COVID-19: An update with future urgent priorities and a case study of repurposing drug design

Juliana Silva Novais, Reinaldo Barros Geraldo, Camila Ferreira Mattos, Victor Gustavo Oliveira Evangelho, Aldo Rodrigues da Silva, Nayra Cordeiro da Conceição, Marcos da Veiga Kalil, Lúcio Mendes Cabral, Norman Arthur Ratcliffe, Carlos Rangel Rodrigues, Helena Carla Castro

Article ID: 2348
Vol 1, Issue 1, 2023

VIEWS - 84 (Abstract)

Abstract

SARS-CoV-2 is highly transmissible and pathogenic, with nearly 6.5 million infected people dying worldwide. A severe acute respiratory syndrome is one of the primary COVID-19 outcomes, often related to bacterial co-infections. In addition, infective variants of SARS-CoV-2 have constantly emerged in different countries, causing recurrent waves of infection. These variants increase the chances of vaccine failure, even in countries with accelerated vaccination programs, such as Israel and the USA. In this brief review, the subjects addressed include aspects of the SARS-CoV-2 variants, vaccines, drug therapy, and new alternative therapies. Finally, this review also discussed articles that addressed the repositioning of drugs against the SarsCov2 MPro enzyme using in silico approaches. In addition, we discussed the repositioning of drugs in silico, which can be a valuable strategy to guide and optimize the selection of elective compounds already approved for human use. Bearing in mind that few drugs, such as nirmatrelvir, ritonavir (Paxlovid), molnupiravir, and some monoclonal antibodies, have received authorization throughout the COVID-19 pandemic, according to Food and Drug Administration guidelines.


Keywords

COVID-19; variants; vaccination; anti-viral drugs; off-label drugs

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References

1. Guo YR, Cao QD, Hong ZS, et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak—An update on the status. Military Medical Research 2020; 7(1): 11. doi: 10.1186/s40779-020-00240-0

2. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet 2020; 395(10223): 497–506. doi: 10.1016/s0140-6736(20)30183-5

3. World Health Organization. WHO Coronavirus (COVID-19) dashboard. Available online: https://covid19.who.int/ (accessed on 22 December 2023).

4. World Health Organization. WHO Director-General’s opening remarks at the media briefing on COVID-19 - 11 March 2020. Available online: https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020 (accessed on 22 December 2023).

5. WHO. Novel coronavirus. Available online: https://covid19.who.int/ (accessed on 22 December 2023).

6. Parums DV. Editorial: The XBB.1.5 (‘Kraken’) subvariant of Omicron SARS-CoV-2 and its rapid global spread. Medical Science Monitor 2023; 29: e939580. doi: 10.12659/msm.939580

7. Kali A. Unveiling the Eris subvariant: The next challenge in the COVID-19 pandemic? Journal of Laboratory Physicians 2023. doi: 10.1055/s-0043-1774410

8. World Health Organization. Tracking SARS-CoV-2 variants. Available online: https://www.who.int/activities/tracking-SARS-CoV-2-variants (accessed on 22 December 2023).

9. Wang Y, Wang Y, Chen Y, Qin Q. Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID‐19) implicate special control measures. Journal of Medical Virology 2020; 92(6): 568–576. doi: 10.1002/jmv.25748

10. Liu L. The dynamics of early-stage transmission of COVID-19: A novel quantification of the role of global temperature. Gondwana Research 2023; 114: 55–68. doi: 10.1016/j.gr.2021.12.010

11. World Health Organization. Enhancing response to Omicron SARS-CoV-2 variant: Technical brief and priority actions for member states. Available online: https://www.who.int/publications/m/item/enhancing-readiness-for-omicron-(b.1.1.529)-technical-brief-and-priority-actions-for-member-states (accessed on 22 December 2023).

12. Zhou H, Chen X, Hu T, et al. A novel bat coronavirus closely related to SARS-CoV-2 contains natural insertions at the S1/S2 cleavage site of the spike protein. Current Biology 2020; 30(11): 2196–2203. doi: 10.1016/j.cub.2020.05.023

13. Menni C, Valdes AM, Polidori L, et al. Symptom prevalence, duration, and risk of hospital admission in individuals infected with SARS-CoV-2 during periods of omicron and delta variant dominance: A prospective observational study from the ZOE COVID study. The Lancet 2022; 399(10335): 1618–1624. doi: 10.1016/s0140-6736(22)00327-0

14. Centers for Disease Control and Prevention. Morbidity and mortality weekly report. Available online: https://www.cdc.gov/mmwr/volumes/70/wr/mm7050e1.htm (accessed on 22 December 2023)

15. Fan Y, Li X, Zhang L, et al. SARS-CoV-2 Omicron variant: Recent progress and future perspectives. Signal Transduction and Targeted Therapy 2022; 7(1): 141. doi: 10.1038/s41392-022-00997-x

16. Campbell F, Archer B, Laurenson-Schafer H, et al. Increased transmissibility and global spread of SARS-CoV-2 variants of concern as at June 2021. Eurosurveillance 2021; 26(24). doi: 10.2807/1560-7917.es.2021.26.24.2100509

17. Hadfield J, Megill C, Bell SM, et al. Nextstrain: Real-time tracking of pathogen evolution. Bioinformatics 2018; 34(23): 4121–4123. doi: 10.1093/bioinformatics/bty407

18. Araf Y, Akter F, Tang Y, et al. Omicron variant of SARS‐CoV‐2: Genomics, transmissibility, and responses to current COVID‐19 vaccines. Journal of Medical Virology 2022; 94(5): 1825–1832. doi: 10.1002/jmv.27588

19. Liu Y, Liu J, Plante KS, et al. The N501Y spike substitution enhances SARS-CoV-2 infection and transmission. Nature 2021; 602(7896): 294–299. doi: 10.1038/s41586-021-04245-0

20. Prathiviraj R, Chellapandi P, Begum A, et al. Identification of genotypic variants and its proteomic mutations of Brazilian SARS-CoV-2 isolates. Virus Research 2022; 307: 198618. doi: 10.1016/j.virusres.2021.198618

21. Johnson BA, Zhou Y, Lokugamage KG, et al. Nucleocapsid mutations in SARS-CoV-2 augment replication and pathogenesis. Available online: https://www.researchgate.net/publication/355333711_Nucleocapsid_mutations_in_SARS-CoV-2_augment_replication_and_pathogenesis (accessed on 22 December 2023).

