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Olfactory disorders in COVID-19 patients as a prognostic factor: a systematic review

Abstract

Background

The reduction, loss, or impaired sense of smell and taste is common in patients with COVID-19. We aimed to investigate olfactory disorders (ODs) in patients with COVID-19 as a prognostic factor.

Methods

In this systematic review and meta-analysis, studies that assessed ODs in patients with COVID-19 were included. International databases, including PubMed, Embase, MEDLINE, Web of Science, and Scopus, were searched up to 20 March 2021. The random-effects model was used to combine the results of studies. Results were reported with a 95% confidence interval.

Results

In this study, out of 724 references, ten studies had the inclusion criteria. The odds of death in patients with the OD were 69% lower than in those without the ODs (OR = 0.31, 95% CI: 0.14, 0.69), and OD increased the odds of positive polymerase chain reaction (PCR) test (OR = 13.34, 95% CI: 4.2, 42.37).

Conclusions

The findings of our study showed that OD had an inverse and significant relationship with death in COVID-19 patients, and the patients with OD seemed to have a lower risk of mortality.

Background

COVID-19 is an infectious disease with a high rate of transmission and spread, which causes increased morbidity and mortality in patients. According to the studies, COVID-19 disease has various clinical symptoms, including dry cough, with or without fever, chills, sore throat and fatigue, shortness of breath, hypoxemia, and gastrointestinal symptoms such as nausea, vomiting, and diarrhea [1]. The severe form of COVID-19 can lead to death due to significant alveolar damage and progressive respiratory failure [2,3,4]. Many patients, especially those with its severe form, have underlying diseases such as high blood pressure, cardiovascular disease, chronic lung disease, diabetes, obesity, immunodeficiency, and malignancies [1].

The reduction, loss, or impaired sense of smell and taste is common in patients with COVID-19 [5,6,7,8]. Anosmia and hyposmia, the inability or reduced ability to smell, and parosmia, or the sense of unpleasant smell, are a disorder that affects 3 to 20% of the population and increases with age [9]. These patients usually have difficulty detecting olfactory and gustatory functions [10], which are often ignored by medical professionals [11]. It is noteworthy that acute anosmia usually occurs following viral infections or trauma [12].

Upper respiratory tract infection is one of the common causes of smell loss, which includes 22 to 36% of cases [13]. It is believed that the mechanism of olfactory disorder (OD) in anosmia is due to damage in the olfactory epithelium by the virus and is independent of nasal congestion [9]. It has been observed that in patients with a reduced sense of smell after infection, the volume of olfactory bulbs, which is related to olfactory function, decrease and even acts as a prognostic factor in these patients [14]. In 2020, clinicians realized that many patients with COVID-19 had experienced a decrease in the sense of smell or taste [15], and its incidence was reported to be 22 to 68% [5, 6].

A review of the reduced sense of smell following infection suggests the hypothesis that the virus may cause an inflammatory reaction in the nasal mucosa or direct damage to the olfactory neuroepithelium. However, the loss of the sense of smell in patients with COVID-19 can be significant without the presence of other rhinological symptoms or signs of inflammation. Finally, the researchers concluded that the pathological mechanism is still unknown. Still, it is most likely that the primary infection of nonolfactory nerve epithelial cells causes damage to the olfactory nerve. Decreased sense of smell and taste can be good signs and symptoms for early diagnosis of COVID-19 and the self-quarantine process. The prognosis of reduced sense of smell and taste in COVID-19 is better than in other viral infections [8]. It has been also noted that the use of sodium gluconate may improve the OD post-COVID-19 infection [16]. Considering the importance of a comprehensive investigation of COVID-19, this systematic review and meta-analysis aimed to assess olfactory and taste disorders in COVID-19 as a prognostic factor.

Methods

This systematic review and meta-analysis was conducted and reported based on the PRISMA statement [17]. This study was approved by the ethics committee of Hamadan University of Medical Sciences (IR.UMSHA.REC.1399.1010).

Eligibility criteria

All cross-sectional, case-control, and cohort studies that investigated the prognostic factors of COVID-19 disease were included in the study, regardless of the date, place, and language of publication.

