In the modern COVID-19 pandemic, reverse transcription-polymerase chain reaction (RT-PCR) positivity has a major role in the diagnosis of the disease. However, in deciding the patient's discharge or de-isolation, its role is still debatable. We are, hereby, describing three cases (an intern, a nursing officer and a caretaker of another patient) where only RT-PCR could not help much since it was persistently positive for >20 days of the illness course. Instead, the cycle threshold (Ct) values could have better correlated with the infectivity of COVID. We propose a rising trend (24 h apart) and absolute Ct value >25, instead of RT-PCR negativity (which was taken as Ct value >36 in our laboratory), to be used in deciding the infective potential of the patients, their discharge from the hospital and de-isolation of the patients. This will help in the timely discharge of patients from health-care institutions and home isolation, which, as a result, will lead to optimal utilisation of the limited hospital resources we have available in the line of the ongoing pandemic. Future studies are required to define the exact cutoff of Ct value for de-isolation purposes.