22. Giron CC, Laaksonen A, Barroso da Silva FL. Differences between Omicron SARS-CoV-2 RBD and other variants in their ability to interact with cell receptors and monoclonal antibodies. Journal of Biomolecular Structure and Dynamics 2022; 41(12): 5707–5727. doi: 10.1080/07391102.2022.2095305

23. Posani E, Dilucca M, Forcelloni S, et al. Temporal evolution and adaptation of SARS-CoV-2 codon usage. Frontiers in Bioscience-Landmark 2022; 27(1): 13. doi: 10.31083/j.fbl2701013

24. Vadgama N, Kreymerman A, Campbell J, et al. SARS-CoV-2 Susceptibility and ACE2 Gene Variations Within Diverse Ethnic Backgrounds. Frontiers in Genetics 2022; 13: 888025. doi: 10.3389/fgene.2022.888025

25. Markosian C, Staquicini DI, Dogra P, et al. Genetic and structural analysis of SARS-CoV-2 spike protein for universal epitope selection. Molecular Biology and Evolution 2022; 39(5): msac091. doi: 10.1093/molbev/msac091

26. Alkhatib M, Salpini R, Carioti L, et al. Update on SARS-CoV-2 Omicron variant of concern and its peculiar mutational profile. Microbiology Spectrum 2022; 10(2). doi: 10.1128/spectrum.02732-21

27. Nunes DR, Braconi CT, Ludwig-Begall LF, et al. Deep phylogenetic-based clustering analysis uncovers new and shared mutations in SARS-CoV-2 variants as a result of directional and convergent evolution. PLoS One 2022; 17(5): e0268389. doi: 10.1371/journal.pone.0268389

28. Kronstein-Wiedemann R, Stadtmüller M, Traikov S, et al. SARS-CoV-2 infects red blood cell progenitors and dysregulates hemoglobin and iron metabolism. Stem Cell Reviews and Reports 2022; 18(5): 1809–1821. doi: 10.1007/s12015-021-10322-8

29. Martínez-González B, Soria ME, Vázquez-Sirvent L, et al. SARS-CoV-2 point mutation and deletion spectra and their association with different disease outcomes. Microbiology Spectrum 2022; 10(2). doi: 10.1128/spectrum.00221-22

30. Sonnleitner ST, Sonnleitner S, Hinterbichler E, et al. The mutational dynamics of the SARS-CoV-2 virus in serial passages in vitro. Virologica Sinica 2022; 37(2): 198–207. doi: 10.1016/j.virs.2022.01.029

31. Pellegrina D, Bahcheli AT, Krassowski M, et al. Human phospho‐signaling networks of SARS‐CoV‐2 infection are rewired by population genetic variants. Molecular Systems Biology 2022; 18(5). doi: 10.15252/msb.202110823

32. Ahamad S, Hema K, Ahmad S, et al. Insights into the structure and dynamics of SARS-CoV-2 spike glycoprotein double mutant L452R-E484Q. 3 Biotech 2022; 12(4): 87. doi: 10.1007/s13205-022-03151-0

33. Quaranta EG, Fusaro A, Giussani E, et al. SARS-CoV-2 intra-host evolution during prolonged infection in an immunocompromised patient. International Journal of Infectious Diseases 2022; 122: 444–448. doi: 10.1016/j.ijid.2022.06.023

34. Mykytyn AZ, Rissmann M, Kok A, et al. Antigenic cartography of SARS-CoV-2 reveals that Omicron BA.1 and BA.2 are antigenically distinct. Science Immunology 2022; 7(75). doi: 10.1126/sciimmunol.abq4450

35. Talotta R, Bahrami S, Laska MJ. Sequence complementarity between human noncoding RNAs and SARS-CoV-2 genes: What are the implications for human health? Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 2022; 1868(2): 166291. doi: 10.1016/j.bbadis.2021.166291

36. Zhang C, Verma A, Feng Y, et al. Impact of natural selection on global patterns of genetic variation and association with clinical phenotypes at genes involved in SARS-CoV-2 infection. Proceedings of the National Academy of Sciences 2022; 119(21): e2123000119. doi: 10.1073/pnas.2123000119

37. Uddin MB, Sajib EH, Hoque SF, et al. Genomic diversity and molecular dynamics interaction on mutational variances among RB domains of SARS-CoV-2 interplay drug inactivation. Infection, Genetics and Evolution 2022; 97: 105128. doi: 10.1016/j.meegid.2021.105128

38. Yamamoto M, Gohda J, Kobayashi A, et al. Metalloproteinase-dependent and TMPRSS2-independent cell surface entry pathway of SARS-CoV-2 requires the Furin cleavage site and the S2 domain of spike protein. mBio 2022; 13(4). doi: 10.1128/mbio.00519-22

39. Patil S, Alzahrani KJ, Banjer HJ, et al. Receptor binding domain of SARS‐CoV‐2 from Wuhan strain to Omicron B.1.1.529 attributes increased affinity to variable structures of human ACE2. Journal of Infection and Public Health 2022; 15(7): 781–787. doi: 10.1016/j.jiph.2022.06.004

