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

NCT06208540 | Completed Phase 4

• 1 other identifier: AU-FM-covid-00325_2021
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Post-covid-19 Persistent Smell and Taste Disorders

Keywords

COVID-19; SARS-CoV-2; variants of concern; variants of interest; Alpha strain; Delta strain; Omicron strain; Predelta period; Delta period; Omicron and its variants period

Outcome Measures

Primary Outcomes (2)

• subjective evaluation

  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

• Objective evaluation

  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

Secondary Outcomes (3)

• The Globas Rating for smell (GRS)

  after 6, 8, 12, 16, 20 and 24 weeks from baseline

• The Globas Rating for taste (GRT)

  after 6, 8, 12, 16, 20 and 24 weeks from baseline

• Objective re-evaluation

  After 6, 8, 10, 12, 16, 20 and 24 weeks from baseline

Study Arms (2)

Patients group (with interventional treatment)

ACTIVE COMPARATOR

Patients with persistent smell and taste disorders and treated with cerebrolysin

Drug: Cerebrolysin; Other: olfactory and gustatory trainings

Control

PLACEBO COMPARATOR

Patients with persistent smell and taste disorders but untreated with cerebrolycin (no intervention)

Other: olfactory and gustatory trainings

Interventions

Cerebrolysin DRUG

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.

Also known as: Active arm

Patients group (with interventional treatment)

olfactory and gustatory trainings OTHER

olfactory and gustatory trainings using oils of strong odors for the same time frame as for the drug intervention

Also known as: controls

Control; Patients group (with interventional treatment)

Eligibility Criteria

• Age: 10 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sherifa Ahmed Hamed: lead

Study Sites (2)

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

Asyut, 71516, Egypt

Location

Assiut University, Faculty of Medicine, Hospital of Neurology, Psychiatry and Neurosurgery

Asyut, 71516, Egypt

Location

Related Publications (7)

• Hamed SA, Ahmed MAA. The effectiveness of cerebrolysin, a multi-modal neurotrophic factor, for treatment of post-covid-19 persistent olfactory, gustatory and trigeminal chemosensory dysfunctions: a randomized clinical trial. Expert Rev Clin Pharmacol. 2023 Jul-Dec;16(12):1261-1276. doi: 10.1080/17512433.2023.2282715. Epub 2023 Dec 9.

  PMID: 37950370 RESULT

• Hamed SA. Post-COVID-19 persistent olfactory, gustatory, and trigeminal chemosensory disorders: definitions, mechanisms, and potential treatments. World J Otorhinolaryngol. 2023;10(2):4-22. doi: 10.5319/wjo.v10.i2.448

  RESULT

• Taquet M, Sillett R, Zhu L, Mendel J, Camplisson I, Dercon Q, Harrison PJ. Neurological and psychiatric risk trajectories after SARS-CoV-2 infection: an analysis of 2-year retrospective cohort studies including 1 284 437 patients. Lancet Psychiatry. 2022 Oct;9(10):815-827. doi: 10.1016/S2215-0366(22)00260-7. Epub 2022 Aug 17.

  PMID: 35987197 RESULT

• Yau JWK, Lee MYK, Lim EQY, Tan JYJ, Tan KBJC, Chua RSB. Genesis, evolution and effectiveness of Singapore's national sorting logic and home recovery policies in handling the COVID-19 Delta and Omicron waves. Lancet Reg Health West Pac. 2023 Jun;35:100719. doi: 10.1016/j.lanwpc.2023.100719. Epub 2023 Mar 2.

  PMID: 37360873 RESULT

• Micheletti C, Medori MC, Dhuli K, Maltese PE, Cecchin S, Bonetti G, Fioretti F, Assoni L, Calzoni A, Praderio A, De Angelis MG, Donato K, Arabia G, Lorusso L, Manganotti P, Capelli E, Marceddu G, Bertelli M, Nodari S. Linking pathogenic and likely pathogenic gene variants to long-COVID symptoms. Eur Rev Med Pharmacol Sci. 2023 Dec;27(6 Suppl):20-32. doi: 10.26355/eurrev_202312_34686.

  PMID: 38112945 RESULT

• Velavan TP, Ntoumi F, Kremsner PG, Lee SS, Meyer CG. Emergence and geographic dominance of Omicron subvariants XBB/XBB.1.5 and BF.7 - the public health challenges. Int J Infect Dis. 2023 Mar;128:307-309. doi: 10.1016/j.ijid.2023.01.024. Epub 2023 Jan 19. No abstract available.

  PMID: 36681145 RESULT

• Hamed SA, Kamal-Eldeen EB, Ahmed MAA. Evaluation of children and adults with post-COVID-19 persistent smell, taste and trigeminal chemosensory disorders: A hospital based study. World J Clin Pediatr. 2023 Jun 9;12(3):133-150. doi: 10.5409/wjcp.v12.i3.133. eCollection 2023 Jun 9.

  PMID: 37342446 RESULT

MeSH Terms

Conditions

Taste Disorders; COVID-19

Interventions

cerebrolysin; Smell

Condition Hierarchy (Ancestors)

Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Sensation; Nervous System Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Sherifa A Hamed

  Assiut University, Faculty of Medicine, Hospital of Neurology, Neurosurgery and Psychiatry

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: January 11, 2024
• First Posted: January 17, 2024
• Study Start: August 30, 2021
• Primary Completion: April 30, 2024
• Study Completion: May 30, 2024
• Last Updated: August 5, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 4-6 months
• Access Criteria: The published work

Locations

EG (2)