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

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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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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Can the Severe Acute Respiratory Syndrome Coronavirus 2 Polymerase Chain Reaction Cycle Threshold Value and Time From Symptom Onset to Testing Predict Infectivity?

Clinical Infectious Diseases ◽

10.1093/cid/ciaa735 ◽

2020 ◽

Vol 71 (10) ◽

pp. 2667-2668 ◽

Cited By ~ 6

Author(s):

Matthew J Binnicker

Keyword(s):

Polymerase Chain Reaction ◽

Severe Acute Respiratory Syndrome ◽

Symptom Onset ◽

Threshold Value ◽

Polymerase Chain Reaction Cycle ◽

Chain Reaction ◽

Reaction Cycle ◽

Cycle Threshold ◽

Polymerase Chain

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.561 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S283-S283

Author(s):

Danielle Dixon ◽

Julieta Madrid-Morales ◽

Jose Cadena-Zuluaga ◽

Christopher R Frei

Keyword(s):

Symptom Onset ◽

Medical Center ◽

Quantitative Polymerase Chain Reaction ◽

Symptom Duration ◽

Threshold Values ◽

Indirect Measure ◽

Cycle Threshold ◽

Mild Disease ◽

Ct Value ◽

Transmissible Disease

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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Correlation between Cycle Threshold (Ct) Value and IL-6 and D-Dimer in Chip-based RT-PCR Positive COVID-19 Cases: Study from a Stand-alone Laboratory

Asian Journal of Research in Infectious Diseases ◽

10.9734/ajrid/2021/v8i330236 ◽

2021 ◽

pp. 1-9

Author(s):

Chhavi Gandhi ◽

H. N. Ravikumar ◽

Vani Ravikumar ◽

C. Vani

Keyword(s):

Interleukin 6 ◽

Clinical Sample ◽

Threshold Value ◽

Clinical Samples ◽

Rt Pcr ◽

Cycle Threshold ◽

Ct Value ◽

Asymptomatic Patients ◽

Significant Difference ◽

D Dimer

Background: Novel Coronavirus (SARS-COV-2) is a leading cause of morbidity and mortality since the beginning of 2020 leading to range of symptoms from mild flu to respiratory distress, which is called COVID-19. RTPCR being the main diagnostic test can confirm the presence of the virus in the clinical samples, while various studies have defined Interleukin-6 and D-dimer as potent biomarker for severity. In this study, we have attempted to correlate the severity of COVID-19 with the presence of IL-6 and D-dimer and the Cycle threshold (Ct vlue) as determined by chip based RTPCR. Aim: The study aims to correlate the Cycle threshold value obtained after chip-based RT-PCR with markers such as IL-6 and D-Dimers. Methodology: It is a retrospective, observational study done in 799 subjects in a span of three months (August 2020 to October 2020) at R V Metropolis Diagnostic and Healthcare Pvt Ltd. All symptomatic patients who tested positive in the Laboratory for COVID-19 by chip-based RT-PCR were included. Chip based RTPCR or Truenat test was performed on Nasopharyngeal swabs of the suspected subjects. Interleukin-6 was determined by Electrochemiluminiscence assay while D-dimer was done on the principle of Chemiluminiscence. Statistical Analysis Used: SPSS 12.0 version. Results: Total number of subjects enrolled were 799, with mean age of the subjects being 46.80± 17.55 years. In the study, males were found to be affected by COVID-19 more than females with ratio of male to female being 1.65:1. 498 (62.3%) of males presented with COVID-19 while it was observed in 301 (37.6%) females. Out of 799 subjects, 289 (36.2%) were symptomatic and out of 289 subjects, 140 (17.5% of total subjects) required hospitalisation. Cycle threshold values of both screening as well as confirmatory genes were determined separately in the cases of symptomatic and asymptomatic cases and there was no significant difference between the Ct values in cases of symptomatic and asymptomatic patients. Symptomatic patients were subcategorised under hospitalised and non-hospitalised and Again, no significant difference was seen between the two subset of patients in terms of Ct-value and, indirectly, the viral load of their clinical sample. The results convey that IL-6 and D-Dimer was significantly high (p=0.001 and <0.001 respectively) in case of symptomatic patients.D-Dimer was significantly high (p= <0.001) in the patients who needed hospitalisation. IL-6 was significantly raised as well (p=0.02). Screening and confirmatory gene were found to have no significant relationship with IL-6 and D-Dimer, neither any correlation was observed with them. Conclusion: Biomarkers such as Interleukin-6 and D-dimer can very well help in determining the severity and need for hospitalisation in a COVID-19 affected patient, but they have been found to have no relationship with cycle threshold value of RTPCR in our study.

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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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