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Review
. 2021 Aug 31;8(9):ofab453.
doi: 10.1093/ofid/ofab453. eCollection 2021 Sep.

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

Vishal P Shah  1 , Wigdan H Farah  1 , James C Hill  1 , Leslie C Hassett  2 , Matthew J Binnicker  3 , Joseph D Yao  3 , M Hassan Murad  1
Affiliations
Review

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

Vishal P Shah et al. Open Forum Infect Dis. .

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.

Keywords: COVID-19; SARS-CoV-2; clinical outcomes; cycle threshold; meta-analysis; prognosis.

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Figures

Figure 1.
Figure 1.
PRISMA flowchart. Abbreviations: CT, cycle threshold; PCR, polymerase chain reaction.
Figure 2.
Figure 2.
Forest plot of mean CT value difference between hospitalized and nonhospitalized patients. Abbreviation: CT, cycle threshold.
Figure 3.
Figure 3.
Forest plots of disease severity outcome among hospitalized patients. A, CT value <25 vs >30. B, CT value 25–30 vs >30. C, Mean CT value difference between patients with severe and nonsevere disease in subgroup analysis by sample source. Abbreviation: CT, cycle threshold.
Figure 4.
Figure 4.
Forest plots of mortality outcome among hospitalized patients. A, CT value <25 vs >30. B, CT <25 vs >30, subgroup analysis by sample source. C, CT value 25–30 vs >30. D, Mean CT value difference between survivors and nonsurvivors. Abbreviations: CT, cycle threshold; NP, nasopharyngeal.
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