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

Cycle threshold (C(T)) 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, C(T) 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 C(T) 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 C(T) 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 C(T) values between hospitalized and nonhospitalized patients. Among hospitalized patients, those with C(T) values <25 had a high risk of more severe disease and mortality than patients with C(T) 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 C(T) values of 25–30 compared with >30.