Long COVID Clusters of Symptoms Persist beyond Two Years after Infection: Insights from the CARDIO COVID 20-21 Registry.

Long COVID presents with diverse symptoms after COVID-19. Different clusters of symptoms have been reported; however, their persistence beyond 2 years after COVID-19 remains unclear. In this cohort study, we prospectively evaluated individuals with previous severe COVID-19 presenting with long COVID at a two-year follow-up. We characterized the included patients and performed a cluster analysis of symptoms through multiple correspondence analysis and hierarchical clustering. A total of 199 patients with long COVID were included. The median age was 58 years (48-69), 56% were male, and the median follow-up time since the COVID-19 diagnosis was 26 months (IQR: 25, 27). Three symptom clusters were identified: Cluster 1 is characterized by fatigue, myalgia/arthralgia, a low prevalence of symptoms, and a lack of specific symptoms; Cluster 2 is defined by a high prevalence of fatigue, myalgia/arthralgia, and cardiorespiratory symptoms, including palpitations, shortness of breath, cough, and chest pain; and Cluster 3 is demonstrated a high prevalence of ageusia, anosmia, fatigue, and cardiorespiratory symptoms. Our study reinforces the concept of symptom clustering in long COVID, providing evidence that these clusters may persist beyond two years after a COVID-19 diagnosis. This highlights the chronic and debilitating nature of long COVID and the importance of developing strategies to mitigate symptoms in these patients.

The long-term loss of smell and taste in Covid-19 patients ­ a systematic review and meta-analysis / A perda de olfato e paladar a longo prazo em pacientes com Covid-19 ­ uma revisão sistemática e meta-análise

INTRODUCTION: Olfactory symptoms have been reported as particular in COVID-19 patients. OBJECTIVE: To synthesize and analyze the existing evidence on the monitoring loss of sense of smell and taste in COVID-19 patients, and for how long symptoms persist after the virus is no longer active in the organism. METHODS: A search was implemented in PubMed, Embase, Scopus, Science Direct, and Web of Science databases. This systematic review and meta-analysis were conducted according to PRISMA, and the risk of bias was assessed through the Newcastle-Ottawa Scale. The review protocol is registered in PROSPERO. RESULTS: Our systematic review included data from 14 articles with a total of 2143 participants. The most reported sensory symptom of COVID-19 was anosmia, which was detected in 1499 patients, being the only symptom to appear in all studies. Ageusia was detected in 595 patients, dysgeusia in 514 patients, and hyposmia in 209 patients. The studies provided the number of 729 patients with sensory symptoms during the acute COVID-19 infection of 15 days, and 1020 patients with lasting sensory symptoms, presenting sensory dysfunctions after the average latent period of 15 days of the acute COVID-19 infection. CONCLUSION: Evidence points to the loss or dysfunction of taste and smell as one of the symptoms of COVID-19 persisting for an average time of 15 days, with 44% of COVID-19 patients with persistent symptoms for more than 15 days. Nevertheless, most studies do not perform a follow-up with those patients. Therefore, further research on sensory symptoms and their follow-up is required.

INTRODUÇÃO: Sintomas olfativos foram relatados como específicos em pacientes com COVID-19. OBJETIVO: Sintetizar e analisar as evidências existentes sobre o monitoramento da perda de olfato e paladar em pacientes com COVID-19 e por quanto tempo os sintomas persistem. MÉTODOS: Foi realizada uma busca nas bases de dados PubMed, Embase, Scopus, Science Direct e Web of Science. Esta revisão sistemática e metanálise foi realizada de acordo com o PRISMA, e o risco de viés foi avaliado por meio da Escala de Newcastle-Ottawa. O protocolo de revisão está registrado no PROSPERO. RESULTADOS: Nossa revisão sistemática incluiu dados de 14 artigos com um total de 2143 participantes. O sintoma sensorial mais comumente relatado de COVID-19 foi anosmia, detectado em 1.499 pacientes, sendo o único sintoma a aparecer em todos os estudos. Ageusia foi detectada em 595 pacientes, disgeusia em 514 pacientes e hiposmia em 209 pacientes. Os estudos forneceram o número de 729 pacientes com sintomas sensoriais por 15 dias durante a infecção aguda por COVID-19 e 1020 pacientes com sintomas sensoriais duradouros, apresentando disfunções sensoriais após o período latente médio de 15 dias da infecção aguda por COVID-19. CONCLUSÃO: Evidências apontam a perda ou disfunção do paladar e olfato como um dos sintomas da COVID-19 persistindo por um tempo médio de 15 dias, com 44% dos pacientes com COVID-19 com sintomas persistentes por mais de 15 dias. No entanto, a maioria dos estudos não realiza acompanhamento desses pacientes. Portanto, mais pesquisas sobre sintomas sensoriais e seu acompanhamento são necessárias.

Bilateral hypogeusia and food aversion due to lacunar infarct in the right dorsomedial pontine tegmentum.

