Coronavirus Disease 2019 (COVID-19) Re-infection by a Phylogenetically Distinct Severe Acute Respiratory Syndrome Coronavirus 2 Strain Confirmed by Whole Genome Sequencing
Open accessAbstract
Background: Waning immunity occurs in patients who have recovered from Coronavirus Disease 2019 (COVID-19). However, it remains unclear whether true re-infection occurs. Methods: Whole genome sequencing was performed directly on respiratory specimens collected during 2 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 Severe Acute Respiratory Syndrome Coronavirus 2 (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 evidence of acute infection including elevated C-reactive protein and SARS-CoV-2 IgG seroconversion. Viral genomes from first and second episodes belong to different clades/lineages. The virus genome from the first episode contained a a stop codon at position 64 of ORF8, leading to a truncation of 58 amino acids. 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. Compared to viral genomes in GISAID, the first virus genome 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. 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 humans despite herd immunity due to natural infection. Further studies of patients with re-infection will shed light on protective immunological correlates for guiding vaccine design.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Reinfections with clearly different SARS-CoV-2 strains have been documented.
“Nonetheless, reinfections with clearly different SARS-CoV-2 strains have now been documented50,51 (Supplementary Table 2).”
From Prospects for durable immune control of SARS-CoV-2 and prevention of reinfection (2021) · cites this paper as [51]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability
Katoh, K., & Standley, D. M. (2013) · Molecular Biology and Evolution · doi:10.1093/molbev/mst010 · Cited by 46,209 · see citing works
BLAST+: architecture and applications
Camacho, C., Coulouris, G., Avagyan, V., Ma, N., Papadopoulos, J., Bealer, K., & Madden, T. L. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-421 · Cited by 22,074 · see citing works
IQ-TREE 2: New Models and Efficient Methods for Phylogenetic Inference in the Genomic Era
Minh, B. Q., Schmidt, H. A., Chernomor, O., Schrempf, D., Woodhams, M. D., von Haeseler, A., & Lanfear, R. (2020) · Molecular Biology and Evolution · doi:10.1093/molbev/msaa015 · Cited by 16,873 · see citing works
Chan, J., Yuan, S.-F., Kok, K.-H., To, K., Chu, H., Yang, J., Xing, F., Liu, J.-L., Yip, C., Poon, R., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30154-9 · Cited by 8,450 · see citing works
Self-citationGrifoni, A., Weiskopf, D., Ramirez, S. I., Mateus, J., Dan, J. M., Moderbacher, C. R., Rawlings, S. A., Sutherland, A., Premkumar, L., Jadi, R. S., et al. (2020) · Cell · doi:10.1016/j.cell.2020.05.015 · Cited by 3,595 · see citing works
To, K. K., Tsang, O. T.-Y., Leung, W.-S., Tam, A. R., Wu, T.-C., Lung, D. C., Yip, C. C., Cai, J., Chan, J. M., Chik, T. S., et al. (2020) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(20)30196-1 · Cited by 3,045 · see citing works
Self-citationClinical and immunological assessment of asymptomatic SARS-CoV-2 infections
