key: cord-0881462-oq8atfnh authors: Tomassini, Sara; Kotecha, Deevia; Bird, Paul W; Folwell, Andrew; Biju, Simon; Tang, Julian W title: Setting the criteria for SARS-CoV-2 reinfection – six possible cases date: 2020-08-12 journal: J Infect DOI: 10.1016/j.jinf.2020.08.011 sha: bb507e6d0f0c17467d9581020350e4c448d13ba4 doc_id: 881462 cord_uid: oq8atfnh nan We read with interest the article by Batisse et al. 1 describing 11 possible cases of symptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) reinfection. However, the intervening period of 'clinical cure' was not confirmed by a negative SARS-CoV-2 PCR test result. Similarly, Lafaie et al. 2 reported three elderly patients who were infected with SARS-CoV-2 who recovered 'clinically' then were readmitted with 'new' coronavirus disease 2019 (COVID-19) symptoms, again with no SARS-CoV-2 PCR negative result between the two COVID-19 episodes. This SARS-CoV-2 reinfection phenomenon is indeed one of the many ongoing debates during the present COVID-19 pandemic and it is still unclear to what extent this is due to true reinfection, or possible persistent low level infection. 3, 4 Part of the problem is that there is no well-defined, consensus definition or criteria for deciding what constitutes true SARS-CoV-2 reinfection. Here we present 6 cases of hospitalised patients or staff with likely SARS-CoV-2 reinfection based on objective laboratory-based criteria and rationales. From our diagnostic laboratory database, we searched for a pattern of SARS-CoV-2 POS-NEG-POS polymerase chain reaction (PCR) results in any COVID-19 case, then extracted and tabulated the details of the clinical episodes for each patient fitting these initial search criteria. The SARS-CoV-2 PCR assay that we were using during this time was the commercial AusDiagnostics SARS-CoV-2 PCR kit (AusDiagnostics UK Ltd., Chesham, England) with a manufacturer's stated sensitivity and specificity of 97.7% (90.8-100%) and 99.4% (97.4-100%), respectively. The SARS-CoV-2 IgG antibody testing was performed using the commercial DiaSorin Liaison SARS-CoV-2 S1/S2 IgG assay (Diasorin Ltd., Kent, England) with a stated manufacturer's sensitivity and specificity of 97% (86.8%-99.5%) and 98.5% (97.6%-99.1%), respectively. Patients or staff meeting the following criteria were included in this possible SARS-CoV-2 reinfection cohort: -an initial SARS-CoV-2 PCR-confirmed acute coronavirus disease 2019 (COVID-19) illness -followed by clinical recovery and discharge with at least one negative SARS-CoV-2 PCR result -followed by a confirmed SARS-CoV-2 PCR positive result (with or without symptoms) at least 28 days after the previous SARS-COV-2 PCR result These criteria were based on the findings that in most COVID-19 cases, viral shedding reaches a minimum by day 28 after an initial acute SARS-CoV-2 infection. 5 It is still unclear how protective SARS-CoV-2 IgG antibodies are in the convalescent period, and how long any such protection may last. Such antibodies start to rise 5-10 days post-onset of infection, peaking by days 12-15, 6 and will contain a proportion of neutralising antibodies, 7 making any SARS-CoV-2 reinfection very unlikely within this period. Hence, we assumed that SARS-CoV-2 reinfection cannot occur within the first 28 days post-illness onset. As patients move beyond 28 days post-illness onset, SARS-CoV-2 IgG antibodies gradually wane, 8 increasing the possibility that SARS-CoV reinfection may occur. We identified 6 patients or staff that fit the criteria above ( Table 1 asymptomatic. This was a staff member whose testing had been conducted as part of the routine screening for staff who worked on immunosuppressed patient wards. The same argument can be applied to Cases 9 (symptomatic reinfection), 25 (asymptomatic reinfection) and 27 (asymptomatic reinfection), where the second SARS-CoV-2 PCR and SARS-CoV IgG positive results occurred within 5-10 days of each other (Table 1, Figure 1) . We did not culture the second COVID-19 episode SARS-CoV-2 PCR positive swabs to check for virus viability. Batisse et al. 1 , however, did find viable SARS-CoV-2 in one out of two patient samples tested during their second COVID-19 episodes. Thus while SARS-CoV-2 reinfection is a possibility for any of these 6 cases, we are the most confident of Cases 24 and 26 being true cases of SARS-CoV-2 reinfection, as they exhibited the largest interval (87 and 84 days, respectively) between their two COVID-19 episodes. Also, their two positive SARS-CoV-2 IgG antibody tests showed that antibodies were present after the first and persisted through to the second COVID-19 episode, and were therefore less likely to be a false positive finding. Reinfection with the four known human seasonal coronavirus infections has been described, even in the presence of pre-existing coronavirus antibodies, and is not unusual. 9 However, 'reactivated', 'relapsed' or 'latent' infection seems less likely and is not yet described for the family of coronaviruses. 10 Our SARS-CoV-2 reinfection criteria are not perfect and will inevitably be refined as new findings accumulate. Yet our small case series here indicates that symptomatic and asymptomatic SARS-CoV-2 reinfection can occur in the presence of SARS-CoV-2 IgG antibodies. Further studies are needed to determine to what extent SARS-CoV-2 shedding and transmission occur during symptomatic and asymptomatic reinfection. Clinical recurrences of COVID-19 symptoms after recovery: viral relapse, reinfection or inflammatory rebound? Recurrence or Relapse of COVID-19 in Older Patients: A Description of Three Cases Positive RT-PCR Test Results in Patients Recovered From COVID-19 COVID-19 and Postinfection Immunity: Limited Evidence, Many Remaining Questions Virological assessment of hospitalized patients with COVID-2019 Antibody responses to SARS-CoV-2 in patients with COVID-19 Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections Longitudinal evaluation and decline of antibody responses in SARS-CoV-2 infection Coronavirus protective immunity is short-lasting Coronaviruses: an overview of their replication and pathogenesis