A 70-year-old right-handed housewife suffered an acute loss of taste, an unpleasant change in the taste of foods and liquids, and a strong aversion to all kinds of food due to a small lacune in the right dorsomedial pontine tegmentum. Eating became so unpleasant that she lost 7 kg in three weeks. Olfaction and the sensibility of the tongue were spared. The right medial longitudinal fascicle, the central tegmental tract, or both, were injured by the tegmental lesion. A discrete right-sided lesion in the upper pontine tegmentum may cause a reversible syndrome consisting of bilateral hypogeusia which is more severe ipsilaterally.

Can photobiomodulation restore anosmia and ageusia induced by COVID-19? A pilot clinical study.

Along with other COVID-19 clinical manifestations, management of both olfactory and gustatory dysfunction have drawn a considerable attention. Photobiomodulation (PBM) has emerged to be a possible effective therapy in restoring taste and smell functionality, but the evidence is scarce. Hence, the present pilot study is aimed to evaluate the effectiveness of intranasal and intraoral PBM administrations in management of anosmia and ageusia respectively. Twenty Caucasian subjects who diagnosed with anosmia and ageusia were recruited. Visual analogue scale was utilised to evaluate patients' self-reported for both olfactory and gustatory functionality. The laser-PBM parameters and treatment protocols for anosmia and ageusia were as follows respectively: 660 nm, 100 mW, two points intranasally, 60 J/session, 12 sessions; dual wavelengths (660 nm and 808 nm), 100 mW, three points intraorally, 216 J/session, 12 sessions. Our results showed a significant functionality improvement of both olfactory and gustatory functionality. Extensive studies with large data and long-term follow-up period are warranted.

Neurological symptoms and comorbidity profile of hospitalized patients with COVID-19.

BACKGROUND: The neurological manifestations in COVID-19 adversely impact acute illness and post-disease quality of life. Limited data exist regarding the association of neurological symptoms and comorbid individuals. OBJECTIVE: To assess neurological symptoms in hospitalized patients with acute COVID-19 and multicomorbidities. METHODS: Between June 2020 and July 2020, inpatients aged 18 or older, with laboratory-confirmed COVID-19, admitted to the Hospital São Paulo (Federal University of São Paulo), a tertiary referral center for high complexity cases, were questioned about neurological symptoms. The Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaire was used. The data were analyzed as a whole and whether subjective olfactory dysfunction was present or not. RESULTS: The mean age of the sample was 55 ± 15.12 years, and 58 patients were male. The neurological symptoms were mostly xerostomia (71%), ageusia/hypogeusia (50%), orthostatic intolerance (49%), anosmia/hyposmia (44%), myalgia (31%), dizziness (24%), xerophthalmia (20%), impaired consciousness (18%), and headache (16%). Furthermore, 91% of the patients had a premorbidity. The 44 patients with subjective olfactory dysfunction were more likely to have hypertension, diabetes, weakness, shortness of breath, ageusia/hypogeusia, dizziness, orthostatic intolerance, and xerophthalmia. The COMPASS-31 score was higher than that of previously published controls (14.85 ± 12.06 vs. 8.9 ± 8.7). The frequency of orthostatic intolerance was 49% in sample and 63.6% in those with subjective olfactory dysfunction (2.9-fold higher risk compared to those without). CONCLUSION: A total of 80% of inpatients with multimorbidity and acute COVID-19 had neurological symptoms. Chemical sense and autonomic symptoms stood out. Orthostatic intolerance occurred in around two-thirds of the patients with anosmia/hyposmia. Hypertension and diabetes were common, mainly in those with anosmia/hyposmia.

ANTECEDENTES: As manifestações neurológicas na COVID-19 impactam adversamente na enfermidade aguda e na qualidade de vida após a doença. Dados limitados existem em relação a associação de sintomas neurológicos e indivíduos com comorbidades. OBJETIVO: Avaliar os sintomas neurológicos em pacientes de hospitalizados com COVID-19 aguda e múltiplas comorbidades. MéTODOS: Entre junho e julho de 2020, pacientes de hospitais com idade 18 anos ou acima e COVID-19 laboratorialmente confirmada, admitidos no Hospital São Paulo (Universidade Federal de São Paulo), um centro de referência terciário para casos de alta complexidade, foram perguntados sobre sintomas neurológicos. O questionário Pontuação composta de sintoma autonômico (COMPASS-31) foi usado. Os dados foram analisados no geral e se a disfunção olfatória subjetiva estava presente ou não. RESULTADOS: A média de idade da amostra foi 55 ± 15.12 anos. 58 pacientes eram homens. Os sintomas neurológicos foram principalmente xerostomia (71%), ageusia/hipogeusia (50%), intolerância ortostática (49%), anosmia/hiposmia (44%), mialgia (31%), tontura (24%), xeroftalmia (20%), comprometimento na consciência (18%) e cefaleia (16%). Além disso, 91% dos pacientes tinham uma pré-morbidade. Os 44 pacientes com disfunção olfatória tinham maior chance de ter hipertensão, diabetes, fraqueza, falta de ar, ageusia/hipogeusia, tontura, intolerância ortostática e xeroftalmia. A pontuação do COMPASS-31 foi maior do que a de controles previamente publicados (14,85 ± 12,06 vs. 8,9 ± 8,7). A frequência de intolerância ortostática foi 49% na amostra e 63,6% naqueles com disfunção olfatória subjetiva (risco 2.9 vezes maior comparado com os sem). CONCLUSãO: Um total de 80% dos pacientes hospitalizados com múltiplas morbidades e COVID-19 aguda tinham sintomas neurológicos. Os sintomas do sentido químico e autonômicos se destacaram. A intolerância ortostática ocorreu em cerca de dois terços dos pacientes com anosmia/hiposmia. A hipertensão e o diabetes foram comuns, principalmente naqueles com anosmia/hiposmia.

