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

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

10.1101/2020.09.01.20186254 ◽

2020 ◽

Cited By ~ 1

Author(s):

Isao Yokota ◽

Takeshi Hattori ◽

Peter Y Shane ◽

Satoshi Konno ◽

Atsushi Nagasaka ◽

...

Keyword(s):

Symptom Onset ◽

Detection Sensitivity ◽

Rank Test ◽

Nasopharyngeal Swab ◽

Viral Loads ◽

Ct Value ◽

Signed Rank ◽

Signed Rank Test ◽

Polymerase Chain ◽

High Degree

COVID-19 is diagnosed by detecting SARS-CoV-2 by nasopharyngeal swab (NPS) using real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Emerging evidences have shown the utility of saliva, although conflicting results have been reported regarding viral loads between NPS and saliva. We conducted a study to compare the viral loads in 42 patients with COVID-19. Both NPS and saliva specimens were simultaneously obtained at a median of 6 days (range, 1-12) after symptom onset. SARS-CoV-2 was detected in 34 (81%) using NPS (median Ct value [IQR]=27.4 [21.3, 35.6]) and 38 (90%) using saliva (median Ct value [IQR]= 28.9 [23.1, 33.6]). There was no significance difference between them (Wilcoxon signed rank test: P=0.79) and 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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SARS-CoV-2 is associated with high viral loads in asymptomatic and recently symptomatic healthcare workers

PLoS ONE ◽

10.1371/journal.pone.0248347 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0248347

Author(s):

M. Catherine McEllistrem ◽

Cornelius J. Clancy ◽

Deanna J. Buehrle ◽

Nina Singh ◽

Aaron Lucas ◽

...

Keyword(s):

Healthcare Workers ◽

Infection Prevention ◽

Nasopharyngeal Swab ◽

Symptom Duration ◽

Rt Pcr ◽

Personal Protection Equipment ◽

Duration Of Symptoms ◽

Viral Loads ◽

Ct Value ◽

Increased Risk

Background Healthcare workers (HCW) are at increased risk of SARS-CoV-2 infection from both patients and other HCW with coronavirus disease 2019 (COVID-19). RT-PCR cycle threshold (Ct) values of SARS-CoV-2 ≤ 34 and the first 7–9 days of symptoms are associated with enhanced infectivity. We determined Ct values and duration of symptoms of HCW with a positive SARS-CoV-2 test. As HCW often assume their greatest risk of acquiring SARS-CoV-2 is working on a COVID-19 unit, we also determined Ct values and symptom duration of inpatients with a positive SARS-CoV-2 test. Methods From 6/24/2020-8/23/2020, Ct values and duration of symptoms from 13 HCW, 12 outpatients, and 28 inpatients who had a positive nasopharyngeal swab for SARS-CoV-2 were analyzed. Results Among HCW with a positive SARS-CoV-2 test, 46.2% (6/13) were asymptomatic and requested testing due to an exposure to someone with COVID-19; 83.3% (5/6) of those exposures occurred in the community rather than in the hospital. The median Ct value of HCW was 23.2, and 84.6% (11/13) had a Ct value ≤ 34. The median Ct value of 29.0 among outpatients with COVID-19 did not significantly differ from HCW. In contrast, inpatients with a positive SARS-CoV-2 test had a median Ct value of 34.0 (p = 0.003), which translated into a median ~1,000-fold lower viral load than observed in HCW. Among those with symptoms related to COVID-19, no (0/6) HCW compared to 50% (6/12) of inpatients had symptoms for at least one week (p = 0.04). Conclusions At our institution, asymptomatic COVID-19 accounted for nearly half of the cases among HCW. Symptomatic HCW had high viral loads and short duration of symptoms, both of which are associated with peak infectivity. Infection prevention programs should educate HCW on these findings in an effort to increase adherence to the requirement to maintain six feet separation in workspaces and breakrooms, in addition to consistently wearing personal protection equipment.

