Prevalence, risk factors, and impact of long COVID in a socially vulnerable community in Brazil: a prospective cohort study.

Background: Long COVID is an emerging global public health issue. Socially vulnerable communities in low- and-middle-income countries were severely impacted by the pandemic and are underrepresented in research. This prospective study aimed to determine the prevalence of long COVID, its impact on health, and associated risk factors in one such community in Rio de Janeiro, Brazil. Methods: A total of 710 individuals aged 18 and older, with confirmed SARS-CoV-2 infection at least three months prior, were enrolled between November 25, 2021, and May 5, 2022. Participants were assessed via telephone or in person using a standardized questionnaire to evaluate their perception of recovery, symptoms, quality of life, and functional status. Findings: Twenty percent of participants did not feel fully recovered, 22% experienced new or persistent symptoms, 26% had worsened functional status, 18% had increased dyspnoea, and 32% reported a worse quality of life. Persistent symptoms included headache, cough, fatigue, muscle pain, and shortness of breath. Dyspnoea during the acute phase was the strongest independent predictor of worsening outcomes. Females and individuals with comorbidities were more likely to report worse recovery, functioning, dyspnoea, and quality of life. Interpretation: Our findings reveal a high burden of severe and persistent physical and mental health sequelae in a socially vulnerable community following COVID-19. Funding: UK Foreign, Commonwealth and Development Office and Wellcome Trust Grant (222048/Z/20/Z), Fundação Oswaldo Cruz (FIOCRUZ), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), and the Centers for Disease Control and Prevention (CDC).

Neurological symphony: post-acute COVID-19 syndrome, an innovative pathophysiological exploration from neuraltherapeutic medicine.

The SARS-CoV-2 pandemic has affected 771 million people and caused 6.9 million confirmed deaths as of November 2023. Beyond the adversity, a crucial and less-explored chapter unfolds: adaptive sequelae. These have altered social, mental, and emotional conditions, leaving an imprint on biological systems. While some cases fully resolve the pathological process post-acute infection, others persist with symptoms, posing a challenge that underscores the need to comprehend pathophysiology from innovative perspectives. The article delves into "Long COVID" or Post-Acute COVID-19 Syndrome (PACS), where symptoms persist for ≥4 weeks irrespective of initial severity. Risk factors include a history of severe illness, in-hospital management, and intensive care. This article also explores theories, derived from various experimental models, that have demonstrated the involvement of the nervous system in coordination with the psychoneuroimmunoendocrine axes in the expression of inflammation. It is posited that PACS involves processes of peripheral and central sensitization (corticalization), facilitating dishomeostasis and the chronicity of the inflammatory process. In this context, various therapeutic strategies grounded in modulating the inflammatory reflex are reviewed, primarily through the infiltration of local anesthetics via linear and non-linear approaches. Neural therapeutic use is considered to stimulate the regulatory inflammatory circuits coordinated by the neuroimmune-endocrine system.

Clinical and Physiological Variables in Patients with Post-COVID-19 Condition and Persistent Fatigue.

Background/Objectives: Post-COVID-19 condition can manifest through various symptoms such as dyspnea, cognitive disturbances, and fatigue, with mechanisms related to these symptoms, particularly those related to fatigue, still requiring further clarification. Therefore, our aim was to assess the clinical and physiological variables in patients with post-COVID-19 condition and persistent fatigue. Methods: After one year post-COVID-19 infection, the patients underwent a comprehensive evaluation, including a complete blood count, a metabolic panel, complete spirometry, and assessments of dyspnea, quality of life, anxiety and depression, physical capacity, body composition, muscle strength, comorbidities, and medications. The participants were categorized into two groups: G1-fatigue and G2-non-fatigue. Results: Seventy-seven patients (53% female; 55 ± 11.8 years) were included, 37 in G1 and 40 in G2. As for clinical markers and symptoms of illness, in those with persistent fatigue symptoms, a greater sensation of dyspnea [BDI score: 7.5 (6-9) vs. 12 (9-12), p < 0.001; mMRC score: 1 (1-2) vs. 0 (0-1), p = 0.002], worse quality of life [SGRQ total score: 1404 (1007-1897) vs. 497 (274-985); p < 0.001], higher levels of anxiety [HADS-A score: 8 (5-9) vs. 3 (0.5-4); p < 0.001], and a reduction in peripheral and inspiratory muscle strength [handgrip strength: 34 (28-40) vs. 40 (30-46.5) kgf, p = 0.044; MIP: -81 ± 31 vs. -111 ± 33 mmHg, p < 0.001)] were observed. Conclusions: Those with persistent fatigue exhibited a greater sensation of dyspnea, higher levels of anxiety, reduced peripheral and inspiratory muscle strength, and a greater impairment of quality of life. The severity of fatigue was influenced by the worsening quality of life, heightened anxiety levels, and decreased peripheral muscle strength. Additionally, the worse quality of life was associated with a higher sensation of dyspnea, lower muscle strength, and reduced physical capacity.

Persistent headache and chronic daily headache after COVID-19: a prospective cohort study.