Applying fuzzy qualitative comparative analysis to identify typical symptoms of COVID-19 infection in a primary care unit, Rio de Janeiro, Brazil.

This study aims to identify a set of symptoms that could be predictive of SARS-CoV-2 cases in the triage of Primary Care services with the contribution of Qualitative Comparative Analysis (QCA) using Fuzzy Sets (fsQCA). A cross-sectional study was carried out in a Primary Health Care Unit/FIOCRUZ from 09/17/2020 to 05/05/2021. The study population was suspect cases that performed diagnostic tests for COVID-19. We collected information about the symptoms to identify which configurations are associated with positive and negative cases. For analysis, we used fsQCA to explain the outcomes "being a positive case" and "not being a positive case". The solution term "loss of taste or smell and no headache" showed the highest degree of association with the positive result (consistency = 0.81). The solution term "absence of loss of taste or smell combined with the absence of fever" showed the highest degree of association (consistency = 0,79) and is the one that proportionally best explains the negative result. Our results may be useful to the presumptive clinical diagnosis of COVID-19 in scenarios where access to diagnostic tests is not available. We used an innovative method used in complex problems in Public Health, the fsQCA.

Frequency and burden of neurological manifestations upon hospital presentation in COVID-19 patients: Findings from a large Brazilian cohort.

BACKGROUND: Scientific data regarding the prevalence of COVID-19 neurological manifestations and prognosis in Latin America countries is still lacking. Therefore, the study aims to understand neurological manifestations of SARS-CoV 2 infection and outcomes in the Brazilian population. METHODS: This study is part of the Brazilian COVID-19 Registry, a multicentric cohort, including data from 37 hospitals. For the present analysis, patients were grouped according to the presence of reported symptoms (i.e., headache; anosmia and ageusia; syncope and dizziness) vs. clinically-diagnosed neurological manifestations (clinically-defined neurological syndrome: neurological signs or diagnoses captured by clinical evaluation) and matched with patients without neurological manifestations by age, sex, number of comorbidities, hospital of admission, and whether or not patients had underlying neurological disease. RESULTS: From 6,635 hospitalized patients with COVID-19, 30.8% presented reported neurological manifestations, 10.3% were diagnosed with a neurological syndrome and 60.1% did not show any neurological manifestations. In patients with reported symptoms, the most common ones were headache (20.7%), ageusia (11.1%) and anosmia (8.0%). In patients with neurological syndromes, acute encephalopathy was the most common diagnosis (9.7%). In the matched analysis, patients with neurological syndromes presented more cases of septic shock (17.0 vs. 13.0%, p = 0.045), intensive care unit admission (45.3 vs. 38.9%, p = 0.023), and mortality (38.7 vs. 32.6%, p = 0.026; and 39.2 vs. 30.3%, p < 0.001) when compared to controls. CONCLUSION: COVID-19 in-hospital patients with clinically defined neurological syndromes presented a higher incidence of septic shock, ICU admission and death when compared to controls.

Negative correlation between ACE2 gene expression levels and loss of taste in a cohort of COVID-19 hospitalized patients: New clues to long-term cognitive disorders.

In early 2020, one of the most prevalent symptoms of SARS-CoV-2 infection was the loss of smell (anosmia), found in 60-70% of all cases. Anosmia used to occur early, concomitantly with other symptoms, and often persisted after recovery for an extended period, sometimes for months. In addition to smell disturbance, COVID-19 has also been associated with loss of taste (ageusia). The latest research suggests that SARS-CoV-2 could spread from the respiratory system to the brain through receptors in sustentacular cells localized to the olfactory epithelium. The virus invades human cells via the obligatory receptor, angiotensin-converting enzyme II (ACE2), and a priming protease, TMPRSS2, facilitating viral penetration. There is an abundant expression of both ACE2 and TMPRSS2 in sustentacular cells. In this study, we evaluated 102 COVID-19 hospitalized patients, of which 17.60% presented anosmia and 9.80% ageusia. ACE1, ACE2, and TMPRSS2 gene expression levels in nasopharyngeal tissue were obtained by RT-qPCR and measured using ΔCT analysis. ACE1 Alu287bp association was also evaluated. Logistic regression models were generated to estimate the effects of variables on ageusia and anosmia Association of ACE2 expression levels with ageusia. was observed (OR: 1.35; 95% CI: 1.098-1.775); however, no association was observed between TMPRSS2 and ACE1 expression levels and ageusia. No association was observed among the three genes and anosmia, and the Alu287bp polymorphism was not associated with any of the outcomes. Lastly, we discuss whetherthere is a bridge linking these initial symptoms, including molecular factors, to long-term COVID-19 health consequences such as cognitive dysfunctions.

