Review Article
Volume 14 Issue 6 - 2022
A SARS-COV-2 Entry Pathway Shift for the Omicron Variant Might Explain a Less Severe Disease
Calixto Machado-Curbelo1*, Joel Gugierrez-Gil1 and Alina González-Quevedo2
1Department of Clinical Neurophysiology, Institute of Neurology and Neurosurgery, Havana, Cuba
2Department of Neurobiology, Institute of Neurology and Neurosurgery, Havana, Cuba
*Corresponding Author: Calixto Machado-Curbelo, Department of Clinical Neurophysiology, Institute of Neurology and Neurosurgery, Havana, Cuba.
Received: February 28, 2022; Published: May 27, 2022




Abstract

The Omicron variant led to exponential increases in cases and a sharp rise in hospital admissions. The wave increased faster than previous waves, completely displacing the Delta variant within weeks, creating worldwide worries about the final pandemic control. Omicron is the fifth variant to be named as a variant of concern (VOC) by the World Health Organisation (WHO) and the third (after Alpha and Delta) to achieve global dominance. Although Omicron is fast-moving, several initial reports suggest a less severe disease. Some authors have emphasized that the symptoms associated with Omicron have differed from these "traditional" symptoms and are closer to the common cold. It is also curious that one major COVID-19 symptom rare-the loss of taste and smell. Dr. Machado has suggested that one of the main causes to explain ARDS refractory to treatments is the direct invasion of SARS-CoV-2 to the brainstem from the olfactory nerves through transsynaptic pathways. SARS-CoV-2 infection of the brainstem can deeply damage the respiratory center, triggering functional deviations that affect involuntary respiration leading to ARDS refractory to treatments, which is the main cause of death in Covid-19 patients. A shift in the Omicron SARS-CoV-2 entry pathway from cell surface fusion, triggered by TMPRSS2, to cathepsin-dependent fusion within the endosome, may impact transmission, cellular tropism, and pathogenesis. Therefore, we can hypothesize that this entrance modification may impact transmission from the olfactory nerve to the brainstem through transsynaptic pathways. Hence, a decrement of the virus's direct invasion to the brainstem would diminish respiratory center dysfunction, with less possibility of an ARDS complication and the need for mechanical ventilation in ICUs.

 

Keywords: Covid-19; SARS-CoV-2; Omicron Variant; Acute Respiratory Distress Syndrome (ARDS); Entry Route