Background: Little is known about the frequency and impact of the persistent headache and about the incidence of chronic daily headache (CDH) after coronavirus disease 2019 (COVID-19). The aim of this prospective cohort study was to assess the incidence, risk factors, characteristics, and impact of CDH in patients with COVID-19. Methods: In the first stage, 288 patients were interviewed by telephone after the acute phase of COVID-19. Subsequently, 199 patients who presented headache were reinterviewed at least one year after COVID-19. Headaches that persisted beyond the acute phase of COVID-19 for three or more months and presented frequency ≥ 45 days over the first three months were considered to be CDH. Results: One hundred and twenty-three patients were included, 56% were females; median age: 50 years (25th and 75th percentile: 41;58). The headache persisted beyond the acute phase of COVID-19 in 52%, and 20.3% had CDH (95% confidence interval: 13.6-28.2). Individuals who previously had headaches and who had headaches of greater intensity during the acute phase were at higher risk of developing CDH. The group with CDH included more females, greater impact of headache, more persistence of headache beyond the 120th day of COVID-19 and less throbbing headache than did the other individuals whose headache persisted. Conclusions: Patients who had COVID-19 had a high incidence of CDH. Previous headache and greater intensity of headache were associated with higher risk of CDH.

Standardization use of the international classification of functioning, disability and health in the determination of health status in patients with post-acute COVID-19 syndrome.

PURPOSE: To propose a standardized method for the use of the International Classification of Functioning, Disability and Health (ICF) to describe the health status in Post-Acute COVID-19 Syndrome (PACS) and investigate interrater agreement in the linking process in instruments and clinical exams using the ICF categories. MATERIALS AND METHODS: Cross-sectional and interrater agreement study that followed the Guidelines for Reporting Reliability and Agreement Studies. Two raters performed the linking coding process in instruments of quality of life, anxiety and depression, fatigue and pulmonary function, inspiratory muscle strength and cardiopulmonary exercise testing. The codes were qualified by standards defined to each instrument and exams. RESULTS: The instrument with the lowest Cohen's Kappa coefficient was anxiety and depression (k = 0.57). Forty ICF codes were linked to clinical instruments and exams. The fatigue instrument presented a higher degree of disability by the qualification process, from severe to complete, in the linked codes. CONCLUSION: The study presents a standardized method for the assessment of the health status of patients with PACS through ICF. Restriction in work performance, socialization and family relationships as well as disabilities in physical endurance, fatigue and exercise tolerance were found in the sample. The agreement between the raters was moderate to perfect, demonstrating that the method can be reproducible.

The body structures and functions, environmental factors, activities and participation in a person's environment are determinant aspects of his health.Ways to measure these aspects are key to assessing health not only as absence of disease, so the International Classification of Disability and Functional Health demonstrates the ability to fully describe health.This study proposes a standardization in the use of the tool to facilitate usability in clinical practice.

Lower Urinary Tract Symptoms in a prospective cohort of COVID-19 survivors

ABSTRACT Purpose: To analyze the prevalence of lower urinary tract symptoms (LUTS) in patients who survived moderate and severe forms of COVID-19 and the risk factors for LUTS six months after hospitalization. Materials and Methods: In this prospective cohort study, patients were evaluated six months after hospitalization due to COVID-19. LUTS were assessed using the International Prostate Symptom Score. General health was assessed through the Hospital Anxiety and Depression Scale and the EQ5D-L5 scale, which evaluates mobility, ability to perform daily activities, pain and discomfort and completed a self-perception health evaluation. Results: Of 255 participants, 54.1% were men and the median age was 57.3 [44.3 - 66.6] years. Pre-existing comorbidities included diabetes (35.7%), hypertension (54.5%), obesity (30.2%) and physical inactivity (65.5%). One hundred and twenty-four patients (48.6%) had a hospital stay >15 days, 181 (71.0%) were admitted to an ICU and 124 (48.6%) needed mechanical ventilation. Median IPSS was 6 [3-11] and did not differ between genders. Moderate to severe LUTS affected 108 (42.4%) patients (40.6% men and 44.4% women; p=0.610). Nocturia (58.4%) and frequency (45.9%) were the most prevalent symptoms and urgency was the only symptom that affected men (29.0%) and women (44.4%) differently (p=0.013). LUTS impacted the quality of life of 60 (23.5%) patients with women more severely affected (p=0.004). Diabetes, hypertension, and self-perception of worse general health were associated with LUTS. Conclusions: LUTS are highly prevalent and bothersome six months after hospitalization due to COVID-19. Assessment of LUTS may help ensure appropriate diagnosis and treatment in these patients.

Histological and Ultrastructural Changes in Lungs One Year Post Asymptomatic or Mild SARS-CoV-2 Infection: Evaluating the Potential for Active Virus Presence / Cambios Histológicos y Ultraestructurales en los Pulmones un Año Después de una Infección Asintomática o Leve por SARS-CoV-2: Evaluación del Potencial de Presencia Activa del Virus

SUMMARY: Prior research on post-COVID-19 or long COVID primarily focused on the presence of SARS-CoV-2 mostly in symptomatic patients. This study aimed to investigate the persistence of SARS-CoV-2 after 1 year of asymptomatic or mild COVID-19. SARS-CoV-2 infected and control K18-hACE2 transgenic mice (n=25) were studied. Moderate and severe symptomatic subjects were sacrificed after eight days, while mild or asymptomatic mice were kept in BSL-III for twelve months. Analyses included general condition, histochemistry, immunohistochemistry, transmission electron microscopy, and qRT-PCR. Lungs from the twelve-month group showed thickening of alveolar walls, with some lungs exhibiting the recruitment of inflammatory cells, the presence of SARS- CoV-2 mRNA, immunopositivity for the SARS-CoV-2 spike protein, and TEM showed viruses (60-125 nm) within vesicles, indicating continued replication. Certain lung samples showed persistent SARS-CoV-2 presence in Club cells, endothelial cells, and macrophages. The eight-day group exhibited viral interstitial pneumonitis, SARS-CoV-2 immunopositivity, and mRNA. The eight-day hearts displayed viral mRNA, while the twelve-month hearts tested negative. Some asymptomatic twelve-month subjects presented reduced surfactant, basal membrane thickening, fibrosis, and mild autonomic nerve degeneration. In this study conducted on mice, findings indicate the potential for chronic persistence of SARS-CoV-2 in the lungs one year post initial mild or asymptomatic infection, which could suggest the possibility of recurrent episodes in similar human conditions. The observed thickening of alveolar walls and potential fibrotic areas in these mice may imply an increased risk of post-COVID fibrosis in humans. Furthermore, the presence of SARS-CoV-2-positive inflammatory cells in some asymptomatic murine cases could herald a progression toward ongoing inflammation and chronic lung disease in humans. Therefore, the necessity for further studies in human subjects and vigilant monitoring of high-risk human populations is underscored.

