Unraveling the Dynamics of Omicron (BA.1, BA.2, and BA.5) Waves and Emergence of the Deltacton Variant: Genomic Epidemiology of the SARS-CoV-2 Epidemic in Cyprus (Oct 2021-Oct 2022).

Andreas C Chrysostomou, Bram Vrancken, Christos Haralambous, Maria Alexandrou, Ioanna Gregoriou, Marios Ioannides, Costakis Ioannou, Olga Kalakouta, Christos Karagiannis, Markella Marcou, Christina Masia, Michail Mendris, Panagiotis Papastergiou, Philippos C Patsalis, Despo Pieridou, Christos Shammas, Dora C Stylianou, Barbara Zinieri, Philippe Lemey, Leondios G Kostrikis
Author Information
  1. Andreas C Chrysostomou: Department of Biological Sciences, University of Cyprus, Aglantzia, 2109 Nicosia, Cyprus. ORCID
  2. Bram Vrancken: Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, 3000 Leuven, Belgium. ORCID
  3. Christos Haralambous: Unit for Surveillance and Control of Communicable Diseases, Ministry of Health, 1148 Nicosia, Cyprus.
  4. Maria Alexandrou: Microbiology Department, Larnaca General Hospital, 6301 Larnaca, Cyprus.
  5. Ioanna Gregoriou: Unit for Surveillance and Control of Communicable Diseases, Ministry of Health, 1148 Nicosia, Cyprus.
  6. Marios Ioannides: Medicover Genetics, 2409 Nicosia, Cyprus.
  7. Costakis Ioannou: Medical Laboratory of Ammochostos General Hospital, Ammochostos General Hospital, 5310 Paralimni, Cyprus.
  8. Olga Kalakouta: Unit for Surveillance and Control of Communicable Diseases, Ministry of Health, 1148 Nicosia, Cyprus.
  9. Christos Karagiannis: Microbiology Department, Nicosia General Hospital, 2029 Nicosia, Cyprus.
  10. Markella Marcou: Department of Microbiology, Archbishop Makarios III Hospital, 2012 Nicosia, Cyprus.
  11. Christina Masia: Medical Laboratory of Ammochostos General Hospital, Ammochostos General Hospital, 5310 Paralimni, Cyprus.
  12. Michail Mendris: Microbiology Department, Limassol General Hospital, 4131 Limassol, Cyprus.
  13. Panagiotis Papastergiou: Microbiology Department, Limassol General Hospital, 4131 Limassol, Cyprus.
  14. Philippos C Patsalis: Medicover Genetics, 2409 Nicosia, Cyprus.
  15. Despo Pieridou: Microbiology Department, Nicosia General Hospital, 2029 Nicosia, Cyprus.
  16. Christos Shammas: S.C.I.N.A. Bioanalysis Sciomedical Centre Ltd., 4040 Limassol, Cyprus.
  17. Dora C Stylianou: Department of Biological Sciences, University of Cyprus, Aglantzia, 2109 Nicosia, Cyprus.
  18. Barbara Zinieri: Microbiology Department, Paphos General Hospital, Achepans, 8026 Paphos, Cyprus.
  19. Philippe Lemey: Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, 3000 Leuven, Belgium.
  20. Leondios G Kostrikis: Department of Biological Sciences, University of Cyprus, Aglantzia, 2109 Nicosia, Cyprus. ORCID