Epidemiological and clinical characteristics of survivors of SARS-COV-2 infection: A descriptive study. / Características epidemiológicas y clínicas de sobrevivientes a infección por SARS-CoV-2: estudio descriptivo.

Introduction: In March 2020, the World Health Organization (WHO) declared a pandemic for coronavirus 19. Typical symptoms were fever, cough, asthenia, dyspnea, and muscle pain. Pulmonary and central nervous system compromise presented challenging characteristics for healthcare physicians. The objectives of this study were to identify epidemiological and clinical characteristics of SARS-COV-2 infection survivors in a region of Argentina and to determine differences between gender, age groups, year of infection, and evolution time since diagnosis. Methods: A descriptive and analytical cross-sectional observational study was carried out. A self-administered questionnaire was applied, which was available between August and December 2021. Results: Among 1868 individuals included, the mean age was 39.4 ± 13.9 years, and 72.8% were female. Arterial hypertension was the most frequent comorbidity (11.7%). The majority were outpatients (81.9%). The most frequent presentation symptoms at all ages were asthenia (83.7%), fever (54.9%), headache (60.8%), anosmia (64.8%), ageusia (53.2%), cough (54.4%) and myalgias (53.7%). For the 18 to 29 years old age group, the most prevalent presentation symptoms were: headache (69.4%), anosmia (69.1%), ageusia (60.2%), odynophagia (45%), and rhinitis/nasal congestion (46.9%). In the 30 to 64 years old age group, there was a higher prevalence of myalgias (55.8%), arthralgias (41%), and concentration/memory disorder (28.3%). Male showed higher prevalence of fever (64.9% versus 51.1%; p < 0.001) and pneumonia (23.5% versus 13.4%; p < 0.001). After 12 weeks from diagnosis, 38.1% of patients persisted with asthenia, 23.6% with anosmia/dysosmia, and 21.2% with concentration/memory disorders. Conclusions: Systemic symptoms were common to all age groups with coronavirus 19 disease; however, younger, and intermediate age groups presented a higher prevalence of central nervous system symptoms such as anosmia and cognitive disorders, respectively. Symptoms beyond 12 weeks of diagnosis reached slightly more than 10% of the participants.

Introducción: En marzo de 2020 la enfermedad por coronavirus 19 fue declarada pandemia por la Organización Mundial de la Salud. Los síntomas más comunes fueron fiebre, tos, astenia, disnea y dolor muscular. Los compromisos pulmonar y del sistema nervioso central presentaron características desafiantes para los médicos asistenciales. Los objetivos del estudio fueron conocer las características epidemiológicas y clínicas de sobrevivientes a infección por SARS-CoV-2 en una región de Argentina, y determinar las diferencias entre género, grupos etarias, año de contagio, tiempo de evolución desde el diagnóstico. Métodos: Se realizó un estudio observacional descriptivo y analítico de corte transversal. Se aplicó un cuestionario auto administrado, que estuvo disponible entre agosto y diciembre de 2021. Resultados: La media de edad fue de 39,4 ± 13,9 años, el 72,8% fueron mujeres. La comorbilidad más frecuente fue hipertensión arterial (11,7%). La mayoría de los pacientes fueron ambulatorios (81,9%). Los síntomas de presentación más frecuentes a cualquier edad, fueron astenia (83,7%), fiebre (54,9%), cefalea (60,8%), anosmia (64,8%), ageusia (53,2%), tos (54,4%) y mialgias (53,7%). Para el grupo de 18 a 29 años los síntomas de presentación más prevalentes fueron cefalea (69,4%), anosmia 69,1%), ageusia (60,2%), odinofagia (45%) y rinitis/congestión nasal (46,9%). En el grupo de 30 a 64 años se observó mayor prevalencia de mialgias (55,8%), artralgias (41%), falta de concentración/memoria (28,3%). Los hombres mostraron más prevalencia de fiebre (64,9% versus 51,1%; p < 0,001) y neumonía (23,5% versus 13,4%; p < 0,001). Luego de las 12 semanas del diagnóstico 38,1% de los pacientes persistían con astenia, 23,6% con anosmia/disosmia y 21,2% con trastornos de concentración/memoria. Conclusiones: La enfermedad por coronavirus 19 presenta un patrón de síntomas sistémicos común a todos los grupos etarios. No obstante, los grupos más jóvenes presentan más prevalencia de síntomas de afección del sistema nervioso central como la anosmia y los grupos intermedios, mayor prevalencia de trastornos cognitivos. Los síntomas más allá de las 12 semanas del diagnóstico alcanzaron a algo más del 10% de los participantes.

