Anosmia in COVID-19 patients

Hornuß, Daniel; Lange, Berit; Schröter, Nils; Rieg, Siegbert; Kern, Winfried V.; Wagner, Dirk

doi:10.1101/2020.04.28.20083311

Cited by 63 publications

(75 citation statements)

References 10 publications

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“…Indeed, a proportion of patients with hRSV-associated severe bronchiolitis can develop neurological abnormalities, such as seizures ( Kho et al, 2004 , Ng et al, 2001 , Cha et al, 2019 ), central apnea ( Kho et al, 2004 ); lethargy, ( Sweetman et al, 2005 , Kho et al, 2004 ) feeding or swallowing difficulties ( Sweetman et al, 2005 , Kho et al, 2004 ), strabismus ( Antonucci and Fanos, 2005 ), encephalopathy ( Eisenhut, 2007 , Millichap and Wainwright, 2009 , Picone et al, 2019 , Bohmwald et al, 2014 , Bohmwald et al, 2018 ), and elevated cytokines levels or increased cellularity in the cerebrospinal fluid (CSF) ( Kawashima et al, 2012 , Kho et al, 2004 , Otake et al, 2007 ). Additionally, studies in rodents have shown that hRSV can cause cognitive alterations, similarly to what has been reported for the other respiratory viruses, such as the influenza virus and SARS-CoV-2 ( Jurgens et al, 2012 , Jang et al, 2009 , Mao et al, 2020 , Meinhardt, 2020 , Moriguchi et al, 2020 , Bernard-Valnet, 2020 , Hornuss, 2020 , Rogers et al, 2020 ). These observations suggest that hRSV could alter the proper function of the CNS.…”

Section: Introductionsupporting

confidence: 59%

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Lung pathology due to hRSV infection impairs blood–brain barrier permeability enabling astrocyte infection and a long-lasting inflammation in the CNS

Böhmwald

Soto

Andrade

et al. 2021

Brain, Behavior, and Immunity

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The human respiratory syncytial virus (hRSV) is the most common infectious agent that affects children before two years of age. hRSV outbreaks cause a significant increase in hospitalizations during the winter season associated with bronchiolitis and pneumonia. Recently, neurologic alterations have been associated with hRSV infection in children, which include seizures, central apnea, and encephalopathy. Also, hRSV RNA has been detected in cerebrospinal fluids (CSF) from patients with neurological symptoms after hRSV infection. Additionally, previous studies have shown that hRSV can be detected in the lungs and brains of mice exposed to the virus, yet the potential effects of hRSV infection within the central nervous system (CNS) remain unknown. Here, using a murine model for hRSV infection, we show a significant behavior alteration in these animals, up to two months after the virus exposure, as shown in marble-burying tests. hRSV infection also produced the expression of cytokines within the brain, such as IL-4, IL-10, and CCL2. We found that hRSV infection alters the permeability of the blood-brain barrier (BBB) in mice, allowing the trespassing of macromolecules and leading to increased infiltration of immune cells into the CNS together with an increased expression of pro-inflammatory cytokines in the brain. Finally, we show that hRSV infects murine astrocytes both, in vitro and in vivo . We identified the presence of hRSV in the brain cortex and colocalizes with vWF, MAP-2, Iba-1, and GFAP, which are considered markers for endothelial cells, neurons, microglia, and astrocyte, respectively. hRSV-infected murine astrocytes displayed increased production of nitric oxide (NO) and TNF-α. Our results suggest that hRSV infection alters the BBB permeability to macromolecules and immune cells and induces CNS inflammation which can contribute to the behavioral alterations observed on infected mice. A better understanding of the neuropathy caused by hRSV could help to reduce the potential detrimental effects on the CNS in hRSV-infected patients.

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Section: Introductionsupporting

confidence: 59%

“…During inflammatory conditions, the downregulation of CD200 leads to increased activation of microglia ( Rogers et al, 2020 ). Moreover, it has been observed that the downregulation of CD200 leads to cognitive impairment ( Hornuss, 2020 ). Thus, the levels of CD200 mRNA and protein were measured in the brains of hRSV-infected mice.…”

Section: Resultsmentioning

confidence: 99%

Lung pathology due to hRSV infection impairs blood–brain barrier permeability enabling astrocyte infection and a long-lasting inflammation in the CNS

