ORIGINAL ARTICLE
Olfactory and Gustatory Recovery Time Evaluation of COVID-19: A Systematic Review and Meta-Analysis Mohadeseh Poudineh1#.
Amirhesam Amirbeik2#.
Mohammad D.
Firouzabadi3,4#.
Mahsa Hajizadeh5#.
Farima Kahe6.
Sepideh Babaniamansour7.
Amirhossein Poopak4.
Farbod Zahedi Tajrishi8.
Niloofar Deravi9.
Mohammad Rahmanian9.
Hamidreza Ghasemirad10.
Mahta Malek11.
Masoud Noroozi12.
Mobina Fathi9.
Kimia Keylani13.
Ali Dehghani Firouzabadi14.
Ghader Dargahi Abbasabad15.
Forough Yazdanian16.
Sara Ramezanpour17.
Amirmohammad Babaniamansour18.
Faryar Zahedi Tajrishi19.
Soheil Mohammadi20.
Golnoosh Ansari21*.
Fatemeh Dehghani Firouzabadi22*.
David M.
Yousem21* School of Medicine.
Zanjan University of Medical Sciences.
Zanjan.
Iran.
Student Research Committee.
School of Medicine.
Mashhad University of Medical Sciences.
Mashhad.
Iran.
ENT and Head & Neck Research Center.
The Five Senses Health Institute.
Iran University of Medical Sciences.
Tehran.
Iran Endocrinology and Metabolism Research Center (EMRC).
Vali-Asr Hospital.
School of Medicine.
Tehran University of Medical Sciences.
Tehran.
Iran.
Division of Immunology.
Department of Pathology.
The Johns Hopkins University School of Medicine.
Baltimore.
MD 21205.
USA.
Beth Israel Deaconess Medical Center.
Harvard Medical School.
USA School of Medicine.
Islamic Azad University.
Tehran Faculty of Medicine.
Tehran.
Iran.
Pulmonary and Critical Care Medicine, and Physical Medicine and Rehabilitation.
Johns Hopkins University.
Baltimore.
MD.
Student research committee.
Shahid Beheshti University of Medical Sciences.
Tehran.
Iran Student research committee.
Shahid Sadoughi University of Medical Sciences.
Yazd.
Iran Faculty of dentistry.
Tehran Medical Sciences.
Islamic Azad University.
Tehran.
Iran Department of Biomedical Engineering.
Tarbiat Modares University.
Tehran.
IranAU School of pharmacy.
Shahid Beheshti University of Medical Sciences.
Tehran.
Iran.
Mississippi State Department of Health.
Jackson.
Mississippi.
USA.
Health Service Research.
University of New Brunswick.
Canada Department of Neurosurgery.
Brigham and Women's Hospital.
Harvard Medical School.
Boston.
MA.
USA.
Department of Radiology and Biomedical Imaging.
University of California.
San Francisco.
USA Department of Orthotics and Prosthetics.
Rehabilitation school.
Iran University of Medical Science Tehran.
Iran Faculty of Science.
University of Tehran.
Tehran.
Iran School of Medicine.
Tehran University of Medical Sciences.
Tehran.
Iran.
Russell H.
Morgan Department of Radiology and Radiological Sciences.
Johns Hopkins University School of Medicine.
Baltimore.
MD.
USA Department of Radiology.
Boston ChildrenAos Hospital.
Harvard Medical School.
Boston.
MA.
USA.
#These authors contributed equally to this work.
Acta Med Indones - Indones J Intern Med A Vol 57 A Number 1 A January 2025 Vol 57 A Number 1 A January 2025 Olfactory and Gustatory Recovery Time Evaluation of COVID-19 *Corresponding Authors:
David M.
Yousem.
MD.
MBA.
Russell H.
Morgan Department of Radiology and Radiological Science.
Johns Hopkins Medical Institution 600 N.
Wolfe Street.
Phipps B112D.
Baltimore.
MD 21287.
USA.
E-mail: dyousem1@jhu.
Fatemeh Dehghani Firouzabadi.
MD.
Department of Radiology.
Boston ChildrenAos Hospital.
Harvard Medical School.
Boston.
MA.
USA.
Email: Fatemeh.
dehghanifirouzabadi@childrens.
Golnoosh Ansari.
MD.
Russell H.
Morgan Department of Radiology and Radiological Science.
Johns Hopkins Medical Institution.
Baltimore.
MD.
USA.
Email: gansari2@jhmi.
ABSTRACT
Background: Olfactory dysfunction is a common symptom of Coronavirus disease 2019 (COVID-.
In this study, we aimed to evaluate the recovery rate and duration of these symptoms in COVID-19patients.
Methods: This systematic review was conducted by searching PubMed and Google Scholar from April 1st, 2020, until October 1st, 2022, using the terms AoAoCOVID-19AoAo OR AoAoCOV-2,AoAo OR AoAoCoronavirus 2AoAo OR coronavirus AND AoAoloss of smellAoAo OR Anosmia OR Hyposmia OR olfaction OR AoAoolfactory lossAoAo AND ageusia OR Hypogeusia OR dysgeusia OR AoAogustatory lossAoAo OR gustation OR AoAoloss of tasteAoAo.
The references of included studies were also manually screened.
Random-effects meta-analysis was performed.
Results: One hundred and twenty-five studies with test-confirmed COVID-19 infection from 31 countries were included.
62 publications which reported data on loss of taste were used to estimate patients' recovery rate in 13700 COVID-19 patients.
Accordingly, the time to recovery of loss of taste among COVID-19 patients ranged from 2A0.
352 to 43.
6 A 28.
5 days.
The estimated overall pooled recovery rate of loss of taste among COVID-19 patients was 74%.
The estimated overall pooled time to recover loss of taste among COVID-19 patients was 11.
44 days .
% CI 8.
11, 14.
77(].
90 publications which reported data on loss of smell were used to estimate patients' recovery rate in 20027 COVID-19 patients.
Accordingly, the time to recover the loss of smell among COVID-19 patients ranged from 2.
44A0.
352 to 31.
7 days The estimated overall pooled recovery rate of loss of smell among COVID-19 patients was 72%.
The estimated overall pooled time to recover loss of smell among COVID-19 patients was 12.
87 days .
% CI)1011, 64(].
Conclusion: The recovery rate of loss of smell and taste among COVID-19 patients was high globally, and time to recovery of loss of smell and taste among COVID-19 patients usually was less than 2 weeks.
differences supported the relevance of these symptoms as important markers.
Health workers must consider smell and taste symptoms as suspicion indices for the empirical diagnosis of COVID-19 infection and reassure patients with their high recovery rate in a short period of time.
Keywords: Olfactory Dysfunction.
Smell.
Taste.
Gustatory Dysfunction.
COVID-19.
SARS- CoV-2.
MetaAnalysis.
Recovery rate.
INTRODUCTION
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-.
, the identified causative agent for this disease, potentially causes a variable range of symptoms in affected individuals.
Olfactory and gustatory dysfunctions are among the relatively common symptoms of COVID-19.
According to a meta-analysis, almost half of the patients with confirmed COVID-19 infection experience some degree of olfactory dysfunction, and 60 percent experience gustatory dysfunction.
Based on the standard classification, olfactory disorders can range from anosmia .
otal absence of smel.
to hyposmia .
ecreased sense of smel.
, and dysosmia .
istortion of normal Taste disturbances include ageusia .
omplete absence of tast.
, hypogeusia .
ecreased taste sensatio.
