Abstract
Background: Zika Virus (ZIKV) infection has been associated with Guillain-Barré Syndrome (GBS). Yet, little is known about the consequence of ZIKV infection on olfaction in humans. Methods: Just right before the COVID-19 outbreak, we prospectively investigated the olfacto-ry capacities of 19 patients with ZIKV-associated GBS from the French West Indies and com-pared them to 9 controls from the same population, with a GBS of similar severity but inde-pendent of Zika infection. To provide further evidence that ZIKV infection induces smell altera-tion, we investigated the consequences of ZIKV infection on olfactory abilities using a mouse model.Results: Patients with GBS-Zika+ had a poorer olfactory function than GBS-non-Zika, even one to two years after the acute phase. The proportion of patients with hyposmia was signifi-cantly higher in GBS-Zika+ than in GBS-non-Zika group (68.4% versus 22.2%, P=0.042). These deficits were characterized by lower threshold and identification scores and were inde-pendent from GBS severity. Additionally, ZIKV infection was found to impair olfaction in immu-nodeficient mice infected with ZIKV. High viral load was observed in their olfactory system and downstream brain structures. ZIKV promoted both cellular damages in the olfactory neuroepi-thelium and protracted inflammation of the olfactory bulb, likely accounting for smell alteration. Conclusions: Patients with ZIKV-related GBS had a poorer long-term olfactory function than patients with GBS-non-Zika and ZIKV-infected mice are hyposmic. These observations sug-gest that ZIKV belongs to the list of viruses affecting the olfactory system. Clinical evaluation of the olfactory system should be considered for ZIKV-infected patients.