Böhmwald

Soto

Andrade

et al. 2021

Brain, Behavior, and Immunity

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“…Olfactory ability was assessed by: using validated questionnaires focused on smell dysfunction, in three studies; obtaining objective information on smell impairment through standardised chemosensitive tests with odorants, in five studies; and considering both methods, in five studies (Table 3). 18,20,[24][25][26]29,32,34,37,[40][41][42][43][47][48][49][50][51][52][53][54][55][56][57][58][59] The remaining studies assessed olfactory ability through anamnestic data collection, simple surveys and/or structured, non-validated questionnaires (Table 4). 2,16,17,19,[21][22][23]27,28,30,31,33,35,36,38,39,[44][45][46]…”

Section: Resultsmentioning

confidence: 99%

Olfactory disorders in coronavirus disease 2019 patients: a systematic literature review

et al. 2020

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Objective Recent scientific literature has widely described a possible major role of smell dysfunction as a specific symptom of coronavirus disease 2019. This systematic review may provide a more holistic approach to current knowledge of the disease. Methods A systematic review was completed using Embase, PubMed and Web of Science databases that considered original articles focused on olfactory evaluation in coronavirus disease 2019 patients, published between March and May 2020, in English language. Results From the 483 research papers initially identified, 32 original studies were selected, comprising a total of 17 306 subjects with a laboratory confirmed diagnosis of coronavirus disease 2019. Individual study sample sizes ranged from 6 to 6452 patients. This comprehensive analysis confirmed that olfactory disorders represent an important clinical feature in coronavirus disease 2019, with a prevalence of 11–100 per cent in included patients, although there was heterogeneity in terms of assessment tools and population selection criteria. Conclusion The results indicate that an accurate clinical evaluation should be carried out using structured questionnaires and tests with olfactory substances.

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“…Two categories of the MMAT were employed based on the study design to examine the methodological quality of these studies; quantitative non-randomized category for cross-sectional and case-control studies and quantitative descriptive category for case-report and case series ones. Of the 28 included studies, one (44) had a MMAT score of 100%, six (19,26,27,38,42,43) (19,29,40); and one study (31) was conducted in European and American countries jointly.…”

Section: Quality Assessmentmentioning

confidence: 99%

“…Four studies (28,29,31,33) did not report how to measure, just extracted from medical records. In three studies (26,27,42), the Sni n' Sticks screening test for smelling disorders was used to perform psychophysical olfactory evaluation. The other methods contain:…”

Section: Olfactory and Gustatory Dysfunction Measurementmentioning

confidence: 99%

Olfactory and gustatory dysfunction in 2019 novel coronavirus: An updated systematic review and meta-analysis

Esmaeili

Abdi

Shafiee

et al. 2020

Preprint

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BackgroundEvidence showed that partial or complete loss of smell and taste might be a possible primary symptom of the 2019 novel coronavirus (COVID-19). This study aimed to systematically review and pool all available evidence on the olfactory and gustatory dysfunction in COVID-19 patients. MethodsIn this systematic review, a comprehensive search was carried out systematically through e-databases including PubMed, EMBASE, Scopus, and Web of Science (WoS); that was limited to English-language studies published from 2019 up to 6th May 2020. Afterward, all studies reported the taste and smell dysfunction in the COVID-19 patients were included. The quality of the studies was assessed by the Mixed Methods Appraisal Tool (MMAT). The pooled prevalence of olfactory and gustatory dysfunction was estimated using the random effects meta-analysis method.ResultsAmong 28 eligible included studies in this systematic review, finally, 22 studies met the eligibility criteria and were included in the meta-analysis. According to the random effect meta-analysis, the global pooled prevalence (95% confidence interval) of any olfactory dysfunction, anosmia, and hyposmia was 55% (40%-70%), 40% (22%-57%), and 40% (20%-61%) respectively. The pooled estimated prevalence of any gustatory dysfunction, ageusia, and dysgeusia was 41% (23%-59%), 31% (3%-59%), and 34% (19%-48%) respectively. ConclusionOlfactory and gustatory dysfunction is prevalent among COVID-19 patients. Therefore, olfactory and gustatory dysfunction seems to be part of important symptoms and notify for the diagnosis of COVID-19, especially in the early phase of the infection.

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Anosmia in COVID-19 patients

Abstract: Word Count 206 (of 250) 20

Cited by 63 publications

References 10 publications

Lung pathology due to hRSV infection impairs blood–brain barrier permeability enabling astrocyte infection and a long-lasting inflammation in the CNS

Lung pathology due to hRSV infection impairs blood–brain barrier permeability enabling astrocyte infection and a long-lasting inflammation in the CNS

Olfactory disorders in coronavirus disease 2019 patients: a systematic literature review

Olfactory and gustatory dysfunction in 2019 novel coronavirus: An updated systematic review and meta-analysis

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