Características epidemiológicas y clínicas de sobrevivientes a infección por SARS-CoV-2: estudio descriptivo / Epidemiological and clinical characteristics of survivors of SARS-COV-2 infection: a descriptive study

INTRODUCCIÓN: En marzo de 2020 la enfermedad por coronavirus 19 fue declarada pandemia por la Organización Mundial de la Salud. Los síntomas más comunes fueron fiebre, tos, astenia, disnea y dolor muscular. Los compromisos pulmonar y del sistema nervioso central presentaron características desafiantes para los médicos asistenciales. Los objetivos del estudio fueron conocer las características epidemiológicas y clínicas de sobrevivientes a infección por SARS-CoV-2 en una región de Argentina, y determinar las diferencias entre género, grupos etarias, año de contagio, tiempo de evolución desde el diagnóstico. MÉTODOS: Se realizó un estudio observacional descriptivo y analítico de corte transversal. Se aplicó un cuestionario auto administrado, que estuvo disponible entre agosto y diciembre de 2021. RESULTADOS: La media de edad fue de 39,4 ± 13,9 años, el 72,8% fueron mujeres. La comorbilidad más frecuente fue hipertensión arterial (11,7%). La mayoría de los pacientes fueron ambulatorios (81,9%). Los síntomas de presentación más frecuentes a cualquier edad, fueron astenia (83,7%), fiebre (54,9%), cefalea (60,8%), anosmia (64,8%), ageusia (53,2%), tos (54,4%) y mialgias (53,7%). Para el grupo de 18 a 29 años los síntomas de presentación más prevalentes fueron cefalea (69,4%), anosmia 69,1%), ageusia (60,2%), odinofagia (45%) y rinitis/congestión nasal (46,9%). En el grupo de 30 a 64 años se observó mayor prevalencia de mialgias (55,8%), artralgias (41%), falta de concentración/memoria (28,3%). Los hombres mostraron más prevalencia de fiebre (64,9% versus 51,1%; p < 0,001) y neumonía (23,5% versus 13,4%; p < 0,001). Luego de las 12 semanas del diagnóstico 38,1% de los pacientes persistían con astenia, 23,6% con anosmia/disosmia y 21,2% con trastornos de concentración/memoria. CONCLUSIONES: La enfermedad por coronavirus 19 presenta un patrón de síntomas sistémicos común a todos los grupos etarios. No obstante, los grupos más jóvenes presentan más prevalencia de síntomas de afección del sistema nervioso central como la anosmia y los grupos intermedios, mayor prevalencia de trastornos cognitivos. Los síntomas más allá de las 12 semanas del diagnóstico alcanzaron a algo más del 10% de los participantes.

INTRIDUCTION: In March 2020, the World Health Organization (WHO) declared a pandemic for coronavirus 19. Typical symptoms were fever, cough, asthenia, dyspnea, and muscle pain. Pulmonary and central nervous system compromise presented challenging characteristics for healthcare physicians. The objectives of this study were to identify epidemiological and clinical characteristics of SARS-COV-2 infection survivors in a region of Argentina and to determine differences between gender, age groups, year of infection, and evolution time since diagnosis. METHODS: A descriptive and analytical cross-sectional observational study was carried out. A self-administered questionnaire was applied, which was available between August and December 2021. RESULTS: Among 1868 individuals included, the mean age was 39.4 ± 13.9 years, and 72.8% were female. Arterial hypertension was the most frequent comorbidity (11.7%). The majority were outpatients (81.9%). The most frequent presentation symptoms at all ages were asthenia (83.7%), fever (54.9%), headache (60.8%), anosmia (64.8%), ageusia (53.2%), cough (54.4%) and myalgias (53.7%). For the 18 to 29 years old age group, the most prevalent presentation symptoms were: headache (69.4%), anosmia (69.1%), ageusia (60.2%), odynophagia (45%), and rhinitis/nasal congestion (46.9%). In the 30 to 64 years old age group, there was a higher prevalence of myalgias (55.8%), arthralgias (41%), and concentration/memory disorder (28.3%). Male showed higher prevalence of fever (64.9% versus 51.1%; p < 0.001) and pneumonia (23.5% versus 13.4%; p < 0.001). After 12 weeks from diagnosis, 38.1% of patients persisted with asthenia, 23.6% with anosmia/dysosmia, and 21.2% with concentration/memory disorders. CONCLUSIONS: Systemic symptoms were common to all age groups with coronavirus 19 disease; however, younger, and intermediate age groups presented a higher prevalence of central nervous system symptoms such as anosmia and cognitive disorders, respectively. Symptoms beyond 12 weeks of diagnosis reached slightly more than 10% of the participants.

