Background There is limited and controverting evidence looking at possible associations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA copies and patient variables in large cohorts of symptomatic and asymptomatic patients. Methods We studied 2275 symptomatic and asymptomatic patients from Colombia with coronavirus disease 2019 (COVID-19) and analyzed the associations between RT-PCR cycle threshold (Ct) value with gender, age, comorbidities, symptomatology, and disease severity. Results 15.4 % of the samples (n = 428) reported at least one comorbidity. There were 2011 symptomatic cases (72.4 %), being the most common reported symptom cough (57.2 %, n = 1586). Respiratory distress was present in 21.4 % of patients (n = 595), and 435 patients (15.6 %) required hospital admission. We observed that patients with no prior medical history harbored higher RNA copies than patients with comorbidities (p = 0.02). No significant differences in RNA copies were observed between symptomatic and asymptomatic patients (p = 0.82). Strong correlations were detected between Ct values and the presence of odynophagia (p = 0.03), diarrhea (p = 0.04), and headache (p = 0.0008). An inverse association was found between RNA copy number and markers of disease severity, namely, respiratory distress (P < 0.0001) and hospitalization requirement (P < 0.0001). Conclusions SARS-CoV-2 RT-PCR cycle thresholds reveal strong associations with a prior medical history, specific symptomatology, and disease severity markers. Further research controlling potential confounding variables needs to be conducted to evaluate the nature and usefulness of these associations in managing COVID-19 patients.