Lack of correlation between the SARS‐CoV‐2 cycle threshold (Ct) value and clinical outcomes in patients with COVID‐19

Abstract Background The Infectious Diseases Society of America has identified the potential use of SARS-CoV-2 genomic load for prognostication purposes as a key research question. Methods We designed a retrospective cohort study that included adult patients with COVID-19 pneumonia who had at least 2 positive nasopharyngeal tests at least 24 hours apart to study the correlation between the change in the genomic load of SARS-CoV-2 in nasopharyngeal samples, as reflected by the Cycle threshold (Ct) value of the real-time Polymerase Chain Reaction (PCR) assay, with change in clinical status. The Sequential Organ Failure Assessment (SOFA) score was used as a surrogate for patients’ clinical status. A linear mixed-effects regression analysis was performed. Results Among 457 patients who presented to the emergency department between 3/31/2020- 4/10/2020, we identified 42 patients who met the inclusion criteria. The median initial SOFA score was 2 (IQR 2–3). 20 out of 42 patients had a lower SOFA score on their subsequent tests. We identified a statistically significant inverse correlation between the change in SOFA score and change in the Ct value with a decrease in SOFA score by 0.05 (SE 0.02; p < 0.05) for an increase in Ct values by 1. This correlation was independent of the duration of symptoms. Flow chart A graph of the Cycle Threshold (Ct) values of the of Cepheid Xpert® Xpress SARS-CoV-2 assay measured on repeat screening of the 42 included patients. Graph of the fitted SOFA scores based on the Cycle Threshold values per patient. Conclusion Our findings suggest that an increasing Ct value in sequential tests may be of prognostic value for patients diagnosed with COVID-19 pneumonia. Before repeat testing can be recommended routinely in clinical practice as a predictor of disease outcomes, prospective studies with a standardized interval between repeat tests should confirm our findings. Disclosures All Authors: No reported disclosures

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

Journal of Occupational Medicine and Toxicology ◽

10.1186/s12995-021-00321-3 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Ai Chien ◽

Sandra Domeracki ◽

Sandeep Guntur ◽

Kristopher Taylor ◽

Chuanyi M. Lu ◽

...

Keyword(s):

Health Care ◽

Viral Load ◽

Health Care Workers ◽

Bivariate Model ◽

Cycle Threshold ◽

Ct Value ◽

Care Workers ◽

Polymerase Chain ◽

Ct Data ◽

Multivariable Modelling

Abstract 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.

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#27: Comparison of RT-PCR Cycle Threshold Values from Respiratory Specimens in Symptomatic and Asymptomatic Children with SARS CoV-2 Infection

Journal of the Pediatric Infectious Diseases Society ◽

10.1093/jpids/piab031.022 ◽

2021 ◽

Vol 10 (Supplement_2) ◽

pp. S10-S11

Author(s):

John Strutner ◽

Nanda Ramchandar ◽

Shruti Dubey ◽

Mary Gamboa ◽

Michelle K Vanderpool ◽

...

Keyword(s):

Medical Record ◽

Electronic Medical Record ◽

Tertiary Care ◽

Severe Illness ◽

Rt Pcr ◽

Respiratory Specimen ◽

Cycle Threshold ◽

Ct Value ◽

Asymptomatic Children ◽

The Mean

Abstract Background Understanding viral kinetics of SARS-CoV-2 is important to assess risk of transmission, manage treatment, and determine the need for isolation and protective equipment. Children have been noted to have less severe illness than adults and may have less transmission potential. We sought to determine whether children deemed to be asymptomatic had a difference in the PCR cycle threshold (Ct) value of respiratory samples from symptomatic children with SARS CoV-2 infection. Methods This was a retrospective cross-sectional study to compare PCR Ct values of 728 children who tested positive for SARS-CoV-2 by respiratory samples collected over a 4-month period. The study was a single center review of patients who tested positive for SARS-CoV-2 by RT-PCR from a respiratory specimen at a large tertiary care children’s hospital. Inclusion criteria included children 0–18 years of age who tested positive for SARS-CoV-2 by RT-PCR from a respiratory specimen for whom clinical information was available in the electronic medical record. Results We analyzed 728 children who tested positive for SARS-CoV-2 by RT-PCR from a respiratory sample over a 4-month period and for whom data was available in the electronic medical record. Overall, 71.2% of infected children were symptomatic. The mean Ct value for symptomatic patients (Ct mean 19.9, SD 6.3) was significantly lower than asymptomatic patients (Ct mean 23.5, SD 6.5) (P value < 0.001, CI95th 2.6 - 4.6). The mean PCR Ct value was lowest in children less than 5 years of age. Conclusions and Relevance In this retrospective review of children who tested positive by RT-PCR for SARS CoV-2, the mean Ct was significantly lower in symptomatic children and was lowest in children under 5 years of age.

