SARS-CoV-2 persistence is associated with antigen-specific CD8 T-cell responses

Abstract

Background: Upon SARS-CoV-2 infection, most individuals develop neutralizing antibodies and T-cell immunity. However, some individuals reportedly remain SARS-CoV-2 PCR positive by pharyngeal swabs weeks after recovery. Whether viral RNA in these persistent carriers is contagious and stimulates SARS-CoV-2-specific immune responses is unknown. Methods: This cohort study was conducted between April 3 rd ÀJuly 9 th 2020, recruiting COVID-19 recovered individuals that were symptom-free for at least 14 days. We collected serum for SARS-CoV-2-specific total Ig, IgA and IgM detection by ELISA, pharyngeal swabs (two time points) for ddPCR and PBMCs for anti-SARS-CoV-2 CD8 T-cell dextramer analyses. Findings: We enrolled 203 post-symptomatic participants with a previous RT-PCR-verified SARS-CoV-2 infection. At time point 1, a median of 23 days (range 15À44) after recovery, 26 individuals (12Á8%) were PCR positive. At time point 2, 90 days (median, range 85À105) after recovery, 5 (5Á3%) were positive. There was no difference in SARS-CoV-2 antibody levels between the PCR negative and positive group. The persistent PCR positive group however, had SARS-CoV-2-specific CD8 T-cell responses of significantly increased breadth and magnitude. Assisted contact tracing among persistent PCR positive individuals revealed zero new COVID-19 diagnoses among 757 close contacts. Interpretation: Persistent pharyngeal SARS-CoV-2 PCR positivity in post-symptomatic individuals is associated with elevated cellular immune responses and thus, the viral RNA may represent replicating virus. However, transmission to close contacts was not observed indicating that persistent PCR positive individuals are not contagious at the post-symptomatic stage of the infection.

SARS-CoV-2 Infections and Viral Isolations among Serially Tested Cats and Dogs in Households with Infected Owners in Texas, USA

“…With this approach, we detected viral RNA from the sequential sampling events of two infected cats (TAMU-013 and 057) at least three weeks after their initial positive tests. Prolonged duration of PCR-positivity has also been observed in pharyngeal swabs from post-symptomatic humans recovered from COVID-19 [ 35 ]. In that study, although the observed ongoing cellular anti-SARS-CoV-2 response is indicative of persistent viral replication, the studied human cases were not associated with any transmission to close contacts, leading to the interpretation that persistent PCR positive individuals are not contagious [ 35 ].…”

“…Prolonged duration of PCR-positivity has also been observed in pharyngeal swabs from post-symptomatic humans recovered from COVID-19 [ 35 ]. In that study, although the observed ongoing cellular anti-SARS-CoV-2 response is indicative of persistent viral replication, the studied human cases were not associated with any transmission to close contacts, leading to the interpretation that persistent PCR positive individuals are not contagious [ 35 ]. Further, persistent infections have been reported for other coronavirus infections, and the role of persistent infection with SARS-CoV-2 in animals is yet to be fully explored.…”

Dynamic causal modelling of immune heterogeneity

“…If this phenotype exists at all, it is likely that such people are in the minority. Interestingly, there is emerging evidence in favour of an association between the T-cell response and positive PCR testing weeks following recovery from infection 59 , as this model would predict.…”

Phylogenomic Evidence of Reinfection and Persistence of SARS-CoV-2: First Report from Colombia

“…Persistence has been widely documented in COVID-19, characterized by extensive lung thrombosis, long-term persistence of viral RNA in pneumocytes and endothelial cells, along with the presence of infected cell syncytia [24]. This feature has been mainly reported in patients with impaired immunity or cancer around the globe [25,26]. However, information of SARS-CoV-2 persistence using whole-genome sequencing is scarce, with only one case of follow-up in an immunocompromised patient [27].…”