The gold standard for diagnosing COVID-19 infection is RT-PCR because it detects viral RNA with high sensitivity and specificity. It can identify the virus even in early infection stages when viral loads are low, enabling accurate diagnosis. Unlike rapid antigen tests, which have lower sensitivity, RT-PCR minimizes false negatives. Imaging (like chest X-ray) and serology tests do not detect active infection but rather complications or immune response, respectively. Therefore, RT-PCR remains the most reliable method for confirming COVID-19 infection.

Reference: Harrison's Principles of Internal Medicine, Jameson et al., 20th Edition.