Long, Q.-X., Tang, X.-J., Shi, Q.-L., Li, Q., Deng, H.-J., Yuan, J., Hu, J.-L., Xu, W., Zhang, Y., Lv, F.-J., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0965-6 · Cited by 2,686 · see citing works
A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology
Rambaut, A., Holmes, E. C., O’Toole, Á., Hill, V., McCrone, J. T., Ruis, C., du Plessis, L., & Pybus, O. G. (2020) · Nature Microbiology · doi:10.1038/s41564-020-0770-5 · Cited by 2,543 · see citing works
SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls
Le Bert, N., Tan, A. T., Kunasegaran, K., Tham, C. Y. L., Hafezi, M., Chia, A., Chng, M. H. Y., Lin, M., Tan, N., Linster, M., et al. (2020) · Nature · doi:10.1038/s41586-020-2550-z · Cited by 1,887 · see citing works
Convergent Antibody Responses to SARS-CoV-2 in Convalescent Individuals
Robbiani, D. F., Gaebler, C., Muecksch, F., Lorenzi, J. C. C., Wang, Z., Cho, A., Agudelo, M., Barnes, C. O., Gazumyan, A., Finkin, S., et al. (2020) · Nature · doi:10.1038/s41586-020-2456-9 · Cited by 1,853 · see citing works
Zheng, S., Fan, J., Yu, F., Feng, B., Lou, B., Zou, Q., Xie, G., Lin, S., Wang, R., Yang, X., et al. (2020) · BMJ · doi:10.1136/bmj.m1443 · Cited by 1,439 · see citing works
The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity
Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., et al. (2020) · Cell · doi:10.1016/j.cell.2020.07.012 · Cited by 1,420 · see citing works
Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike
Liu, L., Wang, P., Nair, M. S., Yu, J., Rapp, M., Wang, Q., Luo, Y., Chan, J. F.-W., Sahi, V., Figueroa, A., et al. (2020) · Nature · doi:10.1038/s41586-020-2571-7 · Cited by 1,349 · see citing works
Self-citationSARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19
Braun, J., Loyal, L., Frentsch, M., Wendisch, D., Georg, P., Kurth, F., Hippenstiel, S., Dingeldey, M., Kruse, B., Fauchere, F., et al. (2020) · Nature · doi:10.1038/s41586-020-2598-9 · Cited by 1,310 · see citing works
Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants
Weisblum, Y., Schmidt, F., Zhang, F., DaSilva, J., Poston, D., Lorenzi, J. C., Muecksch, F., Rutkowska, M., Hoffmann, H.-H., Michailidis, E., et al. (2020) · eLife · doi:10.7554/elife.61312 · Cited by 1,308 · see citing works
Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans
Mateus, J., Grifoni, A., Tarke, A., Sidney, J., Ramirez, S. I., Dan, J. M., Burger, Z. C., Rawlings, S. A., Smith, D. M., Phillips, E., et al. (2020) · Science · doi:10.1126/science.abd3871 · Cited by 1,120 · see citing works
Liu, L., Wei, Q., Lin, Q., Fang, J., Wang, H., Kwok, H., Tang, H., Nishiura, K., Peng, J., Tan, Z., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.123158 · Cited by 830 · see citing works
Self-citationSARS-CoV-2 infection protects against rechallenge in rhesus macaques
Chandrashekar, A., Liu, J., Martinot, A. J., McMahan, K., Mercado, N. B., Peter, L., Tostanoski, L. H., Yu, J., Maliga, Z., Nekorchuk, M., et al. (2020) · Science · doi:10.1126/science.abc4776 · Cited by 816 · cited 2× · see citing works
“In rhesus macaques that have recovered from SARS-CoV-2 infection and re-challenged with the same virus, the peak viral load during re-challenge was >5 log10 lower in the BAL but only ~2 log10 lower in the nasal swab when compared with those during the first challenge [25].”
