COVID-19 and its effects on neurological functions.

Ever since the first reported case series on SARS-CoV-2-induced neurological manifestation in Wuhan, China in April 2020, various studies reporting similar as well as diverse symptoms of COVID-19 infection relating to the nervous system were published. Since then, scientists started to uncover the mechanism as well as pathophysiological impacts it has on the current understanding of the disease. SARS-CoV-2 binds to the ACE2 receptor which is present in certain parts of the body which are responsible for regulating blood pressure and inflammation in a healthy system. Presence of the receptor in the nasal and oral cavity, brain, and blood allows entry of the virus into the body and cause neurological complications. The peripheral and central nervous system could also be invaded directly in the neurogenic or hematogenous pathways, or indirectly through overstimulation of the immune system by cytokines which may lead to autoimmune diseases. Other neurological implications such as hypoxia, anosmia, dysgeusia, meningitis, encephalitis, and seizures are important symptoms presented clinically in COVID-19 patients with or without the common symptoms of the disease. Further, patients with higher severity of the SARS-CoV-2 infection are also at risk of retaining some neurological complications in the long-run. Treatment of such severe hyperinflammatory conditions will also be discussed, as well as the risks they may pose to the progression of the disease. For this review, articles pertaining information on the neurological manifestation of SARS-CoV-2 infection were gathered from PubMed and Google Scholar using the search keywords "SARS-CoV-2", "COVID-19", and "neurological dysfunction". The findings of the search were filtered, and relevant information were included.

Oral manifestations of Covid-19-A literature review.

Initially, it was reported that coronavirus 2019 disease (Covid-19) affects respiratory, gastrointestinal and neurological systems, but the oral, olfactory and integumentary systems are also involved. This review discusses various oral manifestations of Covid-19 reported in the literature along with possible underlying mechanisms. The reported manifestations include taste impairment, oral mucosal changes (petechiae, ulcers, plaque-like lesions, reactivation of herpes simplex virus 1(HSV1), geographical tongue and desquamative gingivitis) and dry mouth. The prominent location for mucosal lesions are tongue, palate and labial mucosa. The exact pathogenesis of these oral symptoms is not known. Angiotensin-converting enzyme 2 (ACE2) cell receptors are expressed in abundance on oral mucosa allowing severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) to infect them. Gustatory impairment along with olfactory changes is now listed as a symptom of Covid-19 by the World Health Organization, but further research is needed to confirm a link between reported additional oral symptoms and Covid-19. Dental professionals may encounter individuals with Covid-19 and be called upon to identify various oral manifestations of this disease.

COVID-19 with and without anosmia or dysgeusia: A case-control study.

Various new clinical signs and symptoms, such as dysfunction of smell (anosmia) and taste (dysgeusia) have emerged ever since the coronavirus disease 2019 (COVID-19) pandemic begun. The objective of this study was to identify the clinical presentation and factors associated with 'new loss/change of smell (anosmia) or taste (dysgeusia)' at admission in patients positive by real time polymerase chain reaction for SARS-CoV-2 infection. All adult COVID-19 patients with new onset anosmia or dysgeusia at admission were included in study group. Equal number of age and gender matched COVID-19 patients without anosmia or dysgeusia at admission were included in the control group. A total of 261 COVID-19 patients were admitted during the study period of which 55 (21%) had anosmia and or dysgeusia. The mean (SD) age was 36 (13) years and majority were males (58%, n = 32). Comorbidity was present in 38% of cases (n = 21). Anosmia and dysgeusia were noted in more than 1/5th of the cases. Anosmia (96%, n = 53) was more common than dysgeusia (75%, n = 41). Presence of both ansomia and dysgeusia was noted in 71% of patients (n = 39). On comparing the cases with the controls, on univariate analysis, fever (higher in cases), rhinitis (lower in cases), thrombocytopenia, elevated creatinine and bilirubin (all higher in cases) were significantly associated with anosmia or dysgeusia. On multivariate analysis, only rhinitis (odds ratio [OR]: 0.28; 95% confidence interval [CI]: 0.09-0.83; p = .02) thrombocytopenia (OR: 0.99; 95% CI: 0.99-0.99; p = .01) and elevated creatinine (OR: 7.6; 95% CI: 1.5-37.6; p = .01) remained significant. In this retrospective study of COVID-19 patients, we found anosmia and dysgeusia in more than 1/5th of the cases. Absence of rhinitis, low platelet counts and elevated creatinine were associated with anosmia or dysgeusia in these patients.