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A CYCLE THRESHOLD VALUE-BASED EPIDEMIC PROGNOSTICATION TO MONITOR LONG-TERM EPIDEMIOLOGIC TRENDS OF SARS-COV-2 VIRUS

10.36106/gjra/8200797 ◽

2021 ◽

pp. 24-30

Author(s):

Aditi Munmun Sengupta ◽

Diptendu Chatterjee ◽

Bibhuti Saha

Keyword(s):

Meta Analysis ◽

Threshold Value ◽

High Viral Load ◽

World Health ◽

Rt Pcr ◽

Cycle Threshold ◽

Ct Value ◽

Health Organization ◽

The Impact

The real-time reverse transcription-polymerase chain reaction (RT-PCR) is considered as the sensitive proof for detecting the viral infection of the SARS-CoV-2 virus obtained from respiratory samples. The quantitative values for the analysis are benecial for estimating the transmissibility of people who test positive for SARS-CoV-2. This can be further achieved by analyzing the samples by semiquantitative means through the interpretation of the cycle threshold (Ct) values of RT-PCR that represent the rst cycle of PCR at which a detectable signal appears during the assays. The Ct value shows a correlation between high viral load and disease infectiousness, which is observed with other respiratory viruses, including the inuenza B infection and rhinovirus infection. Hence, the present study aims to analyze the surveillance of COVID-19 to monitor longer-term epidemiologic trends and trends in deaths due to COVID-19. In order to achieve this aim, the present review was reported to the preferred reporting items for systematic reviews and meta-analysis statements (PRISMA) for analyzing the Ct value-based epidemic predictions and to monitor long-term epidemiologic trends of SARS-CoV-2 virus. Total 33 studies have been nalized for nding out the results of the study. The epidemiologic parameter and a representative of the surveillance data for reporting to the World Health Organization were fullled by analyzing the systematic review and metaanalysis of the selected study. Moreover, the evaluation of the impact of the pandemic on the health care system and society was achieved by analyzing the studies mentioned here.

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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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Systematic Review on the Correlation of Quantitative PCR Cycle Threshold Values of Gastrointestinal Pathogens With Patient Clinical Presentation and Outcomes

Frontiers in Medicine ◽

10.3389/fmed.2021.711809 ◽

2021 ◽

Vol 8 ◽

Author(s):

Stéphane Bonacorsi ◽

Benoit Visseaux ◽

Donia Bouzid ◽

Josep Pareja ◽

Sonia N. Rao ◽

...

Keyword(s):

Systematic Review ◽

Clinical Outcomes ◽

Cochrane Library ◽

Gastrointestinal Infections ◽

Duration Of Symptoms ◽

Cycle Threshold ◽

Risk Of Death ◽

Gastrointestinal Pathogens ◽

Increased Risk ◽

Parasitic Pathogens

Background: Quantitative (q) polymerase chain reaction (PCR) cycle threshold (Ct) values represent the number of amplification cycles required for a positive PCR result and are a proxy of pathogen quantity in the tested sample. The clinical utility of Ct values remains unclear for gastrointestinal infections.Objectives: This systematic review assesses the global medical literature for associations between Ct values of gastrointestinal pathogens and patient presentation and clinical outcomes.Data Sources: MEDLINE, EMBASE, Cochrane library databases: searched January 14–17, 2020.Study Eligibility Criteria: Studies reporting on the presence or absence of an association between Ct values and clinical outcomes in adult and pediatric populations were included. Animal studies, reviews, meta-analyses, and non-English language studies were excluded.Participants: Humans infected with gastrointestinal pathogens, detected with qPCR.Interventions: Diagnostics assessing Ct values. Extracted data were reported narratively.Results: Thirty-three eligible studies were identified; the most commonly studied pathogens were Clostridioides difficile (n = 15), norovirus (n = 10), and rotavirus (n = 9). Statistically significant associations between low C. difficile Ct values and increased symptom severity or poor outcome were reported in 4/8 (50%) studies, and increased risk of death in 1/2 (50%) studies; no significant associations were found between Ct value and duration of symptoms or length of hospital stay. Among studies of norovirus, 5/7 (71%), mainly genogroup II, reported symptomatic cases with significantly lower median Ct values than controls. Significantly lower rotavirus Ct values were also observed in symptomatic cases vs. controls in 3/7 (43%) studies, and associated with more severe symptoms in 2/2 studies. Contradictory associations were identified for non-C. difficile bacterial and parasitic pathogens.Conclusions: In conclusion, some studies reported clinically useful associations between Ct values and patient or healthcare outcomes; additional, well-designed, large-scale trials are warranted based on these findings.Systematic Review Registration: [PROSPERO], identifier [CRD42020167239].

