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

Abstract

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.

Association of COVID-19 Real-Time Reverse Transcription-Polymerase Chain Reaction (RT-PCR) Cycle Threshold Value With Surrogate Markers of Disease Severity

“…However, Yuan et al found no such correlation [ 22 ]. Two more recent studies also failed to observe any correlation between the Ct value and D-dimer level [ 24 , 25 ]. Although neither study compared D-dimer values between subjects with different Ct values, the results of both studies support our findings showing significantly higher D-dimer values in subjects with low Ct values.…”