SARS‐CoV‐2 re‐infection versus prolonged shedding: A case series

Abstract Since the start of the SARS‐CoV‐2 pandemic, it has been difficult to differentiate between SARS‐CoV‐2 re‐infection and prolonged RNA shedding. In this report, we identified patients with positive RT‐PCR results for SARS‐CoV‐2 ≥70 days apart. Clinical and laboratory data were collected and criteria were applied to discern whether the presentation was consistent with SARS‐CoV‐2 re‐infection or prolonged viral RNA shedding. Eleven individuals met the initial testing criteria, of which, seven met at least one criteria for re‐infection and four were consistent with prolonged RNA shedding. These data demonstrate the need for criteria to differentiate SARS‐CoV‐2 re‐infection from prolonged RNA shedding.

We included patients with 2 or more positive RT-PCR tests for SARS-CoV-2 that were at least 70 days apart in order to fully capture a spectrum of patients with prolonged viral RNA shedding vs re-infection.
Based on proposed re-infection criteria in the literature, we defined three separate criteria to classify a patient as having a reinfection with SARS-CoV-2. The criteria are as follows: (1) a positive SARS-CoV-2 RT-PCR test at least 90 days after individuals first became symptomatic with SARS-CoV-2 and subsequently become asymptomatic, 4 (2) at least 2 negative RT-PCR tests for SARS-CoV-2 between two positive tests, 10,11 and (3) at least one negative RT-PCR test for SARS-CoV-2 between two positive tests more than 28 days apart. 12 For our analysis, only one criterion was needed to be considered a probable re-infection.
We collected demographic, laboratory, and clinical data from retrospective chart review and performed phone interviews using a structured questionnaire. The protocol was approved by the institutional review board at Baylor College of Medicine.

| IgG assay
The humoral IgG anti-spike enzyme-linked immunosorbent assays (ELISA) were performed as part of our IRB-approved research study.
The SARS-CoV-2 full spike (S) protein used in the ELISA was kindly provided by Gale Smith (Novavax). 13

| Clinical presentation
Of these 11 individuals, 6 were female with an average age of 49 years (

| Probable re-infection definition
We used three criteria to assess the likelihood of a SARS-CoV-2 reinfection that occurred greater than 70 days after primary infection (described above). We found that 7 of the 11 individuals met at least one criterion for probable re-infection and all 7 of these individuals met Criteria 1 (see Figure 1 and Table 1).

| Serology
Six of the 11 individuals had IgG serology testing for SARS-CoV-2 (Table 1). Only two individuals (patients 1 and 3) had a paired sample whose sera was collected before and after their probable re-infection. Neither of these individuals mounted an increase in IgG anti-S antibody levels after their probable re-infection (Table 1).

| Limitations
This was a single site cohort study that reported on approximately seven months of RT-PCR testing for SARS-CoV-2. The low viral RNA content in the samples collected from probable re-infection cases precluded our ability to confirm the re-infection event using sequencing.

| CON CLUS IONS
The occurrence of probable re-infection with SARS-CoV-2 in our population seemed to be an uncommon occurrence that was associated with mild symptomatology at the time of their primary infection. Our data does support the CDC's recommendation that testing for SARS-CoV-2 re-infection is not needed prior to 90 days after symptoms arise.

PE E R R E V I E W
The peer review history for this article is available at https://publo ns.com/publo n/10.1111/irv.12879.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.