Neuromodulation : journal of the International Neuromodulation Society · 2026
Noninvasive Neuromodulation Techniques in the Recovery of Olfactory Dysfunction in Long COVID: A Systematic Review and Bayesian Meta-Analysis.
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Modesto Heitor Correa, Modesto Lucas Correa, Castanho Leandro Correia, Pereira Lizomar de Jesus Maués, Norte Raimunda Silvia Gatti, Pereira José Alfredo Coelho, Andriolo Regis Bruni
Аннотация
OBJECTIVES: Long COVID is a multisystemic condition in which olfactory disorders are among the most prevalent manifestations. Noninvasive neuromodulation has emerged as a promising therapeutic approach for post-COVID sequelae. This systematic review and Bayesian meta-analysis aimed to synthesize the available evidence on neuromodulation for olfactory improvement in patients with Long COVID.
MATERIALS AND METHODS: A systematic search was conducted in PubMed and/or MEDLINE, Embase, and Cochrane Library from inception through January 22, 2026, in accordance with Preferred Reporting items for Systematic Reviews and Meta-Analyses 2020 guidelines. Studies were eligible if they included patients with Long COVID undergoing any noninvasive neuromodulation modality for olfactory disturbances and had a control group. Risk of bias was assessed using Cochrane risk of bias 2 tool for randomized controlled trials and the risk of bias in nonrandomized studies of interventions tool for nonrandomized intervention studies. A Bayesian random-effects meta-analysis was performed using the brms package in R, with risk ratios (RRs) and 95% credible intervals (CrIs) as effect measures.
RESULTS: A total of four studies were included, using heterogeneous neuromodulation modalities. The pooled RR for complete olfactory recovery (normosmia) was 1.59 (95% CrI, 0.41-6.28), with a 73.9% posterior probability of benefit (RR > 1); however, the CrI included the null value. For clinically meaningful olfactory improvement, the pooled RR was 2.20 (95% CrI, 0.63-7.52), with an 88.8% posterior probability of benefit, although the interval marginally included the null value. Sensitivity analyses using wider priors yielded substantially different estimates, indicating that the results were prior-dependent. No serious adverse events were reported across the studies.
CONCLUSIONS: The available evidence suggests a possible favorable direction of effect of noninvasive neuromodulation on olfactory dysfunction in Long COVID, but the certainty is very low. These findings should be interpreted as hypothesis-generating. Larger trials using standardized olfactory testing and prespecified stimulation protocols are warranted before any clinical recommendations can be made.
MATERIALS AND METHODS: A systematic search was conducted in PubMed and/or MEDLINE, Embase, and Cochrane Library from inception through January 22, 2026, in accordance with Preferred Reporting items for Systematic Reviews and Meta-Analyses 2020 guidelines. Studies were eligible if they included patients with Long COVID undergoing any noninvasive neuromodulation modality for olfactory disturbances and had a control group. Risk of bias was assessed using Cochrane risk of bias 2 tool for randomized controlled trials and the risk of bias in nonrandomized studies of interventions tool for nonrandomized intervention studies. A Bayesian random-effects meta-analysis was performed using the brms package in R, with risk ratios (RRs) and 95% credible intervals (CrIs) as effect measures.
RESULTS: A total of four studies were included, using heterogeneous neuromodulation modalities. The pooled RR for complete olfactory recovery (normosmia) was 1.59 (95% CrI, 0.41-6.28), with a 73.9% posterior probability of benefit (RR > 1); however, the CrI included the null value. For clinically meaningful olfactory improvement, the pooled RR was 2.20 (95% CrI, 0.63-7.52), with an 88.8% posterior probability of benefit, although the interval marginally included the null value. Sensitivity analyses using wider priors yielded substantially different estimates, indicating that the results were prior-dependent. No serious adverse events were reported across the studies.
CONCLUSIONS: The available evidence suggests a possible favorable direction of effect of noninvasive neuromodulation on olfactory dysfunction in Long COVID, but the certainty is very low. These findings should be interpreted as hypothesis-generating. Larger trials using standardized olfactory testing and prespecified stimulation protocols are warranted before any clinical recommendations can be made.