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Volume 27, Number 5—May 2021
Research

Genetic Evidence and Host Immune Response in Persons Reinfected with SARS-CoV-2, Brazil

Natalia Fintelman-Rodrigues, Aline P.D. da Silva, Monique Cristina dos Santos, Felipe B. Saraiva, Marcelo A. Ferreira, João Gesto, Danielle A.S. Rodrigues, André M. Vale, Isaclaudia G. de Azevedo, Vinícius C. Soares, Hui Jiang, Hongdong Tan, Diogo A. Tschoeke, Carolina Q. Sacramento, Fernando A. Bozza, Carlos M. Morel, Patrícia T. Bozza, and Thiago Moreno L. SouzaComments to Author 
Author affiliations: Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil (N. Fintelman-Rodrigues, A.P.D. da Silva, M.C. dos Santos, F.B. Saraiva, M.A. Ferreira, J. Gesto, I.G. de Azevedo, V.C. Soares, C.Q. Sacramento, F.A. Bozza, C.M. Morel, P.T. Bozza, T.M.L. Souza); Universidade Federal do Rio de Janeiro, Rio de Janeiro (D.A.S. Rodrigues, A.M. Vale, V.C. Soares, D.A. Tschoeke); MGI Tech Co., Ltd., Shenzhen, China (H. Jiang, H. Tan); D’Or Institute for Research and Education (F.A. Bozza)

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Figure 2

Phylogenetic analysis of severe acute respiratory syndrome coronavirus 2 genomes from reinfected patients, Brazil, 2020. Representative genomes deposited in GISAID (Appendix Table 1, Figure 3) were compared with sequences from virus genomes found in the respiratory samples from the first infection of patients B and C, and the second infection of patients A–D. A condensed phylogenetic tree rooted by reference genome Wuhan-Hu-1 (EPI_ISL_402125) was created with 1,000 bootstraps. Initial trees for the heuristic search were obtained automatically by applying neighbor-joining and BioNJ algorithms to a matrix of pairwise distances estimated using the Jukes-Cantor model (24), and then selecting the topology with a superior log-likelihood value. The tree with the highest log likelihood (−46487.36) is shown. The final dataset included a total of 29,920 positions. Evolutionary analyses were conducted in MEGA version 7.0 (22,23). Evolutionary history was inferred using the maximum-likelihood method and Jukes-Cantor model. Brown represents the emerging clade 19A, orange the clade 20A, and blue the clade 20B. Scale bar indicates substitutions per site. hCoV, human coronavirus.

Figure 2. Phylogenetic analysis of severe acute respiratory syndrome coronavirus 2 genomes from reinfected patients, Brazil, 2020. Representative genomes deposited in GISAID (Appendix Table 1, Figure 3) were compared with sequences from virus genomes found in the respiratory samples from the first infection of patients B and C, and the second infection of patients A–D. A condensed phylogenetic tree rooted by reference genome Wuhan-Hu-1 (EPI_ISL_402125) was created with 1,000 bootstraps. Initial trees for the heuristic search were obtained automatically by applying neighbor-joining and BioNJ algorithms to a matrix of pairwise distances estimated using the Jukes-Cantor model (24), and then selecting the topology with a superior log-likelihood value. The tree with the highest log likelihood (−46487.36) is shown. The final dataset included a total of 29,920 positions. Evolutionary analyses were conducted in MEGA version 7.0 (22,23). Evolutionary history was inferred using the maximum-likelihood method and Jukes-Cantor model. Brown represents the emerging clade 19A, orange the clade 20A, and blue the clade 20B. Scale bar indicates substitutions per site. hCoV, human coronavirus.