, and dysgeusia .
istortion of normal tast.
5, 6 In addition to their diagnostic value for COVID-19.
, smell and taste disturbances have other aspects that could potentially enhance our understanding of the disease and its management.
Since the emergence of this pandemic, several studies have attempted to report the recovery rate Mohadeseh Poudineh Acta Med Indones-Indones J Intern Med of olfactory and/or gustatory dysfunctions in COVID-19 patients.
however, a lack of consensus still persists.
The reported recovery rate of post infectionolfactory loss in viral infections other than COVID-19 ranges from 32% to 67%.
Notably, around 20% of these patients may not recover even after one year from the initial infection .
Knowing the recovery rate in COVID-19 patients is essential since these symptoms could negatively affect the quality of life of patients, as well as lengthening the recovery from the disease itself as smell/taste dysfunction can negatively affect the patientAos appetite and nutritional status which is vital for their recovery.
this systematic review and meta-analysis, we aimed to investigate the recovery rate and time to recovery of olfactory and gustatory dysfunctions in COVID-19 patients.
METHODS
This systematic review and meta-analysis is conducted under PRISMA guidelines.
This study employed a rigorous protocol that included standardized checklists for comprehensive study searching and screening processes.
The systematic review protocol was registered on Prospero (International prospective register of Systematic Review.
The registration id is:
CRD42024623799.
Data Sources and Search Strategy We searched for published studies that reported findings on abnormalities of smell and taste in patients with AoAoacute respiratory coronavirus 2 (SARS-CoV-.
AoAo infection or COVID-19 using PubMed.
Scopus and Google Scholar .
ttps://scholar.
These databases were searched for studies with data on the incidence or prevalence of loss of smell and/or taste between April 2019 and October 2022.
The studies were restricted to only those involving human subjects and written in English.
The search strategy used the exploded Medical Subject Headings terms and text words: ((AoAoCOVID-19AoA.
OR (AoAoCOV2AoA.
OR (AoAoCorona virus 2AoA.
OR .
OR ("SARS-CoV-2")) AND ((AoAoloss of smellAoA.
OR (Anosmi.
OR (Hyposmi.
OR .
OR (AoAoolfactory lossAoA.
) AND (.
OR (Hypogeusi.
OR .
OR (AoAogustatory lossAoA.
OR .
OR (AoAoloss of tasteAoA.
In addition, we searched some reference lists of relevant articles manually to identify further relevant literature but found none.
We also imported relevant articles to EndNote X8 and deleted duplicates (Table .
Table 1.
The search strategy of PubMed, and Scopus Database PubMed Scopus Search terms ("COVID-19"[Title/Abstrac.
OR "COV2"[Title/Abstrac.
OR "corona virus 2"[Title/Abstrac.
OR "coronavirus"[Title/ Abstrac.
OR "SARS-CoV-2"[Title/ Abstrac.
) AND ("loss of smell"[Title/ Abstrac.
OR "Anosmia"[Title/Abstrac.
OR "Hyposmia"[Title/Abstrac.
OR "olfaction"[Title/Abstrac.
OR "olfactory loss"[Title/Abstrac.
) AND ("ageusia"[Title/ Abstrac.
OR "Hypogeusia"[Title/ Abstrac.
OR "dysgeusia"[Title/Abstrac.
OR "gustatory loss"[Title/Abstrac.
OR "gustation"[Title/Abstrac.
OR "loss of taste"[Title/Abstrac.
) (TITLE-ABS-KEY ( "COV-2" OR "corona virus 2" OR "COVID-19" OR "coronavirus" OR "SARS-CoV-2" ) ) AND ( TITLEABS-KEY ( "loss of smell" OR "Anosmia" OR "Hyposmia" OR "olfaction" OR "olfactory loss" ) ) AND ( TITLE-ABSKEY ( "ageusia" OR "Hypogeusia" OR "dysgeusia" OR "gustatory loss" OR "gustation" OR "loss of taste" ) ) Results .
earch date: October 22, 2.
N= 1014
N= 3213
Vol 57 A Number 1 A January 2025 Olfactory and Gustatory Recovery Time Evaluation of COVID-19 Study Selection and Eligibility Criteria IdentiAcation This was a systematic review and metaanalysis performed in 2022 according to the book named AuA systematic review to support evidencebased medicine.
We included published journal articles that reported data on any recovery time evaluation of loss of smell and/or taste in COVID-19 patients.
We performed title and abstract screening for the studies with objectives/ focus on the desired results.
The steps followed in the selection process were in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram (Figure .
Studies were chosen based on the presence of data on loss of smell and taste in COVID-19 patients in the abstract or the Records identiAed through database searching .
= 3.
body of the article.
Subsequently, each eligible article was read to fully identify the relevant data.
Only studies that met the inclusion criteria were reviewed and analyzed.
We recognized that different researchers used different case definitions for smell and taste We have therefore defined our outcome of interest as a partial or complete loss of smell, taste, or both.
Thus, the 3 outcomes examined in this systematic review were AoAopartial or complete loss of smell,AoAo AoAopartial or complete loss of taste,AoAo and AoAoconcurrent partial or complete loss of smell and taste.
AoAo We also performed sub-group analyses based on the geographical locations of the studies.
Additional records found through the reference of the articles .
= 27 ) Eligibility Screening Records after duplicates removed .
= 2593 Title and abstract of records screened .
=2.
Full-text articles assessed for eligibility .
= 695 ) Records excluded .
= 1.
Full-text articles excluded, with reasons (Reviews = 17 ) Only loss of smell .
= .
(No relevant Data= .
Included Studies included in qualitative synthesis .
= 125 ) Studies included in quantitative synthesis .
eta-analysi.
Loss of smell and taste, n = .
Figure 1.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram for study selection and exclusion.
Mohadeseh Poudineh Inclusion and Exclusion Criteria We have included studies that investigated or described the follow-up duration, recovery rate, and time to recovery of loss of smell and taste in patients with the diagnosis of COVID-19.
Only studies that confirmed the diagnosis of COVID-19 by a positive result of RT-PCR were included.
Olfactory and gustatory dysfunction were assessed by either subjective evaluation .
self-report questionnaires or survey.
or objective test .
, smell, taste identification, or threshold tes.
We also included studies that reported complete or only partial recovery by subjective evaluation .
, self-report questionnaires or survey.
or objective test .
, smell or taste identification test or threshold tes.
Conversely, studies that were published as letters to the editor, conference proceedings, and editorials, as well as animal studies, were excluded.
Quality Appraisal Assessment:
The Joanna Briggs Institute (JBI) quality appraisal checklists indicated that 65 of the included studies were rated good, while 56 were of fair quality.
Four reviewers separately reviewed the titles and abstracts to provide full-text reviews of the studies.
The quality of the studies was evaluated using the standard assessment criteria of the Joanna Briggs Institute (JBI) https://jbi.
global/criticalappraisal-tools in cohort and cross-sectional studies and case series .
ample of check list in Supplementary .
The following elements were used: .
appropriateness of inclusion criteria.
description of study subject and setting.
valid and reliable measurement of exposure.
objective, standard criteria.
identification of .
strategies for handling .
outcome measurement.
appropriateness of statistical analysis.
Studies of the quality scale that exceeded 70% and higher were considered as low risk of bias.
Any disparities were resolved by consensus.
Acta Med Indones-Indones J Intern Med Statistical Analysis The extracted data were entered into Microsoft Excel and analyzed using Stata/ SE 16 for Windows (StataCorp LP).
