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

Abstract

IntroductionThe cycle threshold (Ct) value in real-time reverse transcription-polymerase chain reaction (RT-PCR) serves as a criterion to diagnose coronavirus disease 2019 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. MethodologyThis 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. ObservationsLDH, 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. ConclusionPolymorph, 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.

The specialized pro-resolving lipid mediator Protectin D1 affects macrophages differentiation and activity in Adult-onset Still’s disease and COVID-19, two hyperinflammatory diseases sharing similar transcriptomic profiles

“…Surprisingly, we did not find any correlation between PD1 levels and ferritin. It is well known that both in COVID19 and in AOSD the levels of ferritin strongly correlate with disease the severity of the diseases , and also our study confirms the significance of this biomarker in this setting (32)(33)(34)(35). Probably, the lack of a significant correlation between PD1 and ferritin might be referred to a relatively small sample size of our cohorts.…”