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Comparison of saliva with healthcare workers- and patient-collected swabs in the diagnosis of COVID-19 in a large cohort

BMC Infectious Diseases ◽

10.1186/s12879-021-06343-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Mitnala Sasikala ◽

Yelamanchili Sadhana ◽

Ketavarapu Vijayasarathy ◽

Anand Gupta ◽

Sarala Kumari Daram ◽

...

Keyword(s):

Healthcare Workers ◽

Early Stage ◽

Cost Effective ◽

Hospitalized Patients ◽

Detection Sensitivity ◽

Nasopharyngeal Swab ◽

Predictive Values ◽

Qrt Pcr ◽

Asymptomatic Patients ◽

Sensitivity Specificity

Abstract Background A considerable amount of evidence demonstrates the potential of saliva in the diagnosis of COVID-19. Our aim was to determine the sensitivity of saliva versus swabs collected by healthcare workers (HCWs) and patients themselves to assess whether saliva detection can be offered as a cost-effective, risk-free method of SARS-CoV-2 detection. Methods This study was conducted in a hospital involving outpatients and hospitalized patients. A total of 3018 outpatients were tested. Of these, 200 qRT-PCR-confirmed SARS-CoV-2-positive patients were recruited for further study. In addition, 101 SARS-CoV-2-positive hospitalized patients with symptoms were also enrolled in the study. From outpatients, HCWs collected nasopharyngeal swabs (NPS), saliva were obtained. From inpatients, HCWs collected swabs, patient-collected swabs, and saliva were obtained. qRT-PCR was performed to detect SARS-CoV-2 by TAQPATH assay to determine the sensitivity of saliva detection. Sensitivity, specificity and positive/negative predictive values (PPV, NPV) of detecting SARS-CoV-2 were calculated using MedCalc. Results Of 3018 outpatients (asymptomatic: 2683, symptomatic: 335) tested by qRT-PCR, 200 were positive (males: 140, females: 60; aged 37.9 ± 12.8 years; (81 asymptomatic, 119 symptomatic). Of these, saliva was positive in 128 (64%); 39 of 81 asymptomatic (47%),89 of 119 symptomatic patients (74.8%). Sensitivity of detection was 60.9% (55.4–66.3%, CI 95%), with a negative predictive value of 36%(32.9–39.2%, CI 95%).Among 101 hospitalized patients (males:65, females: 36; aged 53.48 ± 15.6 years), with HCW collected NPS as comparator, sensitivity of saliva was 56.1% (47.5–64.5, CI 95%), specificity 63.5%(50.4–75.3, CI95%) with PPV of 77.2% and NPV of 39.6% and that of self-swab was 52.3%(44–60.5%, CI95%), specificity 56.6% (42.3–70.2%, CI95%) with PPV 77.2% and NPV29.7%. Comparison of positivity with the onset of symptoms revealed highest detection in saliva on day 3 after onset of symptoms. Additionally, only saliva was positive in 13 (12.8%) hospitalized patients. Conclusion Saliva which is easier to collect than nasopharyngeal swab is a viable alternate to detect SARS-COV-2 in symptomatic patients in the early stage of onset of symptoms. Although saliva is currently not recommended for screening asymptomatic patients, optimization of collection and uniform timing of sampling might improve the sensitivity enabling its use as a screening tool at community level.

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Comparison of Quidel Sofia SARS FIA Test to Hologic Aptima SARS-CoV-2 TMA Test for Diagnosis of COVID-19 in Symptomatic Outpatients

Journal of Clinical Microbiology ◽

10.1128/jcm.02727-20 ◽

2020 ◽

Author(s):

Eric T. Beck ◽

Wendy Paar ◽

Lara Fojut ◽

Jordan Serwe ◽

Renee R. Jahnke

Keyword(s):