Abstract

Commencing in December 2019 with the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), three years of the coronavirus disease 2019 (COVID-19) pandemic have transpired. The virus has consistently demonstrated a tendency for evolutionary adaptation, resulting in mutations that impact both immune evasion and transmissibility. This ongoing process has led to successive waves of infections. This study offers a comprehensive assessment spanning genetic, phylogenetic, phylodynamic, and phylogeographic dimensions, focused on the trajectory of the SARS-CoV-2 epidemic in Cyprus. Based on a dataset comprising 4700 viral genomic sequences obtained from affected individuals between October 2021 and October 2022, our analysis is presented. Over this timeframe, a total of 167 distinct lineages and sublineages emerged, including variants such as Delta and Omicron (1, 2, and 5). Notably, during the fifth wave of infections, Omicron subvariants 1 and 2 gained prominence, followed by the ascendancy of Omicron 5 in the subsequent sixth wave. Additionally, during the fifth wave (December 2021-January 2022), a unique set of Delta sequences with genetic mutations associated with Omicron variant 1, dubbed "Deltacron", was identified. The emergence of this phenomenon initially evoked skepticism, characterized by concerns primarily centered around contamination or coinfection as plausible etiological contributors. These hypotheses were predominantly disseminated through unsubstantiated assertions within the realms of social and mass media, lacking concurrent scientific evidence to validate their claims. Nevertheless, the exhaustive molecular analyses presented in this study have demonstrated that such occurrences would likely lead to a frameshift mutation-a genetic aberration conspicuously absent in our provided sequences. This substantiates the accuracy of our initial assertion while refuting contamination or coinfection as potential etiologies. Comparable observations on a global scale dispelled doubt, eventually leading to the recognition of Delta-Omicron variants by the scientific community and their subsequent monitoring by the World Health Organization (WHO). As our investigation delved deeper into the intricate dynamics of the SARS-CoV-2 epidemic in Cyprus, a discernible pattern emerged, highlighting the major role of international connections in shaping the virus's local trajectory. Notably, the United States and the United Kingdom were the central conduits governing the entry and exit of the virus to and from Cyprus. Moreover, notable migratory routes included nations such as Greece, South Korea, France, Germany, Brazil, Spain, Australia, Denmark, Sweden, and Italy. These empirical findings underscore that the spread of SARS-CoV-2 within Cyprus was markedly influenced by the influx of new, highly transmissible variants, triggering successive waves of infection. This investigation elucidates the emergence of new waves of infection subsequent to the advent of highly contagious and transmissible viral variants, notably characterized by an abundance of mutations localized within the spike protein. Notably, this discovery decisively contradicts the hitherto hypothesis of seasonal fluctuations in the virus's epidemiological dynamics. This study emphasizes the importance of meticulously examining molecular genetics alongside virus migration patterns within a specific region. Past experiences also emphasize the substantial evolutionary potential of viruses such as SARS-CoV-2, underscoring the need for sustained vigilance. However, as the pandemic's dynamics continue to evolve, a balanced approach between caution and resilience becomes paramount. This ethos encourages an approach founded on informed prudence and self-preservation, guided by public health authorities, rather than enduring apprehension. Such an approach empowers societies to adapt and progress, fostering a poised confidence rooted in well-founded adaptation.