Investigaciones anteriores sobre COVID-19 o COVID prolongado se centraron principalmente en la presencia de SARS-CoV-2 principalmente en pacientes sintomáticos. Este estudio tuvo como objetivo investigar la persistencia del SARS-CoV-2 después de 1 año de COVID-19 asintomático o leve. Se estudiaron ratones transgénicos K18-hACE2 infectados con SARS-CoV-2 y de control (n=25). Los animales con síntomas moderados y graves se sacrificaron después de ocho días, mientras que los ratones con síntomas leves o asintomáticos se mantuvieron en BSL-III durante doce meses. Los análisis incluyeron estado general, histoquímica, inmunohistoquímica, microscopía electrónica de transmisión y qRT- PCR. Los pulmones del grupo de doce meses mostraron engrosamiento de las paredes alveolares, y algunos pulmones exhibieron reclutamiento de células inflamatorias, presencia de ARNm del SARS-CoV-2, inmunopositividad para la proteína de la espícula del SARS-CoV-2 y TEM mostró virus (60 -125 nm) dentro de las vesículas, lo que indica una replicación continua. Ciertas muestras de pulmón mostraron una presencia persistente de SARS- CoV-2 en exocrinocitos bronquiolares, células endoteliales y macrófagos. El grupo de ocho días presentó neumonitis intersticial viral, inmunopositividad al SARS-CoV-2 y ARNm. Los corazones de ocho días mostraron ARNm viral, mientras que los corazones de doce meses dieron negativo. Algunos animales asintomáticos de doce meses presentaron disminución del surfactante, engrosamiento de la membrana basal, fibrosis y degeneración leve del nervio autónomo. En este estudio realizado en ratones, los hallazgos indican la posibilidad de persistencia crónica del SARS-CoV-2 en los pulmones un año después de la infección inicial leve o asintomática, lo que podría sugerir la posibilidad de episodios recurrentes en condiciones humanas similares. El engrosamiento observado de las paredes alveolares y las posibles áreas fibróticas en estos ratones puede implicar un mayor riesgo de fibrosis post-COVID en humanos. Además, la presencia de células inflamatorias positivas para SARS- CoV-2 en algunos casos murinos asintomáticos podría presagiar una progresión hacia una inflamación continua y una enfermedad pulmonar crónica en humanos. Por lo tanto, se subraya la necesidad de realizar más estudios en seres humanos y realizar un seguimiento atento de las poblaciones humanas de alto riesgo.

Post-COVID-19 cognitive symptoms in patients assisted by a teleassistance service: a retrospective cohort study.

Introduction: Four years after the onset of the COVID-19 pandemic, the frequency of long-term post-COVID-19 cognitive symptoms is a matter of concern given the impact it may have on the work and quality of life of affected people. Objective: To evaluate the incidence of post-acute COVID-19 cognitive symptoms, as well as the associated risk factors. Methods: Retrospective cohort, including outpatients with laboratory-confirmed COVID-19 and who were assisted by a public telehealth service provided by the Telehealth Network of Minas Gerais (TNMG), during the acute phase of the disease, between December/2020 and March/2022. Data were collected through a structured questionnaire, applied via phone calls, regarding the persistence of COVID-19 symptoms after 12 weeks of the disease. Cognitive symptoms were defined as any of the following: memory loss, problems concentrating, word finding difficulties, and difficulty thinking clearly. Results: From 630 patients who responded to the questionnaire, 23.7% presented cognitive symptoms at 12 weeks after infection. These patients had a higher median age (33 [IQR 25-46] vs. 30 [IQR 24-42] years-old, p = 0.042) with a higher prevalence in the female sex (80.5% vs. 62.2%, p < 0.001) when compared to those who did not present cognitive symptoms, as well as a lower prevalence of smoking (8.7% vs. 16.2%, p = 0.024). Furthermore, patients with persistent cognitive symptoms were more likely to have been infected during the second wave of COVID-19 rather than the third (31.0% vs. 21.3%, p = 0.014). Patients who needed to seek in-person care during the acute phase of the disease were more likely to report post-acute cognitive symptoms (21.5% vs. 9.3%, p < 0,001). In multivariate logistic regression analysis, cognitive symptoms were associated with female sex (OR 2.24, CI 95% 1.41-3.57), fatigue (OR 2.33, CI 95% 1.19-4.56), depression (OR 5.37, CI 95% 2.19-13.15) and the need for seek in-person care during acute COVID-19 (OR 2.23, CI 95% 1.30-3.81). Conclusion: In this retrospective cohort of patients with mostly mild COVID-19, cognitive symptoms were present in 23.7% of patients with COVID-19 at 12 weeks after infection. Female sex, fatigue, depression and the need to seek in-person care during acute COVID-19 were the risk factors independently associated with this condition.

Follow-up of cognitive impairment and inflammatory profile in individuals with mild COVID-19.