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References
  1. World Health Organization. Coronavirus disease (COVID-19) dashboard. 2020 [cited 2020 Nov 12]. https://covid19.who.int/
  2. Rodda  LB, Netland  J, Shehata  L, Pruner  KB, Morawski  PA, Thouvenel  CD, et al. Functional SARS-CoV-2-specific immune memory persists after mild COVID-19. Cell. 2021;184:169183.e17. DOIPubMedGoogle Scholar
  3. Centers for Disease Control and Prevention. Cases, data, and surveillance. 2020 [cited 2021 Feb 12]. https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant-surveillance/variant-info.html
  4. Hartley  GE, Edwards  ESJ, Aui  PM, Varese  N, Stojanovic  S, McMahon  J, et al. Rapid generation of durable B cell memory to SARS-CoV-2 spike and nucleocapsid proteins in COVID-19 and convalescence. Sci Immunol. 2020;5:eabf8891. DOIPubMedGoogle Scholar
  5. Le Bert  N, Tan  AT, Kunasegaran  K, Tham  CYL, Hafezi  M, Chia  A, et al. SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature. 2020;584:45762. DOIPubMedGoogle Scholar
  6. Ripperger  TJ, Uhrlaub  JL, Watanabe  M, Wong  R, Castaneda  Y, Pizzato  HA, et al. Detection, prevalence, and duration of humoral responses to SARS-CoV-2 under conditions of limited population exposure. Immunity. 2020;53:92533. DOIPubMedGoogle Scholar
  7. Hueston  L, Kok  J, Guibone  A, McDonald  D, Hone  G, Goodwin  J, et al. The antibody response to SARS-CoV-2 infection. Open Forum Infect Dis. 2020;7:a387. DOIPubMedGoogle Scholar
  8. Edridge  AWD, Kaczorowska  J, Hoste  ACR, Bakker  M, Klein  M, Loens  K, et al. Seasonal coronavirus protective immunity is short-lasting. Nat Med. 2020;26:16913. DOIPubMedGoogle Scholar
  9. Dan  JM, Mateus  J, Kato  Y, Hastie  KM, Yu  ED, Faliti  CE, et al. Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection. Science. 2021;371:eabf4063. DOIPubMedGoogle Scholar
  10. Tillett  RL, Sevinsky  JR, Hartley  PD, Kerwin  H, Crawford  N, Gorzalski  A, et al. Genomic evidence for reinfection with SARS-CoV-2: a case study. Lancet Infect Dis. 2021;21:528. DOIPubMedGoogle Scholar
  11. To  KK-W, Hung  IF-N, Ip  JD, Chu  AW-H, Chan  W-M, Tam  AR, et al. Coronavirus disease 2019 (COVID-19) reinfection by a phylogenetically distinct severe acute respiratory syndrome coronavirus 2 strain confirmed by whole genome sequencing. Clin Infect Dis. 2020;•••:ciaa1275; Epub ahead of print. DOIGoogle Scholar
  12. Van Elslande  J, Vermeersch  P, Vandervoort  K, Wawina-Bokalanga  T, Vanmechelen  B, Wollants  E, et al. Symptomatic SARS-CoV-2 reinfection by a phylogenetically distinct strain. Clin Infect Dis. 2020;•••:ciaa1330; Epub ahead of print. DOIPubMedGoogle Scholar
  13. Prado-Vivar  B, Becerra-Wong  M, Guadalupe  JJ, Marquez  S, Gutierrez  B, Rojas-Silva  P, et al. COVID-19 reinfection by a phylogenetically distinct SARS-CoV-2 variant, first confirmed event in South America. SSRN. 2020 September 9 [cited 2021 Mar 19]. DOIGoogle Scholar
  14. Mulder  M, van der Vegt  DSJM, Oude Munnink  BB, GeurtsvanKessel  CH, van de Bovenkamp  J, Sikkema  RS, et al. Reinfection of severe acute respiratory syndrome coronavirus 2 in an immunocompromised patient: a case report. Clin Infect Dis. 2020;•••:ciaa1538; Epub ahead of print. DOIGoogle Scholar
