Whole genome sequencing analysis
Prior to having the WGS data, several findings, i.e., chronology of SARS-CoV-2 infections, dates of symptom onset, positive SARS-CoV-2 RT-PCRs, and room coincidences, led clinicians to assume that Case R recurrence was a reinfection due to the exposure to a patient with whom he had shared the hospital room (Case A) and who had been admitted 11 days before due to an intestinal obstruction, had a bilateral pneumonia and subsequent positive SARS-CoV-2 RT-PCR. However WGS data (obtained in a larger study analysing a wide nosocomial outbreak in the Gastroenterology ward, under evaluation) indicated that fully different strains were identified in Case A and Case R (Figure 2). In addition, Case R was part of Cluster which also included Cases S and T, infected by an identical strain (0 SNPs, Figure 2). Cases S and T had shared a room, but Case R at the time of his positive-RT-PCR was in a different one. However, tracking back his previous movements revealed that Case R had shared room with case S seven days before, confirming a link between them; SARS-CoV-2 infection in Case S had a fatal outcome.
WGS data ruled out our initial hypothesis of reinfection after nosocomial exposure and led us to consider, alternatively, Case R as a reactivation, causing a subsequent nosocomial transmission. The sequences of the positive specimens collected from Case R first and second episodes (July and September, 2020) belonged to the same lineage (B.1.177) and showed nearly identical sequences; they shared 16 SNPs and differed in two (Figure 3, Supplementary Table). Given the marked diversity of circulating SARS-CoV-2 in the second COVID-19 wave, the high similarity between the sequences strongly supports that Case R recurrence most likely corresponded to a reactivation.