Clinical Characteristics and Treatment of Anosmia and Ageusia Due to SARS-CoV2 Variants

August 1, 2024 updated by: Sherifa Ahmed Hamed

Persistent Olfactory and Gustatory Dysfunctions Due to Different SARS-CoV-2 Variants: Clinical Characteristics and Treatment

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

160

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Assiut, Egypt, 71516
        • Assiut University Hospitals, Faculty of Medicine, Hospital of Neurology, Neurosurgery and Psychiatry, Assiut University Hospital, Assiut, Egypt
      • Assiut, Egypt, 71516
        • Assiut University, Faculty of Medicine, Hospital of Neurology, Psychiatry and Neurosurgery

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Patients group (with interventional treatment)
Patients with persistent smell and taste disorders and treated with cerebrolysin
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 Names:
  • controls
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 Names:
  • Active arm
Placebo Comparator: Control
Patients with persistent smell and taste disorders but untreated with cerebrolycin (no intervention)
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 Names:
  • controls

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective evaluation
Time Frame: Baseline
It included application of modified Arabic translated and validated sniffin' odor, taste and flavor identification tests were used for objective evaluations. We used 16 different odorants which are well-known for our population. According to the results, patients were classified as normosmic (score: 12-16), hyposmic (score: 9-11) or anosmic (score: equal or less than 8). Flavor identification test was done using the same recipes as in olfactory identification test. Taste identification test was done using a five known tastants which represented the five base taste sensations (salty, sweet, bitter, sour and Umami". Answers used for the result of this test was either correct or incorrect.
Baseline
subjective evaluation
Time Frame: Baseline
It included data collection of demographic, general and systemic clinical and treatment characteristics of patients infected by different SARS-CoV-2 variants. it also included the smell and taste questionnaire component of the National Health and Nutrition Examination Survey (NHNES).The dominant viral variant was defined according to the period of the development of viral manifestations including olfactory and gustatory disorders. We defined pre-delta period as February 2020 to end of May 2021; delta period as first of June 2021 till the end of December 2021; Omicron variant and its subvariants period as early in January 2022 till the end of the recruitment period.
Baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Globas Rating for smell (GRS)
Time Frame: after 6, 8, 12, 16, 20 and 24 weeks from baseline
It is a single-item, global rating that asks the patient to rate his current sense of smell as follow: excellent, very good, good, fair, poor or absent
after 6, 8, 12, 16, 20 and 24 weeks from baseline
The Globas Rating for taste (GRT)
Time Frame: after 6, 8, 12, 16, 20 and 24 weeks from baseline
it is a single-item, global rating that asks the patient to rate his current sense of taste as follow: excellent, very good, good, fair, poor or absent
after 6, 8, 12, 16, 20 and 24 weeks from baseline
Objective re-evaluation
Time Frame: After 6, 8, 10, 12, 16, 20 and 24 weeks from baseline
Sniffin' odor, taste and flavor identification tests as described in the previous section.
After 6, 8, 10, 12, 16, 20 and 24 weeks from baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sherifa Ahmed Hamed

Investigators

  • Principal Investigator: Sherifa A Hamed, Assiut University, Faculty of Medicine, Hospital of Neurology, Neurosurgery and Psychiatry

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 30, 2021

Primary Completion (Actual)

April 30, 2024

Study Completion (Actual)

May 30, 2024

Study Registration Dates

First Submitted

January 11, 2024

First Submitted That Met QC Criteria

January 11, 2024

First Posted (Actual)

January 17, 2024

Study Record Updates

Last Update Posted (Estimated)

August 5, 2024

Last Update Submitted That Met QC Criteria

August 1, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AU-FM-covid-00325_2021

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

http://orcid.org/0000-0002-1441-3530

IPD Sharing Time Frame

4-6 months

IPD Sharing Access Criteria

The published work

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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