References

  1. Tureček P and Kleisner K. “Symptomic Mimicry Between SARS-CoV-2 and the Common Cold Complex”. Biosemiotics (2022): 1-6.
  2. Abdullah F., et al. “Decreased severity of disease during the first global omicron variant covid-19 outbreak in a large hospital in tshwane, South Africa”. International Journal of Infectious Diseases 116 (2021): 38-42.
  3. Papanikolaou V., et al. “From delta to Omicron: S1-RBD/S2 mutation/deletion equilibrium in SARS-CoV-2 defined variants”. Gene 814 (2022): 146134.
  4. World Health Organization. Tracking SARS-CoV-2 variants. World Health Organization (2021).
  5. Gu H., et al. “Probable Transmission of SARS-CoV-2 Omicron Variant in Quarantine Hotel, Hong Kong, China, November 2021”. Emerging Infectious Diseases 2 (2021): 460-462.
  6. Wang Y., et al. “The significant immune escape of pseudotyped SARS-CoV-2 variant Omicron”. Emerging Microbes and Infections 1 (2022): 1-5.
  7. Chen J., et al. “Omicron Variant (B.1.1.529): Infectivity, Vaccine Breakthrough, and Antibody Resistance”. Journal of Chemical Information and Modeling 2 (2022): 412-422.
  8. Ito K., et al. “Relative instantaneous reproduction number of Omicron SARS-CoV-2 variant with respect to the Delta variant in Denmark”. Journal of Medical Virology 5 (2021): 2265-2268.
  9. Tong C., et al. “Tracking and controlling the spatiotemporal spread of SARS-CoV-2 Omicron variant in South Africa”. Travel Medicine and Infectious Disease 46 (2021): 102252.
  10. Karim SSA and Karim QA. “Omicron SARS-CoV-2 variant: a new chapter in the COVID-19 pandemic”. Lancet 10317 (2021): 2126-2128.
  11. Abdelnabi R., et al. “The omicron (B.1.1.529) SARS-CoV-2 variant of concern does not readily infect Syrian hamsters”. Biorxivorg (2021).
  12. Diamond M., et al. “The SARS-CoV-2 B.1.1.529 Omicron virus causes attenuated infection and disease in mice and hamsters”. Research Square (2021).
  13. Wong SC., et al. “Transmission of Omicron (B.1.1.529) - SARS-CoV-2 Variant of Concern in a designated quarantine hotel for travelers: a challenge of elimination strategy of COVID-19”. Lancet Regional Health -Western Pacific 18 (2021): 100360.
  14. He X., et al. “SARS-CoV-2 Omicron variant: Characteristics and prevention”. MedComm 4 (2020): 838-845.
  15. Weir EM., et al. “Massively collaborative crowdsourced research on COVID19 and the chemical senses: Insights and outcomes”. Food Quality and Preference 97 (2022): 104483.
  16. Jansen L., et al. “Investigation of a SARS-CoV-2 B.1.1.529 (Omicron) Variant Cluster - Nebraska, November-December 2021”. Morbidity and Mortality Weekly Report (MMWR) 5152 (2021): 1782-1784.
  17. Machado-Curbelo C. “Silent or 'Happy' Hypoxemia: An Urgent Dilemma for COVID-19 Patient Care”. MEDICC Review 4 (2020): 85-86.
  18. Machado C. “Severe Covid-19 cases: Is respiratory distress partially explained by central nervous system involvement?”. MEDICC Review 2 (2020): 38-41.
  19. Machado C., et al. “It Is Imperative the use of Positive Air Pressure (CPAP) in Covid-19 Patients as Soon as the First Respiratory Symptoms Start”. Frontiers Journal of Neurology and Neuroscience 1 (2020): 1-14.
  20. Machado C., et al. “Continuous positive air pressure (CPAP) should be used in all COVID-19 patients when the first and mild respiratory symptoms commence”. Journal of Respiratory Diseases and Medicine 2 (2020): 1-6.
  21. Wang L., et al. “Clinical manifestations and evidence of neurological involvement in 2019 novel coronavirus SARS-CoV-2: a systematic review and meta-analysis”. Journal of Neurology 10 (2020): 2777-2789.
  22. Machado-Curbelo C. “Severe COVID-19 Cases: Is Respiratory Distress Partially Explained by Central Nervous System Involvement?” MEDICC Review 2 (2020): 38-39.
  23. Burbach JP. “[The 2004 Nobel Prize for Physiology or Medicine for research into smell receptors and the organization of the olfactory system]”. Nederlands Tijdschrift voor Geneeskunde 52 (2004): 2576-2579.
  24. Levy LM., et al. “Anatomic olfactory structural abnormalities in congenital smell loss: magnetic resonance imaging evaluation of olfactory bulb, groove, sulcal, and hippocampal morphology”. Journal of Computer Assisted Tomography 5 (2013): 650-657.
  25. Callahan CD and Hinkebein JH. “Assessment of anosmia after traumatic brain injury: performance characteristics of the University of Pennsylvania Smell Identification Test”. Journal of Head Trauma Rehabilitation 3 (2002): 251-256.
  26. Hummel C., et al. “Cerebral processing of gustatory stimuli in patients with taste loss”. Behavioural Brain Research 1 (2007): 59-64.
  27. Machado C and Gutierrez JV. “Anosmia and ageusia as initial or unique symptoms after SARS-CoV-2 virus infection (Review article)”. Preprints (2020): 2020040272.
  28. Machado C and González-Quevedo A. “Hypoximia and cytokine storms in COVID-19: clinical implications”. MEDICC Review 3-4 (2021): 54-59.
  29. Machado C. “Reader response: SARS-CoV-2 related encephalitis: MRI pattern of the olfactory tract involvement”. Neurology4 (2021): e645-e646.
  30. Sun Y., et al. “Origin and evolutionary analysis of the SARS-CoV-2 Omicron variant”. Journal of Biosafety and Biosecurity 1 (2021): 33-37.
  31. Sommerstein R., et al. “Coronavirus Disease 2019 (COVID-19): Do Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers Have a Biphasic Effect?” Journal of the American Heart Association 7 (2020): e016509.
  32. Guzzi PH., et al. “Master Regulator Analysis of the SARS-CoV-2/Human Interactome”. Journal of Clinical Medicine 4 (2020): 982.
  33. Lukassen S., et al. “SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells”. EMBO Journal 10 (2020): e105114.
  34. Brann DH., et al. “Non-neural expression of SARS-CoV-2 entry genes in the olfactory epithelium suggests mechanisms underlying anosmia in COVID-19 patients”. Science Advances31 (2020): eabc5801.
  35. Casez O., et al. “SARS-CoV-2 Related Encephalitis: MRI Pattern of the Olfactory Tract Involvement”. Neurology 4 (2020): e645-e646.
  36. Machado C DP. “Covid-19: Anosmia and Ageusia Might be Initial or Unique Symptoms”. SF Journal of Clinical Neurology and Brain 1 (2020): 1-7.
  37. Peacock T., et al. “The SARS-CoV-2 variant, Omicron, shows rapid replication in human primary nasal epithelial cultures and efficiently uses the endosomal route of entry”. bioRxiv (2022).
  38. Jackson CB., et al. “Mechanisms of SARS-CoV-2 entry into cells”. Nature Reviews Molecular Cell Biology1 (2022): 3-20.
  39. Klingenstein M., et al. “Evidence of SARS-CoV2 Entry Protein ACE2 in the Human Nose and Olfactory Bulb”. Cells, Tissues, Organs 209 (2020): 155-164.
  40. Matarese A., et al. “miR-98 Regulates TMPRSS2 Expression in Human Endothelial Cells: Key Implications for COVID-19”. Biomedicines11 (2020): 462.
  41. Chatterjee SK., et al. “Molecular Pathogenesis, Immunopathogenesis and Novel Therapeutic Strategy Against COVID-19”. Frontiers in Molecular Biosciences 7 (2020): 196.
  42. Hoffmann M., et al. “SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor”. Cell 2 (2020): 271-280.e278.
  43. Hoffmann M., et al. “A Multibasic Cleavage Site in the Spike Protein of SARS-CoV-2 Is Essential for Infection of Human Lung Cells”. Molecular Cell4 (2020): 779-784.e775.
  44. Liu JM., et al. “Evidence of central nervous system infection and neuroinvasive routes, as well as neurological involvement, in the lethality of SARS-CoV-2 infection”. Journal of Medical Virology 3 (2021): 1304-1313.
Citation: Calixto Machado-Curbelo., et al. “A SARS-COV-2 Entry Pathway Shift for the Omicron Variant Might Explain a Less Severe Disease”. EC Neurology 14.6 (2022): 14-20.

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