Individuals who experience mild COVID-19 can suffer from long-lasting cognitive symptoms. Notably, 26% of these individuals experience difficulties with visuospatial abilities six months after infection. However, among those who initially exhibited visuoconstructive impairments, 66% showed improvement or complete reversal over time. Additionally, changes in cytokine levels, particularly CCL11, HGF, and CXCL10, were observed. These results suggest a potential link between ongoing cognitive issues and elevated levels of pro-inflammatory cytokines, which merits further investigation.

Lower Urinary Tract Symptoms in a prospective cohort of COVID-19 survivors.

PURPOSE: To analyze the prevalence of lower urinary tract symptoms (LUTS) in patients who survived moderate and severe forms of COVID-19 and the risk factors for LUTS six months after hospitalization. MATERIALS AND METHODS: In this prospective cohort study, patients were evaluated six months after hospitalization due to COVID-19. LUTS were assessed using the International Prostate Symptom Score. General health was assessed through the Hospital Anxiety and Depression Scale and the EQ5D-L5 scale, which evaluates mobility, ability to perform daily activities, pain and discomfort and completed a self-perception health evaluation. RESULTS: Of 255 participants, 54.1% were men and the median age was 57.3 [44.3 - 66.6] years. Pre-existing comorbidities included diabetes (35.7%), hypertension (54.5%), obesity (30.2%) and physical inactivity (65.5%). One hundred and twenty-four patients (48.6%) had a hospital stay >15 days, 181 (71.0%) were admitted to an ICU and 124 (48.6%) needed mechanical ventilation. Median IPSS was 6 [3-11] and did not differ between genders. Moderate to severe LUTS affected 108 (42.4%) patients (40.6% men and 44.4% women; p=0.610). Nocturia (58.4%) and frequency (45.9%) were the most prevalent symptoms and urgency was the only symptom that affected men (29.0%) and women (44.4%) differently (p=0.013). LUTS impacted the quality of life of 60 (23.5%) patients with women more severely affected (p=0.004). Diabetes, hypertension, and self-perception of worse general health were associated with LUTS. CONCLUSIONS: LUTS are highly prevalent and bothersome six months after hospitalization due to COVID-19. Assessment of LUTS may help ensure appropriate diagnosis and treatment in these patients.

Long COVID: neurological manifestations - an updated narrative review.

Infection with the SARS-CoV-2 virus can lead to neurological symptoms in the acute phase and in the Long COVID phase. These symptoms usually involve cognition, sleep, smell disorders, psychiatric manifestations, headache and others. This condition is more commonly described in young adults and women. This symptomatology can follow severe or mild cases of the disease. The importance of this issue resides in the high prevalence of neurological symptoms in the Long COVID phase, which entails significant morbidity in this population. In addition, such a condition is associated with high health care costs, with some estimates hovering around 3.7 trillion US dollars. In this review, we will sequentially describe the current knowledge about the most prevalent neurological symptoms in Long COVID, as well as their pathophysiology and possible biomarkers.

A infecção pelo vírus SARS-CoV-2 pode levar a sintomas neurológicos na fase aguda e na fase de COVID longa. Esses sintomas geralmente envolvem cognição, sono, distúrbios do olfato, manifestações psiquiátricas, dor de cabeça e outros. Esta condição é mais comumente descrita em adultos jovens e mulheres. A sintomatologia pode acompanhar casos graves ou leves da doença. A importância desta questão reside na elevada prevalência de sintomas neurológicos na fase de COVID longa, o que acarreta morbilidade significativa nesta população. Além disso, tal condição está associada a elevados custos de cuidados de saúde, com algumas estimativas em torno de 3,7 trilhões de dólares americanos. Nesta revisão, descrevemos sequencialmente o conhecimento atual sobre os sintomas neurológicos mais prevalentes na COVID longa, bem como sua fisiopatologia e possíveis biomarcadores.

Tras las huellas de la convalecencia de la Covid-19

La propuesta de extender hasta dos o tres años la observación de las consecuencias negativas de la infección por el virus SARS-CoV-2 se considera razonable, al alargar el tiempo de seguimiento de un padecimiento anteriormente desconocido. El propósito de esta comunicación es aportar nuevas consideraciones sobre una realidad: existen personas que no se han recuperado totalmente, en un tiempo prudencial, después de haber padecido de COVID-19. Se enfatiza que todavía estamos lejos de conocer todos los efectos biológicos que tendrá en el tiempo, la "inmunoestimulación masiva" de la pandemia en algunas personas. Se plantean algunas recomendaciones prácticas como a) Incluir el dato de haber padecido de COVID-19 en los antecedentes patológicos personales de los pacientes; b) Insistir en el seguimiento periódico de los enfermos, sobre todo los que manifiesten quejas de una convalecencia prolongada. Otras consecuencias, además de las netamente biológicas, son también importantes, entre ellas: mentales, sociales, laborales, económicas, consumo de servicios de salud y de servicios sociales. En relación a la pos-COVID siempre el reto estará vinculado a la aplicación de estrategias eficaces para la prevención y el control de la COVID-19. Pero si se presentan enfermos, el desafío consistirá en evitar las posibles causas de la pos-COVID, así como prevenir o atenuar la aparición de sus diferentes formas clínicas con conductas coherentes, en dependencia de las características de cada caso, así como atenuar, por todos, las consecuencias que se han provocado en las personas afectadas y para la sociedad.