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Comorbidities of COVID-19 Patients With Low Cycle Threshold (Ct) Value of Nucleocapsid (N) Gene: An Application to Cluster-Based Logistic Model.

10.21203/rs.3.rs-147576/v1 ◽

2021 ◽

Author(s):

SUJAN RUDRA ◽

SHUVA DAS ◽

MD. EHSANUL HOQUE ◽

ABUL KALAM ◽

MOHAMMAD ARIFUR RAHMAN ◽

...

Keyword(s):

N Gene ◽

Cure Rate ◽

Health Crisis ◽

Cycle Threshold ◽

Medical College ◽

Ct Value ◽

Unit Management ◽

Pcr Method ◽

Biology Laboratory

Abstract Background: Coronavirus disease 2019 (COVID-19) is a health crisis throughout the world. The widely used Real-time Reverse Transcriptase Polymerase Chain Reaction (rRT-PCR) method is most capable to demonstrate the patient’s condition. Comorbidities can make patients more critical.Materials and methods: In this study, we shed light on the low cycle threshold (Ct) value of the N gene in the rRT-PCR test of the COVID-19 patients who had comorbidities and their cure rate as well as the needfulness of ICU (Intensive Care Unit) management. We conducted the research in the Molecular Biology Laboratory of Chittagong Medical College between May and August 2020, then took the telephone interview with 300 positive patients who fulfilled the study criteria. We applied cluster-based logistic regression to analyze the data.Results: Low Ct value of the N gene was found 1.324 times more in Type 2 DM patients and 1.871 times higher in hypertensive patients. Hospitalized patients are 2.480 times more vulnerable to shift in ICU in case of low Ct value of the N gene. Conclusion: While infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) frequently causes severe diseases, suspected cases with comorbid conditions should go through the rRT-PCR as early as possible.

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Association Between SARS-CoV-2 Cycle Threshold Values and Clinical Outcomes in Patients With COVID-19: A Systematic Review and Meta-analysis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab453 ◽

2021 ◽

Vol 8 (9) ◽

Author(s):

Vishal P Shah ◽

Wigdan H Farah ◽

James C Hill ◽

Leslie C Hassett ◽

Matthew J Binnicker ◽

...

Keyword(s):

Systematic Review ◽

Clinical Outcomes ◽

Disease Severity ◽

Meta Analysis ◽

Severe Disease ◽

Sample Type ◽

Sample Collection ◽

Cycle Threshold ◽

Significant Difference ◽

Polymerase Chain

Abstract Cycle threshold (CT) values are correlated with the amount of viral nucleic acid in a sample and may be obtained from some qualitative real-time polymerase chain reaction tests used for diagnosis of most patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, CT values cannot be directly compared across assays, and they must be interpreted with caution as they are influenced by sample type, timing of sample collection, and assay design. Presently, the correlation between CT values and clinical outcomes is not well understood. We conducted a systematic review and meta-analysis of published studies through April 19, 2021, that reported an association between CT values and hospitalization, disease severity, and mortality in patients ≥18 years old with SARS-CoV-2. A meta-analysis of 7 studies showed no significant difference in mean CT values between hospitalized and nonhospitalized patients. Among hospitalized patients, those with CT values <25 had a high risk of more severe disease and mortality than patients with CT values >30 (odds ratio [OR], 2.31; 95% CI, 1.70 to 3.13; and OR, 2.95; 95% CI, 2.19 to 3.96; respectively). The odds of increased disease severity and mortality were less pronounced in patients with CT values of 25–30 compared with >30.

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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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