Keywords

References

  1. China CDC Wkly. 2022 Apr 8;4(14):285-287 [PMID: 35433090]
  2. Nature. 2023 May;617(7960):229-230 [PMID: 37127700]
  3. J Med Virol. 2022 Nov;94(11):5096-5102 [PMID: 35815524]
  4. Emerg Infect Dis. 2022 Jul;28(7):1442-1445 [PMID: 35551714]
  5. N Engl J Med. 2022 Jun 16;386(24):2340-2342 [PMID: 35584183]
  6. Ann Med Surg (Lond). 2022 Jul;79:104032 [PMID: 35757314]
  7. Viruses. 2022 Dec 05;14(12): [PMID: 36560720]
  8. Viruses. 2022 Mar 19;14(3): [PMID: 35337047]
  9. Lancet Microbe. 2020 Jul;1(3):e99-e100 [PMID: 32835336]
  10. PLoS Pathog. 2021 Jan 21;17(1):e1009233 [PMID: 33476327]
  11. mBio. 2022 Oct 26;13(5):e0106021 [PMID: 35972143]
  12. J Med Virol. 2022 Aug;94(8):3739-3749 [PMID: 35467028]
  13. Sci Rep. 2023 Apr 6;13(1):5629 [PMID: 37024541]
  14. Int J Surg. 2022 Mar;99:106261 [PMID: 35167986]
  15. Int J Appl Posit Psychol. 2023;8(1):1-36 [PMID: 36196257]
  16. Emerg Microbes Infect. 2022 Dec;11(1):172-181 [PMID: 34842496]
  17. Ann Med Surg (Lond). 2022 Jun 20;79:104034 [PMID: 35770273]
  18. J Med Virol. 2022 Nov;94(11):5077-5079 [PMID: 35770368]
  19. Science. 2022 Jun 24;376(6600):eabq4411 [PMID: 35608440]
  20. Rev Med Virol. 2023 Jan;33(1):e2373 [PMID: 35662313]
  21. PLoS Pathog. 2020 Aug 21;16(8):e1008762 [PMID: 32822426]
  22. J Virol. 2022 Mar 23;96(6):e0207721 [PMID: 35225672]
  23. Mol Biol Evol. 2013 Apr;30(4):772-80 [PMID: 23329690]
  24. Bioinformatics. 2014 Nov 15;30(22):3276-8 [PMID: 25095880]
  25. Int J Surg. 2022 Jun;102:106654 [PMID: 35545169]
  26. Nat Commun. 2022 Sep 30;13(1):5736 [PMID: 36180428]
  27. Diseases. 2023 Mar 31;11(2): [PMID: 37092436]
  28. J Med Virol. 2022 May;94(5):1821-1824 [PMID: 34936120]
  29. Clin Infect Dis. 2022 Nov 14;75(10):1841-1844 [PMID: 35535770]
  30. Vaccines (Basel). 2023 Mar 30;11(4): [PMID: 37112676]
  31. Int J Mol Sci. 2022 Jun 30;23(13): [PMID: 35806320]
  32. Acta Pharmacol Sin. 2020 Sep;41(9):1141-1149 [PMID: 32747721]
  33. Front Microbiol. 2020 Sep 17;11:2112 [PMID: 33042039]
  34. Nature. 2022 Mar;603(7902):679-686 [PMID: 35042229]
  35. J Prim Care Community Health. 2023 Jan-Dec;14:21501319231170164 [PMID: 37083205]
  36. Syst Biol. 2016 Jan;65(1):82-97 [PMID: 26424727]
  37. Vaccines (Basel). 2022 Dec 25;11(1): [PMID: 36679891]
  38. China CDC Wkly. 2021 Dec 3;3(49):1049-1051 [PMID: 34934514]
  39. Nat Methods. 2023 Apr;20(4):512-522 [PMID: 36823332]
  40. Nature. 2020 Aug;584(7821):450-456 [PMID: 32698192]
  41. Int J Surg. 2020 Jun;78:185-193 [PMID: 32305533]
  42. Cell. 2023 Jan 19;186(2):279-286.e8 [PMID: 36580913]
  43. J Infect Dis. 2022 Oct 17;226(8):1418-1427 [PMID: 36017801]
  44. Nat Commun. 2023 Feb 14;14(1):824 [PMID: 36788246]
  45. Bioinformatics. 2022 Mar 4;38(6):1735-1737 [PMID: 34954792]
  46. Philos Trans R Soc Lond B Biol Sci. 2008 Dec 27;363(1512):3985-95 [PMID: 18852111]
  47. Cureus. 2023 Jun 1;15(6):e39816 [PMID: 37397651]
  48. J Med Virol. 2022 Apr;94(4):1300-1314 [PMID: 34811761]
  49. Curr Psychol. 2023;42(9):7403-7413 [PMID: 34276170]
  50. Biophys J. 2021 Mar 16;120(6):1105-1119 [PMID: 33631204]
  51. J Biomol Struct Dyn. 2023 Sep-Oct;41(16):7665-7676 [PMID: 36129018]
  52. Nature. 2023 May 5;: [PMID: 37147368]
  53. Vaccines (Basel). 2023 Jan 18;11(2): [PMID: 36851091]
  54. BMJ Open. 2022 Apr 20;12(4):e061602 [PMID: 35443965]
  55. PLoS Comput Biol. 2022 Aug 26;18(8):e1010435 [PMID: 36026483]