The proposal to extend the negative consequences of infection with the SARS-CoV-2 virus observation to two or three years is considered reasonable, by lengthening the follow-up time of a previously unknown condition. This communication' purpose is to provide new considerations about a fact: there are people who have not fully recovered, in a reasonable time, after having suffered from COVID-19. It is emphasized that we are still far from knowing all the biological effects that the "massive immunostimulation" of the pandemic will have over time on some people. Some practical recommendations are proposed, such as a) Include the information of having suffered from COVID-19 in the patients' personal pathological history; b) Insist on periodic monitoring of patients, especially those who express complaints of prolonged convalescence. Other consequences, in addition to the purely biological ones, are also important, including: mental, social, labor, economic, consumption of health services and social services. In relation to post-COVID, the challenge will always be linked to the application of effective strategies for the COVID-19 prevention and control. But if illness people appear, the challenge will be to avoid the possible causes of post-COVID, as well as prevent or mitigate the appearance of its different clinical forms with coherent behaviors, depending on the characteristics of each case, as well as mitigate, by all, the consequences that have been caused to the affected people and to society.

Alpha-lipoic acid does not improve olfactory training results in olfactory loss due to COVID-19: a double-blind randomized trial.

OBJECTIVES: Olfactory loss is a recognized long-term dysfunction after Coronavirus Disease 2019 (COVID-19) infection. This investigation aimed to assess the effect of alpha-lipoic acid as an adjuvant treatment of olfactory training on the improvement of smell loss in post-COVID-19 patients. METHODS: This randomized controlled trial included 128 adult outpatients who had persistent smell loss for more than 3-months after COVID-19 infection. The participants were randomly allocated into two groups: the intervention treatment group, which received alpha-lipoic acid associated to olfactory training, and comparison treatment group, which received placebo pills associated to olfactory training. The participants were followed-up for 12-weeks. Olfactory dysfunction was assessed in terms of Visual Analog Scale (VAS), and the Connecticut Chemosensory Clinical Research Center (CCCRC) test for the Brazilian population. RESULTS: A total of 100 participants completed the follow-up period and were analyzed in this study. Both groups have improved CCCRC score (p = 0.000), olfactory threshold (p = 0.000), identification score (p = 0.000) and VAS score (p = 0.000) after 12-weeks follow-up. No significant differences were determined between the intervention and comparison treatment groups in CCCRC score (p = 0.63), olfactory threshold (p = 0.50), identification score (p = 0.96) and VAS score (p = 0.97). In all these criteria, comparison treatment group went slightly worse. At the endpoint of the study, the frequency of anosmia reduced to 2% in the intervention treatment group and to 7.8% in the comparison treatment group. Also, 16.8% of the intervention group' subjects, and 15.7% of comparison treatment group's patients reached normosmia. CONCLUSIONS: Overall, there was a strongly significant difference in olfactory function between baseline and endpoint for both groups. However, based on the lack of significant difference between the intervention treatment and the comparison treatment groups in terms of olfactory changes, our study appoints that the alpha-lipoic acid is not better than olfactory training alone to treat olfactory loss after COVID-19. LEVEL OF EVIDENCE: Level 2.

Neurological and neuropsychiatric manifestations of post-COVID-19 condition in South America: a systematic review of the literature / Manifestações neurológicas e neuropsiquiátricas da condição pós-COVID-19 na América do Sul: revisão sistemática da literatura

Abstract Background The post-COVID-19 condition is a major modern challenge in medicine and has a high global impact on the health of the population. Objective To determine the main neurological and neuropsychiatric manifestations after acute COVID-19 infection in South American countries. Methods This is a systematic review study, registered on the PROSPERO platform following the PRISMA model. 4131 articles were found with the search strategies used. Neurological and neuropsychiatric manifestations were investigated in individuals three months or more after acute COVID-19 infection, and older than 18 years, including studies conducted in South American countries published between 2020 and 2022. Results Six studies (four from Brazil and two from Ecuador) were analyzed. Regarding the type of study: three were cohorts, two were case reports, and one was cross-sectional. The main outcomes found were new pain (65.5%) and new chronic pain (19.6%), new headache (39.1%), daily chronic headache (13%), paresthesia (62%), in addition to neuropsychiatric diseases, such as generalized anxiety disorder (15.1%), post-traumatic stress syndrome (13.4%), depression and anxiety (13.5%), suicidal ideation (10.1%), and several cognitive disorders. Conclusion Neurological and neuropsychiatric manifestations related to depression and anxiety, and cognition disorders are reported during the post-COVID-19 condition in South America. Symptoms associated with chronic pain appear to be associated with the condition. More studies on post-COVID-19 conditions are needed in the South America region.

Resumo Antecedentes A condição pós-COVID-19 é um grande desafio moderno na medicina e tem alto impacto global na saúde da população. Objetivo Determinar as principais manifestações neurológicas e neuropsiquiátricas após a infecção aguda da COVID-19 nos países da América do Sul. Métodos Trata-se de um estudo de revisão sistemática, registrado na plataforma PROSPERO seguindo o modelo PRISMA. Foram encontrados 4131 artigos com as estratégias de buscas empregadas. Investigaram-se manifestações neurológicas e neuropsiquiátricas em indivíduos com três meses ou mais desde a infecção aguda por COVID-19, maiores de 18 anos, incluindo estudos realizados em países da América do Sul publicados entre 2020 e 2022. Resultados Foram analisados seis estudos (quatro do Brasil e dois do Equador). Em relação ao tipo de estudo: três eram coortes, dois relatos de casos e um transversal. Os principais desfechos encontrados foram em relação à dor nova (65,5%) e dor crônica nova (19,6%), cefaleia nova (39,1%), cefaleia crônica diária (13%), parestesia (62%), além de doenças neuropsiquiátricas como transtorno de ansiedade generalizada (15,1%), síndrome do estresse pós-traumático (13,4%), depressão e ansiedade (13,5%), ideação suicida (10,1%) e diversos distúrbios cognitivos. Conclusão Manifestações neurológicas e neuropsiquiátricas relacionadas à depressão e ansiedade e distúrbios de cognição são relatados durante a condição pós-COVID-19 na América do Sul. Os sintomas associados a quadros de dor crônica parecem estar associados à condição. Mais estudos sobre condições pós COVID-19 são necessários na região da América do Sul.