BackgroundSingle-Shot Ad26 Vaccine Protects Against SARS-CoV-2 in Rhesus Macaques
Mercado, N. B., Zahn, R., Wegmann, F., Loos, C., Chandrashekar, A., Yu, J., Liu, J., Peter, L., McMahan, K., Tostanoski, L. H., et al. (2020) · Nature · doi:10.1038/s41586-020-2607-z · Cited by 789 · see citing works
Acute SARS-CoV-2 Infection Impairs Dendritic Cell and T Cell Responses
Zhou, R., To, K. K.-W., Wong, Y.-C., Liu, L., Zhou, B., Li, X., Huang, H., Mo, Y., Luk, T.-Y., Lau, T. T.-K., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.07.026 · Cited by 531 · see citing works
Self-citationSnyder, T. M., Gittelman, R. M., Klinger, M., et al. (2020) · medRxiv · doi:10.1101/2020.07.31.20165647 · Cited by 234 · see citing works
Escape from neutralizing antibodies by SARS-CoV-2 spike protein variantsPreprint
Weisblum, Y., Schmidt, F., Zhang, F., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.07.21.214759 · Cited by 172 · see citing works
High neutralizing antibody titer in intensive care unit patients with COVID-19
Liu, L., To, K. K., Chan, K., Wong, M. Y.-C., Zhou, R., Kwan, K., Fong, C. H.-Y., Chen, L., Choi, C. Y.-K., Lu, L., et al. (2020) · Emerging Microbes & Infections · doi:10.1080/22221751.2020.1791738 · Cited by 132 · see citing works
Self-citationHung, I. F., Cheng, V. C., Li, X., et al. (2020) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(20)30364-9 · Cited by 120 · see citing works
Self-citationMining of epitopes on spike protein of SARS-CoV-2 from COVID-19 patients
Zhang, B., Hu, Y., Chen, L., Yau, T. C. C., Tong, Y., Hu, J., Cai, J., Chan, K., Dou, Y., Deng, J., et al. (2020) · Cell Research · doi:10.1038/s41422-020-0366-x · Cited by 114 · see citing works
Self-citationYuan, B., Liu, H., Yang, Z., Chen, Y., Liu, Z., Zhang, K., Wang, C., Li, W., An, Y., Wang, J., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-68782-w · Cited by 113 · see citing works
Coronavirus protective immunity is short-lastingPreprint
Edridge, A. W. D., Kaczorowska, J., Hoste, A. C. R., et al. (2020) · medRxiv · doi:10.1101/2020.05.11.20086439 · Cited by 106 · see citing works
To, K. K., Cheng, V. C., Cai, J., Chan, K., Chen, L., Wong, L. S., Choi, C. Y.-K., Fong, C. H.-Y., Ng, A. C., Lu, L., et al. (2020) · The Lancet Microbe · doi:10.1016/s2666-5247(20)30053-7 · Cited by 90 · see citing works
Self-citationIs novel coronavirus 2019 reinfection possible? Interpreting dynamic SARS-CoV-2 test results
Duggan, N. M., Ludy, S., Shannon, B. C., Reisner, A. T., & Wilcox, S. R. (2020) · The American Journal of Emergency Medicine · doi:10.1016/j.ajem.2020.06.079 · Cited by 87 · see citing works
Yip, C. C., Sridhar, S., Cheng, A. K.-W., et al. (2020) · Journal of Clinical Virology · doi:10.1016/j.jcv.2020.104476 · Cited by 57 · see citing works
Hao, S., Lian, J., Lu, Y., Jia, H., Hu, J., Yu, G., Wang, X., Xu, K., Ni, Q., Li, Y., et al. (2020) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiaa311 · Cited by 49 · see citing works
To, K. K., Chan, W.-M., Ip, J. D., et al. (2020) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa1119 · Cited by 48 · see citing works
Self-citationMolina, L. P., Chow, S.-K., Nickel, A., et al. (2020) · Obstetrics and Gynecology · doi:10.1097/aog.0000000000004086 · Cited by 42 · see citing works
Lee, P. H., Tay, W. C., Sutjipto, S., Fong, S., Ong, S. W. X., Wei, W. E., Chan, Y., Ling, L. M., Young, B. E., Toh, M. P. H., et al. (2020) · Clinical & Translational Immunology · doi:10.1002/cti2.1160 · Cited by 34 · see citing works
Improved Detection of Antibodies against SARS-CoV-2 by Microsphere-Based Antibody Assay
Fong, C. H.-Y., Cai, J., Dissanayake, T. K., Chen, L., Choi, C. Y.-K., Wong, L. S., Ng, A. C.-K., Pang, P. K. P., Ho, D. T.-Y., Poon, R. W., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186595 · Cited by 21 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 3
- To KK, Chan WM, Ip JD, et al. Unique SARS-CoV-2 clusters causing a large COVID-19 outbreak in Hong Kong. Clin Infect Dis 2021; 73:137-42.
