptom onset. Results 1,210 women gave birth during the study period with 84 (6.9%) positive for SARS-CoV-2. Higher cycle threshold values were seen in asymptomatic SARS-CoV-2 positive patients (8/38 (21.1%) of asymptomatic women had cycle threshold <30 compared to 22/32 (68.0%) of symptomatic women, p<0.0001). In symptomatic women, values increased as time from symptom onset increased. Conclusion This study demonstrates higher cycle threshold values in asymptomatic patients and symptomatic patients tested remote from symptom onset, signifying older infections and detection of lower levels of viral RNA. Assessment of standardized cycle threshold values may help to understand disease characteristics and progression.

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Equivalent SARS-CoV-2 viral loads by PCR between nasopharyngeal swab and saliva in symptomatic patients

Scientific Reports ◽

10.1038/s41598-021-84059-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Isao Yokota ◽

Takeshi Hattori ◽

Peter Y. Shane ◽

Satoshi Konno ◽

Atsushi Nagasaka ◽

...

Keyword(s):

Symptom Onset ◽

Diagnostic Tool ◽

Healthcare Workers ◽

Detection Sensitivity ◽

Nasopharyngeal Swab ◽

Cycle Threshold ◽

Viral Loads ◽

Ct Value ◽

High Degree ◽

Over Time

AbstractEmerging evidences have shown the utility of saliva for the detection of SARS-CoV-2 by PCR as alternative to nasopharyngeal swab (NPS). However, conflicting results have been reported regarding viral loads between NPS and saliva. We conducted a study to compare the viral loads between NPS and saliva in 42 COVID-19 patients. Viral loads were estimated by the cycle threshold (Ct) values. SARS-CoV-2 was detected in 34 (81%) using NPS with median Ct value of 27.4, and 38 (90%) using saliva with median Ct value of 28.9 (P = 0.79). Kendall’s W was 0.82, showing a high degree of agreement, indicating equivalent viral loads in NPS and saliva. After symptom onset, the Ct values of both NPS and saliva continued to increase over time, with no substantial difference. Self-collected saliva has a detection sensitivity comparable to that of NPS and is a useful diagnostic tool with mitigating uncomfortable process and the risk of aerosol transmission to healthcare workers.

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