40. Ahmad SU, Hafeez Kiani B, Abrar M, et al. A comprehensive genomic study, mutation screening, phylogenetic and statistical analysis of SARS-CoV-2 and its variant omicron among different countries. Journal of Infection and Public Health 2022; 15(8): 878–891. doi: 10.1016/j.jiph.2022.07.002

41. Hossain MdJ, Rabaan AA, Mutair AA, et al. Strategies to tackle SARS-CoV-2 Mu, a newly classified variant of interest likely to resist currently available COVID-19 vaccines. Human Vaccines & Immunotherapeutics 2022; 18(1): 2027197. doi: 10.1080/21645515.2022.2027197

42. Magalis BR, Mavian C, Tagliamonte M, et al. Low‐frequency variants in mildly symptomatic vaccine breakthrough infections presents a doubled‐edged sword. Journal of Medical Virology 2022; 94(7): 3192–3202. doi: 10.1002/jmv.27726

43. Zguro K, Baldassarri M, Fava F, et al. Carriers of ADAMTS13 rare variants are at high risk of life-threatening COVID-19. Viruses 2022; 14(6): 1185. doi: 10.3390/v14061185

44. Castro HC, Geraldo RB. COVID-19, SARS-Cov-2 and mutations: The future of the pandemic still demands proteomics and bioinformatics evaluations. International Journal of Proteomics & Bioinformatics 2021; 6(1): 10–13.

45. World Health Organization. Coronavirus disease (COVID-19): Vaccines and vaccine safety. Available online: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/question-and-answers-hub/q-a-detail/coronavirus-disease-(covid-19)-vaccines?adgroupsurvey={adgroupsurvey}&gad_source=1&gclid=CjwKCAiArfauBhApEiwAeoB7qF8mfxeJ7EzCDgH6qTU0BJ0p_3vtar19AmWuhvf_Ay9wQCvp7CX3sBoCoiMQAvD_BwE (accessed on 22 December 2023).

46. Qu P, Faraone J, Evans JP, et al. Neutralization of the SARS-CoV-2 Omicron BA.4/5 and BA.2.12.1 subvariants. New England Journal of Medicine 2022; 386(26): 2526–2528. doi: 10.1056/nejmc2206725

47. Wang Q, Guo Y, Iketani S, et al. Antibody evasion by SARS-CoV-2 Omicron subvariants BA.2.12.1, BA.4 and BA.5. Nature 2022; 608(7923): 603–608. doi: 10.1038/s41586-022-05053-w

48. World Health Organization. Weekly epidemiological update on COVID-19 - 17 August 2022. Available online: https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19---17-august-2022 (accessed on 22 December 2023).

49. World Health Organization. The COVID-19 vaccine tracker and landscape compiles detailed information of each COVID-19 vaccine candidate in development by closely monitoring their progress through the pipeline. Available online: https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines (accessed on 22 December 2023).

50. World Health Organization. Background document on the AZD1222 vaccine against COVID-19 developed by Oxford University and AstraZeneca: Background document to the WHO interim recommendations for use of the AZD1222 (‎ChAdOx1-S [‎recombinant]‎)‎ vaccine against COVID19 developed by Oxford University and AstraZeneca. Available online: https://iris.who.int/bitstream/handle/10665/339882/WHO-2019-nCoV-vaccines-SAGE-recommendation-AZD1222-background-2021.2-eng.pdf?sequence=1 (accessed on 22 December 2023).

51. World Health Organization. Interim recommendations for use of the ChAdOx1-S. Available online: https://www.nitag-resource.org/sites/default/files/2022-09/WHO-2019-nCoV-vaccines-SAGE-recommendation-AZD1222-2022.1-eng%20%281%29.pdf (accessed on 22 December 2023).

52. World Health Organization. Background document on the Janssen Ad26.COV2.S (COVID-19) vaccine: Background document to the WHO interim recommendations for use of Ad26.COV2.S (COVID-19) vaccine. Available online: https://iris.who.int/bitstream/handle/10665/340180/WHO-2019-nCoV-vaccines-SAGE-recommendation-Ad26.COV2.S-background-2021.1-eng.pdf?sequence=1 (accessed on 22 December 2023).

53. World Health Organization. Interim recommendations for the use of the Janssen Ad26.COV2.S (COVID-19) vaccine. Available online: https://iris.who.int/bitstream/handle/10665/355160/WHO-2019-nCoV-vaccines-SAGE-recommendation-Ad26.COV2.S-2022.1-eng.pdf?sequence=1 (accessed on 22 December 2023).

54. World Health Organization. Interim recommendations for use of the Moderna mRNA-1273 vaccine against COVID-19. Available online: https://iris.who.int/bitstream/handle/10665/361718/WHO-2019-nCoV-vaccines-SAGE-recommendation-mRNA-1273-2022.2-eng.pdf?sequence=1 (accessed on 22 December 2023).

55. World Health Organization. Interim recommendations for use of the inactivated COVID-19 vaccine BIBP developed by China National Biotec Group (CNBG), Sinopharm. Available online: https://iris.who.int/bitstream/handle/10665/352470/WHO-2019-nCoV-vaccines-SAGE-recommendation-BIBP-2022.1-eng.pdf?sequence=1 (accessed on 22 December 2023).

56. World Health Organization. Interim recommendations for use of the inactivated COVID-19 vaccine, CoronaVac, developed by Sinovac: Interim guidance. Available online: https://iris.who.int/bitstream/handle/10665/352472/WHO-2019-nCoV-vaccines-SAGE-recommendation-Sinovac-CoronaVac-2022.1-eng.pdf?sequence=1 (accessed on 22 December 2023).

57. World Health Organization. Background document on the Novavax (‎NVX-CoV2373)‎ vaccine against COVID-19: Background document to the WHO interim recommendations for use of the Novavax (‎NVX-CoV2373)‎ vaccine against COVID-19. Available online: https://iris.who.int/bitstream/handle/10665/351165/WHO-2019-nCoV-vaccines-SAGE-recommendation-Novavax-NVX-CoV2373-background-2021.1-eng.pdf?sequence=1 (accessed on 22 December 2023).

