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

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Abstract

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.

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Author and article information

Journal

Journal ID (nlm-ta): Clin Infect Dis

Journal ID (iso-abbrev): Clin. Infect. Dis

Journal ID (publisher-id): cid

Title: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America

Publisher: Oxford University Press (US )

ISSN (Print): 1058-4838

ISSN (Electronic): 1537-6591

Publication date (Electronic): 25 August 2020

Electronic Location Identifier: ciaa1275

Affiliations

[1 ] State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology , Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China

[2 ] Department of Microbiology, Queen Mary Hospital , Hong Kong Special Administrative Region, China

[3 ] Department of Medicine, Queen Mary Hospital , Hong Kong Special Administrative Region, China

[4 ] Department of Accident and Emergency Medicine, Tin Shui Wai Hospital , Hong Kong Special Administrative Region, China

[5 ] Department of Medicine, North Lantau Hospital , Hong Kong Special Administrative Region, China

[6 ] Department of Medicine, United Christian Hospital , Hong Kong SAR, China

[7 ] Department of Pathology, Princess Margaret Hospital , Hong Kong, China

[8 ] Centre for Health Protection , Department of Health, Hong Kong

[9 ] School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong , Hong Kong Special Administrative Region, China

Author notes

These authors contribute equally.

Corresponding author: Kwok-Yung Yuen, Email: kyyuen@ 123456hku.hk , Phone number: (852)-22552413, Carol Yu Centre for Infection, State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China

Article

Publisher ID: ciaa1275

DOI: 10.1093/cid/ciaa1275

PMC ID: 7499500

PubMed ID: 32840608

SO-VID: 7a9d0fa9-1b93-4df2-9200-452a03a4ae6b

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