Alpha-lipoic acid does not improve olfactory training results in olfactory loss due to COVID-19: a double-blind randomized trial

Abstract Objectives Olfactory loss is a recognized long-term dysfunction after Coronavirus Disease 2019 (COVID-19) infection. This investigation aimed to assess the effect of alpha-lipoic acid as an adjuvant treatment of olfactory training on the improvement of smell loss in post-COVID-19 patients. Methods This randomized controlled trial included 128 adult outpatients who had persistent smell loss for more than 3-months after COVID-19 infection. The participants were randomly allocated into two groups: the intervention treatment group, which received alpha-lipoic acid associated to olfactory training, and comparison treatment group, which received placebo pills associated to olfactory training. The participants were followed-up for 12-weeks. Olfactory dysfunction was assessed in terms of Visual Analog Scale (VAS), and the Connecticut Chemosensory Clinical Research Center (CCCRC) test for the Brazilian population. Results A total of 100 participants completed the follow-up period and were analyzed in this study. Both groups have improved CCCRC score (p= 0.000), olfactory threshold (p= 0.000), identification score (p= 0.000) and VAS score (p= 0.000) after 12-weeks follow-up. No significant differences were determined between the intervention and comparison treatment groups in CCCRC score (p= 0.63), olfactory threshold (p= 0.50), identification score (p= 0.96) and VAS score (p= 0.97). In all these criteria, comparison treatment group went slightly worse. At the endpoint of the study, the frequency of anosmia reduced to 2% in the intervention treatment group and to 7.8% in the comparison treatment group. Also, 16.8% of the intervention group' subjects, and 15.7% of comparison treatment group's patients reached normosmia. Conclusions Overall, there was a strongly significant difference in olfactory function between baseline and endpoint for both groups. However, based on the lack of significant difference between the intervention treatment and the comparison treatment groups in terms of olfactory changes, our study appoints that the alpha-lipoic acid is not better than olfactory training alone to treat olfactory loss after COVID-19. Level of evidence Level 2.

Síndrome pós-COVID-19 entre hospitalizados por COVID-19: estudo de coorte após 6 e 12 meses da alta hospitalar / Síndrome post-COVID-19 entre hospitalizados por COVID-19: estudio de cohorte tras 6 y 12 meses del alta hospitalaria / Post-COVID-19 syndrome among hospitalized COVID-19 patients: a cohort study assessing patients 6 and 12 months after hospital discharge

A síndrome pós-COVID-19 é um termo usado para descrever um conjunto diversificado de sintomas que persistem por mais de 12 semanas da infecção diagnosticada. O objetivo deste estudo foi analisar a síndrome pós-COVID-19 entre hospitalizados por COVID-19 após 6 e 12 meses da alta hospitalar. Trata-se de estudo de coorte ambidirecional, realizado com indivíduos que receberam alta em três dos principais hospitais da capital de Mato Grosso, Brasil, entre outubro e dezembro de 2021 e janeiro e março de 2022. Após coleta de dados em prontuários, os indivíduos foram entrevistados por telefone após 6 e 12 meses da alta hospitalar, sendo questionados sobre a presença de sintomas persistentes ou novos, para a avaliação de sua frequência segundo características sociodemográficas, econômicas, relativas à internação e condições de saúde. Dos 277 prontuários avaliados, 259 pacientes foram elegíveis para o estudo, 190 aos seis meses e 160 após 12 meses da alta hospitalar. Aos seis meses, 59% eram mulheres, 40% com 60 anos ou mais de idade e 87,4% referiram a presença de pelo menos um sintoma. Aos 12 meses, 58,7% eram mulheres, 37,5% com 30 a 49 anos e 67,5% referiram a presença de pelo menos um sintoma. A fadiga foi o sintoma mais comum após 6 e 12 meses de alta hospitalar (55,3% e 40,6%, respectivamente), seguido de problemas de memória (36,8%; 20%) e perda de cabelo (26,8%; 11,2%). Foi maior a prevalência de síndrome pós-COVID-19 entre indivíduos de maior faixa etária, menor renda, hipertensos, diabéticos e com maior gravidade durante a internação. Os fatores de risco da síndrome pós-COVID-19 contribuem para a compreensão dos efeitos a longo prazo e da importância do acompanhamento após a fase aguda da doença.