58. World Health Organization. Background document on the CanSinoBio Ad5-nCoV-S [recombinant] vaccine (ConvideciaTM) against COVID-19: Background document to the WHO Interim recommendations for use of the CanSinoBio Ad5-nCoV-S vaccine (ConvideciaTM) against COVID-19. Available online: cntcm.com.cn/2019-06/24/content_62165.htm (accessed on 22 December 2023).

59. Bowen JE, Addetia A, Dang HV, et al. Omicron spike function and neutralizing activity elicited by a comprehensive panel of vaccines. Science 2022; 377(6608): 890–894. doi: 10.1126/science.abq0203

60. González S, Olszevicki S, Gaiano A, et al. Effectiveness of BBIBP-CorV, BNT162b2 and mRNA-1273 vaccines against hospitalisations among children and adolescents during the Omicron outbreak in Argentina: A retrospective cohort study. The Lancet Regional Health - Americas 2022; 13: 100316. doi: 10.1016/j.lana.2022.100316

61. Stokel-Walker C. How are vaccines being adapted to meet the changing face of SARS-CoV-2? Available online: https://www.bmj.com/content/377/bmj.o1257 (accessed on 22 December 2023).

62. Wanlapakorn N, Suntronwong N, Phowatthanasathian H, et al. Safety and immunogenicity of heterologous and homologous inactivated and adenoviral-vectored COVID-19 vaccine regimens in healthy adults: A prospective cohort study. Human Vaccines & Immunotherapeutics 2022; 18(1): 2029111. doi: 10.1080/21645515.2022.2029111

63. van der Ley PA, Zariri A, van Riet E, et al. An intranasal OMV-based vaccine induces high mucosal and systemic protecting immunity against a SARS-CoV-2 infection. Frontiers in Immunology 2021; 12: 781280. doi: 10.3389/fimmu.2021.c

64. van Doremalen N, Purushotham JN, Schulz JE, et al. Intranasal ChAdOx1 nCoV-19/AZD1222 vaccination reduces viral shedding after SARS-CoV-2 D614G challenge in preclinical models. Science Translational Medicine 2021; 13(607). doi: 10.1126/scitranslmed.abh0755

65. Hameed SA, Paul S, Dellosa GKY, et al. Towards the future exploration of mucosal mRNA vaccines against emerging viral diseases, lessons from existing next-generation mucosal vaccine strategies. npj Vaccines 2022; 7(1): 71. doi: 10.1038/s41541-022-00485-x

66. Hartwell BL, Melo MB, Xiao P, et al. Intranasal vaccination with lipid-conjugated immunogens promotes antigen transmucosal uptake to drive mucosal and systemic immunity. Science Translational Medicine 2022; 14(654). doi: 10.1126/scitranslmed.abn1413

67. Alu A, Chen L, Lei H, et al. Intranasal COVID-19 vaccines: From bench to bed. eBioMedicine 2022; 76: 103841. doi: 10.1016/j.ebiom.2022.103841

68. Ratcliffe NA, Castro HC, Paixão IC, et al. Nasal therapy—The missing link in optimising strategies to improve prevention and treatment of COVID-19. PLOS Pathogens 2021; 17(11): e1010079. doi: 10.1371/journal.ppat.1010079

69. Shang J, Ye G, Shi K, et al. Structural basis of receptor recognition by SARS-CoV-2. Nature 2020; 581(7807): 221–224. doi: 10.1038/s41586-020-2179-y

70. Fernandes Q, Inchakalody VP, Merhi M, et al. Emerging COVID-19 variants and their impact on SARS-CoV-2 diagnosis, therapeutics and vaccines. Annals of Medicine 2022; 54(1): 524–540. doi: 10.1080/07853890.2022.2031274

71. Mitjà O, Corbacho-Monné M, Ubals M, et al. A cluster-randomized trial of hydroxychloroquine for prevention of Covid-19. New England Journal of Medicine 2021; 384(5): 417–427. doi: 10.1056/nejmoa2021801

72. Chen H, Zhang Z, Wang L, et al. First clinical study using HCV protease inhibitor danoprevir to treat COVID-19 patients. Medicine 2020; 99(48): e23357. doi: 10.1097/md.0000000000023357

73. Min J, Jang Y. Macrolide therapy in respiratory viral infections. Mediators of Inflammation 2012; 2012: 1–9. doi: 10.1155/2012/649570

74. Abella BS, Jolkovsky EL, Biney BT, et al. Efficacy and safety of hydroxychloroquine vs placebo for pre-exposure SARS-CoV-2 prophylaxis among health care workers. JAMA Internal Medicine 2021; 181(2): 195–202. doi: 10.1001/jamainternmed.2020.6319

75. Borba MGS, Val FFA, Sampaio VS, et al. Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. JAMA Network Open 2020, 3(4): e208857. doi: 10.1001/jamanetworkopen.2020.8857

76. Pathak DSK, Salunke DAA, Thivari DP, et al. No benefit of hydroxychloroquine in COVID-19: Results of systematic review and meta-analysis of randomized controlled trials”. Diabetes & Metabolic Syndrome: Clinical Research & Reviews 2020; 14(6): 1673–1680. doi: 10.1016/j.dsx.2020.08.033

77. Fiolet T, Guihur A, Rebeaud ME, et al. Effect of hydroxychloroquine with or without azithromycin on the mortality of coronavirus disease 2019 (COVID-19) patients: A systematic review and meta-analysis. Clinical Microbiology and Infection 2021; 27(1): 19–27. doi: 10.1016/j.cmi.2020.08.022

78. Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: Results of an open-label non-randomized clinical trial. International Journal of Antimicrobial Agents 2020; 56(1): 105949. doi: 10.1016/j.ijantimicag.2020.105949

79. World Health Organization. WHO advises that ivermectin only be used to treat COVID-19 within clinical trials. Available online: https://www.who.int/news-room/feature-stories/detail/who-advises-that-ivermectin-only-be-used-to-treat-covid-19-within-clinical-trials (accessed on 22 December 2023).

