Olfactory outcomes in Zika virus-associated Guillain-Barré syndrome.

BACKGROUND AND PURPOSE: Zika virus (ZIKV) infection has been associated with Guillain-Barré 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.

SARS-CoV-2 infection and psychiatric manifestations in a previous healthy patient.

BACKGROUND: The clinical presentation of SARS-CoV-2 infection was initially dominated by respiratory symptoms. However, the clinical spectrum is wide and neuropsychiatric syndromes are also a source of medical concern. Our aims are to present an atypical clinical presentation of SARS-CoV-2 infection characterized by auditory hallucinations and unusual behavior and to emphasize the diversity of clinical manifestations of SARS-CoV-2 infection. CASE PRESENTATION: A 33-year-old woman was admitted to the emergency department (ED) with a one-day history of auditory hallucinations, unusual behavior, changes in her sleeping habits and incoherent speech. No other symptoms were reported. Blood examinations confirmed high elevated white cell count and C-reactive protein. The head CT scan was normal but the chest scan showed right ground-glass opacities in the lower zones. The oropharyngeal swab was positive for SARS-CoV-2. Based on these results, the diagnosis of SARS-CoV-2 infection was retained. The patient received no specific treatment for SARS-CoV-2 infection and only needed oxygen therapy support for 7 days. The additional dose of Olanzapine 10 mg daily was initially prescribed but the patient was back to her usual self on day 14 of hospital admission leading to its discontinuation. This clinical course was consistent with a first episode of psychosis triggered by SARS-CoV-2 infection. CONCLUSION: Neuroinflammation owing to SARS-CoV-2 infection could be responsible for a wide and unknown spectrum of neuropsychiatric manifestations. During this pandemic, special attention should be given to patients with no previous history of psychiatric disorders presenting to ED with neuropsychiatric syndromes of unknown etiology.

SARS-CoV-2 infection induces the dedifferentiation of multiciliated cells and impairs mucociliary clearance.

Understanding how SARS-CoV-2 spreads within the respiratory tract is important to define the parameters controlling the severity of COVID-19. Here we examine the functional and structural consequences of SARS-CoV-2 infection in a reconstructed human bronchial epithelium model. SARS-CoV-2 replication causes a transient decrease in epithelial barrier function and disruption of tight junctions, though viral particle crossing remains limited. Rather, SARS-CoV-2 replication leads to a rapid loss of the ciliary layer, characterized at the ultrastructural level by axoneme loss and misorientation of remaining basal bodies. Downregulation of the master regulator of ciliogenesis Foxj1 occurs prior to extensive cilia loss, implicating this transcription factor in the dedifferentiation of ciliated cells. Motile cilia function is compromised by SARS-CoV-2 infection, as measured in a mucociliary clearance assay. Epithelial defense mechanisms, including basal cell mobilization and interferon-lambda induction, ramp up only after the initiation of cilia damage. Analysis of SARS-CoV-2 infection in Syrian hamsters further demonstrates the loss of motile cilia in vivo. This study identifies cilia damage as a pathogenic mechanism that could facilitate SARS-CoV-2 spread to the deeper lung parenchyma.

COVID-19-related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters.

Whereas recent investigations have revealed viral, inflammatory, and vascular factors involved in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lung pathogenesis, the pathophysiology of neurological disorders in coronavirus disease 2019 (COVID-19) remains poorly understood. Olfactory and taste dysfunction are common in COVID-19, especially in mildly symptomatic patients. Here, we conducted a virologic, molecular, and cellular study of the olfactory neuroepithelium of seven patients with COVID-19 presenting with acute loss of smell. We report evidence that the olfactory neuroepithelium is a major site of SARS-CoV2 infection with multiple cell types, including olfactory sensory neurons, support cells, and immune cells, becoming infected. SARS-CoV-2 replication in the olfactory neuroepithelium was associated with local inflammation. Furthermore, we showed that SARS-CoV-2 induced acute anosmia and ageusia in golden Syrian hamsters, lasting as long as the virus remained in the olfactory epithelium and the olfactory bulb. Last, olfactory mucosa sampling from patients showing long-term persistence of COVID-19-associated anosmia revealed the presence of virus transcripts and of SARS-CoV-2-infected cells, together with protracted inflammation. SARS-CoV-2 persistence and associated inflammation in the olfactory neuroepithelium may account for prolonged or relapsing symptoms of COVID-19, such as loss of smell, which should be considered for optimal medical management of this disease.