The included studies were subjected to metaanalysis.
We used the random-meta-analysis model of weighted inverse variances to obtain an overall summary assessment of the prevalence across studies.
A sensitivity analysis for the consistency of the summary estimate was conducted.
The publication bias was assessed using funnel plots and EggerAos linear regression test.
The I 2 statistics also measured the heterogeneity of the studies.
In addition, publication bias was investigated using the trim-and-fill analysis .
unnel plot.
RESULTS
A total of 3822 articles were identified through literature searches.
After removing duplicates, 2593 articles were screened by title and abstract, and 126 were found to be eligible for full-text assessment.
these full-text articles, 56 studies with a total of 42084 COVID-19 patients were qualified for meta-analysis (Figure .
Table 2 demonstrates the characteristics of the included studies.
Characteristics of COVID-19 Patients with Loss of Taste Sixty-two publications that reported data on loss of taste were used to estimate patients' recovery rate with 13700 COVID-19 patients.
Accordingly, the time to recovery of loss of taste among COVID-19 patients ranged from 2A0.
6 A 28.
5 days.
Recovery Rate Duration of Loss of Taste in COVID-19 Patients The recovery rate of loss of taste among COVID-19 patients ranged from 0%.
in Le Bon, al to 100%.
In Khodeir et al.
The estimated overall pooled recovery rate of loss of taste among COVID-19 patients was 0.
CI )0.
69, 0.
78(].
(Figure 2 and .
Vol 57 A Number 1 A January 2025 Olfactory and Gustatory Recovery Time Evaluation of COVID-19 Table 2.
A review of the studies about olfactory dysfunction in COVID-19 Authors Country Time Gender Design Lechien, et al Europe 154/357 Cohort study Klopfenstein, et al.
France 18/54 Cohort study Beltran, et al.
Spain
19/31
Case-control Viara, et al.
Italy 27/72 Cohort study Viara, et al.
Italy 146/345 Cohort study Lechian, et al.
Belgium
30/86
Cohort study Kosugi, et al.
Brazil
68/145
Cohort study DellAoEra, et al.
Italy 115/237 Cross-sectional Paderno, et al.
Italy 138/283 Cross-sectional Meini et al.
Suardi .
Italy 28/42 Cohort study Freni, et al.
Italy 30/50 Cohort study Sakalli, et al.
Turkey
44/88
Cohort study Cervilla, et al.
Spain
7/51
Cohort study Paderno et al.
Italy 56/151 Cohort study DAoAscanio, et Italy 8/19 Case-control n Main outcomes Quality Quality n 85.
6% reported olfactory 88% gustatory Olfactory dysfunction 10/11 (OD) preceded other symptoms 8% of cases.
Early olfactory recovery rate was 44%, with females more affected.
n 47% reported anosmia .
ean duration: 8.
9 day.
11/11
recovered within 28 days.
Dysgeusia observed in 85%.
n Smell/taste disorders (STD.
were significantly higher in 8/10 younger COVID-19 patients.
Mean duration was 7.
5 days, with 40% showing complete recovery.
6% had chemosensitive Recovery varied based 10/11 on age and symptom onset time.
2% self-reported chemosensitive dysfunction.
25% had long-lasting symptoms.
10/11
Duration correlated with severe COVID-19 outcomes.
4% reported anosmia.
objective testing found 47.
11/11
anosmic and 14% hyposmic.
correlation with nasal obstruction.
n COVID-positive patients had lower recovery rates .
7/11
and longer recovery durations .
edian 15 day.
n 70% prevalence of smell/taste Median recovery time:
10 days.
5% fully recovered by 14 days.
n OD/GD prevalence was 56%-63% recovery rates around 52%-55%, with a mean duration of 9 days.
n 42% reported chemosensory dysfunction, with recovery mean
10/11
times of 18 and 16 days for OD and GD, respectively.
n 92% had olfactory dysfunction, 70% gustatory dysfunction.
11/11
Significant differences noted in related quality-of-life scores.
2% reported anosmia.
Mean recovery times: 10/11 8 days for both.
n Subjective loss of smell was objective testing 6/11 confirmed 22% olfactory n OD and GD observed in 83O% of subjects.
Resolution rates 10/11 at 30 days: 87% (OD) and 82% (GD).
n Outpatients reported higher olfactory dysfunction rates.
Most 7/10 recovered within 30 days.
Mohadeseh Poudineh NinchritzBecerra.
SorianoReixach .
Spain
380/1043
29/59
Cross-sectional Yan, et al.
Salmon Ceron.
France et al.
24/55
Cohort study Jalessi, et al.
Iran
13/22
Cohort study Parente-Arias, et al.
Spain
53/151
Cohort study Barillari, et al.
Italy 90/179 Cohort study Le Bon, et.
Belgium
23/72
Cohort study Spadera et al.
Italy 76/180 Case-control Cocco, et al.
Italy 41/78 Case-control Boscolo-Rizzo.
Italy et al.
84/187
Cross-sectional Fjaeldstad, et
Denmark
21/100
Cohort study Cho, et al.
China
48/83
cross-sectional Brandauo Neto.
Brazil et al.
231/655
Cohort study ChiesaEstomba,et al.
France 274/751 Cohort study Hao Lv, et al.
China
25/39
Cohort study Otte et al, .
46/91 Al-Ani and Acharya .
14/19 Cross-sectional Amer, et al.
Egypt
40/96
Cohort study KarimiGalougah, et
Iran
31/76
cross-sectional Chary.
Carsuzaa .
France 19/81 Cohort study Acta Med Indones-Indones J Intern Med Germany Qatar n 79.
2% reported OD.
8% GD.
Females more affected.
recovered within 4 weeks.
10/11
n Smell/taste loss strongly associated with COVID-19 Recovery noted in 74% with illness resolution.
n Loss of smell was the first
11/11
symptom in many cases.
recovered partially within 15 days.
9% reported OD.
Recovery 10/11 observed in all but one patient.
n OD reported by 49.
GD by 3% recovered within 2 10/11 n 70.
4% reported OD and 59.
GD.
Smell dysfunction preceded 10/11 symptoms in 11.
n 37% had persistent OD after 37 Longer anosmia duration 9/11 correlated with lower olfactory n 46.
7% reported OD as initial 9/10 7% had OD as the only symptom.
n STD reported in 74.
3% of patients, more frequent in women .
%) compared to men .
%).
n Patients with STD were 10 years 6/10 younger on average than those without STD.
n Recovery rates within 20 days:
3%) and taste .
3%).
n At 4 weeks, 48.
7% completely resolved symptoms.
n Recovery rates: 44% for OD and 11/11 50% for GD after 30 days.
n OD recovery: 71.
recovery: 83.
Mean recovery times: 10.
3 days for smell, 9.
days for taste.
4% reported OD.
10/11
rates were 53.
8% .
and 7% .
after 2 months.
n 83% reported anosmia.
7/11
rates: 49% complete, 37% persistent after 47 days.
9% reported OD/GD.
10/11
took >4 weeks in 51.
1% tested hyposmic at 8 Self-assessments poorly 11/11 matched objective tests.
n Recovery within 6.
89 days for smell/taste dysfunctions.
n 83% reported sudden anosmia.
8/11
recovery patterns: 33.
3% full, 7% partial.
n Sudden anosmia reported by recovery observed in 3% .
n 64% fully recovered within 15
10/11
Vol 57 A Number 1 A January 2025 Olfactory and Gustatory Recovery Time Evaluation of COVID-19 Moein, et al.