80. Kato Y, Bloom NI, Sun P, et al. Memory b-cell development after asymptomatic or mild symptomatic SARS-CoV-2 infection. The Journal of Infectious Diseases 2022; 227(1): 18–22. doi: 10.1093/infdis/jiac319

81. Drożdżal S, Rosik J, Lechowicz K, et al. An update on drugs with therapeutic potential for SARS-CoV-2 (COVID-19) treatment. Drug Resistance Updates 2021; 59: 100794. doi: 10.1016/j.drup.2021.100794

82. National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. Available online: https://www.covid19treatmentguidelines.nih.gov/ (accessed on 22 December 2023).

83. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of Covid-19—Final report. New England Journal of Medicine 2020; 383(19): 1813–1826. doi: 10.1056/nejmoa2007764

84. National Institutes of Health. SARS-CoV-2 variants and susceptibility to anti-SARS-CoV-2 monoclonal antibodies. Available online: https://www.covid19treatmentguidelines.nih.gov/tables/variants-and-susceptibility-to-mabs/ (accessed on 22 December 2023).

85. Rosa SGV, Santos WC. Clinical trials on drug repositioning for COVID-19 treatment. Revista Panamericana de Salud Pública 2020; 44: e40. doi: 10.26633/rpsp.2020.40

86. Ippolito M, Misseri G, Catalisano G, et al. Ventilator-associated pneumonia in patients with COVID-19: A systematic review and meta-analysis. Antibiotics 2021; 10(5): 545. doi: 10.3390/antibiotics10050545

87. Luo P, Liu Y, Qiu L, et al. Tocilizumab treatment in COVID‐19: A single center experience. Journal of Medical Virology 2020; 92(7): 814–818. doi: 10.1002/jmv.25801

88. Kory P, Meduri GU, Varon J, et al. Review of the emerging evidence demonstrating the efficacy of ivermectin in the prophylaxis and treatment of COVID-19. American Journal of Therapeutics 2021; 28(3): e299–e318. doi: 10.1097/mjt.0000000000001377

89. Contou D, Claudinon A, Pajot O, et al. Bacterial and viral co-infections in patients with severe SARS-CoV-2 pneumonia admitted to a French ICU. Annals of Intensive Care 2020; 10(1): 119. doi: 10.1186/s13613-020-00736-x

90. Zarogoulidis P, Papanas N, Kioumis I, et al. Macrolides: From in vitro anti-inflammatory and immunomodulatory properties to clinical practice in respiratory diseases. European Journal of Clinical Pharmacology 2011; 68(5): 479–503. doi: 10.1007/s00228-011-1161-x

91. Lee N, Wong CK, Chan MCW, et al. Anti-inflammatory effects of adjunctive macrolide treatment in adults hospitalized with influenza: A randomized controlled trial. Antiviral Research 2017; 144: 48–56. doi: 10.1016/j.antiviral.2017.05.008

92. Ledford H. Hundreds of COVID trials could provide a deluge of new drugs. Nature 2022; 603(7899): 25–27. doi: 10.1038/d41586-022-00562-0

93. Edwards DA, Ausiello D, Salzman J, et al. Exhaled aerosol increases with COVID-19 infection, age, and obesity. Proceedings of the National Academy of Sciences 2021; 118(8): e2021830118. doi: 10.1073/pnas.2021830118

94. Ratcliffe NA, Castro HC, Paixão IC, et al. Nasal therapy—The missing link in optimising strategies to improve prevention and treatment of COVID-19. PLOS Pathogens 2021; 17(11): e1010079. doi: 10.1371/journal.ppat.1010079

95. Tandon M, Wu W, Moore K, et al. SARS-CoV-2 accelerated clearance using a novel nitric oxide nasal spray (NONS) treatment: A randomized trial. The Lancet Regional Health - Southeast Asia 2022; 3: 100036. doi: 10.1016/j.lansea.2022.100036

96. Zarabanda D, Vukkadala N, Phillips KM, et al. The effect of povidone‐iodine nasal spray on nasopharyngeal SARS‐CoV‐2 viral load: A randomized control trial. The Laryngoscope 2021; 132(11): 2089–2095. doi: 10.1002/lary.29935

97. Winchester S, John S, Jabbar K, et al. Clinical efficacy of nitric oxide nasal spray (NONS) for the treatment of mild COVID-19 infection. Journal of Infection 2021; 83(2): 237–279. doi: 10.1016/j.jinf.2021.05.009

98. Meister TL, Todt D, Brüggemann Y, et al. Virucidal activity of nasal sprays against severe acute respiratory syndrome coronavirus-2. Journal of Hospital Infection 2022; 120: 9–13. doi: 10.1016/j.jhin.2021.10.019

99. Castellarnau A, Heery GP, Seta A, et al. Astodrimer sodium antiviral nasal spray for reducing respiratory infections is safe and well tolerated in a randomized controlled trial. Scientific Reports 2022; 12(1): 10210. doi: 10.1038/s41598-022-14601-3

100. Figueroa JM, Lombardo ME, Dogliotti A, et al. Efficacy of a nasal spray containing iota-carrageenan in the postexposure prophylaxis of COVID-19 in hospital personnel dedicated to patients care with COVID-19 disease. International Journal of General Medicine 2021; 14: 6277–6286. doi: 10.2147/ijgm.s328486