Symptom Onset ◽

Care Center ◽

Urgent Care ◽

Molecular Diagnostic ◽

Nasopharyngeal Swab ◽

Urgent Care Center ◽

Ct Value ◽

High Prevalence ◽

Nasal Swabs ◽

Molecular Diagnostic Test

The Quidel Sofia SARS FIA test (SOFIA) is a rapid antigen immunoassay for detection of SARS-CoV-2 viral proteins from nasal or nasopharyngeal swab specimens. The purpose of this study was to compare the results of the SOFIA test to the Hologic Aptima SARS-CoV-2 TMA test (APTIMA TMA), a high-throughput molecular diagnostic test that uses transcription mediated amplification for detection of SARS-CoV-2 nucleic acid from upper respiratory specimens. Three hundred and 40-seven symptomatic patients, from an urgent care center in an area with a high prevalence of SARS-CoV-2 infections, were tested in parallel using nasal swabs on the SOFIA test and nasopharyngeal swabs on the APTIMA TMA test. The SOFIA test demonstrated an 82.0% positive percent agreement (PPA) compared to the APTIMA TMA test for symptomatic patients tested ≤ 5 days from symptom onset and a 54.5% PPA for symptomatic patients > 5 days from symptom onset. The Cepheid Xpert Xpress SARS-CoV-2 RT-PCR test was used to determine the cycle threshold (Ct) value from any specimens that were discrepant between the SOFIA and APTIMA TMA tests. Using a Ct value of ≤ 35 as a surrogate for SARS-CoV-2 culture positivity, we estimate that the SOFIA test detected 87.2% of symptomatic patients tested ≤ 5 days from symptom onset that were likely to be culture positive.

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Factors Associated With Viral Load Kinetics of Middle East Respiratory Syndrome Coronavirus During the 2015 Outbreak in South Korea

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa466 ◽

2020 ◽

Author(s):

Jeong-Sun Yang ◽

Min-Gyu Yoo ◽

Hye-Ja Lee ◽

Han Byul Jang ◽

Hee-Dong Jung ◽

...

Keyword(s):

Viral Load ◽

Middle East ◽

Symptom Onset ◽

Healthcare Workers ◽

Middle East Respiratory Syndrome ◽

Viral Loads ◽

Hospitalization Period ◽

Using Data ◽

Kinetics Of ◽

Respiratory Specimens

Abstract We conducted a retrospective study of Middle East respiratory syndrome coronavirus (MERS-CoV) viral load kinetics using data from patients hospitalized with MERS-CoV infection between 19 May and 20 August 2015. Viral load trajectories were considered over the hospitalization period using 1714 viral load results measured in serial respiratory specimens of 185 patients. The viral load levels were significantly higher among nonsurvivors than among survivors (P = .003). Healthcare workers (P = .001) and nonspreaders (P < .001) had significantly lower viral loads. Viral RNA was present on the day of symptom onset and peaked 4–10 days after symptom onset.

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High amounts of SARS-CoV-2 precede sickness among asymptomatic healthcare workers

The Journal of Infectious Diseases ◽

10.1093/infdis/jiab099 ◽

2021 ◽

Author(s):

Joakim Dillner ◽

K Miriam Elfström ◽

Jonas Blomqvist ◽

Lars Engstrand ◽

Mathias Uhlén ◽

...

Keyword(s):

Logistic Regression ◽

Sick Leave ◽

Healthcare Workers ◽

Multinomial Logistic Regression ◽

Excess Risk ◽

University Hospital ◽

Cycle Threshold ◽

The Past ◽

Ct Value

Abstract Background Whether SARS-CoV-2 positivity among symptomatic subjects reflects past or future disease may be difficult to ascertain. Methods We tested a cohort of 9449 employees at work at the Karolinska University Hospital, Stockholm, Sweden for SARS-CoV-2 RNA and antibodies, linked the testing results to sick leave records and determined associations with past or future sick leave using multinomial logistic regression. ClinicalTrials.gov NCT04411576. Results Subjects with high amounts of SARS-CoV-2 virus, as indicated by the Cycle threshold (Ct) value in the PCR, had the highest risk for sick leave in the two weeks after testing (OR 11.97 (CI 95% 6.29-22.80)) whereas subjects with low amounts of virus had the highest risk for sick leave in the past three weeks before testing (OR 6.31 (4.38-9.08)). Only 2.5% of employees were SARS-CoV-2 positive while 10.5% were positive by serology and 1.2% were positive in both tests. Serology-positive subjects were not at excess risk for future sick leave (OR 1.06 (95% CI, 0.71-1.57)). Conclusions High amounts of SARS-CoV-2 virus, as determined using PCR Ct values, associates with development of sickness in the next few weeks. The results support the concept that PCR Ct may be informative when testing for SARS-CoV-2 is performed.