Search strategy

In this study, international electronic databases including PubMed, Embase, MEDLINE, Web of Science, and Scopus were searched using a pre-designed search strategy. The following keywords were used in the search strategy: COVID-19, SARS-CoV-2, olfaction disorders, dysgeusia, mortality, intubation, intensive care unit (ICU), critical care, critical care nursing, ICU requirements, and duration of hospitalization. To access more resources, we explored the World Health Organization (WHO), the Centers for Disease Control and Prevention (CDC), the European Centre for Disease Prevention and Control (ECDC), and the website of conferences related to COVID-19. The list of sources of selected articles was reviewed, and we contacted the authors of the included studies to access the unpublished articles.

Selection of studies

Two researchers (MR and LM) were independently responsible for screening the references based on the title and abstract. Any disagreement between the researchers was resolved through negotiation or with the supervisor’s guidance.

Data extraction

After selecting the studies, the required variables such as the name of the first author, place and time of the study, type of study, sample size, demographic characteristics, and the number of patients with COVID-19 who suffered the consequences of intubation and hospitalization in the ICU were entered in an electronic checklist.

Risk of bias assessment

In this study, the Newcastle Ottawa scale (NOS) [18] was used to evaluate possible biases depending on the type of study. By this scale, in case-control/cohort studies, three domains including selection, comparability, and exposure/outcome were evaluated. In cross-sectional studies, a modified version of this scale was used, and three domains including selection, comparability, and outcome were evaluated. In this scale, each item of the mentioned domains with high quality was given a star. Overall studies with seven and more stars were low, and studies with six and lower stars were high risk of bias. The evaluation was done by two researchers (MR and LM) independently. Any disagreement between the researchers was resolved through negotiation or with the supervisor’s guidance.

The outcomes

The outcomes investigated in this study were olfactory and taste disorders in patients with COVID-19. In case-control and cross-sectional studies, the odds ratio (OR) with a 95% confidence interval of the relationship between smell or taste disorder and the prognosis of patients was extracted. In cohort studies, the relative risk (RR) or odds ratio was used to assess the relationship between olfactory and taste disorders and disease prognosis.

Also, the mean and standard deviation of the hospitalization period in patients with olfactory or taste disorders were extracted. The statistical heterogeneity among the results of the included studies was tested using the chi-square test and the quantities by I2 statistics [19].

Data analysis

Review Manager 5 and Stata 14.2 (StataCorp, TX, USA) were used for data analysis. In this study, the random-effects model was used to report the results of the meta-analysis. The results were reported with a 95% confidence interval (CI).

Results

In this systematic review, out of 724 references, ten studies finally had the inclusion criteria [20,21,22,23,24,25,26,27,28,29] (Fig. 1). The total number of participants in the included studies was 1035. Both sexes were included in the studies, and the mean age was from 39 to 67 years. As shown in Table 1, 1599 individuals in these ten studies had ODs, 1403 had gustatory disorders, and 1261 had both disorders.

Fig. 1
figure 1

PRISMA flowchart

Table 1 The characteristics of included studies

The presence of OD had a significant association with the reduced odds of death. The chance of death in patients with OD was 69% lower than in those without OD (OR = 0.31, 95% CI: 0.14, 0.69) (Fig. 2).

Fig. 2
figure 2

Forest plot for the association of OD with death in COVID-19

It was found that the odds of hospitalization in the ICU for patients with OD were 24% lower than for those without OD (OR = 0.76, 95% CI: 0.28, 2.05). However, this association was not statistically significant (Fig. 3).

Fig. 3
figure 3

Forest plot for the association of OD with hospitalization in ICU in COVID-19

Assessing the relationship between OD and PCR test positivity in COVID-19 patients showed that there is a significant association between OD and PCR test positivity (OR = 13.34, 95% CI: 4.2, 42.37) (Fig. 4).

Fig. 4
figure 4

Forest plot for the association of OD with PCR test positivity in COVID-19

It was found that the odds of hospital admission for patients with OD were 45% lower than that of patients without OD (OR = 0.55, 95% CI: 0.24–1.29). However, this relationship was not statistically significant (Fig. 5).

Fig. 5
figure 5

Forest plot for the association of OD with hospital admission in COVID-19

Discussion

The present study aimed to investigate OD in COVID-19 as a prognostic factor. In examining the relationship between OD and death in COVID-19 patients, it was found that these two variables had an inverse and significant relationship, and the patients with OD seemed to have a lower risk of mortality. Also, there was a direct and significant relationship between OD and PCR test positivity, and OD increased the risk of PCR test positivity. However, no significant association was noted between ODs with ICU hospitalization and hospital admission.