- Camacho C, Coulouris G, Avagyan V, et al. BLAST+: architecture and applica- tions. BMC Bioinformatics 2009; 10:421.
- Hu J, He CH, Gao QZ, et al. The D614G mutation of SARS-CoV-2 spike protein enhances viral infectivity and decreases neutralization sensitivity to individual convalescent sera. bioRxiv 2020; doi:10.1101/2020.06.20.161323. · DOI
Cited by
Sorted by citations
Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection.
Dan, J. M., Mateus, J., Kato, Y., Hastie, K. M., Yu, E. D., Faliti, C. E., Grifoni, A., Ramirez, S. I., Haupt, S., Frazier, A., et al. (2021) · Science · doi:10.1126/science.abf4063 · Cited by 2,656 · see citing works
Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7
Wang, P., Nair, M. S., Liu, L., Iketani, S., Luo, Y., Guo, Y., Wang, M., Yu, J., Zhang, B., Kwong, P. D., et al. (2021) · Nature · doi:10.1038/s41586-021-03398-2 · Cited by 2,312 · see citing works
Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants
Weisblum, Y., Schmidt, F., Zhang, F., DaSilva, J., Poston, D., Lorenzi, J. C., Muecksch, F., Rutkowska, M., Hoffmann, H.-H., Michailidis, E., et al. (2020) · eLife · doi:10.7554/elife.61312 · Cited by 1,308 · see citing works
Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers
Lumley, S. F., O’Donnell, D., Stoesser, N. E., Matthews, P. C., Howarth, A., Hatch, S. B., Marsden, B. D., Cox, S., James, T., Warren, F., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2034545 · Cited by 940 · see citing works
Functional SARS-CoV-2-Specific Immune Memory Persists after Mild COVID-19
Rodda, L. B., Netland, J., Shehata, L., Pruner, K. B., Morawski, P. A., Thouvenel, C. D., Takehara, K. K., Eggenberger, J., Hemann, E. A., Waterman, H. R., et al. (2021) · Cell · doi:10.1016/j.cell.2020.11.029 · Cited by 647 · see citing works
Hansen, C. H., Michlmayr, D., Gubbels, S. M., Mølbak, K., & Ethelberg, S. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00575-4 · Cited by 586 · see citing works
Buss, L. F., Prete, C. A., Abrahim, C. M. M., Mendrone, A., Salomon, T., de Almeida-Neto, C., França, R. F. O., Belotti, M. C., Carvalho, M. P. S. S., Costa, A. G., et al. (2021) · Science · doi:10.1126/science.abe9728 · Cited by 488 · see citing works
Röltgen, K., Powell, A. E., Wirz, O. F., Stevens, B. A., Hogan, C. A., Najeeb, J., Hunter, M., Wang, H., Sahoo, M. K., Huang, C., et al. (2020) · Science Immunology · doi:10.1126/sciimmunol.abe0240 · Cited by 452 · see citing works
Learning the language of viral evolution and escape
Hie, B., Zhong, E. D., Berger, B., & Bryson, B. (2021) · Science · doi:10.1126/science.abd7331 · Cited by 361 · see citing works
Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19
Wheatley, A. K., Juno, J. A., Wang, J. J., Selva, K. J., Reynaldi, A., Tan, H.-X., Lee, W. S., Wragg, K. M., Kelly, H. G., Esterbauer, R., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21444-5 · Cited by 351 · see citing works
Prospects for durable immune control of SARS-CoV-2 and prevention of reinfection
Cromer, D., Juno, J. A., Khoury, D., Reynaldi, A., Wheatley, A. K., Kent, S. J., & Davenport, M. P. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-021-00550-x · Cited by 265 · see citing works
Muecksch, F., Wise, H., Batchelor, B., Squires, M., Semple, E., Richardson, C., McGuire, J., Clearly, S., Furrie, E., Greig, N., et al. (2021) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiaa659 · Cited by 308 · see citing works