El síndrome post-COVID-19 es un término utilizado para describir un conjunto diversificado de síntomas que persisten durante más de 12 semanas de la infección diagnosticada. El objetivo fue analizar el síndrome post-COVID-19 entre hospitalizados por COVID-19 tras 6 y 12 meses del alta hospitalaria. Se trata de un estudio de cohorte ambidireccional, realizado con individuos que fueron dados de alta en tres de los principales hospitales de la capital de Mato Grosso, Brasil, entre octubre y diciembre de 2021 y enero y marzo de 2022. Tras recolectar los datos en registros médicos, se entrevistaron los individuos por teléfono tras 6 y 12 meses del alta hospitalaria, cuestionándoles sobre la presencia de síntomas persistentes o nuevos y evaluando su frecuencia conforme las características sociodemográficas, económicas, relacionadas con la hospitalización y condiciones de salud. De los 277 registros médicos evaluados, se eligieron 259 pacientes para el estudio, 190 a los 6 meses y 160 tras 12 meses del alta hospitalaria. A los 6 meses, el 59% eran mujeres, el 40% tenían 60 años o más y el 87,4% refirieron la presencia de al menos un síntoma. A los 12 meses, el 58,7% eran mujeres, el 37,5% tenían entre 30 y 49 años y el 67,5% refirieron la presencia de al menos un síntoma. La fatiga fue el síntoma más común tras 6 y 12 meses del alta hospitalaria (el 55,3% y el 40,6%, respectivamente), seguido de los problemas de memoria (el 36,8% y el 20%) y caída del pelo (el 26,8% y el 11,2%). La prevalencia de síndrome post-COVID-19 fue más alta entre los individuos de mayor edad, menor renta, hipertensos, diabéticos y con mayor gravedad durante la hospitalización. Los factores de riesgo del síndrome post-COVID-19 contribuyen para la comprensión de los efectos a largo plazo y de la importancia del seguimiento tras la fase aguda de la enfermedad.

Post-COVID-19 syndrome involves a variety of symptoms that last more than 12 weeks after COVID diagnosis. This study aimed to analyze post-COVID-19 syndrome among hospitalized COVID-19 patients 6 and 12 months after hospital discharge. This is an ambidirectional cohort study conducted with individuals who were discharged from three main hospitals in the capital of Mato Grosso State, Brazil, between October and December 2021 and January and March 2022. After data collection from medical records, the individuals were interviewed by telephone 6 and 12 months after hospital discharge, when they were asked about the presence of ongoing or new symptoms and when symptom frequency was evaluated according to sociodemographic and economic characteristics hospitalization, and health conditions. Of all 277 medical records evaluated, 259 patients were eligible to participate in the study, 190 patients six months after discharge and 160 patients 12 months after hospital discharge. At six months, 59% were female patients, 40% were aged 60 years or older, and 87.4% reported at least one symptom. At 12 months, 58.7% were female patients, 37.5% were aged 30 to 49 years, and 67.5% reported at least one symptom. Fatigue was the most common symptom 6 and 12 months after hospital discharge (55.3% and 40.6%, respectively), followed by memory problems (36.8%; 20%), and hair loss (26.8%; 11.2%). The prevalence of post-COVID-19 syndrome was higher among patients of older age, lower income, with hypertension, diabetes, and more severe infection during hospitalization. The risk factors for post-COVID-19 syndrome help understand the long-term effects and the importance of monitoring after the acute phase of the disease.

Long COVID: neurological manifestations - an updated narrative review / COVID longa: manifestações neurológicas - uma revisão narrativa atualizada

ABSTRACT. Infection with the SARS-CoV-2 virus can lead to neurological symptoms in the acute phase and in the Long COVID phase. These symptoms usually involve cognition, sleep, smell disorders, psychiatric manifestations, headache and others. This condition is more commonly described in young adults and women. This symptomatology can follow severe or mild cases of the disease. The importance of this issue resides in the high prevalence of neurological symptoms in the Long COVID phase, which entails significant morbidity in this population. In addition, such a condition is associated with high health care costs, with some estimates hovering around 3.7 trillion US dollars. In this review, we will sequentially describe the current knowledge about the most prevalent neurological symptoms in Long COVID, as well as their pathophysiology and possible biomarkers.

RESUMO. A infecção pelo vírus SARS-CoV-2 pode levar a sintomas neurológicos na fase aguda e na fase de COVID longa. Esses sintomas geralmente envolvem cognição, sono, distúrbios do olfato, manifestações psiquiátricas, dor de cabeça e outros. Esta condição é mais comumente descrita em adultos jovens e mulheres. A sintomatologia pode acompanhar casos graves ou leves da doença. A importância desta questão reside na elevada prevalência de sintomas neurológicos na fase de COVID longa, o que acarreta morbilidade significativa nesta população. Além disso, tal condição está associada a elevados custos de cuidados de saúde, com algumas estimativas em torno de 3,7 trilhões de dólares americanos. Nesta revisão, descrevemos sequencialmente o conhecimento atual sobre os sintomas neurológicos mais prevalentes na COVID longa, bem como sua fisiopatologia e possíveis biomarcadores.

Persistence of symptoms and lung function in mild cases of COVID-19 six months after infection: a cross-sectional study / Persistência de sintomas e função pulmonar em casos leves de COVID-19 seis meses após a infecção: um estudo transversal

ABSTRACT Objectives: To describe persistent symptoms and lung function in mild cases of COVID-19 six months after infection. Methods: Data collection was performed through a semi-structured questionnaire containing information on the participants' demographic and anthropometric data, the disease in the acute phase, and persistent symptoms six months after COVID-19 using spirometry and manovacuometry. Results: A total of 136 participants were evaluated, of whom 64% were male, with a mean age of 38.17 ± 14.08 years and a body mass index (BMI) of 29.71 ± 17.48 kg/m2. The main persistent symptoms reported were dyspnea on exertion (39.7%), memory loss (38.2%), and anxiety (48.5%). Considering lung function, the participants reached 88.87 ± 17.20% of the predicted forced vital capacity (FVC), 86.03 ± 22.01% of the forced expiratory volume in one second (FEV1), and 62.71 ± 25.04% of peak expiratory flow (PEF). Upon manovacuometry, 97.41 ± 34.67% of the predicted inspiratory force (Pimax) and 66.86 ± 22.97% of the predicted expiratory force (Pemax) were observed. Conclusions: Six months after COVID-19 infection, a reduction in PEF and MEP was observed. Among the most commonly reported persistent symptoms were fatigue, tiredness with the slightest exertion, anxiety and depression, memory loss, and deficits in concentration.