Iran
58/82
Cohort study Iannuzzi, et al.
Italy 14/30 Cohort study Konstantinidis, et al.
Greece 16/30 Case-control Panda, et al.
India
159/225
systematic rev.
&meta-analysis Klein, et al.
Israel
72/112
Cohort study Schynegger, et al.
Austria case series Al-Zaidi, et al.
Iraq
24/58
Cohort study Sheng, et al.
Taiwan 26/78 Cross-sectional Samimi Ardestani.
H, et al.
Iran
155/207
Cross-sectional Kacem.
Tunisia
348/646
Luers, et al.
Germany Gorzkowski et France Andrews et al.
Pendolino .
n Olfactory dysfunction persisted for 37% but improved over time.
n TDI scores improved significantly after 1 month.
no anosmia n Two recovery types: rapid full recovery or slow partial recovery.
n Recovery rates: Anosmia: 53.
at 2 weeks, 96% by 4 weeks.
n Smell/taste symptoms lasted 18 days.
46% had persistent symptoms at 6 months.
n Dysosmia/dysgeusia occurred early but no neuroinvasiveness n Recovery of smell/taste dysfunction within 1-3 weeks for most cases.
n Recovery within 3 weeks for median recovery time: 12
11/11
7/11
9/10
11/11
10/11
10/10
10/11
4% recovered from OD within 1 month.
Retrospective Cohort study n OD reported in 37.
rate: 72.
10/11
41/72
Cross-sectional 51/140 Cohort study 10/11 28/114 Case-control
9/10
Matt Lechner
301/1039
Case-control
10/10
Horvath et al.
Australia
41/102
Retrospective cohort study 10/11 Ugurlu, et al.
Turkey
19/42
Cross-sectional Yadav et al.
India
78/152
11/11
Bulgurcu, ynztutgan .
Turkey
222/418
Cross-sectional n Symptoms peaked within 6Ae22 days, incubation time: 3 days.
n Recovery started in 11.
6 days.
4% fully recovered.
8% fully recovered OD.
recovery negatively influenced by job role.
3% reported smell/taste loss, 5% had ongoing symptoms.
n 74% reported smell/taste loss.
34% had ongoing hyposmia.
n Recovery rates: 85.
7% fully recovered by 3 months.
n Complete recovery of OD and dysgeusia in all patients.
n Recovery rates: 95%-100% for smell/taste dysfunctions.
MandiNRajseviN et al, .
Italy 73/172 Case series n Recovery took 23Ae41 days for healthcare workers.
8/10
Sahoo et al.
India
65/77
Case-control n 92%-96% recovered OD/GD within 14 days.
9/10
Kumar et al.
10/34
Cohort study n A.
10/11
Dal.
Akcan
Turkey
4/14
Cross-sectional Lechien, et al.
Italy 478/1363 Case-control
10/10
Niklassen et
Turkey
59/111
cohort study 10/11 n 19.
7% of patients had anosmia.
recovery time ranged from 1Ae14 days, with 42.
8% recovering within 9Ae14 days.
n Olfactory dysfunction (OD) prevalence was significantly higher in mild cases .
compared to moderate-severe cases .
5%-6.
9%).
3% had persistent OD at 60 days.
n 21% were anosmic, 49% hyposmic, and 30% normosmic during infection.
Only 1% remained anosmic post-infection.
Mohadeseh Poudineh Acta Med Indones-Indones J Intern Med Man.
Nima .
Iran
551/561
case-series Sun.
Wang .
China
375/932
case-series AntolynAmyrigo.
Cubero .
Spain
62/234
case-series Koul.
Begh .
India
222/300
case-series Gupta.
Banavara Rajanna .
India
OD:113/167
Case-control GD:
100/153
Klein.
Asseo
Israel
64/144
Abbas.
Tahir Ghulam .
Pakistan OD: 73/130 Cross-sectional OG: 78/116 study Aknc, et al Cross-sectional Akram, et al.
Bangladesh 2021
63/75
Cross-sectional Al-Rawi , et al.
United Arab Emirats OD:
138/220
OG:
138/215
Cross-sectional Alghatani, et
Saudi Arabia
OD: 241/
OG: 212/
Cross-sectional Al Radini, et Saudi Arabia Cross-sectional Al Shakhs, et Saudi Arabia Cross-sectional Amin, et al.
Bangladesh 2021 Turkey OD:
181/218
OG:
201/281
Cohort study Cross-sectional n 64.
3% had smell and taste partial/full recovery 9/10 occurred in 95.
2% after 8 weeks 3% after 16 weeks.
n Smell/taste disturbances were infrequent .
2%-3.
1%) but 10/10 resolved in most patients by 3 months post-hospitalization.
4% reported taste and smell
mean recovery time
8/10
was longer for patients over 55 n 53% reported olfactory/gustatory 9/10 dysfunction within 5 days of testing positive for COVID-19.
15% reported OD, and 53% reported GD.
Recovery 9/10 rates were high .
%) within 4-6 n Taste and smell changes were the longest-lasting symptoms, 11/11 with durations of 17Ae19 days.
46% had unresolved symptoms at 6 months.
n Anosmia and ageusia occurred 1% and 43.
8% of patients, with a median recovery time of 8Ae8.
5 days.
9% reported persistent smell/ taste dysfunction at 3 months.
headaches were significantly associated with persistence.
n Smell and taste recovery occurred in 63% of patients within a week, 20% within two weeks, and 17% in three weeks.
n Extreme reductions in taste and smell were more frequent in younger individuals.
Recovery patterns differed by symptom n Anosmia was reported in 8%, and ageusia in 26.
Female sex was associated with increased incidence and n Loss of smell and taste were experienced in approximately 5% of cases as late symptoms .
ost-COVID conditio.
n Most common ENT-related symptoms included insomnia .
3%), headache .
%), and dysgeusia .
6%).
Symptoms affected daily activities n Symptoms: Fever, exhaustion, cough, loss of taste, sore throat, body ache, and hair loss common in >50% of patients.
n Shortness of breath: Higher in males (OR 1.
, significantly associated with comorbidities and age >40.
n Recovery time influenced by age and comorbidities.
Fair Good Good Good Good Fair Good Vol 57 A Number 1 A January 2025 Olfactory and Gustatory Recovery Time Evaluation of COVID-19 Jungbauer, et Zifko, et al.
Austria
44/82
Cross-sectional Bhatta, et al.
India
101/188
Cross-sectional Lee, et al.
Canad/ Israel
149/350
Cross-sectional Aydemir, et al.
Turkey
86/133
Cohort Study Kumar, et al.
India
10/34
Cohort Study Lal , et al.
India
144/435
Cohort Study Chaturvedi, et
India
94/153
Cross-sectional Reis , et al.
Brazil
68/305
Cross-sectional Ramasamy, et
Malaysia
90/145
Cross-sectional Ciofalo, et al.
Italy 17/44 Cohort study Sehanobish, et United .
States 261/486 Cohort study Bhatta, et al.
India
337/600
Cohort Syudy Elvan-Tuz, et
Turkey
410/1053
Cohort Study Fisher, et al.
Israel 1 female Case Report Germany Cross-sectional n Subjective hyposmia and hypogeusia were rare and associated with nasal obstruction.
n Useful diagnostic markers for SARS-CoV-2 infection.
n 83% experienced neurological symptoms, including loss of taste .
%) and smell .