Trastornos del gusto: actualización y aproximación clínica / Taste disorders: update and clinical approach

Resumen Los trastornos del gusto constituyen un grupo de alteraciones relativamente frecuentes en la práctica clínica. Son de etiología diversa, pudiendo afectar la vía gustativa en distintos niveles, manifestándose, clínicamente, con alteraciones cuantitativas y/o cualitativas de la sensibilidad gustativa. En gran parte de los casos se puede lograr un diagnóstico etiológico con una anamnesis adecuada, examen físico y exploraciones complementarias básicas. No obstante, existe poco entendimiento de su patogénesis, así como limitadas opciones terapéuticas, lo que implica la falta de algoritmos de diagnóstico y tratamiento completamente validados. El objetivo de la presente revisión es otorgar una actualización y un abordaje práctico de los trastornos del gusto.

Abstract Taste disorders represent a group of alterations relatively frequent in clinical practice. They have a diverse etiology, and they can affect the gustatory pathway at different levels, clinically manifesting with quantitative/qualitative alterations on taste sensitivity. In most of cases it is possibly to achieve an etiologically diagnosis with appropriate anamnesis, physical exploration, and basic complementary tests. However, their pathogenesis is not well understood, and they have limited therapeutic options, which determines a lack of well-validated diagnosis and treatment algorithms. The objective of this review is to provide and update and a practical approach to taste disorders.

Subjective assessment of taste and smell disfunction in patients with COVID-19 in Paraguay / Evaluación subjetiva de las alteraciones del sentido del gusto y del olfato en pacientes con COVID-19 en Paraguay

The alteration of the senses of taste and smell in relation to COVID-19 is a widely known phenomenon; however, this alteration has not been exhaustively characterized in the international literature. The following study is proposed with the aim of describing the alterations in the senses of taste and smell in relation to COVID-19 by means of their subjective evaluation. The nature of the study is observational, descriptive and cross-sectional, and was applied to patients who sought medical attention via remote consultations carried out on virtual platforms of the Service of Otorhinolaryngology and Head and Neck Surgery of the Clínicas Hospital, San Lorenzo, between the months of March and October of 2021. We included 440 patients aged 31.3 ± 9.9 years (18 to 60 years), 308 (70%) female, 388 (88%) from urban areas, with evidence of infection by SARS-CoV-2 by RT-PCR in 260 (59%), predominantly without comorbidities 232 (53%), with fever as the most frequently reported symptom 352 (80%), treated more frequently with NSAIDs 208 (47%) and/or Paracetamol 216 (49%). Both taste and smell alterations in patients who have had COVID-19 have been shown to appear more frequently 1 to 7 days after the onset of symptoms (207 for smell, 184 for taste), occurring more frequently with a total decrease of both senses (anosmia 302 and ageusia 216), recovering completely in most cases (214 and 216) and within a period of 1 to 4 weeks (140 and 130).

La alteración de los sentidos del gusto y del olfato en relación con el COVID-19 es un fenómeno ampliamente conocido, sin embargo, esta alteración no ha sido caracterizada de forma exhaustiva en la literatura internacional. Se plantea el siguiente estudio con el objetivo de describir las alteraciones del sentido del gusto y del olfato en relación con el COVID-19 a través de la evaluación subjetiva del mismo. El mismo es observacional, descriptivo, de corte transversal, aplicado a pacientes que consultaron a través de teleconsultas realizadas sobre plataformas virtuales de la Cátedra y Servicio de Otorrinolaringología y Cirugía de Cabeza y Cuello del Hospital de Clínicas, de San Lorenzo, durante los meses de marzo a octubre del 2021. Fueron incluidos 440 pacientes de 31,3 ± 9,9 años (18 a 60 años), 308 (70%) de sexo femenino, 388 (88%) provenientes de zona urbana, con evidencia de infección por SARS-CoV-2 por RT-PCR en 260 (59%), predominantemente sin comorbilidades 232 (53%), con fiebre como síntoma asociado al COVID-19 más frecuentemente reportado 352 (80%), tratados más frecuentemente con AINES 208 (47%) y/o Paracetamol 216 (49%). Tanto la alteración del gusto como del olfato en pacientes que han cursado con COVID-19 ha demostrado ser aparecer más frecuentemente en 1 a 7 días del inicio del cuadro (207 para el olfato. 184 para el gusto), cursando más frecuentemente con disminución total de ambos sentidos (anosmia 302 y ageusia 216), recuperándose más frecuentemente de forma total (214 y 216) y en un plazo de 1 a 4 semanas (140 y 130).

SARS-CoV-2 infection in children and adolescents: a Brazilian experience.

