J Rhinol.  2024 Mar;31(1):1-7. 10.18787/jr.2024.00006.

Efficacy of Platelet-Rich Plasma in the Treatment of Persistent Olfactory Impairment After COVID-19: A Systematic Review and Meta-Analysis

• Bae AY
• Kim DH
• Hwang SH

• KMID: 2554084
• DOI: http://doi.org/10.18787/jr.2024.00006

Abstract

Background and Objectives
This study aimed to evaluate the impact of topical platelet-rich plasma (PRP) injection on persistent refractory olfactory dysfunction after COVID-19 infection.
Methods
A systematic review was conducted, focusing on studies that compared the efficacy of topical PRP treatment with a control group (receiving either placebo or no treatment) in ameliorating olfactory dysfunction. Pre- and post-treatment comparisons were evaluated, along with a subgroup analysis of olfactory function evaluation.
Results
The analysis revealed a significant improvement in olfactory scores between 1 to 3 months post-treatment (standardized mean difference=1.4376; 95% confidence interval [CI]=0.5934–2.2818; I²=84.1%) in the treatment group compared to the control group. Moreover, a notable disparity was observed between the two groups in the incidence of substantial recovery from anosmia or hyposmia (odds ratio=8.6639; 95% CI=2.9752–25.2292; I²=0.0%). PRP treatment led to a clinically significant increase in the threshold, discrimination, and identification (TDI) score for the Sniffin’ Sticks test by >5.5 (minimum clinically significant difference; mean difference, 6.3494; 95% CI=4.0605–8.6384; I²=0.0%), as confirmed by verified examinations. The odds ratio for significant improvement among patients after treatment was determined to be 0.7654 (95% CI=0.6612–0.8451). Furthermore, all TDI subdomains exhibited significant and comparable improvements post-treatment.
Conclusion
This meta-analysis indicates that the injection of PRP into the olfactory fissure or surrounding mucosal areas is an effective treatment for persistent refractory olfactory dysfunction.

Keyword

Anosmia; Smell; Platelet-rich plasma; Outcome assessment; Health care; Meta-analysis

Figure

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  Fig. 1. Diagram of study selection.

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  Fig. 2. Comparison of topical platelet-rich plasma and control. Changes in olfactory scores at 1 to 3 months post-treatment (A) and the proportion of patients with significant improvements after treatment (B).

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  Fig. 3. Changes in olfactory measurements after topical platelet-rich plasma compared to pre-treatment. The proportion of patients with significant improvements after treatment (A) and changes in the TDI scores of the Sniffin’ Sticks test (B) and individual subdomains (threshold, discrimination, and identification) (C).

Reference

References

1. Croy I, Nordin S, Hummel T. Olfactory disorders and quality of life--an updated review. Chem Senses. 2014; 39(3):185–94.

2. Hummel T, Whitcroft KL, Andrews P, Altundag A, Cinghi C, Costanzo RM, et al. Position paper on olfactory dysfunction. Rhinol Suppl. 2017; 54(26):1–30.

3. Whitcroft KL, Altundag A, Balungwe P, Boscolo-Rizzo P, Douglas R, Enecilla MLB, et al. Position paper on olfactory dysfunction: 2023. Rhinology. 2023; Jul. 16. [Epub]. Available from: https://www.rhinologyjournal.com/Abstract.php?id=3097.

4. Kim DH, Kim SW, Hwang SH, Kim BG, Kang JM, Cho JH, et al. Prognosis of olfactory dysfunction according to etiology and timing of treatment. Otolaryngol Head Neck Surg. 2017; 156(2):371–7.

5. Cavazzana A, Larsson M, Münch M, Hähner A, Hummel T. Postinfectious olfactory loss: a retrospective study on 791 patients. Laryngoscope. 2018; 128(1):10–5.

6. Sundman EA, Cole BJ, Fortier LA. Growth factor and catabolic cytokine concentrations are influenced by the cellular composition of platelet-rich plasma. Am J Sports Med. 2011; 39(10):2135–40.

7. Anjayani S, Wirohadidjojo YW, Adam AM, Suwandi D, Seweng A, Amiruddin MD. Sensory improvement of leprosy peripheral neuropathy in patients treated with perineural injection of platelet-rich plasma. Int J Dermatol. 2014; 53(1):109–13.

8. Kim DH, Lee MH, Lee J, Song EA, Kim SW, Kim SW. Platelet-rich plasma injection in patients with atrophic rhinitis. ORL J Otorhinolaryngol Relat Spec. 2021; 83(2):104–11.