%).
n Women more often had central/ neuromuscular symptoms.
was the most common symptom.
n Anosmia or hyposmia in 63.
ageusia or hypogeusia in 63.
n Symptom resolution longest for breathing difficulty .
6 days in ICU patients, 8.
2 days in nonICU).
n Chemosensory dysfunction prevalence: 47.
1%, higher in Canadians .
7%) than Israelis .
4%).
n Majority recovered sense of smell within 4 weeks.
n Olfactory dysfunction .
and taste impairment .
8%) not associated with disease severity.
4% experienced olfactory or taste dysfunction, lasting 2Ae15 days .
7 day.
n Olfactory/gustatory dysfunction:
recovery took 12.
8 days .
on average.
n Females more affected.
symptoms were rare.
n Olfactory/gustatory disorders reported in 55% of patients.
recovery in younger individuals .
Ae10 day.
n OD: 72.
TD: 67.
4% at 45% and 50%, respectively, persisted after 6 n Positive correlation between age and OD.
4% reported OD, 23.
5% recovered completely within 7 days.
n Recovery: 90.
6% with normosmia within 28 days.
mean recovery time: 22.
9 days .
and 9 days .
n Anosmia and ageusia were more common in younger patients and those with low eosinophil counts.
n OD: 60.
TD: 28.
anosmia cases improved by 4 n Anosmia in 12.
5% of cases, often accompanied by ageusia .
%).
4% persisted after one month.
n Early convalescent plasma therapy accelerated recovery of taste and smell.
Good
Good
Good
Good
10/11
Good
11/11
Good
9/11
Good
Good
Good
Good
11/11
Good
11/11
Good
10/11
Good
10/11
Good Fair Mohadeseh Poudineh Acta Med Indones-Indones J Intern Med Goyal, et al.
India Mendonca , et Brazil Sagar, et al.
India Case-control Study Vahey, et al.
United States 187/364 Cohort Study Hosseininasab.
Iran et al.
9/20
Case-control Study Tham , et al.
Singapore 99/134 Cross-sectional Study Fisher, et al.
United States Silva, et al.
Brazil
63/166
Cross-sectional Kumar, et al.
India
51/68
Observational Mubaraki, et al.
Saudi .
Arabia
406/542
Cohort study Armange, et al.
France .
124/311 Cohort study Faycal, et al.
France 118/429 Cohort study Antolyn 101 Amyrigo, et al.
Spain OD: 41/160 Observational OG: 26/132 Study Arshad, et al.
Korea
88/207
Cross-sectional Babaei, et al.
Iran
131/235
Retrospective Bakhshaee, et
Iran
86/178
Cross-sectional Biadsee, et al.
Israel
OD: 18/65
OG: 19/65
Cross-sectional Celikoyar, et al.
Turkey
10/20
Cross-sectional Inciarte, et al.
Spain
34/59
Cohort Study Jalessi, et al.
Iran
OD: 76/200
Cohort Study OG: 99/269 Cross-sectional Case-control Prospective n Loss of smell: 34.
loss of 10/11 taste: 46.
most recovered within 2 weeks.
n Olfactory dysfunction more prevalent in mild cases (Odds Ratio 4.
symptoms lasted 9 days to 2 months.
n All 6 otolaryngologists had OD and GD.
recovery ranged from 4 9/10 weeks to 3 months.
n Anosmia and ageusia associated with non-hospitalization.
10/11
symptoms occurred later in the disease course.
n OD and GD were early symptoms in 20%.
85% persisted during the 10/10 n OD prevalence: 12.
associated with blocked nose, female gender, and absence of n OD/TD reported by 63% of 9/10 COVID-19 cases.
persisted for >14 days in 50%.
n COVID-19 patients showed significantly higher rates of OD .
%) and TD .
%) than other respiratory syndromes.
n Anosmia in 30%, ageusia in 66%.
11/11
97% recovered within 2 weeks.
n OD: 53%, ageusia: 51.
younger age and female gender
10/11
linked to higher prevalence and faster recovery.
n At 6 weeks, 53.
7% recovered.
9/11
9% ageusia and 16.
anosmia cases persisted.
n Persistent symptoms in 46.
11/11
at day 30 and 6.
5% at day 60, including anosmia and ageusia.
n STD prevalence: 74.
time longer for older patients (>55 10/11 n 81% reported OD/TD.
recovery in most cases within 1Ae2 weeks.
n Anosmia recovery at 4 weeks:
associated with smoking, 10/11 ageusia, and nasal discharge.
n OD in 38.
4% of patients.
recovered within 2 weeks to 1 n 52% reported full recovery of OD.
complete recovery correlated with 7/8 GD recovery.
n 95% recovered from OD/TD within 2 weeks.
n Chemosensory dysfunction prevalence: 73.
recovery rate: 11/11 85% by day 45.
2% reported complete recovery of OD within 21 days.
10/11
recovery slower with rhinological Good Good Good Good Good Good Good Good Good Good Good Good Good Fair Good Good Good Fair Good Good Vol 57 A Number 1 A January 2025 Olfactory and Gustatory Recovery Time Evaluation of COVID-19 Prospective Juvekar, et al.
India Kandakure, et India Karthikeyan, et India Cross-sectional Khodeir, et al.
Cross-sectional Makaronidis, et United .
Kingdom Panda, et al.
India Prospective cohort study Polat, et al.
Turkey Clinical study Printza, et al.
Greece Sagar, et al.
India ahin, et al.
Turkey Sbrana, et al.
Brazil
Saudi Arabia
OD: 6/9
OG: 8/14
110/381
33/57
Observational Cohort study Cross-sectional Cohort study OD: 5/18 OG: 5/18 Cross-sectional Cross-sectional OD:
323/436
OG:
332/436
Schwab, et al.
United Kingdom Shahid, et al.
Pakistan Teaima, et al.
Egypt
328/1031
Prospective Thakur,et al.
India
105/179
Prospective Valletta, et al.
Brazil
125/330
Descriptive.
Yadav, et al.
India Cohort study Retrospective Prospective n Anosmia and ageusia in 88% 10/11 3%, respectively.
recovered within 2Ae3 weeks.
n Anosmia/ageusia recovery within 14Ae21 days in most cases, except 10/11 two long-term anosmia cases.
n Smell disturbance in 74.
recovery took 9.
89 days on n Loss of smell .
%) and taste .
%) were the most severe symptoms among sensory n Smell and taste recovery rates 9/11 lower in antibody-positive n Recovery rates for anosmia/ dysgeusia: 96% by 4 weeks.
10/11
incidence lower than in Western n Anosmia more common in 11/13 no correlation with n 88% recovered from OD by 2 moderate hyposmia resolved faster than severe n 80% reported OD, 84% GD.
10/11
recovery faster in vaccinated n OD/TD prevalence: 10.
smokers had higher rates of GD.
n OD prevalence: 83.
higher in healthcare workers exposed to COVID-19 patients.
n Recovery rates: 55% (GD) and 8% (OD) after 2 months.
10/11
females showed better GD n Sudden onset anosmia in 58.
hypogeusia in 53.
n Anosmia/ageusia in 50.
recovery within 2 weeks for most n OD in 71.
majority recovered within 1Ae2 weeks.
n OD onset within 5 days in 70% of cases.
higher prevalence in n OD in 18.
GD in 13.
mean symptom duration: 2.
Good
Good
Good
Good
Good
Good
Good
Good
Good
Good
Good
Good
6/11
Fair
7/11
Fair
10/11
Good
Good
9/11
Good Mohadeseh Poudineh Acta Med Indones-Indones J Intern Med Study ES .