RESUMO Objetivos: Descrever os sintomas persistentes e a função pulmonar em casos leves de COVID-19 seis meses após a infecção. Métodos: A coleta de dados foi realizada por meio de um questionário semiestruturado contendo informações sobre dados demográficos e antropométricos dos participantes, a doença na fase aguda e os sintomas persistentes seis meses após a COVID-19, utilizando espirometria e manovacuometria. Resultados: Um total de 136 participantes foram avaliados, dos quais 64% eram do sexo masculino, com uma idade média de 38,17 ± 14,08 anos e índice de massa corporal (IMC) de 29,71 ± 17,48 kg/m2. Os principais sintomas persistentes relatados foram dispneia ao esforço (39,7%), perda de memória (38,2%) e ansiedade (48,5%). Considerando a função pulmonar, os participantes atingiram 88,87 ± 17,20% da capacidade vital forçada (CVF) prevista, 86,03 ± 22,01% do volume expiratório forçado no primeiro segundo (VEF1) e 62,71 ± 25,04% do pico de fluxo expiratório (PFE). Na manovacuometria, observou-se 97,41 ± 34,67% da força inspiratória prevista (Pimáx) e 66,86 ± 22,97% da força expiratória prevista (Pemáx). Conclusões: Seis meses após a infecção por COVID-19, observou-se uma redução no PFE e na PEM. Dentre os sintomas persistentes mais comumente relatados estavam fadiga, cansaço com o mínimo esforço, ansiedade e depressão, perda de memória e déficits de concentração.

Cardiorespiratory optimal point in post-COVID-19 patients: a cross-sectional study

ABSTRACT The varied clinical presentations of SARS-CoV-2 infection have raised concerns about long-term consequences, especially "long-COVID" or "post-COVID-19 syndrome." In this context, the cardiorespiratory optimal point (COP) within the Cardiopulmonary Exercise Test (CPET) emerges as a crucial metric for evaluating functional capacities and detecting cardiovascular and pulmonary anomalies post-COVID-19. This study aimed to assess COP values among post-COVID-19 patients and categorized them based on the initial severity of their disease. In this cross-sectional study conducted in the Northeast Brazil, 80 patients (26 females and 54 males) previously infected with SARS-CoV-2 underwent CPET. We clinically stratified patients into mild, moderate, or severe COVID-19 categories and assessed COP values and other cardiorespiratory metrics. We found differences in the predicted COP between patients with mild and severe COVID-19 (p=0.042). Additionally, patients with moderate and severe COVID-19 record had an average COP value exceeding 22. Other parameters, including respiratory exchange ratio, heart rate, and oxygen uptake efficiency slope, did not differ across the groups. Patients with a history of severe COVID-19 showed altered COP values, suggesting potential discrepancies in cardiovascular and respiratory system integration. The outcomes emphasize the importance of continuous monitoring and assessment of the cardiorespiratory domain for post-COVID-19 patients. Further research is needed to understand the relationship between elevated COP in post-severe COVID-19 and its long-term prognostic implications.

Post-COVID-19 syndrome: An investigation of speech-language-hearing symptoms / Síndrome Pós-COVID-19: investigação de sintomas fonoaudiológicos

ABSTRACT Purpose: to investigate speech-language-hearing symptoms in adults after the acute phase of COVID-19 and the impact of these persistent symptoms on their physical and emotional aspects, functional capacity, and social relationships. Methods: 204 adults who tested positive for COVID-19 between January 2021 and July 2022 and who completed an online questionnaire, addressing different variables. Data were analyzed with descriptive statistics. Results: the most prevalent symptoms up to 30 days after infection were tiredness (46%), memory loss (40.2%), and ageusia (26.5%). The most found long-term symptoms were memory loss (34.3%), tiredness (21.1%), and difficulties in starting a sentence or conversation (10.1%). Anosmia and ageusia were also cited. These persistent symptoms had an impact on their emotional aspect (33.3%), followed by the physical (26%) and occupational (25%) ones. Conclusion: this study found persistent symptoms after the acute phase of COVID-19, which can lead to speech-language-hearing disorders, such as impaired oral language and eating. These persistent symptoms impacted the participants' emotional, physical, and occupational aspects.

RESUMO Objetivo: investigar a presença de sintomas fonoaudiológicos em adultos após o período da fase aguda da COVID-19, além do impacto da manutenção desses sintomas nos aspectos físicos, emocionais, capacidade funcional e relações sociais. Métodos: participaram 204 adultos que testaram positivo para COVID-19 no período de janeiro de 2021 a julho de 2022 e que preencheram um questionário on- line, abordando diferentes variáveis. Os dados foram analisados por meio de estatística descritiva. Resultados: os sintomas mais prevalentes até 30 dias após a infecção foram cansaço (46%), perda de memória (40,2%) e ageusia (26,5%). Os sintomas de longa duração mais observados foram perda de memória (34,3%), cansaço (21,1%) e dificuldades para iniciar um diálogo ou frase (10,1%). Anosmia e ageusia também foram citadas. Houve impacto da manutenção desses sintomas no aspecto emocional (33,3%), seguido dos aspectos físicos (26%) e ocupacionais (25%). Conclusão: neste estudo foram encontrados sintomas persistentes após o período da fase aguda da COVID-19 que podem levar a alterações fonoaudiológicas, como prejuízo na linguagem oral e nas questões alimentares. A manutenção desses sintomas impactou nos aspectos emocionais, físicos e ocupacionais dos participantes.