  56. Nucleic Acids Res. 2017 Jan 4;45(D1):D158-D169 [PMID: 27899622]
  57. Int J Mol Sci. 2023 Jan 23;24(3): [PMID: 36768588]
  58. Proc Natl Acad Sci U S A. 2021 Mar 2;118(9): [PMID: 33622786]
  59. Nature. 2022 Feb;602(7895):19 [PMID: 35058630]
  60. Virus Res. 2022 Nov;321:198907 [PMID: 36055471]
  61. Viruses. 2021 Jan 14;13(1): [PMID: 33466921]
  62. Nat Commun. 2022 Aug 9;13(1):4675 [PMID: 35945213]
  63. Cell Rep. 2021 Jan 12;34(2):108630 [PMID: 33417835]
  64. Virus Evol. 2021 Jul 30;7(2):veab064 [PMID: 34527285]
  65. Nature. 2022 Nov;611(7935):213-214 [PMID: 36307585]
  66. Lancet Infect Dis. 2020 May;20(5):533-534 [PMID: 32087114]
  67. Infect Genet Evol. 2023 Mar;108:105405 [PMID: 36681102]
  68. Cell Mol Immunol. 2022 Nov;19(11):1302-1310 [PMID: 36224497]
  69. Hum Vaccin Immunother. 2022 Nov 30;18(5):2068883 [PMID: 35507895]
  70. Immune Netw. 2020 Oct 26;20(5):e41 [PMID: 33163249]
  71. Viruses. 2022 Dec 30;15(1): [PMID: 36680148]
  72. Viruses. 2021 Jun 09;13(6): [PMID: 34207490]
  73. Wellcome Open Res. 2021 Nov 10;6:305 [PMID: 35634532]
  74. Pathogens. 2020 Mar 20;9(3): [PMID: 32245083]
  75. J Med Virol. 2022 Jun;94(6):2336-2342 [PMID: 35118666]
  76. PLoS Pathog. 2014 Feb 20;10(2):e1003932 [PMID: 24586153]
  77. Mol Biol Evol. 2018 Feb 1;35(2):518-522 [PMID: 29077904]
  78. Mol Biol Evol. 2015 Jan;32(1):268-74 [PMID: 25371430]
  79. Nat Commun. 2022 Jul 28;13(1):4375 [PMID: 35902613]
  80. Health Sci Rep. 2022 Oct 13;5(6):e884 [PMID: 36254237]
  81. Nat Rev Microbiol. 2023 Jun;21(6):361-379 [PMID: 37020110]
  82. Int J Surg. 2022 Jun;102:106670 [PMID: 35569759]
  83. Infez Med. 2022 Sep 1;30(3):328-343 [PMID: 36148164]
  84. J Med Virol. 2022 May;94(5):1787-1788 [PMID: 34964490]
  85. Rev Med Virol. 2022 Sep;32(5):e2381 [PMID: 35856385]
  86. Cell Rep. 2023 Apr 25;42(4):112271 [PMID: 36995936]
  87. J Infect. 2023 Aug;87(2):128-135 [PMID: 37270070]
  88. Comput Struct Biotechnol J. 2023 Feb 13;21:1966-1977 [PMID: 36936816]
  89. Nat Rev Microbiol. 2023 Mar;21(3):162-177 [PMID: 36653446]
  90. Med Sci Monit. 2022 Jul 01;28:e937676 [PMID: 35775166]
  91. BMJ. 2022 Aug 2;378:e070695 [PMID: 35918098]
  92. Viruses. 2022 Jun 07;14(6): [PMID: 35746710]
  93. Vaccines (Basel). 2022 Sep 16;10(9): [PMID: 36146623]
  94. Proc Natl Acad Sci U S A. 2022 Jul 12;119(28):e2119761119 [PMID: 35737823]
  95. Life (Basel). 2022 Jan 28;12(2): [PMID: 35207482]
  96. Int J Biol Macromol. 2023 May 31;238:124154 [PMID: 36965551]
  97. Epidemiol Infect. 2021 Nov 04;149:e237 [PMID: 34732275]
  98. PLoS Comput Biol. 2009 Sep;5(9):e1000520 [PMID: 19779555]
  99. Nature. 2021 May;593(7857):130-135 [PMID: 33684923]
  100. Risk Manag Healthc Policy. 2021 May 12;14:1917-1932 [PMID: 34012304]
  101. Syst Biol. 2010 May;59(3):307-21 [PMID: 20525638]
  102. Int J Surg. 2022 Aug;104:106727 [PMID: 35753656]
  103. Ann Med Surg (Lond). 2022 Jun;78:103737 [PMID: 35571678]
  104. Nat Microbiol. 2020 Nov;5(11):1403-1407 [PMID: 32669681]
  105. Cell. 2021 Apr 29;184(9):2332-2347.e16 [PMID: 33761326]

Grants

  1. ERC (grant no.725422-ReservoirDOCS), EU grant 874850 MOOD, Research Foundation-Flanders ('Fonds voor Wetenschappelijk Onderzoek-Vlaanderen', G066215N, G0D5117N and G0B9317N), awarded to Philippe Lemey/European Research Council

MeSH Term

Humans
SARS-CoV-2
Cyprus
Coinfection
Phylogeny
COVID-19
Genomics
Pandemics

Word Cloud

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