% CI) Weight Konstantinidis, et al 90 .
78, 1.
Sahoo et al 97 .
94, 1.
Chary et al.
54, 0.
Fjaeldstad, et al 48 .
38, 0.
Le Bon, et.
00 (-0.
09, 0.
Al-Zaidi, et al 20 .
10, 0.
Cho, et 00 .
99, 1.
Yan, et al 70 .
56, 0.
Freni, et al 89 .
78, 0.
Karimi-Galougah, et al 41 .
29, 0.
Sakalli, et al 23 .
14, 0.
Gorzkowski et al 65 .
56, 0.
Gupta et al.
94, 1.
DellAoEra, et al 67 .
60, 0.
Paderno, et al 55 .
50, 0.
Bulgurcu et al.
28, 0.
Man amanat et al.
43, 0.
Lal , et al.
87, 1.
Ramasamy, et al.
55, 0.
Sehanobish, et al.
75, 0.
Armange, et al.
85, 0.
Faycal, et al.
63, 0.
Aknc.
62, 0.
Bhatta , et al.
91, 1.
Aydemir, et al.
93, 1.
Kumar, et al.
82, 1.
Al Shakhs, et al.
68, 0.
Al-Rawi , et al.
52, 0.
Amin, et al.
98, 1.
Panda et al.
92, 1.
Yadav et al.
98, 1.
Makaronidis et al.
61, 0.
Alghatani, et al.
55, 0.
Chaturvedi, et al.
82, 0.
Sagar, et al.
93, 1.
Printza et al.
68, 0.
Sbrana et al.
61, 0.
Schwab et al.
50, 0.
Biadsee et al.
99, 1.
Inciarte et al.
81, 0.
Kandakure et al.
97, 1.
Akram, et al.
99, 1.
Reis , et al.
43, 0.
Juvekar et al.
78, 0.
Teaima et al.
63, 0.
ahin et al.
74, 1.
Sagar et al.
86, 1.
Khodeir et al.
96, 0.
Fisher, et al.
61, 1.
Beltran 39 .
22, 0.
Viara, et al 1 66 .
53, 0.
Viara, et al 2 97 .
95, 0.
Paderno et al 84 .
78, 0.
Boscolo-Rizzo, et al 76 .
68, 0.
Hao Lv, et al 90 .
80, 0.
Panda, et al 96 .
94, 0.
Meini et al, 66 .
51, 0.
Andrews et al 45 .
35, 0.
Matt Lechner 51 .
47, 0.
Horvath et al 37 .
25, 0.
Sun et al.
16, 0.
Kacem 79 .
74, 0.
Overall (I-squared = 98.
9%, p = 0.
69, 0.
NOTE: Weights are from random effects analysis Figure 2.
Forest plot for recovery rate of gustatory dysfunction in COVID-19 patients.
Vol 57 A Number 1 A January 2025 Olfactory and Gustatory Recovery Time Evaluation of COVID-19 se(ES) Funnel plot with pseudo 95% confidence limits Figure 3.
Funnel plots for recovery rate of gustatory dysfunction in COVID-19 patients Time to Recovery of Loss of Taste in COVID-19 Patients Fifteen publications that reported data on loss of taste were used to estimate the time to recovery in COVID-19 patients.
Accordingly, the time to recover the loss of taste among COVID-19 patients ranged from 2.
% CI )2.
29, 2.
60(].
in Yadav et al.
% CI )10.
43, 32.
77(].
Zifko et al.
The estimated overall pooled time to recover loss of taste among COVID-19 patients 44 days .
% CI 8.
11, 14.
77(].
(Figure .
Sensitivity Analysis The sensitivity analysis of 62 studies that reported data on loss of taste is shown in Figure The sensitivity analysis of the data showed that the effect sizes of the studies are not affected by the studies individually.
Hence, by omitting each of the included studies the significance of the results did not change.
Assessment of Publication Bias Although the distribution of the 62 studies that reported the loss of taste appeared asymmetrical, there were more studies on the left side of the vertical middle line (Figure .
, and Begg and EggerAos test suggested that there was no statistically significant publication bias (Prob > .
= 0.
Characteristics of COVID-19 Patients with Loss of Smell Ninty publications that reported data on loss of smell were used to estimate patients' recovery rate with 20027 COVID-19 patients.
Accordingly, the time to recovery of loss of smell among COVID-19 patients ranged from 44A0.
352 to 31.
9 A 30.
7 days.
Recovery Rate Duration of Loss of Smell in COVID-19 Patients The recovery rate of loss of smell among COVID-19 patients ranged from 4% in Le Bon, et.
al to 100%in Khodeir et al studies.
The estimated overall pooled recovery rate of loss of smell among COVID-19 patients was 0.
CI )0.
69, 0.
75(].
(Supplementary material 2 and Figure .
Mohadeseh Poudineh Acta Med Indones-Indones J Intern Med Study ES .
% CI) Weight Cho, et 50 .
07, 11.
Sakalli, et al 20 .
66, 9.
Paderno, et al 00 .
45, 9.
Lal , et al.
74, 12.
Silva, et al.
29, 10.
Aydemir, et al.
64, 6.
Bhatta, et al.
02, 13.
Mubaraki, et al.
62, 11.
Zifko, 60 .
43, 32.
Yadav et al.
29, 2.
Printza et al.
95, 16.
Antolyn Amyrigo et al.
80, 30.
ahin et al.
62, 22.
Khodeir et al.
52, 15.
Beltran 40 .
59, 8.
Overall (I-squared = 99.
8%, p = 0.
11, 14.
NOTE: Weights are from random effects analysis Figure 4.
Forest plot for time to recovery in COVID-19 patients with gustatory loss Time to Recovery of Loss of Smell in COVID-19 Patients Twenty-one publications that reported data on loss of smell were used to estimate the time to recovery in COVID-19 patients.
Accordingly, the time to recover the loss of smell among COVID-19 patients ranged from 2.
CI)2.
31, 2.
57(].
in Yadav et al.
CI)15.
67, 41.
33(].
in Zifko et al.
The estimated overall pooled time to recover loss of smell among COVID-19 patients were 12.
87 days .
% CI)1011, 15.
(Figure .
Sensitivity Analysis The sensitivity analysis of 90 studies that reported data on loss of taste is shown in Figure The sensitivity analysis of the data showed that the effect sizes of the studies are not affected by the studies individually.
Hence, by omitting each of the included studies the significance of the results did not change.
(Figure .
Assessment of Publication Bias Although the distribution of the eleven studies that reported the loss of taste appears asymmetrical, there were more studies on the right side of the vertical middle line (Figure .
, and Begg and EggerAos test suggested that there was no statistically significant publication bias (Prob > .
= 0.
(Figure .
DISCUSSION
Among 125 studies with a total of 42084 COVID-19 patients from 31 countries meeting for meta-analysis, there were 15 studies that evaluated the time to recovery of loss of taste.
The time to recover the loss of taste among COVID-19 patients in these studies ranged from 44 days .
% CI .
29, 2.
] in Yadav et al.
60 days.
% CI .
43, 32.
] in Zifko et al.
81 This variation in time to recovery might indicate a correlation between the severity of Vol 57 A Number 1 A January 2025 Olfactory and Gustatory Recovery Time Evaluation of COVID-19 -----------------------------------------------------------------------------.
% Conf.
Interva.
Study omitted Estimate ------------------- ---------------------------------------------------------Abbas, et al.
Aknc.
Akram, et al.