OBJECTIVE: To describe clinical and epidemiological aspects of children and adolescents infected with the SARS-CoV-2 in the Municipality of Taubaté, SP, from March to November 2020. METHODS: Cross-sectional study with secondary data obtained from the Epidemiological Surveillance System about confirmed cases in city residents and from medical records of patients who were treated in hospitals in Taubaté, aged between 0 and 19 years. Chi-square and Student's t tests were used for comparisons. RESULTS: 677 cases in the studied age range were reported during the study period, corresponding to 10.1% of cases reported in the municipality. The rapid antibody test was the most used to confirm infection, followed by RT-PCR and serology. Symptoms were described in 57.7% of the cases, mainly fever and cough. Diarrhea was associated with age below 4 years, while fever, cough, headache, odynophagia, ageusia, anosmia, myalgia, and dyspnea were associated with an age ranging from 10 to 19 years. In the study period, there were no deaths from COVID-19 of residents of the municipality in the age group from 0 to 19 years. CONCLUSIONS: The study was able to identify the proportion of involvement of COVID-19 in children and adolescents in the city, and the disease had a mild evolution. The main symptoms were fever and cough, but mainly diarrhea in younger children, and headache, odynophagia, anosmia, ageusia, and myalgia in adolescents.

Randomized clinical trial of BCG vaccine in patients with convalescent COVID-19: Clinical evolution, adverse events, and humoral immune response.

BACKGROUND: The Bacillus Calmette-Guérin (BCG) vaccine may confer cross-protection against viral diseases in adults. This study evaluated BCG vaccine cross-protection in adults with convalescent coronavirus disease 2019 (COVID-19). METHOD: This was a multicenter, prospective, randomized, placebo-controlled, double-blind phase III study (ClinicalTrials.gov: NCT04369794). SETTING: University Community Health Center and Municipal Outpatient Center in South America. PATIENTS: a total of 378 adult patients with convalescent COVID-19 were included. INTERVENTION: single intradermal BCG vaccine (n = 183) and placebo (n = 195). MEASUREMENTS: the primary outcome was clinical evolution. Other outcomes included adverse events and humoral immune responses for up to 6 months. RESULTS: A significantly higher proportion of BCG patients with anosmia and ageusia recovered at the 6-week follow-up visit than placebo (anosmia: 83.1% vs. 68.7% healed, p = 0.043, number needed to treat [NNT] = 6.9; ageusia: 81.2% vs. 63.4% healed, p = 0.032, NNT = 5.6). BCG also prevented the appearance of ageusia in the following weeks: seven in 113 (6.2%) BCG recipients versus 19 in 126 (15.1%) placebos, p = 0.036, NNT = 11.2. BCG did not induce any severe or systemic adverse effects. The most common and expected adverse effects were local vaccine lesions, erythema (n = 152; 86.4%), and papules (n = 111; 63.1%). Anti-severe acute respiratory syndrome coronavirus 2 humoral response measured by N protein immunoglobulin G titer and seroneutralization by interacting with the angiotensin-converting enzyme 2 receptor suggest that the serum of BCG-injected patients may neutralize the virus at lower specificity; however, the results were not statistically significant. CONCLUSION: BCG vaccine is safe and offers cross-protection against COVID-19 with potential humoral response modulation. LIMITATIONS: No severely ill patients were included.

Photobiomodulation therapy for treatment olfactory and taste dysfunction COVID-19-related: A case report.

It is postulated that the inflammatory process resulting from SARS-CoV-2 infection is the main cause of smell and taste dysfunctions in patients. In view of this, photobiomodulation, due to its anti-inflammatory and antioxidant effects, may be a promising therapeutic modality to treat these disorders. In the present case report, we observed clinical improvement in the symptoms of anosmia and ageusia related to COVID-19 after treatment with photobiomodulation. Due to the inflammatory nature of COVID-19 and the anti-inflammatory effects, photobiomodulation antioxidants already proven in the literature make it a promising therapeutic modality, especially sequela COVID-related, including olfactory (anosmia) and taste (ageusia) dysfunction. In the present case report, the patient's olfactory and gustatory functions were re-established after 10 treatment sessions with photobiomodulation.

Headache, anosmia, ageusia and other neurological symptoms in COVID-19: a cross-sectional study.

BACKGROUND: Neurological symptoms are frequent among patients with COVID-19. Little is known regarding the repercussions of neurological symptoms for patients and how these symptoms are related to one another. OBJECTIVES: To determine whether there is an association between the neurological symptoms in patients with COVID-19, and to characterize the headache. METHOD: This was a cross-sectional study. All hospital inpatients and health workers at the Hospital Universitario Oswaldo Cruz with a PCR-confirmed COVID-19 infection between March and June 2020 were considered for the study and were interviewed by telephone at least 2-months after the acute phase of the disease. These patients were identified by the hospital epidemiological surveillance department. A semi-structured questionnaire was used containing sociodemographic and clinical data and the ID-Migraine. RESULTS: A total of 288 patients was interviewed; 53.1% were male; with a median age of 49.9 (41.5-60.5) years; 91.7% presented some neurological symptom; 22.2% reported some neurological symptom as the symptom that troubled them most during COVID-19. Neurological symptoms were: ageusia (69.8%), headache (69.1%), anosmia (67%), myalgia (44.4%), drowsiness (37.2%), agitation (20.8%); mental confusion (14.9%), syncope (4.9%) and epileptic seizures (2.8%). Females, those who presented with fever, sore throat, anosmia/ageusia and myalgia also presented significantly more with headache (logistic regression). The most frequent headache phenotype was a non-migraine phenotype, was of severe intensity and differed from previous headaches. This persisted for more than 30 days in 18% and for more than 90 days in 10% of patients. Thirteen percent of those with anosmia and 11% with ageusia continued with these complaints after more than 90 days of the acute phase of the disease. Aged over 50 years, agitation and epileptic seizures were significantly associated with mental confusion (logistic regression). CONCLUSION: Headache is frequent in COVID-19, is associated with other symptoms such as fever, sore throat, anosmia, ageusia, and myalgia, and may persist beyond the acute phase of the disease.

