Olfactory outcomes in Zika virus-associated Guillain-Barre syndrome

Background and purpose Zika virus (ZIKV) infection has been associated with Guillain-Barre syndrome (GBS). However, little is known about the consequence of ZIKV infection on olfaction in humans. Methods Immediately before the COVID-19 outbreak, we prospectively investigated the olfactory capacities of 19 patients with ZIKV-associated GBS from the French West Indies and compared them to nine controls from the same population, with GBS of similar severity but independent of ZIKV infection. To provide further evidence that ZIKV infection induces smell alteration, we investigated the consequences of ZIKV infection on olfactory abilities using a mouse model. Results Patients with GBS-ZIKA+ had poorer olfactory function than GBS-non-ZIKA, even 1-2 years after the acute phase. The proportion of patients with hyposmia was significantly higher in the GBS-ZIKA+ than in the GBS-non-ZIKA group (68.4% vs. 22.2%, p = 0.042). These deficits were characterized by lower threshold and identification scores and were independent from GBS severity. Additionally, ZIKV infection was found to impair olfaction in immunodeficient mice infected with ZIKV. High viral load was observed in their olfactory system and downstream brain structures. ZIKV promoted both cellular damage in the olfactory neuroepithelium and protracted inflammation of the olfactory bulb, likely accounting for smell alteration. Conclusions Patients with ZIKV-related GBS had poorer long-term olfactory function than patients with GBS-non-ZIKA, and ZIKV-infected mice are hyposmic. These observations suggest that ZIKV belongs on the list of viruses affecting the olfactory system. Clinical evaluation of the olfactory system should be considered for ZIKV-infected patients.