Al-Rawi , et al.
| .
Alghatani, et al.
| .
Al Radini, et al.
| .
Al Shakhs, et al.
| .
Amanat, et al.
Amin, et al.
Jungbauer, et al.
Zifko.
Bhatta , et al.
Lee, et al.
Aydemir, et al.
Kumar, et al.
Lal , et al.
Chaturvedi, et al.
Reis , et al.
Ramasamy, et al.
Ciofalo, et al Sehanobish, et al.
Bhatta, et al.
Elvan-Tuz, et al.
Fisher, et al.
Mendonca , et al.
Sagar, et al.
Vahey, et al.
Hosseininasab, et al.
Tham , et al.
Fisher, et al.
Silva, et al.
Mubaraki, et al.
Armange, et al.
Faycal, et al.
Antolyn Amyrigo et al.
Arifa et al.
Arshad et al.
Babaei et al.
Bakhshaee et al.
| .
Biadsee et al.
Celikoyar et al.
| .
Inciarte et al.
| .
Jalessi et al.
Juvekar et al.
| .
Kandakure et al.
Karthikeyan et al.
Khodeir et al.
| .
Makaronidis et al.
Panda et al.
Polat et al.
Printza et al.
| .
Sagar et al.
ahin et al.
Sbrana et al.
Schwab et al.
Shahid et al.
Sheng et al.
Teaima et al.
Thakur et al.
Valletta et al.
| .
Yadav et al.
Lechien, et al Yan, et al Klopfenstein, et a.
Beltran Viara, et al 1 Viara, et al 2 DellAoEra, et al Paderno, et al Freni, et al Sakalli, et al Paderno et al Gorzkowski et al | Boscolo-Rizzo, et a.
Salmon Ceron, et a.
Jalessi, et al Parente-Arias, et a.
Barillari, et al | Fjaeldstad, et al | Le Bon, et.
Spadera et al Moein, et al Cho, et Brandauo Neto, et a.
Hao Lv, et al Karimi-Galougah, et a.
Konstantinidis, et a.
Panda, et al Klein, et al Al-Zaidi, et al Meini et al.
Otte et al Ninchritz-Becerra | Andrews et al Matt Lechner Horvath et al Sahoo et al Lechien, et al Niklassen et al Man amanat et al.
Sun et al.
Amerigo et al.
Samimi et al.
Kacem Gupta et al.
Chary et al.
Bulgurcu et al.
------------------- ---------------------------------------------------------Combined ------------------------------------------------------------------------------ Figure 5.
Sensitivity analysis for the recovery rate of COVID-19 patients with gustatory loss gustatory dysfunction and the severity of patients' COVID 19 illness.
The estimated overall pooled time to recover loss of taste among COVID-19 patients was 11.
44 days .
% CI .
11, 14.
This might be due to the fact that the viral load of the virus in the pharynx remains high for a Furthermore, the rapid recovery of taste dysfunction in COVID-19 patients can result from the fast turnover of the taste receptor cells within 7 to 10 days.
The recovery rate of loss of taste among COVID-19 patients ranged from 0% in Le Bon, al .
to 100% in Khodeir et al.
118 studies.
This study estimated the overall pooled recovery rate of loss of taste among COVID-19 patients 74.
% CI )0.
69, 0.
78(].
This high recovery rate supports the potential role of regenerable taste sensory receptors in COVID-19 patients.
It is well known that a complex mechanism that involves G-protein coupled receptors and sodium channels in the taste buds are blocked with ACE2-inhibitors and, as a result, causes taste dysfunction.
Although studies manifested a high possibility of recovery from taste dysfunction, there is insufficient evidence concerning the long-term prognosis of gustatory dysfunction in COVID-19 patients.
Ninety publications reported data on loss of smell were used to estimate patients' recovery rate with 20027 COVID-19 patients.
The estimated overall pooled time to recover loss of smell among COVID-19 patients was 12.
87 days .
% CI .
1, 15.
] in this study, which is more than the time to recovery of loss of smell reported in another systematic review by Agyeman et According to Agyeman's analysis, the mean time of recovery from olfactory disorders is 7.
132 The difference could be due to the fewer number of the included studies in the mentioned systematic review.
However, these results should be treated with caution.
as the time to recovery depends on the severity of the olfactory disorder.
and patients with moderate hyposmia had a quicker recovery compared with patients with more severe olfactory dysfunction on a wider research is also necessary to determine the predisposing factors for developing long term olfactory dysfunctions.
The mean recovery rate of loss of smell as Mohadeseh Poudineh Acta Med Indones-Indones J Intern Med Tests for Publication Bias Begg's Test Kendall's Score (P-Q) = Std.
Dev.
of Score = Number of Studies = Pr > .
= Pr > .
= 63 .
orrected for tie.
ontinuity correcte.
ontinuity correcte.
Egger's test Std_Eff Coef.
Std.
Err.
P>.
% Conf.
Interva.
Figure 6.
Publication bias assessment for gustatory dysfunction se(ES) Funnel plot with pseudo 95% confidence limits Figure 7.
Funnel plots for recovery rate of olfactory dysfunction in COVID-19 patients.
measured by the current study, was 0.
CI .
69, 0.
However, the pathophysiology remains unrecognized.
To the best of our knowledge, there are clues on possible injury to neural and/or olfactory epithelial cells.
It may be assumed that COVID-19 infects olfactory epithelium via ACE-2 receptors that are expressed mainly on sustentacular cells.
However, there is a reasonable probability that conductive olfactory dysfunction due to inflammatory changes in olfactory cleft mucosa could also be responsible for hyposmia.
Vol 57 A Number 1 A January 2025 Olfactory and Gustatory Recovery Time Evaluation of COVID-19 Study ES .
% CI) Weight Jalessi, et al 73 .
28, 14.
Klopfenstein, et al 90 .
22, 10.
Cho, et 30 .
76, 12.
Sakalli, et al 02 .
68, 9.
Paderno, et al 00 .
42, 9.
Lal , et al.
55, 14.
Silva, et al.
11, 9.
Aydemir, et al.
65, 7.
Bhatta, et al.
02, 14.
Mubaraki, et al.
98, 11.
Zifko, 50 .
67, 41.
Yadav et al.
31, 2.
Printza et al.
89, 17.
Antolyn Amyrigo et al.
27, 29.
Babaei et al.
29, 20.
ahin et al.
62, 22.
Khodeir et al.
37, 17.
Beltran 40 .
59, 8.
Parente-Arias, et al 70 .
69, 19.
Klein, et al 50 .
65, 28.
Lechien, et al 77 .
47, 10.
Overall (I-squared = 99.
8%, p = 0.
11, 15.
NOTE: Weights are from random effects analysis Figure 8.
Forest plot for time to recovery in COVID-19 patients with olfactory loss The specific pathophysiology of the olfactory dysfunction following viral infections is not thoroughly understood yet.
However, since SARS-CoV-2, like other respiratory viruses, primarily attaches and infects the respiratory epithelium, it is unsurprising that COVID-19 affects the olfactory neuro-epithelium and consequently impairs the sense of smell and 135, 136 Due to these similarities, there are no specific upper respiratory symptoms to allow COVID-19 to be distinguished from other potential viral respiratory infections.
Olfactory dysfunction is found to be associated with several other disease states, including congenital causes, post-infectious disorders, sinonasal diseases, traumatic brain injuries, and neurodegenerative disorders,137, 138.
A cause of postviral upper respiratory infection is identified to be a combined conductive and sensorineural/inflammatory disorder.