A comparative study on the clinical features of COVID-19 with non-SARS-CoV-2 respiratory viral infections.

During this coronavirus disease 2019 (COVID-19) pandemic, physicians have the important task of risk stratifying patients who present with acute respiratory illnesses. Clinical presentation of COVID-19, however, can be difficult to distinguish from other respiratory viral infections. Thus, identifying clinical features that are strongly associated with COVID-19 in comparison to other respiratory viruses can aid risk stratification and testing prioritization especially in situations where resources for virological testing and resources for isolation facilities are limited. In our retrospective cohort study comparing the clinical presentation of COVID-19 and other respiratory viral infections, we found that anosmia and dysgeusia were symptoms independently associated with COVID-19 and can be important differentiating symptoms in patients presenting with acute respiratory illness. On the other hand, laboratory abnormalities and radiological findings were not statistically different between the two groups. In comparing outcomes, patients with COVID-19 were more likely to need high dependency or intensive care unit care and had a longer median length of stay. With our findings, we emphasize that epidemiological risk factors and clinical symptoms are more useful than laboratory and radiological abnormalities in differentiating COVID-19 from other respiratory viral infections.

Covid-19 and oral diseases: Crosstalk, synergy or association?

The coronavirus disease 2019 (Covid-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that clinically affects multiple organs of the human body. Cells in the oral cavity express viral entry receptor angiotensin-converting enzyme 2 that allows viral replication and may cause tissue inflammation and destruction. Recent studies have reported that Covid-19 patients present oral manifestations with multiple clinical aspects. In this review, we aim to summarise main signs and symptoms of Covid-19 in the oral cavity, its possible association with oral diseases, and the plausible underlying mechanisms of hyperinflammation reflecting crosstalk between Covid-19 and oral diseases. Ulcers, blisters, necrotising gingivitis, opportunistic coinfections, salivary gland alterations, white and erythematous plaques and gustatory dysfunction were the most reported clinical oral manifestations in patients with Covid-19. In general, the lesions appear concomitant with the loss of smell and taste. Multiple reports show evidences of necrotic/ulcerative gingiva, oral blisters and hypergrowth of opportunistic oral pathogens. SARS-CoV-2 exhibits tropism for endothelial cells and Covid-19-mediated endotheliitis can not only promote inflammation in oral tissues but can also facilitate virus spread. In addition, elevated levels of proinflammatory mediators in patients with Covid-19 and oral infectious disease can impair tissue homeostasis and cause delayed disease resolution. This suggests potential crosstalk of immune-mediated pathways underlying pathogenesis. Interestingly, few reports suggest recurrent herpetic lesions and higher bacterial growth in Covid-19 subjects, indicating SARS-CoV-2 and oral virus/bacteria interaction. Larger cohort studies comparing SARS-CoV-2 negative and positive subjects will reveal oral manifestation of the virus on oral health and its role in exacerbating oral infection.

[Smell and taste in CoViD-19 patients: the forgotten sense.] / L'olfatto e il gusto nei pazienti CoViD-19: il senso dimenticatoTempi di recupero della funzionalità olfattoria e gustativa nei pazienti CoViD-19.

