INTRODUCTION: Globally, the coronavirus disease 2019 (COVID-19) is still spreading rapidly. At present, there are no specifically approved therapeutic agents or vaccines for its treatment. Previous studies have shown that the convalescent plasma therapy (CPT) is effective in patients with COVID-19. However, its efficacy in patients with persistently positive nucleic acid test is unknown. PATIENT CONCERNS: In this report, we present the clinical data of 5 critically ill COVID-19 patients admitted, between January 16 and February 26, 2020, in intensive care unit of Xiaogan Central Hospital. DIAGNOSIS AND INTERVENTIONS: All these patients had a persistently positive nucleic acid test and received CPT. All 5 patients had severe respiratory failure, and thus, required invasive mechanical ventilation. The median time from the onset of symptoms to initiating the CPT was 37 (Interquartile range, 34-44) days. OUTCOMES: Only 2 patients were cured and subsequently discharged, while 3 patients succumbed due to multiple organ failure. CONCLUSION: The time of initiating the CPT may be an important factor affecting its efficacy, and its therapeutic effect in the treatment of COVID-19, in the late stage, is limited.