Sinonasal diseases, including allergic rhinitis or rhinosinusitis, may cause anatomic barriers to give rise to conductive and inflammatory disorders, preventing odorants from reaching the olfactory receptors.
140, 141 Smell impairment associated with disease severity is frequently reported such that a study suggested that two out of three patients with the common cold or postviral acute rhinosinusitis have impaired smell associated with disease severity.
Additionally, due to the association between long-term pharmacological treatments such as aminoglycosides, tetracycline, opioids, cannabinoids, and sildenafil and olfactory dysfunction, 20 the participants were asked about the past history of treatment with the mentioned substances.
none of the patients with olfactory dysfunction had previously used these kinds of drugs.
Other confounding factors that potentially promote the development of olfactory Mohadeseh Poudineh Acta Med Indones-Indones J Intern Med coupled receptors that can potentially trigger neuronal activity once activated .
AngiotensinAaconverting enzyme 2 (ACE.
was identified as the main receptor for the SARS-CoV-2 virus, in January 2020.
ACE 2 is a class of receptors that are commonly present on the cells of multiple human organs, such as the skeletal muscles and the central nervous system (CNS).
Because of the specified expression and distribution of ACE2, it can be deduced that the SARS-CoV-2 virus may cause some neurologic manifestations directly or indirectly due to the direct damage of cranial nerve endings or the possibility of retrograde invasion of CNS .
lfactory bulb, solitary nucleu.
Olfactory and gustatory dysfunction raise the issue of retrograde invasion of CNS.
However, no evidence of direct invasion of cranial nerves may be present.
Accordingly, olfactory and gustatory dysfunction could depend only on the damage of olfactory epithelial cells that exhibit ACE2 receptors on the surface.
Autopsy results from COVID-19 patients demonstrated that the brain tissue appeared to be hyperemic and edematous, with some neurons looking degenerated.
142, 143 In addition, previous studies have determined that SARSCoV is capable of causing neuronal death in mice through the invasion of the brain via the nose close to the olfactory epithelium.
144 Based on an experimental study, because of the high expression of ACE2 in the taste organs of the mouse.
ACE2 could potentially play an important role in the development of taste dysfunction in COVID-19 patients.
145 Similarly, in humans.
ACE2 receptors has been identified in the oral cavity with high expression level in the tongue during infection with COVID-19 .
Therefore, a possible explanation deduced from the pieces of evidence could be that the SARSCoV-2 spreads into and infects the nerve ending of the taste buds in the oral cavity resulting in gustatory dysfunction or the impairment of salty, sweet, bitter, and sour flavors.
Pure taste disorders are rarely reported, with only a 5% representation in specialized smell and taste 9, 147 -----------------------------------------------------------------------------Study omitted Estimate .
% Conf.
Interva.
------------------- ---------------------------------------------------------Abbas, et al.
Aknc.
Akram, e t al.
Al-Rawi , et al.
Alghatani, et al.
| .
Al Radini, et al.
| .
Al Shakhs, et al.
| .
Amanat, et al.
Amin, et al.
Jungbauer, et al.
Zifko.
Bhatta , et al.
Lee, et al.
Aydemir, et al.
Kumar, et al.
Lal , et al.
Chaturvedi, et al.
Reis , et al.
Ramasamy, et al.
Ciofalo, et al Sehanobish, et al.
Bhatta, et al.
Elvan-Tuz, et al.
Fisher, et al.
Mendonca , et al.
Sagar, et al.
Vahey, et al.
Hosseininasab, et al.
Tham , et al.
Fisher, et al.
Silva, et al.
Mubaraki, et al.
Armange, et al.
Faycal, et al.
Antolyn Amyrigo et al.
Arifa et al.
Arshad et al.
Babaei et al.
Bakhshaee et al.
| .
Biadsee et al.
Celikoyar et al .
| .
Inciarte et al.
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------------------- ---------------------------------------------------------Combined ------------------------------------------------------------------------------ Figure 9.
Sensitivity analysis for the recovery rate of COVID-19 patients with olfactory loss dysfunction are potassium-sparing diuretics, antiplatelet drugs, - and y-blockers, and calcium channel blockers.
In the case of potassiumsparing diuretics, it can be speculated that these drugs interfere with olfactory receptor activity since they contain a large class of G-protein- Vol 57 A Number 1 A January 2025 Olfactory and Gustatory Recovery Time Evaluation of COVID-19 Tests for Publication Bias Begg's Test Kendall's Score (P-Q) = Std.
Dev.
of Score = Number of Studies = Pr > .
= Pr > .
= 92 .
orrected for tie.
ontinuity correcte.
ontinuity correcte.
Egger's test Std_Eff Coef.
Std.
Err.
P>.
% Conf.
Interva.
Figure 10.
Publication bias assessment for olfactory dysfunction Strength of Study The strength of this systematic review lies in the large number of included studies, the population's size, and the geographical spread.
In addition, we have used both quantitative and qualitative methods to establish the validity and inclusiveness of the review.
However, no attempt was made to explore data that may explain the mechanisms or causality of loss of smell and taste in COVID-19 We used a meta-analysis approach to estimate global and regional follow-up duration, time to recovery, and recovery rate by pooling individual data from published studies.
One issue that may limit the generalization of our meta-analysis results is the statistical heterogeneity of the included studies, as demonstrated by the high variability values of greater than 80% in all the forest plots.
On visual inspection of the funnel plots, the individual study effects vary remarkably, suggesting publication bias as a possible source of the observed heterogeneity, but the sensitivity analysis showed that the confidence intervals of all the studies consistently overlapped, and the effect sizes did not vary significantly with the successive exclusion of studies.
The statistical heterogeneity in the results can be attributed to either clinical or methodological diversity or both.
The heterogeneity could have been caused by variations in the studies in the regions.
Considerable statistical variation resulting from methodological variability or outcome estimation variations indicates that not all studies included estimate the same magnitude loss of smell or taste.
Limitations Another issue that might limit our estimate's external validity and precision is follow-up duration, time to recovery, recovery rate, and the exclusion of articles not written in English.
Given the fact that our review was done during the pandemic, it was impracticable to get quick and accurate translations and interpretations of articles written in languages other than English.
Although we conducted a comprehensive literature search using bibliographic databases and gray literature sources via Google Scholar and Pubmed, some unpublished articles and those not indexed in an electronic database linked to our intended sources of gray literature may have been omitted.
Future Plan In the future, systematic reviews of smell and taste loss will need to consider the inclusion of publications written in languages other than English.
It is conceivable that specific Mohadeseh Poudineh demographic and environmental characteristics and preexisting diseases such as hypertension and diabetes may influence the follow-up duration, time to recovery, and recovery rate of loss of smell and/or taste, which were not captured in our review.
Future studies will need to consider the investigation of the possibility of these associations of different factors related to follow-up duration, time to recovery, and recovery rate of loss of smell and/or taste.
CONCLUSION
The recovery rate and time to recovery of loss of smell and taste among COVID-19 patients were high and low, respectively.
Health workers can reassure patients with their high recovery rate of loss of smell and taste in a short period.
DATA AVAILABILITY
Data is available upon request from corresponding author
ACKNOWLEDGMENTS
None to declare.
AUTHORSHIP CONTRIBUTION
Data collection: M.
Drafting manuscript: M.
Data analysis: M.
Supervision: F.
Study design: F.
Revision: M.
A,A.
CONFLICT OF INTEREST
There is no conflict of interest.
REFERENCES