Anosmia has been described as one of the characteristic symptoms of COVID-19. It is even considered a key marker for the diagnosis of COVID-19 according to the CDC [31]. Despite having an estimated frequency of 52.7% [32] and being a clinical marker of COVID-19, there is a shortage of evidence on its relationship with the prognosis of COVID-19 [25]. The previous study associated anosmia with a mild course of COVID-19 and described an association between anosmia and an inverse probability of hospitalization [25]. In contrast, other studies have shown no significant relationship between the presence of olfactory changes and the severity of COVID-19. Indeed, some even suggested that the persistence of severe olfactory dysfunction could be associated with hospitalization after 20 days. Notably, these studies did not assess other known risk factors with the potential contribution to the outcomes [25, 30, 33].

The symptom of anosmia itself usually appears early in the infection [34,35,36], with a mean of 4.4 days after clinical onset and a mean duration of approximately 9 days, as described in a previous French study [25]. Anosmia is present in 60.9% of patients from the first day. In some cases, it has been introduced as the only symptom of the disease [35, 36]. That may be due to public health concerns, because patients with anosmia may be unaware of the condition and have a significant role in the spread of infection [37, 38].

Previous studies, in line of our results, showed that patients with anosmia had lower mortality [32, 34, 39,40,41]. These features have been independently associated with a better prognosis for COVID-19 [42,43,44,45,46,47,48,49]. Although the underlying causes of this association remain unknown, this finding could be related to different clinical manifestations.

In the previous studies, anosmia was independently associated with a higher probability of having a cough and myalgia [24, 50]. Although the pathophysiology of these symptoms is unknown, a greater frequency of systemic symptoms may be associated with an increased systemic response or viral replication and, therefore, a sign of an efficient innate immune response and a better prognosis [39, 48]. In another study, it is essential to emphasize that rhinorrhea, a common cause that can alter smell, was not significantly associated with anosmia [34]. Although anosmia has been associated with rhinorrhea and dysgeusia [25, 48] and myalgia [30], some experts believe that dysgeusia may be caused by an OD rather than affecting taste [51].

In different studies, it has also been stated that patients with anosmia had higher regulated levels of lymphocytes and hemoglobin, and lower levels of d-dimer at admission [24, 52]. The results also showed a higher hospitalization period, lymphocytes, hemoglobin, and glomerular filtration rate levels and lower d-dimer and C-reactive protein (CRP). Further changes in these parameters have been associated with a worse prognosis and an indirect measure of the systemic inflammatory response [15, 41,42,43,44,45,46, 52]. Some authors recommended monitoring these parameters in managing COVID-19 patients [53].

Similarly, patients with anosmia were admitted to the ICU less often, but there was no significant difference in our study [54]. This finding was consistent with the results of other authors who described a milder disease course in patients with anosmia [7, 25, 53]. We encourage investigators to assess whether the clinical presentation of outpatients with anosmia was also different from those without it.

While the pathophysiological mechanism of OD caused by COVID-19 is still not fully understood, a critical step is probably the interaction between the COVID-19 protein and the angiotensin-converting enzyme 2 (ACE2) receptor. The intense expression is in the olfactory neuron epithelium [55,56,57]. ACE2 expression is significantly absent in olfactory sensory neurons, suggesting an indirect effect of SARS-CoV-2 infection on olfactory function, possibly due to loss of integrity in the neuroepithelium, or ionic imbalance interferes with olfactory signals [55,56,57]. Regarding the association between OD and morbidity/mortality, existing studies have provided inconsistent, although significant findings indicate that patients with OD had a more benign immune response profile to COVID-19 infection. Specifically, patients with OD can have less lymphopenia, higher albumin and hemoglobin, and lower D-dimer and C-RP. They have local nonsystemic inflammatory reactions in the upper airways, as shown by radiography [7, 25].

Although taste disturbance may be a biomarker for the prognosis of COVID-19, OD was prioritized for this study because, as reported in studies, taste loss is likely a secondary condition to OD [33, 58]. In addition, we found 1599 patients with olfactory, 1403 with gustatory, and 1261 with both disorders. Eventually, due to data limitations, no significant results were obtained. For this reason, it seems that the existence of more studies that lead to the examination of these variables in a larger sample size will be more helpful in the final conclusion.

