Pathophysiology of the COVID-19 – entry to the CNS through the nose

Ylikoski, Jukka; Markkanen, Marika; Mäkitie, Antti

doi:10.1080/00016489.2020.1773533

Cited by 24 publications

(20 citation statements)

References 19 publications

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“…The duration of the smell and taste disorders in COVID-19 disease is also still unclear. However, it could be of great importance to signal the persistence of the virus close to the CNS and a possible long-term neurological affection [10].…”

Section: Introductionmentioning

confidence: 99%

Olfactory dysfunction in patients after recovering from COVID-19

Otte

Eckel

Poluschkin

et al. 2020

Acta Oto-Laryngologica

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Background: Smell and taste disorders occur in COVID-19 with a high prevalence, but little is known about the duration of the symptoms. In particular, studies using validated olfactory tests are very rare to date. Aims/Objectives: The aim of this study was to determine the olfactory function of COVID-19 recoveries by a detailed olfactory test. Methods: 91 patients with PCR-confirmed, past COVID-19 disease were included. Olfactory history was taken using a questionnaire. Olfactory function was evaluated with the sniffin' sticks test, tasting function with taste sprays. Results: 80 patients had experienced sudden olfactory loss during the course of disease and at the time of testing, 33 patients subjectively still had an impaired olfactory sense. Around 8 weeks had passed since the onset of symptoms. 45.1% of the tested individuals were still hyposmic according to the olfactory test while 53.8% showed an olfactory performance within the normal range. Patients' self-assessment correlated poorly with the measured olfactory performance. Conclusions and significance: Half of the patients with an olfactory loss as a symptom of COVID-19 still have olfactory impairments after two months, although not all of these patients subjectively notice a restriction. Long-term measurements must confirm whether all affected patients will make full recovery.

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Section: Introductionmentioning

confidence: 99%

Olfactory dysfunction in patients after recovering from COVID-19

Otte

Eckel

Poluschkin

et al. 2020

Acta Oto-Laryngologica

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“…It has also been described that symptoms such as dyspnea, anosmia, have appeared in survivors of severe acute respiratory syndrome (SARS-CoV) in 2003, where the individuals presented persistent functional disability, after discharge, it stands out that they were young patients, it is even mentioned that cases were registered, that they presented debilitating symptoms after one year of apparent recovery, and the possibility that these sequelae, were neurological, caused by infection or inflammation in the central nervous system, is discussed in other research [45]. Anosmia is an important symptom, because it could be indicate of intranasal inoculation of SARS-CoV-2 into the olfactory neural circuitry causing a neuroinvasion that could result in chronic neurodegenerative disease [46][47][48].…”

Section: Discussionmentioning

confidence: 99%

Persistence of COVID-19 Symptoms after Recovery in Mexican Population

Galván-Tejada

Herrera-García

Godina-González

et al. 2020

IJERPH

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease (COVID-19), a highly contagious infectious disease that has caused many deaths worldwide. Despite global efforts, it continues to cause great losses, and leaving multiple unknowns that we must resolve in order to face the pandemic more effectively. One of the questions that has arisen recently is what happens, after recovering from COVID-19. For this reason, the objective of this study is to identify the risk of presenting persistent symptoms in recovered from COVID-19. This case-control study was conducted in one state of Mexico. Initially the data were obtained from the participants, through a questionnaire about symptoms that they had at the moment of the interview. Initially were captured the collected data, to make a dataset. After the pre-processed using the R project tool to eliminate outliers or missing data. Obtained finally a total of 219 participants, 141 recovered and 78 controls. It was used confidence level of 90% and a margin of error of 7%. From results it was obtained that all symptoms have an associated risk in those recovered. The relative risk of the selected symptoms in the recovered patients goes from 3 to 22 times, being infinite for the case of dyspnea, due to the fact that there is no control that presents this symptom at the moment of the interview, followed by the nausea and the anosmia with a RR of 8.5. Therefore, public health strategies must be rethought, to treat or rehabilitate, avoiding chronic problems in patients recovered from COVID-19.

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“…This progression is not recapitulated in the mouse model where fulminant lung infection requires direct inoculation of virus into the lungs via the intranasal route. Infection of the brain may occur via the olfactory epithelium ( 38 ) so the reduced infection of brain may reflect the reduced infection of nasal turbinates. Although CNS involvement in COVID-19 in humans is now well documented 32 , the fulminant brain infection seen in this mouse model does not seem to be a feature of human disease.…”

Section: Discussionmentioning

confidence: 99%

Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 By Disrupting The Spike-ACE2 interaction

Mycroft-West

Gandhi

et al. 2020

Preprint

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A major global effort is currently ongoing to search for therapeutics and vaccines to treat or prevent infection by the SARS-CoV-2 virus. Repurposing existing entities is one attractive approach. The heparan sulfate mimetic pixatimod is a clinical-stage synthetic sulfated compound that is a potent inhibitor of the glycosidase heparanase, and has known anti-cancer, anti-inflammatory and also antiviral properties. Here we show that pixatimod binds directly to the SARS-CoV-2 spike protein S1 receptor binding domain (RBD) and alters its conformation. Notably, this site overlaps with the known ACE2 binding site in the S1 RBD. We find that pixatimod inhibits binding of recombinant S1 RBD to Vero cells which express the ACE2 receptor. Moreover, in assays with three different isolates of live SARS-CoV-2 virus we show that pixatimod effectively inhibits viral infection of Vero cells. Importantly, its potency is well within its safe therapeutic dose range. These data provide evidence that pixatimod is a potent antiviral agent against SARS-CoV-2. Together with its other known activities this provides a strong rationale for its clinical investigation as a new multimodal therapeutic for the current COVID-19 pandemic.

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Pathophysiology of the COVID-19 – entry to the CNS through the nose

Cited by 24 publications

References 19 publications

Olfactory dysfunction in patients after recovering from COVID-19

Olfactory dysfunction in patients after recovering from COVID-19

Persistence of COVID-19 Symptoms after Recovery in Mexican Population

Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 By Disrupting The Spike-ACE2 interaction

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