AIM: The aim of the retrospective study is to determine whether CoViD-19 positive patients with olfactory and gustatory dysfunction have the ability to recover chemoreceptorial loss, unlike other viral and inflammatory diseases in which the damage is partial and in some cases is permanent. MATERIALS AND METHODS: The study examined 75 patients admitted, from March to April 2020, at the Poliambulanza Foundation with CoViD-19. In 53 out of 75 patients, chest X-rays were positive for infiltration and/or pleural effusion. Two weeks after discharge, two rhinopharyngeal swabs were performed with negative results for CoViD-19. Enlisted patients responded to a questionnaire, upon informed consent, called the Questionnaire for Olfactory Dysfunction (QOD) which evaluates the severity of the disorder and social impact. In the second phase of the study we carefully researched the recovery times of olfactory dysfunction and dysgeusia. RESULTS AND CONCLUSIONS: The analysis of the scores of the Olfactory Dysfunction Questionnaire CoViD-19 (QOD) recorded the total recovery in all patients of olfactory and gustatory function with an average time of 17.4 days. This study reveals that Coronavirus does not cause a permanent olfactory and gustatory loss. The olfactory and gustatory impairment has been recognized as a distinctive sign of CoViD-19, but should not be considered as a favorable prognostic index.

Dysosmia and dysgeusia in patients with COVID-19 in northern Taiwan.

BACKGROUND/PURPOSE: To investigate the characteristics of dysosmia and dysgeusia among patients diagnosed with coronavirus disease 2019 (COVID-19) in Taiwan. METHODS: Prospective data collection between January 22, 2020 to May 7, 2020 of nucleic acid confirmed COVID-19 hospitalized patients in northern Taiwan by the Taiwan Centers for Disease Control were analyzed. RESULTS: Of 217 patients enrolled, 78 (35.9%) reported dysosmia (n = 73, 33.6%) and/or dysgeusia (n = 62, 28.6%). The median duration of COVID-19 associated symptom-onset to development of dysosmia and/or dysgeusia was <1 days (interquartile range [IQR], <1-6 days) and 53 of 78 (67.9%) patients developed dysosmia and/or dysgeusia as one of the initial symptoms of COVID-19. Of 59 closely monitored patients, 41 (69.5%) patients recovered within 3 weeks after symptoms onset and the median time to recovery was 12 days (IQR, 7-20 days). Only 6 of the 59 (10.2%) patients reported persistent dysosmia and/or dysgeusia before discharge from hospitals. Multivariate analysis showed that younger individuals (adjusted hazard ratio [AHR], 0.93 per one-year increase; 95% confidence interval [95% CI], 0.89-0.97; P = 0.001), women (AHR, 2.76; 95% CI, 1.05-7.25; P = 0.04) and travel to North America (AHR, 2.35; 95% CI, 1.05-5.26; P = 0.04) were the significant factors associated with dysosmia and/or dysgeusia. CONCLUSION: Dysosmia and/or dysgeusia are common symptoms and clues for the diagnosis of COVID-19, particularly in the early stage of the disease. Physicians should be alerted to these symptoms to make timely diagnosis and management for COVID-19 to limit spread.

[Clinical manifestations and course of the first six reported cases of COVID-19 in the medical doctors of Peru]. / Manifestaciones clínicas y evolución de seis primeros casos reportados de COVID-19 en personal médico de Perú.

INTRODUCTION: Health personnel, including physicians, are a fundamental part of the first line of defense against the SARS-CoV-2 pandemic. OBJECTIVE: To characterize the clinical manifestations and course of the first cases of contagion by SARS-CoV-2 in doctors of Peru. METHODOLOGY: We present a series of six cases of doctors infected by SARS-CoV-2, with confirmed positivity for COVID-19, showing the daily evolution from the diagnosis of the disease, its main signs and symptoms, evolution, and until the outcome in each case. RESULTS: Five were men. The median age was 28 years (interquartile range: 27 to 33). In three cases the physician worked more than 12 hours a day in emergency and hospitalization services and not wear a mask at all times. The most frequent symptoms were axillary temperature above 38°C, malaise, dry cough, and odynophagia (the latter in three of the cases). The diagnosis was made at a median of 3 days (interquartile range: 3 to 4 days). The symptoms that persisted the most were dry cough (present during ten days in four doctors). Dysgeusia was the only symptom with the most extended duration (15 days in only one doctor). In the six cases, the course was favorable. However, these doctors found it difficult to return to functions in their hospital centers adequately. DISCUSSION: Despite a small number of cases, it is the first report detailing the evolution of symptoms day by day, which can help for occupational health and even for case surveillance and monitoring.

