COVID-19 re-infection by a phylogenetically distinct SARS-coronavirus-2 strain confirmed by whole genome sequencing

To, Kelvin Kai-Wang; Hung, Ivan Fan-Ngai; Ip, Jonathan Daniel; Chu, Allen Wing-Ho; Chan, Wan-Mui; Tam, Anthony Raymond; Fong, Carol Ho-Yan; Yuan, Shuofeng; Tsoi, Hoi-Wah; Ng, Anthony Chin-Ki; Lee, Larry Lap-Yip; Wan, Polk; Tso, Eugene; To, Wing-Kin; Tsang, Dominic; Chan, Kwok-Hung; Huang, Jian-Dong; Kok, Kin-Hang; Cheng, Vincent Chi-Chung; Yuen, Kwok-Yung

BACKGROUND: Waning immunity occurs in patients who have recovered from COVID-19. However, it remains unclear whether true re-infection occurs. METHODS: Whole genome sequencing was performed directly on respiratory specimens collected during two episodes of COVID-19 in a patient. Comparative genome analysis was conducted to differentiate re-infection from persistent viral shedding. Laboratory results, including RT-PCR Ct values and serum SARS-CoV-2 IgG, were analyzed. RESULTS: The second episode of asymptomatic infection occurred 142 days after the first symptomatic episode in an apparently immunocompetent patient. During the second episode, there was serological evidence of elevated C-reactive protein and SARS-CoV-2 IgG seroconversion. Viral genomes from first and second episodes belong to different clades/lineages. Compared to viral genomes in GISAID, the first virus genome has a stop codon at position 64 of orf8 leading to a truncation of 58 amino acids, and was phylogenetically closely related to strains collected in March/April 2020, while the second virus genome was closely related to strains collected in July/August 2020. Another 23 nucleotide and 13 amino acid differences located in 9 different proteins, including positions of B and T cell epitopes, were found between viruses from the first and second episodes. CONCLUSIONS: Epidemiological, clinical, serological and genomic analyses confirmed that the patient had re-infection instead of persistent viral shedding from first infection. Our results suggest SARS-CoV-2 may continue to circulate among the human populations despite herd immunity due to natural infection or vaccination. Further studies of patients with re-infection will shed light on protective correlates important for vaccine design.