The SARS-CoV-2 pandemic has consisted of multiple surges of infection because ofcontinuous viral mutations. The WHO and CDC have defined the main SARS-CoV-2 variantsbased on international and national data for the circulation of SARS-CoV-2 into at least4 waves. Studies from different parts of the world have demonstrated significantvariations in the clinical manifestations of viral infection in relation to differentSARS-CoV-2 variants. They also indicated that the current high levels of populationimmunity, due to prior infection and/or vaccination, have been associated with a vastlydecreased overall risk of severe disease. Anosmia (with or without ageusia) wasidentified as a hallmark of COVID-19 early in the pandemic (ancestral Wuhan strain, alphaand delta variants), with a prevalence of ~60%. Prolonged olfactory disorders, lasting ≥6months to years, has been reported in ~35-40% of infected individuals. However, studiesreported that olfactory and gustatory disorders were less frequent with Omicron variantscompared to pre-omicron variants. It has been indicated that SARS-CoV-2 can causedestruction, disorganization and molecular changes in the nasal olfactory neuroepitheliumresulting in loss and distortion of the sense of smell. There are several trials to treatthese 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 commerciallyavailable multimodal neurotropic factor, has the ability to cure at least 60% (100%complete and persistent recovery) of post-covid-19 persistent olfactory and gustatorydysfunctions. This drug is available in the market of at least 75 countries since 1996and easily dispensed from local pharmacies after doctors prescriptions. It is used fortreatment of many disorders of the central and peripheral nervous systems. This could bedue to its ability to promote neurogenesis and remodeling of olfactory and gustatoryneurons.
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.
Drug: Cerebrolysin
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 6 weeks till a maximum of 24 weeks.
Other Name: Active arm
Other: olfactory and gustatory trainings
olfactory and gustatory trainings using oils of strong odors for the same time frame as
for the drug intervention
Other Name: controls
Inclusion Criteria:
- Children and adults with sudden hyposmia/anosmia and/or hypoageusia/ageusia during
COVID-19 pandemics (2020-2024).
- Persisting symptoms were defined as disorders lasting ≥6 months.
- Cooperation during objective evaluation
- compliance to drug treatment or olfactory and gustatory trainings for at least 8
weeks.
Exclusion Criteria:
- Prior neurological, medical or psychiatric disease which are known as a cause of
progressive olfactory or gustatory dysfunction
- Nasal congestion
- Nasal polyps
- Surgery or head trauma or radiation for head and neck cancers as may result in
injury to the nerves that control smell
- Exposure to toxic chemicals (such as pesticides and solvents) Cocaine or other drug
abuse
- Lack of compliance to drug treatment or olfactory and gustatory trainings for at
least 8 weeks.
- Lack of cooperation to complete the objective testings.
Assiut University Hospitals, Faculty of Medicine, Hospital of Neurology, Neurosurgery and Psychiatry, Assiut University Hospital, Assiut, Egypt
Asyut 359783, Egypt
Assiut University, Faculty of Medicine, Hospital of Neurology, Psychiatry and Neurosurgery
Asyut 359783, Egypt
Sherifa A Hamed, Principal Investigator
Assiut University, Faculty of Medicine, Hospital of Neurology, Neurosurgery and Psychiatry