Limitations of this study included the differences in studies’ quality, targeted focus on smell reduction as a unique predictor, lack of standardized OD reporting protocols and definitions globally, heterogeneity of patient populations, different treatment protocols, and hospitalizations. Depending on geographic location and evolving treatment regimens (e.g., delaying intubation even as hypoxia levels increase), OD as a recognized symptom of COVID-19 prompts early assessment and intervention and improves outcomes. There are also many asymptomatic and undiagnosed patients with COVID-19, and unknown asymptomatic outbreaks are a problematic factor. Age is another critical confounder, given that older age is associated with lower rates of OD [59, 60] and worse disease outcomes [1, 61,62,63,64]. Although we did not have access to precise data to include age in our analysis, two previous studies [24, 62] (898 patients in total) showed through multivariate analyses that OD was a predictor of better outcomes even after adjusting for age. Further research must clarify whether the association between OD and COVID-19 outcomes is age dependent.

Conclusions

The findings of our study showed that OD had an inverse and significant relationship with death in COVID-19 patients, and the patients with OD seemed to have a lower risk of mortality. It was also found that OD increased the risk of PCR test positivity.

Availability of data and materials

The datasets used and/or analyzed during the present study are available from the corresponding author upon reasonable request.

References

  1. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z et al (2020) Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 395(10229):1054–1062

    Article  CAS  Google Scholar 

  2. Wu Z, McGoogan J (2020) Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA 323(13):1239–1242

    Article  CAS  Google Scholar 

  3. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C et al (2020) Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 8(4):420–422

    Article  CAS  Google Scholar 

  4. Fang Y, Zhang H, Xie J, Lin M, Ying L, Pang P et al (2020) Sensitivity of chest CT for COVID-19: comparison to RT-PCR. Radiology. 296(2):E115–E117

    Article  Google Scholar 

  5. Biadsee A, Biadsee A, Kassem F, Dagan O, Masarwa S, Ormianer Z (2020) Olfactory and oral manifestations of COVID-19: sex-related symptoms-a potential pathway to early diagnosis. Otolaryngol Head Neck Surg 163(4):722–728

    Article  Google Scholar 

  6. Coelho D, Kons Z, Costanzo R, Reiter E (2020) Subjective changes in smell and taste during the COVID-19 pandemic: a national survey-preliminary results. Otolaryngol Head Neck Surg 163(2):302–306

    Article  Google Scholar 

  7. Foster K, Jauregui E, Tajudeen B, Bishehsari F, Mahdavinia M (2020) Smell loss is a prognostic factor for lower severity of coronavirus disease 2019. Ann Allergy Asthma Immunol 125(4):481–483

    Article  CAS  Google Scholar 

  8. Kanjanaumporn J, Aeumjaturapat S, Snidvongs K, Seresirikachorn K, Chusakul S (2020) Smell and taste dysfunction in patients with SARS-CoV-2 infection: a review of epidemiology, pathogenesis, prognosis, and treatment options. Asian Pac J Allergy Immunol 38(2):69–77

    CAS  Google Scholar 

  9. Hummel T, Rothbauer C, Barz S, Grosser K, Pauli E, Kobald G (1998) Olfactory function in acute rhinitis a. Ann N Y Acad Sci 855(1):616–624

    Article  CAS  Google Scholar 

  10. Bromley S (2000) Smell and taste disorders: a primary care approach. Am Fam Physician 61(2):427–436

    CAS  Google Scholar 

  11. Schiffman S (1983) Taste and smell in disease. N Engl J Med 308(22):1337–1343

    Article  CAS  Google Scholar 

  12. Boesveldt S, Postma EM, Boak D, Welge-Luessen A, Schöpf V, Mainland JD et al (2017) Anosmia-a clinical review. Chem Senses 42(7):513–523

    Article  Google Scholar 

  13. Seiden AM, Duncan HJ (2001) The diagnosis of a conductive olfactory loss. Laryngoscope. 111(1):9–14

    Article  CAS  Google Scholar 

  14. Fonteyn S, Huart C, Deggouj N, Collet S, Eloy P, Rombaux P (2014) Non-sinonasal-related olfactory dysfunction: a cohort of 496 patients. Eur Ann Otorhinolaryngol Head Neck Dis 131(2):87–91

    Article  CAS  Google Scholar 

  15. Klopfenstein T, Zahra H, Lepiller Q, Royer P, Toko L, Gendrin V et al (2020) New loss of smell and taste: uncommon symptoms in COVID-19 patients in Nord Franche-Comte cluster, France. Int J Infect Dis 100:117–122

