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

Introduction The cycle threshold (Ct) value in real-time reverse transcription-polymerase chain reaction (RT-PCR) serves as a criterion to diagnose coronavirus disease 2019 (COVID-19) and is inversely proportional to viral load. Levels of inflammatory markers such as aspartate aminotransferase (AST), ferritin, D-dimer, high sensitivity C-reactive protein (hs-CRP), and lactate dehydrogenase (LDH) are used as quantitative measures of COVID-19 severity. We examined the association between these markers and Ct values. Methodology This retrospective data analysis included 400 patients with positive RT-PCR results for COVID-19 who were admitted to a tertiary care hospital. Clinical and biochemical data were accessed from the hospital information management system. Associations of clinical parameters and markers of disease severity (e.g., polymorph, AST, hs-CRP, D-dimer, LDH, and ferritin levels) with Ct values were assessed. Observations LDH, ferritin, D-dimer, and hs-CRP were found to be significantly higher in moderate and severe groups than in the mild COVID-19 group. AST, ferritin, and hs-CRP levels were also significantly higher in severe COVID-19 subjects, compared to moderate COVID-19 subjects. Ct values for the E (envelop) gene and ORF (open reading frame) 1b gene were found to be significantly higher in those with severe COVID-19. Polymorph counts in subjects with Ct values of 25 or higher were significantly increased, compared to those with Ct values under 30. LDH, D-dimer, and hs-CRP levels in subjects with Ct values over 30 were significantly lower than for those with Ct values under 30. Ferritin was the best independent predictor of non-survival in study subjects, with an area under the curve (AUC) of 85.5% (95% confidence interval = 73.2-95.9). The Ct value for the E gene had an AUC of 75.1%, and the ORF1b gene had an AUC of 64.5%. However, no significant correlation was detected between any parameter and Ct value. Conclusion Polymorph, LDH, ferritin, D-dimer, and hs-CRP levels were significantly elevated in subjects with low E gene Ct values. Also, these subjects were at risk of severe disease and fatality. Ct values for the E gene thus could serve as an early indicator for patients at risk of severe disease and death.