101. Zhu C, Lee JY, Woo JZ, et al. An intranasal ASO therapeutic targeting SARS-CoV-2. Nature Communications 2022; 13(1): 4503. doi: 10.1038/s41467-022-32216-0

102. Callaway E. How months-long COVID infections could seed dangerous new variants. Nature 2022; 606(7914): 452–455. doi: 10.1038/d41586-022-01613-2

103. Higdon MM, Baidya A, Walter KK, et al. Duration of effectiveness of vaccination against COVID-19 caused by the omicron variant. The Lancet Infectious Diseases 2022; 22(8): 1114–1116. doi: 10.1016/s1473-3099(22)00409-1

104. Feikin DR, Abu-Raddad LJ, Andrews N, et al. Assessing vaccine effectiveness against severe COVID-19 disease caused by omicron variant. Report from a meeting of the World Health Organization. Vaccine 2022; 40(26): 3516–3527. doi: 10.1016/j.vaccine.2022.04.069

105. Mack I, Sharland M, Berkley JA, et al. Antimicrobial resistance following azithromycin mass drug administration: Potential surveillance strategies to assess public health impact. Clinical Infectious Diseases 2019; 70(7): 1501–1508. doi: 10.1093/cid/ciz893

106. Topçu G, Şenol H, Alim Toraman GÖ, Altan VM. Natural alkaloids as potential anti-coronavirus compounds. Bezmialem Science 2020; 8(3): 131–139. doi: 10.14235/bas.galenos.2020.5035

107. Gyebi GA, Adegunloye AP, Ibrahim IM, et al. Prevention of SARS-CoV-2 cell entry: Insight fromin silicointeraction of drug-like alkaloids with spike glycoprotein, human ACE2, and TMPRSS2. Journal of Biomolecular Structure and Dynamics 2020; 40(5): 2121–2145. doi: 10.1080/07391102.2020.1835726

108. Mohseni M, Bahrami H, Farajmand B, et al. Indole alkaloids as potential candidates against COVID-19: An in silico study. Journal of Molecular Modeling 2022; 28(6): 144. doi: 10.1007/s00894-022-05137-4

109. Jiang B, Wei H. Oxygen therapy strategies and techniques to treat hypoxia in COVID-19 patients. European Review for Medical and Pharmacological Sciences 2020; 24(19): 10239–10246. doi: 10.26355/eurrev_202010_23248

110. Choudhery MS, Harris DT. Stem cell therapy for COVID‐19: Possibilities and challenges. Cell Biology International 2020; 44(11): 2182–2191. doi: 10.1002/cbin.11440

111. Bhuta S, Khokher W, Kesireddy N, et al. Fluvoxamine in nonhospitalized patients with acute COVID-19 infection and the lack of efficacy in reducing rates of hospitalization, mechanical ventilation, and mortality in placebo-controlled trials: A systematic review and meta-analysis. American Journal of Therapeutics 2022; 29(3): e298–e304. doi: 10.1097/mjt.0000000000001496

112. Parray HA, Shukla S, Perween R, et al. Inhalation monoclonal antibody therapy: A new way to treat and manage respiratory infections. Applied Microbiology and Biotechnology 2021; 105(16–17): 6315–6332. doi: 10.1007/s00253-021-11488-4

113. Badakhsh M, Dastras M, Sarchahi Z, et al. Complementary and alternative medicine therapies and COVID-19: A systematic review. Reviews on Environmental Health 2021; 36(3): 443–450. doi: 10.1515/reveh-2021-0012

114. Setyo Budi D, Fahmi Rofananda I, Reza Pratama N, et al. Ozone as an adjuvant therapy for COVID-19: A systematic review and meta-analysis. International Immunopharmacology 2022; 110: 109014. doi: 10.1016/j.intimp.2022.109014

115. de la Fuente M, Lombardero L, Gómez-González A, et al. Enzyme therapy: Current challenges and future perspectives. International Journal of Molecular Sciences 2021; 22(17): 9181. doi: 10.3390/ijms22179181

116. Wu N, Chen LK, Zhu T. Phage therapy for secondary bacterial infections with COVID-19. Current Opinion in Virology 2022; 52: 9–14. doi: 10.1016/j.coviro.2021.11.001

117. Yao J, Zhang Y, Wang XZ, et al. Flavonoids for treating viral acute respiratory tract infections: A systematic review and meta-analysis of 30 randomized controlled trials. Frontiers in Public Health 2022; 10: 814669. doi: 10.3389/fpubh.2022.814669

118. Ku Z, Xie X, Hinton PR, et al. Nasal delivery of an IgM offers broad protection from SARS-CoV-2 variants. Nature 2021; 595(7869): 718–723. doi: 10.1038/s41586-021-03673-2

119. Kasiri H, Rouhani N, Salehifar E, et al. Mometasone furoate nasal spray in the treatment of patients with COVID-19 olfactory dysfunction: A randomized, double blind clinical trial. International Immunopharmacology 2021; 98: 107871. doi: 10.1016/j.intimp.2021.107871

120. Lake MA. What we know so far: COVID-19 current clinical knowledge and research. Clinical Medicine 2020; 20(2): 124–127. doi: 10.7861/clinmed.2019-coron

121. Lin D, Liu L, Zhang M, et al. Co-infections of SARS-CoV-2 with multiple common respiratory pathogens in infected patients. Science China Life Sciences 2020; 63(4): 606–609. doi: 10.1007/s11427-020-1668-5

122. Smith KF, Goldberg M, Rosenthal S, et al. Global rise in human infectious disease outbreaks. Journal of The Royal Society Interface 2014; 11(101): 20140950. doi: 10.1098/rsif.2014.0950

123. Gerver SM, Guy R, Wilson K, et al. National surveillance of bacterial and fungal coinfection and secondary infection in COVID-19 patients in England: Lessons from the first wave. Clinical Microbiology and Infection 2021; 27(11): 1658–1665. doi: 10.1016/j.cmi.2021.05.040