9. Raeissadat SA, Karimzadeh A, Hashemi M, Bagherzadeh L. Safety and efficacy of platelet-rich plasma in treatment of carpal tunnel syndrome; a randomized controlled trial. BMC Musculoskelet Disord. 2018; 19(1):49.

10. Farrag TY, Lehar M, Verhaegen P, Carson KA, Byrne PJ. Effect of platelet rich plasma and fibrin sealant on facial nerve regeneration in a rat model. Laryngoscope. 2007; 117(1):157–65.

11. Ikumi A, Hara Y, Yoshioka T, Kanamori A, Yamazaki M. Effect of local administration of platelet-rich plasma (PRP) on peripheral nerve regeneration: an experimental study in the rabbit model. Microsurgery. 2018; 38(3):300–9.

12. Sariguney Y, Yavuzer R, Elmas C, Yenicesu I, Bolay H, Atabay K. Effect of platelet-rich plasma on peripheral nerve regeneration. J Reconstr Microsurg. 2008; 24(3):159–67.

13. Zheng C, Zhu Q, Liu X, Huang X, He C, Jiang L, et al. Effect of platelet-rich plasma (PRP) concentration on proliferation, neurotrophic function and migration of Schwann cells in vitro. J Tissue Eng Regen Med. 2016; 10(5):428–36.

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

15. Hwang SH, Kim SW, Basurrah MA, Kim DH. Efficacy of steroid-impregnated spacers after endoscopic sinus surgery in chronic rhinosinusitis: a systematic review and meta-analysis. Clin Exp Otorhinolaryngol. 2023; 16(2):148–58.

16. Kim DH, Kim SW, Basurrah MA, Hwang SH. Clinical and laboratory features of various criteria of eosinophilic chronic rhinosinusitis: a systematic review and meta-analysis. Clin Exp Otorhinolaryngol. 2022; 15(3):230–46.

17. Mavrogeni P, Kanakopoulos A, Maihoub S, Krasznai M, Szirmai A. Anosmia treatment by platelet rich plasma injection. Int Tinnitus J. 2017; 20(2):102–5.

18. Yan CH, Mundy DC, Patel ZM. The use of platelet-rich plasma in treatment of olfactory dysfunction: a pilot study. Laryngoscope Investig Otolaryngol. 2020; 5(2):187–93.

19. Aboelmagd EA, Mohamed EF, Abdelmegeed EM, Eltahan AA. Platelet-rich plasma in the management of anosmia. Egypt J Neck Surg Otorhinolaryngol. 2021; 7(1):10–9.

20. Steffens Y, Le Bon SD, Lechien J, Prunier L, Rodriguez A, Saussez S, et al. Effectiveness and safety of PRP on persistent olfactory dysfunction related to COVID-19. Eur Arch Otorhinolaryngol. 2022; 279(12):5951–3.

21. Yan CH, Jang SS, Lin HC, Ma Y, Khanwalkar AR, Thai A, et al. Use of platelet-rich plasma for COVID-19-related olfactory loss: a randomized controlled trial. Int Forum Allergy Rhinol. 2023; 13(6):989–97.

22. Abo El Naga HA, El Zaiat RS, Hamdan AM. The potential therapeutic effect of platelet-rich plasma in the treatment of post-COVID-19 parosmia. Egypt J Otolaryngol. 2022; 38(1):130.

23. Evman MD, Cetin ZE. Effectiveness of platelet-rich plasma on post-COVID chronic olfactory dysfunction. Rev Assoc Med Bras (1992). 2023; 69(11):e20230666.

24. Lechien JR, Le Bon SD, Saussez S. Platelet-rich plasma injection in the olfactory clefts of COVID-19 patients with long-term olfactory dysfunction. Eur Arch Otorhinolaryngol. 2023; 280(5):2351–8.

25. Shawky MA, Hadeya AM. Platelet-rich plasma in management of anosmia (single versus double injections). Indian J Otolaryngol Head Neck Surg. 2023; 75(Suppl 1):1004–8.

26. Sorour SS, Elhady AM, Hosny SM, Gad EMA. Assessment of olfactory dysfunction after treatment with platelet-rich plasma. Egypt J Hosp Med. 2023; 91(1):5094–9.

27. Stavrakas M, Karkos PD, Markou K, Grigoriadis N. Platelet-rich plasma in otolaryngology. J Laryngol Otol. 2016; 130(12):1098–102.