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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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Evaluating the Relationship between Cycle Threshold Values and Reported COVID-19 Symptoms among Healthcare Workers

Antimicrobial Stewardship & Healthcare Epidemiology ◽

10.1017/ash.2021.35 ◽

2021 ◽

Vol 1 (S1) ◽

pp. s19-s20

Author(s):

Mindy Sampson ◽

Catherine Passaretti ◽

Jennifer Priem ◽

Shelley Kester ◽

Kristin Fischer ◽

...

Keyword(s):

Symptom Onset ◽

Healthcare Workers ◽

Current Understanding ◽

Linear Regression Models ◽

Rt Pcr ◽

Cycle Threshold ◽

E Gene ◽

Asymptomatic Individuals ◽

Number Of Cycles ◽

The Relationship

Background: SARS-CoV-2 detected by reverse transcription polymerase chain reaction (RT-PCR) can persist for weeks to months in some individuals. Cycle threshold (Ct) values represent the number of cycles needed to amplify viral ribonucleic acid (RNA) to reach a detectable level. As such, Ct values are inversely related to the amount of virus in a sample. As knowledge of SARS-CoV-2 viral dynamics continues to evolve, understanding the relationship between Ct values, type of symptoms, and timing of symptom onset can help determine when infected individuals are most likely to be infectious. Methods: We conducted a retrospective cohort study of 1,027 healthcare workers (HCWs) who tested positive for SARS-CoV-2 by RT-PCR from nasopharyngeal specimens between June 27, 2020, and September 21, 2020. All HCWs were interviewed within 72 hours of their diagnosis for symptom history. Due to multiple PCR platforms being in use in our facility, only 360 HCWs (35%) had Ct values available for analysis. Multivariate linear regression models examined the effect of COVID-19–related symptoms and timing of symptom onset to test on Ct values. Results: The most frequently reported symptoms were congestion (55.6%), cough (50.3%), and headache (46.7%). Other symptoms less commonly reported were fatigue (36.7%), loss of taste or smell (36.4%), fever (35.4%), muscle aches (33.3%), sore throat (27.4%), and diarrhea (26.7%). Symptomatic HCWs (88.3% of sample) had lower Ct values (ORF-1 M = 22.66, SD = 5.17; E-Gene M = 24.34, SD = 6.60) than asymptomatic individuals (ORF-1 M = 25.46, SD = 6.06; E-Gene M = 29.34, SD = 7.96). Of all symptoms measured, only presence of fever, congestion, and muscle aches predicted significantly lower Ct values. Mean Ct values decreased 2 days prior to symptom onset, were lowest the day of symptom onset, then increased in a curvilinear fashion. There were no significant 2-way interactions between symptoms and time of symptom onset to testing. Conclusions: The curvilinear pattern of Ct values over time from symptom onset are consistent with disease progression patterns and support current understanding of infectivity being highest 2 days prior to symptom onset through day 8. Presence of fever, congestion, and muscle aches are significantly correlated with lower Ct values, suggesting that these symptoms are associated with higher viral load. Although Ct values are not without limitations, our findings support the current understanding that presymptomatic and symptomatic individuals, particularly those with fever, congestion, and muscle aches, may pose higher risk of transmission to others.Funding: NoDisclosures: None

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Investigation of Viral Load Cycle Threshold Values in Patients with SARS-CoV-2 Associated Pneumonia with Real-Time PCR Method

The Journal of Infection in Developing Countries ◽

10.3855/jidc.14281 ◽

2021 ◽

Vol 15 (10) ◽

pp. 1408-1414

Author(s):

Ayfer Bakir ◽

Tugrul Hosbul ◽

Ferhat Cuce ◽

Cumhur Artuk ◽

Gurhan Taskin ◽

...