124. Bhatt K, Agolli A, Patel MH, et al. High mortality co-infections of COVID-19 patients: Mucormycosis and other fungal infections. Discoveries 2021; 9(1): e126. doi: 10.15190/d.2021.5

125. Feldman C, Anderson R. The role of co-infections and secondary infections in patients with COVID-19. Pneumonia 2021; 13(1): 5. doi: 10.1186/s41479-021-00083-w

126. Lai CC, Shih TP, Ko WC, et al. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges. International Journal of Antimicrobial Agents 2020; 55(3): 105924. doi: 10.1016/j.ijantimicag.2020.105924

127. Kusahara DM, Canezin CC da S, Peterlini MAS, et al. Oropharyngeal, gastric and tracheal bacterial colonization and translocation in children undergoing mechanical pulmonary ventilation (Portuguese). Acta Paulista de Enfermagem 2012; 25(3): 393–400. doi: 10.1590/s0103-21002012000300012

128. Fehér Á, Szarvas Z, Lehoczki A, et al. Co-infections in COVID-19 patients and correlation with mortality rate. Minireview. Physiology International 2022; 109(1): 1–8. doi: 10.1556/2060.2022.00015

129. Krumbein H, Kümmel LS, Fragkou PC, et al. Respiratory viral co‐infections in patients with COVID‐19 and associated outcomes: A systematic review and meta‐analysis. Reviews in Medical Virology 2022; 33(1): e2365. doi: 10.1002/rmv.2365

130. Pakzad R, Malekifar P, Shateri Z, et al. Worldwide prevalence of microbial agents’ coinfection among COVID‐19 patients: A comprehensive updated systematic review and meta‐analysis. Journal of Clinical Laboratory Analysis 2021; 36(1). doi: 10.1002/jcla.24151

131. Murray CJL, Ikuta KS, Sharara F, et al. Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis. The Lancet 2022; 399(10325): 629–655. doi: 10.1016/s0140-6736(21)02724-0

132. Salazar F, Bignell E, Brown GD, et al. Pathogenesis of respiratory viral and fungal coinfections. Clinical Microbiology Reviews 2022; 35(1). doi: 10.1128/cmr.00094-21

133. Soltani S, Zandi M, Faramarzi S, et al. Worldwide prevalence of fungal coinfections among COVID-19 patients: A comprehensive systematic review and meta-analysis. Osong Public Health and Research Perspectives 2022; 13(1): 15–23. doi: 10.24171/j.phrp.2021.0293

134. Van Kerkhove MD. COVID-19 in 2022: Controlling the pandemic is within our grasp. Nature Medicine 2021; 27(12): 2070–2070. doi: 10.1038/s41591-021-01616-y

135. Thorp HH. It ain’t over ‘til it’s over. Science 2022; 376(6594): 675–675. doi: 10.1126/science.abq8460

136. Topol E. We need a definitive exit from our Covid-19 pandemic. Here’s the roadmap. Available online: https://www.theguardian.com/commentisfree/2022/may/16/covid-19-pandemic-exit-roadmap (accessed on 22 December 2023).

137. World Health Organization. WHO releases global COVID-19 vaccination strategy update to reach unprotected. Available online: https://www.who.int/news/item/22-07-2022-who-releases-global-covid-19-vaccination-strategy-update-to-reach-unprotected (accessed on 22 December 2023).

138. Zalcman E. Rate of positive COVID testes in Brazil on par with omicron wave. Available online: https:// https://brazilian.report/liveblog/coronavirus/2022/07/11/positive-covid-tests-omicron-wave/ (accessed on 22 December 2023).

139. Altmann DM, Boyton RJ. COVID-19 vaccination: The road ahead. Science 2022; 375(6585): 1127–1132. doi: 10.1126/science.abn1755

140. Tuekprakhon A, Nutalai R, Dijokaite-Guraliuc A, et al. Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum. Cell 2022; 185(14): 2422–2433. doi: 10.1016/j.cell.2022.06.005

141. Kantarcioglu B, Iqbal O, Lewis J, et al. An update on the status of vaccine development for SARS-CoV-2 including variants. Practical considerations for COVID-19 special populations. Clinical and Applied Thrombosis/Hemostasis 2022; 28. doi: 10.1177/10760296211056648

142. Tretyn A, Szczepanek J, Skorupa M, et al. Differences in the concentration of anti-SARS-CoV-2 IgG antibodies post-COVID-19 recovery or post-vaccination. Cells 2021; 10(8): 1952. doi: 10.3390/cells10081952

143. Chavda VP, Vora LK, Pandya AK, et al. Intranasal vaccines for SARS-CoV-2: From challenges to potential in COVID-19 management. Drug Discovery Today 2021; 26(11): 2619–2636. doi: 10.1016/j.drudis.2021.07.021

144. National Institute for Communicable Diseases. Clinical management of COVID-19 disease. Available online: https://www.covid19treatmentguidelines.nih.gov/ (accessed on 22 December 2023).