INTRODUCCIÓN: El personal de salud, entre ellos los médicos, es parte fundamental en primera línea de defensa ante la pandemia de COVID-19, causada por SARS-Cov-2. OBJETIVO: Caracterizar la clínica y evolución de los primeros casos de contagio por coronavirus en médicos de Perú. METODOLOGÍA: Se presentan una serie de seis casos de médicos infectados por coronavirus, con positividad confirmada para COVID-19, mostrando la evolución diaria desde el diagnóstico de la enfermedad, sus principales signos y síntomas, la evolución de los mismos y hasta el desenlace en cada caso. RESULTADOS: De los casos estudiados, cinco fueron hombres, tenían una mediana de edad de 28 años (rango intercuartílico: 27 a 33). Tres de ellos trabajaban más de 12 horas al día en servicios de hospitalización y emergencia; y tres no contaban con mascarilla como método de protección personal. Los síntomas más frecuentes fueron la temperatura axilar superior a 38 grados Celsius, el malestar general, la tos seca y la odinofagia (este último en tres pacientes). En cuanto al diagnóstico con la prueba molecular, tuvo una mediana de tres días de demora (con rango: de 2 a 6 días). Los síntomas que más persistieron fueron la tos seca (presente durante 10 días en cuatro médicos), y la disgeusia como síntoma único, que tuvo la mayor duración (15 días en un solo médico). En los seis casos la evolución fue favorable. Sin embargo, aún se tienen deficiencias para la definición de reincorporación laboral a sus centros hospitalarios. DISCUSIÓN: A pesar de ser un número pequeño de casos, es el primer reporte en personal de salud y que detalla día a día la evolución de los síntomas de COVID-19. Esto puede servir para la salud ocupacional, e incluso como base para la vigilancia y monitorización de los casos en una población mayor.

Does COVID-19 cause permanent damage to olfactory and gustatory function?

The objective of this study was to investigate the status of COVID-19 patients with sudden anosmia and dysgeusia using an olfactory dysfunction questionnaire highlighting recovery times. This prospective study included 75 patients who completed a patient-reported outcome questionnaire. Among these, 46 patients completed an olfactory evaluation based on the duration of anosmia and dysgeusia. The olfactory evaluation revealed that 24% (N = 18) of patients had mild hyposmia, 13% (N = 10) had moderate hyposmia, 30% (N = 23) had severe hyposmia, 32% (N = 24) had anosmia, and 100% had dysgeusia (N = 75). The viral load significantly decreased throughout the 17 days following the onset of the olfactory disorder. The purpose of this study was to understand whether patients with COVID-19 can recover olfactory and gustatory function, in contrast to patients with other rhinoviruses and inflammatory diseases such as rhinosinusitis chronic and rhinosinusitis with polyps. These preliminary clinical findings indicate that the relatively rapid recovery of olfactory and gustative function can mean a resolution of viral infection in most patients. The present study suggests that coronavirus can induce olfactory dysfunction but not permanent damage. Olfactory and gustatory functional impairment has been recognized as a hallmark of COVID-19 and may be an important predictor of clinical outcome. Our study supports the need to add anosmia and dysgeusia to the list of symptoms used in screening tools for possible COVID-19 infection.

Augmented curation of clinical notes from a massive EHR system reveals symptoms of impending COVID-19 diagnosis.

