A 77-year-old male (Case R) who had had a previous diagnosis of mild COVID-19 episode, with fever without developing pneumonia or other complications, was hospitalized 57 days later, due to an acute cholangitis. He had a prolonged hospital stay with severe biliary and infectious complications. On Day 23 post-admission, the patient developed a second COVID-19 episode, now severe, with bilateral pneumonia, multiorgan failure, and finally died. Initially, Case R COVID-19 recurrence was interpreted as a reinfection due to the exposure to a patient with whom he had shared the hospital room, who also had a subsequent positive SARS-CoV-2 RT-PCR. However, whole genome sequencing data indicated that both cases were infected by different strains and clarified that case R recurrence corresponded to a reactivation of the strain involved in his first episode. Case R reactivation had major consequences, not only leading to a much more severe second episode, but causing a subsequent transmission to another two hospitalized patients, one of them with fatal resolution.