    Article  CAS  Google Scholar 

  16. Abdelazim MH, Abdelazim AH (2022) Effect of sodium gluconate on decreasing elevated nasal calcium and improving olfactory function post COVID-19 infection. Am J Rhinol Allergy 36(6):841–848

    Article  Google Scholar 

  17. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372:n71

    Article  Google Scholar 

  18. Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M et al (2011) The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Hospital Research Institute, Ottawa Accessed at www.ohri.ca/programs/clinical_epidemiology/oxford.htm on 14 Nov 2012

    Google Scholar 

  19. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560

    Article  Google Scholar 

  20. Amanat M, Rezaei N, Roozbeh M, Shojaei M, Tafakhori A, Zoghi A et al (2021) Neurological manifestations as the predictors of severity and mortality in hospitalized individuals with COVID-19: a multicenter prospective clinical study. BMC Neurol 21(1):1–2

    Article  Google Scholar 

  21. Avcı H, Karabulut B, Farasoglu A, Boldaz E, Evman M (2020) Relationship between anosmia and hospitalisation in patients with coronavirus disease 2019: an otolaryngological perspective. J Laryngol Otol 134(8):710–716

    Article  Google Scholar 

  22. Porta-Etessam J, Núñez-Gil IJ, González García N, Fernandez-Perez C, Viana-Llamas MC, Eid CM et al (2021) COVID-19 anosmia and gustatory symptoms as a prognosis factor: a subanalysis of the HOPE COVID-19 (Health Outcome Predictive Evaluation for COVID-19) registry. Infection. 49(4):677–684

    Article  CAS  Google Scholar 

  23. Petrocelli M, Cutrupi S, Salzano G, Maglitto F, Salzano FA, Lechien JR et al (2021) Six-month smell and taste recovery rates in coronavirus disease 2019 patients: a prospective psychophysical study. J Laryngol Otol 135(5):436–441

    Article  CAS  Google Scholar 

  24. Talavera B, García-Azorín D, Martínez-Pías E, Trigo J, Hernández-Pérez I, Valle-Peñacoba G et al (2020) Anosmia is associated with lower in-hospital mortality in COVID-19. J Neurol Sci 419:117163

    Article  CAS  Google Scholar 

  25. Yan CH, Faraji F, Prajapati DP, Ostrander BT, DeConde AS (2020) Self-reported olfactory loss associates with outpatient clinical course in COVID-19. Int Forum Allergy Rhinol 10(7):821–831

    Article  Google Scholar 

  26. Vaira LA, Hopkins C, Salzano G, Petrocelli M, Melis A, Cucurullo M et al (2020) Olfactory and gustatory function impairment in COVID-19 patients: Italian objective multicenter-study. Head Neck 42(7):1560–1569

    Article  Google Scholar 

  27. Carignan A, Valiquette L, Grenier C, Musonera JB, Nkengurutse D, Marcil-Héguy A et al (2020) Anosmia and dysgeusia associated with SARS-CoV-2 infection: an age-matched case–control study. CMAJ. 192(26):E702–E707

    Article  CAS  Google Scholar 

  28. Beltrán-Corbellini Á, Chico-García JL, Martínez-Poles J, Rodríguez-Jorge F, Natera-Villalba E, Gómez-Corral J et al (2020) Acute-onset smell and taste disorders in the context of COVID-19: a pilot multicentre polymerase chain reaction based case-control study. Eur J Neurol 27(9):1738–1741

    Article  Google Scholar 

  29. Symptoms of Coronavirus. US Centers for Disease Control and Prevention (2020). https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html Published 2020. Accessed 25 May 2020.

  30. Vaira LA, Hopkins C, Petrocelli M, Lechien JR, Soma D, Giovanditto F et al (2020) Do olfactory and gustatory psychophysical scores have prognostic value in COVID-19 patients? A prospective study of 106 patients. J Otolaryngol Head Neck Surg 49(1):56

    Article  Google Scholar 

  31. Tong J, Wong A, Zhu D, Fastenberg J, Tham T (2020) The prevalence of olfactory and gustatory dysfunction in COVID-19 patients: a systematic review and meta-analysis. Otolaryngol Head Neck Surg 163(1):3–11

    Article  Google Scholar 

  32. Klopfenstein T, Kadiane-Oussou N, Toko L, Royer P, Lepiller Q, Gendrin V et al (2020) Features of anosmia in COVID-19. Med Mal Infect 50(5):436–439