Understanding temporal dynamics of COVID-19 symptoms could provide fine-grained resolution to guide clinical decision-making. Here, we use deep neural networks over an institution-wide platform for the augmented curation of clinical notes from 77,167 patients subjected to COVID-19 PCR testing. By contrasting Electronic Health Record (EHR)-derived symptoms of COVID-19-positive (COVIDpos; n = 2,317) versus COVID-19-negative (COVIDneg; n = 74,850) patients for the week preceding the PCR testing date, we identify anosmia/dysgeusia (27.1-fold), fever/chills (2.6-fold), respiratory difficulty (2.2-fold), cough (2.2-fold), myalgia/arthralgia (2-fold), and diarrhea (1.4-fold) as significantly amplified in COVIDpos over COVIDneg patients. The combination of cough and fever/chills has 4.2-fold amplification in COVIDpos patients during the week prior to PCR testing, in addition to anosmia/dysgeusia, constitutes the earliest EHR-derived signature of COVID-19. This study introduces an Augmented Intelligence platform for the real-time synthesis of institutional biomedical knowledge. The platform holds tremendous potential for scaling up curation throughput, thus enabling EHR-powered early disease diagnosis.

[Neurological aspects of the COVID-19 pandemic caused by the SARS-CoV-2 coronavirus]. / A SARS-CoV-2 koronavírus által okozott COVID-19-járvány neurológiai vonatkozásai.

By the spring of 2020 the COVID-19 outbreak caused by the new SARS-CoV-2 coronavirus has become a pandemic, requiring fast and efficient reaction from societies and health care systems all over the world. Fever, coughing and dyspnea are considered the major signs of COVID-19. In addition to the involvement of the respiratory system, the infection may result in other symptoms and signs as well. Based on reports to date, neurological signs or symptoms appear in 30-50% of hospitalized COVID-19 patients, with higher incidence in those with more severe disease. Classical acute neurological syndromes have also been reported to associate with COVID-19. A drop in the volume of services for other acute diseases has been described in countries with healthcare systems focusing on COVID-19. During the COVID-19 epidemic it is also important to provide appropriate continuous care for those with chronic neurological disorders. It will be the task of the future to estimate the collateral damage caused by the COVID-19 epidemic on the outcome of other neurological disorders, and to screen for the possible late neurological complications of the SARS-CoV-2 coronavirus infection.

Clinical features of COVID-19 and influenza: a comparative study on Nord Franche-Comte cluster.

Clinical descriptions about influenza-like illnesses (ILI) in COVID-19 seem non-specific. We aimed to compare the clinical features of COVID-19 and influenza. We retrospectively investigated the clinical features and outcomes of confirmed cases of COVID-19 and influenza in Nord Franche-Comté Hospital between February 26th and March 14th 2020. We used SARS-CoV-2 RT-PCR and influenza virus A/B RT-PCR in respiratory samples to confirm the diagnosis. We included 124 patients. The mean age was 59 (±19 [19-98]) years with 69% female. 70 patients with COVID-19 and 54 patients with influenza A/B. Regarding age, sex and comorbidities, no differences were found between the two groups except a lower Charlson index in COVID-19 group (2 [±2.5] vs 3 [±2.4],p = 0.003). Anosmia (53% vs 17%,p < 0.001), dysgeusia (49% vs 20%,p = 0.001), diarrhea (40% vs 20%,p = 0.021), frontal headache (26% vs 9%,p = 0.021) and bilateral cracklings sounds (24% vs 9%,p = 0.034) were statistically more frequent in COVID-19. Sputum production (52% vs 29%,p = 0.010), dyspnea (59% vs 34%,p = 0.007), sore throat (44% vs 20%,p = 0.006), conjunctival hyperhemia (30% vs 4%,p < 0.001), tearing (24% vs 6%,p = 0.004), vomiting (22% vs 3%,p = 0.001) and rhonchi sounds (17% vs 1%,p = 0.002) were more frequent with influenza infection. We described several clinical differences which can help the clinicians during the co-circulation of influenza and SARS-CoV-2.

Acute smell and taste loss in outpatients: all infected with SARS-CoV-2?

During SARS-CoV-2 pandemic, our region (Alsace, East of France) became a Covid-19 cluster quite early in Europe. Loss of smell and taste was quickly flagged by the Ears-Nose and Throat scientific community as a potential warning signs of SARS-CoV-2 infection (1). Many patients and medical/paramedical workers with mild to moderate form of SARS-CoV-2 infection complained about their loss of sense of smell and taste to our ENT department. The aim of our study was to compare the characteristics of loss of smell and taste between patients with a clinical diagnosis of SARS-CoV-2 infection to patients with a RT-PCR diagnosis.