Therapeutic supplementation with zinc in the management of COVID-19-related diarrhea and ageusia/dysgeusia: mechanisms and clues for a personalized dosage regimen.

Zinc supplementation is indicated for diarrhea and taste disorders, which are both features of COVID-19 . Nevertheless, this strategy has not been tested for the treatment of these secondary complications in the current pandemic. Through an updated review, a practical appraisal was considered as a means of providing a medical nexus of therapeutic zinc regimens as an adjunct in the management of COVID-19-related diarrhea and ageusia/dysgeusia. While diarrhea and taste disorders are consequences of COVID-19, zinc supplementation is useful for non-COVID-19 patients with these clinical problems. The overwhelming evidence for supplementing with zinc in diarrhea and pneumonia is associated with the treatment of children, while for taste disorders the use of supplementing with zinc is more examined in adults. Whereas COVID-19 is more prevalent in adults, precautions should be exercised not to translate the zinc dosage used for children with diarrhea and taste disorders into the current pandemic. Therapeutic doses of zinc used for adults (∼50-150 mg/day of elemental zinc) could be included in the treatment strategies for COVID-19, but this proposal should be examined through randomized studies.

Oral Manifestations in Patients with COVID-19: A 6-Month Update.

This is the first update of the previously published living systematic review that summarized evidence on the prevalence of oral signs and symptoms in patients with COVID-19. Hitherto, 183 studies were included, reporting data from 64,876 patients with COVID-19 worldwide. The overall prevalence of taste disorders was 38% (95% CI = 22% to 56%, I2 = 98%). Hypogeusia, dysgeusia, and ageusia were also evaluated by a meta-analysis, and the pooled prevalence was 34% for hypogeusia, 33% for dysgeusia, and 26% for ageusia. Taste disorders were associated with a positive COVID-19 test (odds ratio [OR] = 7.54, 95% CI = 5.24 to 10.86, I2 = 93%, P < 0.00001), showing high certainty of evidence. However, the association between taste disorders and mild/moderate severity of COVID-19 (OR = 1.63, 95% CI = 1.33 to 1.99, I2 = 69%, P < 0.0001) and female patients with COVID-19 (OR = 1.77, 95% CI = 1.26 to 2.48, I2 = 79%, P = 0.001) presented low certainty of evidence. Xerostomia was a new feature of this update, and the pooled data demonstrated a prevalence of 43% (95% CI = 36% to 50%, I2 = 71%) in patients with COVID-19. Regarding oral mucosal lesions, the most common clinical pattern was aphthous like, followed by herpes-like lesions, candidiasis, glossitis/depapillation/geographic tongue, parotitis, and angular cheilitis. Oral lesions were more frequent in the tongue, lips, and palate, presenting miscellaneous clinical aspects that are more likely to represent coinfections. Therefore, the reanalysis of current evidence suggests the triad xerostomia, taste dysfunction, and oral mucosal lesions as common manifestations in patients with COVID-19. However, these outcomes are under discussion, and more studies will be necessary to confirm their association with direct SARS-CoV-2 infection in the oral cavity.

Could the oral cavity be a target organ in SARS-CoV-2 infection?

Data sources A series of eight patients with active COVID-19 who also presented with associated oral lesions seen at a hospital in Sao Paulo, Brazil provided the information in this report.Study selection The authors reported a case series with eight COVID-19 patients.Data extraction and synthesis Demographic information, hospitalisation details including signs, symptoms and severity of COVID-19, along with presence of anosmia, dysgeusia, ageusia and oral lesions from all eight patients were documented and reported by the authors.Results All eight patients in this report presented for medical care with well-established respiratory symptoms of COVID-19. These patients also presented with oral ulcers that resembled aphthous ulcers, of which some also had necrosis and haemorrhagic ulcerations. The time to onset ranged between two to ten days and duration lasted between 5-15 days. The painful ulcers were empirically managed using daily photobiomodulation (PBMT) therapy using a PBMT device (Twin Flex, MMOptics, Sao Carlos, Brazil).Conclusions Oral lesions may precede COVID-19 and progressively worse oral lesions are seen in severe COVID-19 patients. Some of these oral lesions also tend to occur early along with loss of taste and smell in some patients. Taken together, these oral manifestations could serve as early indication of COVID-19 and prompt referral for further testing is recommended.