    Article  CAS  Google Scholar 

  33. Moein S, Hashemian S, Mansourafshar B, Khorram-Tousi A, Tabarsi P, Doty RL (2020) Smell dysfunction: a biomarker for COVID-19. Int Forum Allergy Rhinol 10(8):944–950

    Article  Google Scholar 

  34. Lechien J, Chiesa-Estomba C, De Siati D (2020) Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol 277(8):2251–2261

    Article  Google Scholar 

  35. Hjelmesæth J, Skaare D (2020) Loss of smell or taste as the only symptom of COVID-19. Tidsskr Nor Laegeforen 140(7):1–5

    Google Scholar 

  36. Hopkins C, Surda P, Kumar N (2020) Presentation of new onset anosmia during the COVID-19 pandemic. Rhinology. 58(3):295–298

    Article  CAS  Google Scholar 

  37. Kaye R, Chang C, Kazahaya K, Brereton J, Denneny JC 3rd (2020) COVID-19 anosmia reporting tool: initial findings. Otolaryngol Head Neck Surg 163(1):132–134

    Article  Google Scholar 

  38. Karimi-Galougahi M, Raad N, Mikaniki N (2020) Anosmia and the need for COVID-19 screening during the pandemic. Otolaryngol Head Neck Surg 163(1):96–97

    Article  Google Scholar 

  39. Li Y, Bai W, Hashikawa T (2020) The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol 92(6):552–555

    Article  CAS  Google Scholar 

  40. Carod-Artal FJ (2020) Neurological complications of coronavirus and COVID-19. Rev Neurol 70(9):311–322

    CAS  Google Scholar 

  41. Brann D, Tsukahara T, Weinreb C (2020) Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia. Sci Adv 6:eabc5801

    Article  CAS  Google Scholar 

  42. Li Y, Bai W, Hirano N, Hayashida T, Hashikawa T (2012) Coronavirus infection of rat dorsal root ganglia: ultrastructural characterization of viral replication, transfer, and the early response of satellite cells. Virus Res 163(2):628–635

    Article  CAS  Google Scholar 

  43. Huang C, Wang Y, Li X (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 395(10223):497–506

    Article  CAS  Google Scholar 

  44. Wang D, Hu B, Hu C (2020) Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA. 323(11):1061

    Article  CAS  Google Scholar 

  45. Chen N, Zhou M, Dong X (2020) Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 395(10223):507–513

    Article  CAS  Google Scholar 

  46. Guan W, Ni Z, Hu Y (2020) Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 382(18):1708–1720

    Article  CAS  Google Scholar 

  47. Wu C, Chen X, Cai Y (2020) Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med 180(7):934

    Article  CAS  Google Scholar 

  48. Trigo J, García-Azorín D, Planchuelo-Gómez Á, Martínez-Pías E, Talavera B, Hernández-Pérez I et al (2020) Factors associated with the presence of headache in hospitalized COVID-19 patients and impact on prognosis: a retrospective cohort study. J Headache Pain 21(1):1

    Article  Google Scholar 

  49. García-Azorín D, Martínez-Pías E, Trigo J, Hernández-Pérez I, Valle-Peñacoba G, Talavera B, Simón-Campo P et al (2020) Neurological comorbidity is a predictor of death in Covid-19 disease: a cohort study on 576 patients. Front Neurol 11:781

    Article  Google Scholar 

  50. Silverberg JI, Zyskind I, Naiditch H, Zimmerman J, Glatt AE, Pinter A et al (2021) Association of varying clinical manifestations and positive anti–SARS-CoV-2 IgG antibodies: a cross-sectional observational study. J Allergy Clin Immunol 9(9):3331–3338

    CAS  Google Scholar 

  51. Whitcroft K, Hummel T (2020) Olfactory dysfunction in COVID-19. JAMA. 323(24):2512

    Article  CAS  Google Scholar 

  52. Birtay T, Bahadir S, Kabacaoglu E, Yetiz O, Demirci MF, Genctoy G (2021) Prognosis of patients hospitalized with a diagnosis of COVID-19 pneumonia in a tertiary hospital in Turkey. Ann Saudi Med 41(6):327–335

    Article  Google Scholar 

  53. Lippi G, Plebani M (2020) Laboratory abnormalities in patients with COVID-2019 infection. Clin Chem Lab Med 58(7):1131–1134

    Article  CAS  Google Scholar 

  54. Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB (2020) Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a review. JAMA. 323(18):1824–1836