145. Abani O, Abbas A, Abbas F, et al. Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial. The Lancet 2022; 399(10320): 143–151. doi: 10.1016/s0140-6736(21)01825-0

146. Rejdak K, Fiedor P, Bonek R, et al. The use of amantadine in the prevention of progression and treatment of COVID-19 symptoms in patients infected with the SARS-CoV-2 virus (COV-PREVENT): Study rationale and design. Contemporary Clinical Trials 2022; 116: 106755. doi: 10.1016/j.cct.2022.106755

147. Kamel AM, Monem MSA, Sharaf NA, et al. Efficacy and safety of azithromycin in Covid‐19 patients: A systematic review and meta‐analysis of randomized clinical trials. Reviews in Medical Virology 2021; 32(1): e2258. doi: 10.1002/rmv.2258

148. Ely EW, Ramanan AV, Kartman CE, et al. Efficacy and safety of baricitinib plus standard of care for the treatment of critically ill hospitalised adults with COVID-19 on invasive mechanical ventilation or extracorporeal membrane oxygenation: An exploratory, randomised, placebo-controlled trial. The Lancet Respiratory Medicine 2022; 10(4): 327–336. doi: 10.1016/s2213-2600(22)00006-6

149. Pang J, Xu F, Aondio G, et al. Efficacy and tolerability of bevacizumab in patients with severe Covid-19. Nature Communications 2021; 12(1): 814. doi: 10.1038/s41467-021-21085-8

150. Tobback E, Degroote S, Buysse S, et al. Efficacy and safety of camostat mesylate in early COVID-19 disease in an ambulatory setting: A randomized placebo-controlled phase II trial. International Journal of Infectious Diseases 2022; 122: 628–635. doi: 10.1016/j.ijid.2022.06.054

151. Axfors C, Schmitt AM, Janiaud P, et al. Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials. Nature Communications 2021; 12(1): 2349. doi: 10.1038/s41467-021-22446-z

152. The RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19. New England Journal of Medicine 2021; 384(8): 693–704. doi: 10.1056/nejmoa2021436

153. Shinkai M, Tsushima K, Tanaka S, et al. Efficacy and safety of favipiravir in moderate COVID-19 pneumonia patients without oxygen therapy: A randomized, Phase III clinical trial. Infectious Diseases and Therapy 2021; 10(4): 2489–2509. doi: 10.1007/s40121-021-00517-4

154. The ATTACC, ACTIV-4a, and REMAP-CAP Investigators. Therapeutic anticoagulation with heparin in critically Ill patients with Covid-19. New England Journal of Medicine 2021; 385(9): 777–789. doi: 10.1056/nejmoa2103417

155. Alavi Darazam I, Hatami F, Mahdi Rabiei M, et al. An investigation into the beneficial effects of high-dose interferon beta 1-a, compared to low-dose interferon beta 1-a in severe COVID-19: The COVIFERON II randomized controlled trial. International Immunopharmacology 2021; 99: 107916. doi: 10.1016/j.intimp.2021.107916

156. Aman J, Duijvelaar E, Botros L, et al. Imatinib in patients with severe COVID-19: A randomised, double-blind, placebo-controlled, clinical trial. The Lancet Respiratory Medicine 2021; 9(9): 957–968. doi: 10.1016/s2213-2600(21)00237-x

157. Buonfrate D, Chesini F, Martini D, et al. High-dose ivermectin for early treatment of COVID-19 (COVER study): A randomised, double-blind, multicentre, phase II, dose-finding, proof-of-concept clinical trial. International Journal of Antimicrobial Agents 2022; 59(2): 106516. doi: 10.1016/j.ijantimicag.2021.106516

158. Cao B, Wang Y, Wen D, et al. A trial of lopinavir—Ritonavir in adults hospitalized with severe Covid-19. New England Journal of Medicine 2020; 382(19): 1787–1799. doi: 10.1056/nejmoa2001282

159. Salton F, Confalonieri P, Meduri GU, et al. Prolonged low-dose methylprednisolone in patients with severe COVID-19 pneumonia. Open Forum Infectious Diseases 2020; 7(10). doi: 10.1093/ofid/ofaa421

160. Zhuravel SV, Khmelnitskiy OK, Burlaka OO, et al. Nafamostat in hospitalized patients with moderate to severe COVID-19 pneumonia: A randomised Phase II clinical trial. EClinicalMedicine 2021; 41: 101169. doi: 10.1016/j.eclinm.2021.101169

161. Cairns DM, Dulko D, Griffiths JK, et al. Efficacy of niclosamide vs placebo in SARS-

162. CoV-2 respiratory viral clearance, viral shedding, and duration of symptoms among patients with mild to moderate COVID-19: A phase 2 randomized clinical trial. JAMA Network Open 2022; 5(2): e2144942–e2144942. doi: 10.1001/jamanetworkopen.2021.44942

163. Rocco PRM, Silva PL, Cruz FF, et al. Nitazoxanide in patients hospitalized with

164. COVID-19 pneumonia: A multicentre, randomized, double-blind, placebo-controlled trial. Frontiers in Medicine 2022; 9. doi: 10.3389/fmed.2022.844728

165. Zhang F, Wei Y, He L, et al. A trial of pirfenidone in hospitalized adult patients with severe coronavirus disease 2019. Chinese Medical Journal 2021; 135(3): 368–370. doi: 10.1097/cm9.0000000000001614

166. Remdesivir and three other drugs for hospitalised patients with COVID-19: Final results of the WHO solidarity randomised trial and updated meta-analyses. The Lancet 2022; 399(10339): 1941–1953. doi: 10.1016/s0140-6736(22)00519-0

167. Xu Y, Li M, Zhou L, et al. Ribavirin treatment for critically Ill COVID-19 patients: An observational study. Infection and Drug Resistance 2021; 14: 5287–5291. doi: 10.2147/idr.s330743

168. Kow CS, Javed A, Ramachandram D, et al. Clinical outcomes of sofosbuvir-based antivirals in patients with COVID-19: a systematic review and meta-analysis of randomized trials. Expert Review of Anti-infective Therapy 2021; 20(4): 567–575. doi: 10.1080/14787210.2022.2000861

169. Broman N, Feuth T, Vuorinen T, et al. Early administration of tocilizumab in hospitalized COVID-19 patients with elevated inflammatory markers, COVIDSTORM—A prospective, randomized, single-centre, open-label study. Clinical Microbiology and Infection 2022; 28(6): 844–851. doi: 10.1016/j.cmi.2022.02.027

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