Treatment of Persistent Post-Covid-19 Smell and Taste Disorders
Condition: Post-covid-19 Persistent Smell and Taste Disorders
MeSH terms: COVID-19; Taste Disorders
Study type: Interventional
Phase: Phase 4

Summary: 
      The SARS-CoV-2 pandemic has consisted of multiple surges of infection because of continuous
      viral mutations. The WHO and CDC have defined the main SARS-CoV-2 variants based on
      international and national data for the circulation of SARS-CoV-2 into at least 4 waves.
      Studies from different parts of the world have demonstrated significant variations in the
      clinical manifestations of viral infection in relation to different SARS-CoV-2 variants. They
      also indicated that the current high levels of population immunity, due to prior infection
      and/or vaccination, have been associated with a vastly decreased overall risk of severe
      disease. Anosmia (with or without ageusia) was identified as a hallmark of COVID-19 early in
      the pandemic (ancestral Wuhan strain, alpha and delta variants), with a prevalence of ~60%.
      Prolonged olfactory disorders, lasting ≥6 months to years, has been reported in ~35-40% of
      infected individuals. However, studies reported that olfactory and gustatory disorders were
      less frequent with Omicron variants compared to pre-omicron variants. It has been indicated
      that SARS-CoV-2 can cause destruction, disorganization and molecular changes in the nasal
      olfactory neuroepithelium resulting in loss and distortion of the sense of smell. There are
      several trials to treat these persistent disorders but none has shown significant positive
      results except ours (Hamed et al., Expert Review of Clinical Pharmacology
      2023;16(12):1261-1276 DOI: 10.1080/17512433.2023.2282715). Hamed et al. reported that
      cerebrolycin, a commercially available multimodal neurotropic factor, has the ability to cure
      at least 60% (100% complete and persistent recovery) of post-covid-19 persistent olfactory
      and gustatory dysfunctions. This drug is available in the market of at least 75 countries
      since 1996 and easily dispensed from local pharmacies after doctors prescriptions. It is used
      for treatment of many disorders of the central and peripheral nervous systems. This could be
      due to its ability to promote neurogenesis and remodeling of olfactory and gustatory neurons.
    

Detailed description: 
      The diminished senses of smell (or hyposmia/anosmia) and taste (or hypogeusia/ageusia) have
      been commonly reported after infection by ancestral Wuhan, alpha and delta strains of the
      SARS-CoV-2 virus in ≥ 60% of patients. Persisted dysfunctions (deficits and distortions),
      lasting for months to years, were also reported in ~40%.

      The SARS-CoV-2 pandemic has different waves of infection because of the dynamic viral
      mutations. The first wave (ancestral Wuhan strain) has been defined as the period from
      approximately the last week of February 2020 to the first Week of February 2021; the second
      wave (Alpha variant) started from approximately week 7 of February 2021 to July 2021; the
      third wave (Delta variant) was the period from approximately August 2021 to December 2021;
      and the fourth wave (Omicron and its subvariants) was the period from approximately January
      2022 to December 2023 and after. These Viral strains were also categorized according to the
      main variants and their subvariants based on the viral pathogenicity and transmissibility,
      the clinical manifestations, immunity and response to vaccination. Studies from different
      parts of the world reported less severe viral manifestations in the periods of omicron strain
      and its subvariants compared to the pre-omicron years of the pandemic. They also reported
      less frequent involvement of olfactory and gustatory systems with omicron and its subvariants
      compared to previous viral variants (alpha and delta).

      Experimental studies strongly indicated that post-covid olfactory and gustatory disorders are
      due to peripheral damage of the sensory neuroepithelia (olfactory and gustatory) and their
      disorganization by severe viral infection and its immune mediated pathology.

      In general, the characterization of the prevalence and clinical manifestations and risk
      variables of olfactory and gustatory complications of different SARS-CoV-2 variants is
      unclear. furthermore, the treatment of these prolonged complications is still aworldwide
      challenge. Detailed search in clinical trials' websites, for example: WHO International
      Clinical Trials Registry Platform (ICTRP Search Portal-WHO; https://trialsearch.who.int/),
      Cochrane ENT Trials Register (https://ent.cochrane.org), Ovid Embase
      (https://tools.ovid.com), ClinicalTrials.gov, Medfind (https:// medfind.in), Web of Science,
      PubMed and Scopus, demonstrated that there is only a completed and published trial which
      showed promising positive and maintained results (Hamed et al., 2023). In this trial, the
      authors concluded that cerebrolysin, a commercially available multimodal neurotropic factor,
      had fast, promising, and constant effect, with cure rate of >/+ 60%. This could be due to its
      ability to initiate and enhance neuronal regeneration, reorganization and remodeling of
      sensory neuroepithelia.
    

Intervention name(s): Cerebrolysin; olfactory and gustatory trainings
Intervention type(s): Drug; Other
Intervention description(s): Cerebrolysin Dose:5 ml ampoule (1ml contains 215.2 mg cerebrolysin) once daily through intramuscular injection five times per week, for a total of 20 treatments (for 4 weeks), after which the cycle was repeated again for at least 8 more weeks till a maximum of 24 weeks.; olfactory and gustatory trainings using oils of strong odors for the same time frame as for the drug intervention
Intervention MeSH terms: Cerebrolysin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: COVID-19; SARS-CoV-2; variants of concern; variants of interest; Alpha strain; Delta strain; Omicron strain