    CAS  Google Scholar 

  55. Cooper KW, Brann DH, Farruggia MC, Bhutani S, Pellegrino R, Tsukahara T et al (2020) COVID-19 and the chemical senses: supporting players take center stage. Neuron. 107:219–233

    Article  CAS  Google Scholar 

  56. Chen M, Shen W, Rowan NR, Kulaga H, Hillel A, Ramanathan M et al (2020) Elevated ACE-2 expression in the olfactory neuroepithelium: implications for anosmia and upper respiratory SARS-CoV-2 entry and replication. Eur Respir J 56(3):2001948

    Article  CAS  Google Scholar 

  57. Fodoulian L, Tuberosa J, Rossier D, Boillat M, Kan C, Pauli V et al (2020) SARS-CoV-2 receptors and entry genes are expressed in the human olfactory neuroepithelium and brain. Iscience. 23(12):101839

    Article  CAS  Google Scholar 

  58. Wang Z, Zhou J, Marshall B, Rekaya R, Ye K, Liu HX (2020) SARS-CoV-2 receptor ACE2 is enriched in a subpopulation of mouse tongue epithelial cells in nongustatory papillae but not in taste buds or embryonic oral epithelium. ACS Pharmacol Transl Sci 3:749–758

    Article  CAS  Google Scholar 

  59. Agyeman A, Chin K, Landersdorfer C, Liew D, Ofori-Asenso R (2020) Smell and taste dysfunction in patients with COVID-19: a systematic review and meta-analysis. Mayo Clin Proc 95:1621–1631

    Article  CAS  Google Scholar 

  60. Mao L, Jin H, Wang M, Hu Y, Chen S, He Q et al (2020) Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol 77:683–690

    Article  Google Scholar 

  61. Paderno A, Schreiber A, Grammatica A, Raffetti E, Tomasoni M, Gualtieri T et al (2020) Smell and taste alterations in COVID-19: a cross-sectional analysis of different cohorts. Int Forum Allergy Rhinol 10(8):955–962

    Article  Google Scholar 

  62. Sisó-Almirall A, Kostov B, Mas-Heredia M, Vilanova-Rotllan S, Sequeira-Aymar E, Sans-Corrales M et al (2020) Prognostic factors in Spanish COVID-19 patients: a case series from Barcelona. PLoS One 15(8):e0237960

    Article  Google Scholar 

  63. Alizadehsani R, Alizadeh Sani Z, Behjati M, Roshanzamir Z, Hussain S, Abedini N et al (2021) Risk factors prediction, clinical outcomes, and mortality in COVID-19 patients. J Med Virol 93(4):2307–2320

    Article  CAS  Google Scholar 

  64. Elimian KO, Ochu CL, Ebhodaghe B, Myles P, Crawford EE, Igumbor E et al (2020) Patient characteristics associated with COVID-19 positivity and fatality in Nigeria: retrospective cohort study. BMJ Open 10(12):e044079

    Google Scholar 

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Acknowledgements

This study was approved as a proposal by the Vice-Chancellor of Hamedan University of Medical Sciences. It was the thesis of the second author (Dr. Mona Rezazadeh).

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

Authors

Contributions

Study concept and design: FH and MR. Acquisition, analysis, or interpretation of the data, FH, MR, ADI, and LM. Drafting of the manuscript: FH, MR, ADI, and LM. Critical revision of the manuscript for important intellectual content: FH, MR, and ADI. Statistical analysis: ADI and LM. Administrative, technical, or material support: FH, MR, and ADI. Study supervision: FH and MR. The authors read and approved the final manuscript.

Corresponding author

Correspondence to Mona Rezazadeh.

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Ethics approval and consent to participate

The proposal of this study was approved by the ethics committee of Hamadan University of Medical Sciences (IR.UMSHA.REC.1399.1010). The protocol was not registered.

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Not applicable.

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The authors declare that they have no competing interests.

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Hashemian, F., Rezazadeh, M., Irani, A.D. et al. Olfactory disorders in COVID-19 patients as a prognostic factor: a systematic review. Egypt J Otolaryngol 39, 21 (2023). https://doi.org/10.1186/s43163-022-00360-5

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  • DOI: https://doi.org/10.1186/s43163-022-00360-5

Keywords

  • Coronavirus
  • Olfaction disorders
  • Taste disorders
  • Prognosis
  • Systematic review
  • Meta-analysis