COVID-19: to be or not to be; that is the diagnostic question.

Since the first cases in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread across the globe, resulting in the COVID-19 pandemic. Early clinical experiences have demonstrated the wide spectrum of SARS-CoV-2 presentations, including various reports of atypical presentations of COVID-19 and possible mimic conditions.This article summarises the current evidence surrounding atypical presentations of COVID-19 including neurological, cardiovascular, gastrointestinal, otorhinolaryngology and geriatric features. A case from our hospital of pneumocystis pneumonia initially suspected to be COVID-19 forms the basis for a discussion surrounding mimic conditions of COVID-19. The dual-process model of clinical reasoning is used to analyse the thought processes used to make a diagnosis of COVID-19, including consideration of the variety of differential diagnoses.While SARS-CoV-2 is likely to remain on the differential diagnostic list for a plethora of presentations for the foreseeable future, clinicians should be cautious of ignoring other potential diagnoses due to availability bias. An awareness of atypical presentations allows SARS-CoV-2 to be a differential so that it can be appropriately investigated. A knowledge of infectious mimics prevents COVID-19 from overshadowing other diagnoses, hence preventing delayed diagnosis or even misdiagnosis and consequent adverse outcomes for patients.

Sniffing out the evidence; It's now time for public health bodies recognize the link between COVID-19 and smell and taste disturbance.

Since the outbreak of the pandemic, anecdotal observations have been accumulating rapidly that sudden anosmia and dysgeusia are peculiar symptoms associated with the COVID-19 infection. Prof C. Hopkins, as President of British Rhinological Society, published a letter describing "the loss of sense of smell as a marker of COVID-19 infection" and proposed that adults presenting with anosmia but no other symptoms should self-isolate for seven days. The Hopkins team published the first case report and case series as well as other evidence that isolated sudden onset anosmia (ISOA), should be considered highly suspicious for SARS-CoV-2(1). Subsequently, a larger series of 2428 patients presenting with new onset anosmia during the COVID-19 pandemic has been reported, of whom 16% report loss of sense of smell as an isolated symptom. Only 51% reported the recognized symptoms of cough or fever. A major limitation of this series however, was a lack of access to testing to confirm the COVID-19 status of the patients(2); in the 80 who had been tested 74% were positive. In the same way, the American Academy of Otolaryngology-head and neck surgery (AA0-HNS) proposed "that anosmia could be added to the list of screening tools for possible COVID-19 infection. More, they warrant serious consideration for self-isolation and testing those patients".

Updates on What ACS Reported: Emerging Evidences of COVID-19 with Nervous System Involvement.

With the ongoing pandemic of coronavirus disease (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), our knowledge of the pathogenesis of COVID-19 is still in its infancy. Almost every aspect of the pathogen remains largely unknown, ranging from mechanisms involved in infection transmission, interplay with the human immune system, and covert mechanisms of end-organ damage. COVID-19 has manifested itself worldwide with a syndromic appearance that is dominated by respiratory dysregulations. While clinicians are focused on correcting respiratory homeostasis, echoing the original SARS, SARS-CoV-2 is also invading other end-organs, which may not exhibit overt clinical features. Nervous system involvement was not initially considered to play a significant role in patients with COVID-19. However, since this viewpoint was initially published, multiple studies have been released regarding the possible neurovirulence of SARS-CoV-2. In our previous viewpoint, we implored our colleagues to recognize the covert tactics of SARS-CoV-2 and emphasized that symptoms like anosmia, dysgeusia, ataxia, and altered mental status could be early signs of the neurotropic potential of this virus. The past few weeks, after the viewpoint surfaced, it was noticed that it has enabled clinicians and healthcare professionals to compute the neurovirulence associated with SARS-CoV-2 in COVID-19 patients, as evidenced by very recently reported studies.