What reinfections mean for COVID-19
Iwasaki, A. (2021) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(20)30783-0 · Cited by 230 · see citing works
Burden and characteristics of COVID-19 in the United States during 2020
Pei, S., Yamana, T. K., Kandula, S., Galanti, M., & Shaman, J. (2021) · Nature · doi:10.1038/s41586-021-03914-4 · Cited by 190 · see citing works
Comparison of Four SARS-CoV-2 Neutralization Assays
Riepler, L., Rössler, A., Falch, A., Volland, A., Borena, W., von Laer, D., & Kimpel, J. (2020) · Vaccines · doi:10.3390/vaccines9010013 · Cited by 117 · see citing works
Oved, K., Olmer, L., Shemer-Avni, Y., Wolf, T., Supino-Rosin, L., Prajgrod, G., Shenhar, Y., Payorsky, I., Cohen, Y., Kohn, Y., et al. (2020) · EClinicalMedicine · doi:10.1016/j.eclinm.2020.100651 · Cited by 129 · see citing works
A Case of Early Reinfection With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Larson, D., Brodniak, S. L., Voegtly, L. J., Cer, R. Z., Glang, L. A., Malagon, F. J., Long, K. A., Potocki, R., Smith, D. R., Lanteri, C., et al. (2021) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa1436 · Cited by 93 · see citing works
COVID-19 makes B cells forget, but T cells remember
Cañete, P. F., & Vinuesa, C. G. (2020) · Cell · doi:10.1016/j.cell.2020.09.013 · Cited by 83 · see citing works
Discrete SARS-CoV-2 antibody titers track with functional humoral stability
Bartsch, Y. C., Fischinger, S., Siddiqui, S. M., Chen, Z., Yu, J., Gebre, M., Atyeo, C., Gorman, M. J., Zhu, A. L., Kang, J., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21336-8 · Cited by 82 · see citing works
- Authors
- To, K. K.-W., Hung, I. F.-N., Ip, J. D., Chu, A. W.-H., Chan, W.-M., Tam, A. R., Fong, C. H.-Y., Yuan, S., Tsoi, H.-W., Ng, A. C.-K., Lee, L. L.-Y., Wan, P., Tso, E. Y.-K., To, W.-K., Tsang, D. N.-C., Chan, K.-H., Huang, J.-D., Kok, K.-H., Cheng, V. C.-C., & Yuen, K.-Y.
- Affiliations
- Queen Mary Hospital (CN)
- University of Hong Kong (HK)
- Department of Accident and Emergency Medicine, Tin Shui Wai Hospital, Hong Kong Special Administrative Region, China
- Department of Accident and Emergency, North Lantau Hospital, Hong Kong Special Administrative Region, China
- United Christian Hospital (CN)
- Princess Margaret Hospital (HK)
- Department of Health (CN)
- Corresponding author
- Yuen, Kwok-Yung
- ORCID
- Venue
- Clinical Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-08-25
- Volume
- 73
- Issue
- 9
- Pages
- e2946-e2951
- ISSN
- 1058-4838 (ISSN-L)
- 1537-6591
- PMC
- PMC7499500
- OpenAlex
- W3080458234
- Cited by
- 746
- References
- 35
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 35 · 2023: 50 · 2022: 133 · 2021: 364 · 2020: 156 · 2014: 1
- FWCI
- 23.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Clinical Infectious Diseases (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Consultancy Service
- HKSAR
- Theme-Based Research Scheme (T11/707/15)
- Research Grants Council
- Shaw Foundation Hong Kong
- Respiratory Viral Research Foundation Limited
- Charity Fund Limited
- Memorial Charitable Foundation
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
- Keywords
- COVID-19 pandemic, SARS-CoV-2 reinfection, waning immunity, prolonged viral shedding, viral epitopes, herd immunity, vaccine design
- MeSH terms
- Whole Genome Sequencing, Reinfection, COVID-19, SARS-CoV-2, Antibodies, Viral, Humans, Genome, Viral
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