  15. Selhorst  P, Van Ierssel  S, Michiels  J, Mariën  J, Bartholomeeusen  K, Dirinck  E, et al. Symptomatic SARS-CoV-2 reinfection of a health care worker in a Belgian nosocomial outbreak despite primary neutralizing antibody response. Clin Infect Dis. 2020;•••:ciaa1850; Epub ahead of print. DOIPubMedGoogle Scholar
  16. Larson  D, Brodniak  SL, Voegtly  LJ, Cer  RZ, Glang  LA, Malagon  FJ, et al. A case of early reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020;•••:ciaa1436; Epub ahead of print. DOIGoogle Scholar
  17. Centers for Disease Control and Prevention. Research use only 2019-novel coronavirus (2019-nCoV) real-time RT-PCR primers and probes. 2020 [cited 2020 Nov 11]. https://www.cdc.gov/coronavirus/2019-ncov/lab/rt-pcr-panel-primer-probes.html
  18. Metsky  HC, Matranga  CB, Wohl  S, Schaffner  SF, Freije  CA, Winnicki  SM, et al. Zika virus evolution and spread in the Americas. Nature. 2017;546:4115. DOIPubMedGoogle Scholar
  19. Cleemput  S, Dumon  W, Fonseca  V, Abdool Karim  W, Giovanetti  M, Alcantara  LC, et al. Genome Detective Coronavirus Typing Tool for rapid identification and characterization of novel coronavirus genomes. Bioinformatics. 2020;36:35525. DOIPubMedGoogle Scholar
  20. Katoh  K, Kuma  K, Toh  H, Miyata  T. MAFFT version 5: improvement in accuracy of multiple sequence alignment. Nucleic Acids Res. 2005;33:5118. DOIPubMedGoogle Scholar
  21. Larkin  MA, Blackshields  G, Brown  NP, Chenna  R, McGettigan  PA, McWilliam  H, et al. Clustal W and Clustal X version 2.0. Bioinformatics. 2007;23:29478. DOIPubMedGoogle Scholar
  22. Kumar  S, Stecher  G, Li  M, Knyaz  C, Tamura  K. MEGA X: Molecular Evolutionary Genetics Analysis across computing platforms. Mol Biol Evol. 2018;35:15479. DOIPubMedGoogle Scholar
  23. Felsenstein  J. Confidence limits on phylogenies: an approach using the bootstrap. Evolution. 1985;39:78391. DOIPubMedGoogle Scholar
  24. Jukes  TH, Cantor  CR. Evolution of protein molecules. In: Mammalian protein metabolism. Vol. III. Munro HN, editor. New York: Academic Press; 1969. p. 21–132.
  25. Huelsenbeck  JP, Ronquist  F. MRBAYES: Bayesian inference of phylogenetic trees. Bioinformatics. 2001;17:7545. DOIPubMedGoogle Scholar
  26. Ronquist  F, Huelsenbeck  JP. MrBayes 3: Bayesian phylogenetic inference under mixed models. Bioinformatics. 2003;19:15724. DOIPubMedGoogle Scholar
  27. Candido  DS, Claro  IM, de Jesus  JG, Souza  WM, Moreira  FRR, Dellicour  S, et al.; Brazil-UK Centre for Arbovirus Discovery, Diagnosis, Genomics and Epidemiology (CADDE) Genomic Network. Evolution and epidemic spread of SARS-CoV-2 in Brazil. Science. 2020;369:125560. DOIPubMedGoogle Scholar
  28. Secretaria de Saúde do Estado do Rio de Janeiro. Covid-19 monitoring panel in the Rio de Janeiro State [in Portuguese]. 2020 [cited 2020 Nov 24]. http://painel.saude.rj.gov.br/monitoramento/covid19.html#
  29. Kiyuka  PK, Agoti  CN, Munywoki  PK, Njeru  R, Bett  A, Otieno  JR, et al. Human coronavirus NL63 molecular epidemiology and evolutionary patterns in rural coastal Kenya. J Infect Dis. 2018;217:172839 https://academic.oup.com/jid/article/217/11/1728/4948258. DOIPubMedGoogle Scholar