Keyword(s):

Viral Load ◽

Respiratory Tract ◽

Load Cycle ◽

Cross Sectional Study ◽

Chest Ct ◽

Upper Respiratory Tract ◽

Cross Sectional ◽

Cycle Threshold ◽

Viral Loads ◽

Ct Value

Introduction: In this study, we aimed investigate the relationship of SARS-CoV-2 viral load cycle threshold (Ct) values with pneumonia. Methodology: A total of 158 patients in whom SARS-CoV-2 was confirmed in upper respiratory tract (URT) samples with molecular method and who had computed tomography (CT) of the chest, between April 2020 and June 2020 were included in this retrospective cross-sectional study. Results: Mean age of 158 PCR positive patients was 45.22 ± 17.89 and 60.8% of them were male. Pneumonia was detected in 40.5% of the patients on their chest CT. A weak but significant correlation was found between SARS-CoV-2 Ct value detected with PCR in analysis of oropharyngeal/ nasopharyngeal (OP/NP) samples and chest CT score (Pearson’s r: 0.197, p = 0.01). No correlation was found between the first detected viral load Ct value and age, gender and mortality. There was no significant correlation between chest CT score and mortality. While the areas remaining under ROC curve for Ct value in analysis of OP/NP samples in prediction of chest CT score ≥ 1, ≥ 5 and ≥ 10 were 0.564, 0.640 and 0.703 respectively. Conclusions: We found that the amount of SARS-CoV-2 viral load (inverse relationship with Ct) detected in OP/NP samples of patients with COVID-19 pneumonia did not reflect the increasing severity of pulmonary lesions on chest CT. Although primary target of SARS-CoV-2 is all epithelial cells of the respiratory tract we believe studies comparing viral loads in lower respiratory tract samples are needed to determine the severity of pulmonary disease.

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Clinical utility of cycle threshold values in the context of COVID-19

10.21203/rs.3.rs-41867/v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Sonia N. Rao ◽

Davide Manissero ◽

Victoria Steele ◽

Josep Pareja

Keyword(s):

Viral Load ◽

Troponin I ◽

Severe Disease ◽

Clinical Information ◽

High Sensitivity ◽

Clinical Value ◽

Cycle Threshold ◽

Viral Loads ◽

Ct Value ◽

Viral Culture

Abstract BackgroundThe ability to predict likely prognosis and infectiousness for patients with COVID-19 would aid patient management decisions. Diagnosis is usually via real-time PCR and it is unclear whether the semi-quantitative capability of this method, determining viral load through cycle threshold (Ct) values, can be leveraged.ObjectivesWe aim to review available knowledge on correlations between SARS-COV-2 Ct values and patient- or healthcare-related outcomes to determine whether Ct values provide useful clinical information.SourcesA PubMed search was conducted on 1st June 2020 based on a search strategy of (Ct value OR viral load) AND SARS-CoV-2. Data was extracted from studies reporting on the presence or absence of an association between Ct values, or viral loads determined via Ct value, and clinical outcomes.ContentData from 18 studies were relevant for inclusion. One study reported on the correlation between Ct values and mortality and one study reported on the correlation between Ct values and progression to severe disease; both reported a significant association (p < 0.001 and p = 0.008, respectively). Fourteen studies reported on the correlation between Ct value or viral loads determined via Ct value and disease severity and an association was observed in 8 (57%) studies. Studies reporting on the correlation of viral load with biochemical and haematological markers showed an association with at least one marker, including increased lactate dehydrogenase (n = 4), decreased lymphocytes (n = 3) and increased high-sensitivity troponin I (n = 2). Two studies reporting on the correlation with infectivity showed that lower Ct values were associated with higher viral culture positivity.ImplicationsData suggest that lower Ct values may be associated with worse outcomes, and that Ct values may be useful in predicting the clinical course and prognosis of patients with COVID-19; however, further studies are warranted to confirm clinical value.

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