Complexities in Case Definition of SARS-CoV-2 Reinfection: Clinical Evidence and Implications in COVID-19 Surveillance and Diagnosis

Reinfection cases have been reported in some countries with clinical symptoms ranging from mild to severe. In addition to clinical diagnosis, virus genome sequence from the first and second infection has to be confirmed to either belong to separate clades or had significant mutations for the confirmation of SARS-CoV-2 reinfection. While phylogenetic analysis with paired specimens offers the strongest evidence for reinfection, there remains concerns on the definition of SARS-CoV-2 reinfection, for reasons including accessibility to paired-samples and technical challenges in phylogenetic analysis. In light of the emergence of new SARS-CoV-2 variants that are associated with increased transmissibility and immune-escape further understanding of COVID-19 protective immunity, real-time surveillance directed at identifying COVID-19 transmission patterns, transmissibility of emerging variants and clinical implications of reinfection would be important in addressing the challenges in definition of COVID-19 reinfection and understanding the true disease burden.