  30. Decaro  N, Martella  V, Saif  LJ, Buonavoglia  C. COVID-19 from veterinary medicine and one health perspectives: What animal coronaviruses have taught us. Res Vet Sci. 2020;131:213. DOIPubMedGoogle Scholar
  31. Neeland  MR, Bannister  S, Clifford  V, Dohle  K, Mulholland  K, Sutton  P, et al. Innate cell profiles during the acute and convalescent phase of SARS-CoV-2 infection in children. Nat Commun. 2021;12:1084. DOIPubMedGoogle Scholar
  32. Tay  MZ, Poh  CM, Rénia  L, MacAry  PA, Ng  LFP. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020;20:36374. DOIPubMedGoogle Scholar
  33. Sallenave  J-M, Guillot  L. Innate immune signaling and proteolytic pathways in the resolution or exacerbation of SARS-CoV-2 in COVID-19: key therapeutic targets? Front Immunol. 2020;11:1229. DOIPubMedGoogle Scholar
  34. Groves  DC, Rowland-Jones  SL, Angyal  A. The D614G mutations in the SARS-CoV-2 spike protein: Implications for viral infectivity, disease severity and vaccine design. Biochem Biophys Res Commun. 2021;538:1047. DOIPubMedGoogle Scholar
  35. Centers for Disease Control and Prevention. Emerging SARS-CoV-2 variants. 2020 [cited 2021 Feb 12]. https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/scientific-brief-emerging-variants.html
  36. Krafcikova  P, Silhan  J, Nencka  R, Boura  E. Structural analysis of the SARS-CoV-2 methyltransferase complex involved in RNA cap creation bound to sinefungin. Nat Commun. 2020;11:3717. DOIPubMedGoogle Scholar
  37. Cottam  EM, Whelband  MC, Wileman  T. Coronavirus NSP6 restricts autophagosome expansion. Autophagy. 2014;10:142641. DOIPubMedGoogle Scholar
  38. Choi  B, Choudhary  MC, Regan  J, Sparks  JA, Padera  RF, Qiu  X, et al. Persistence and evolution of SARS-CoV-2 in an immunocompromised host. N Engl J Med. 2020;383:22913. DOIPubMedGoogle Scholar
  39. Koyama  T, Platt  D, Parida  L. Variant analysis of SARS-CoV-2 genomes. Bull World Health Organ. 2020;98:495504. DOIPubMedGoogle Scholar
  40. Kiyuka  PK, Agoti  CN, Munywoki  PK, Njeru  R, Bett  A, Otieno  JR, et al. Human coronavirus NL63 molecular epidemiology and evolutionary patterns in rural coastal Kenya. J Infect Dis. 2018;217:172839. DOIPubMedGoogle Scholar
  41. Sun  J, Xiao  J, Sun  R, Tang  X, Liang  C, Lin  H, et al. Prolonged persistence of SARS-CoV-2 RNA in body fluids. Emerg Infect Dis. 2020;26:18348. DOIPubMedGoogle Scholar
  42. de la Rica  R, Borges  M, Gonzalez-Freire  M. COVID-19: in the eye of the cytokine storm. Front Immunol. 2020;11:558898. DOIPubMedGoogle Scholar
  43. Arunachalam  PS, Wimmers  F, Mok  CKP, Perera  RAPM, Scott  M, Hagan  T, et al. Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans. Science. 2020;369:121020. DOIPubMedGoogle Scholar
  44. Sekine  T, Perez-Potti  A, Rivera-Ballesteros  O, Strålin  K, Gorin  J-B, Olsson  A, et al.; Karolinska COVID-19 Study Group. Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19. Cell. 2020;183:158168.e14. DOIPubMedGoogle Scholar

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Page updated: April 20, 2021
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