Persistent SARS-CoV-2 infection in asymptomatic young adults

Intra-host evolution of SARS-CoV-2 has not been reported among asymptomatic cases, though this phenomenon was observed in a few symptomatic and immunocompromised cases. Here, we identified six asymptomatic cases who were persistently positive for SARS-CoV-2 RNA up to 120 days. Phylogenetic analysis of 40 serial whole-genome sequences from the six cases revealed dynamic mutations of the virus. To explore the possible mechanism contributing to the persistent infection, we investigated immune responses. The six cases had comparable specific antibodies with other 24 non-persistent asymptomatic cases, but they had significantly lower antibody levels than symptomatic cases. Although the virus-specific memory B and T cells were detected in the three groups of cases, the six cases showed an upregulation of CD4 regulatory T cells, which was negatively correlated with low levels of activated CD4(+) and CD8(+) T cells. These findings imply that dysregulation of immune responses might contribute to persistent infection.