[Long COVID : which neuropsychological intervention ? The example applied at the Leenaards Memory Centre]. / Covid Long : quelle prise en charge neuropsychologique ? La filière proposée au Centre Leenaards de la Mémoire.

A "Long COVID" care management was created at the Leenaards Memory Centre (Lausanne University Hospital) to meet the high demand for neuropsychological examinations in the patients which have persistent symptoms for several months. A multidisciplinary evaluation specifically addressing aspects of fatigue and sleep as well as cognition has been developed to receive these patients. Depending on the severity of their symptoms, they are then oriented towards a holistic group treatment, integrating cognitive remediation including psycho-education, restorative and compensatory methods to cope with their cognitive difficulties, and tools to manage the various symptoms of COVID-long (fatigue, insomnia, stress, depression and reduced quality of life).

Une filière « Covid long ¼ a vu le jour au Centre Leenaards de la mémoire du CHUV pour répondre à une importante demande d'examens neuropsychologiques chez des patients aux symptômes persistant depuis plusieurs mois. Les patients bénéficient d'une évaluation multidisciplinaire qui inclut les aspects de la fatigue et du sommeil ainsi que la cognition. Ils sont ensuite orientés, selon la sévérité de leurs symptômes, vers une prise en charge groupale holistique qui intègre de la remédiation cognitive incluant de la psychoéducation, des méthodes restauratives et compensatoires pour faire face à leurs difficultés cognitives et des outils permettant de gérer les différents symptômes caractéristiques d'un Covid long (fatigue, insomnie, stress, dépression et diminution de la qualité de vie).

[Psychiatric dimensions of post-COVID-19 condition : an overview]. / Dimensions psychiatriques de l'affection post-Covid-19 : état des lieux.

In the aftermath of the SARS-CoV-2 pandemic, many patients developed a set of persistent and disabling symptoms, commonly referred to as "long COVID" and defined as "post-COVID-19 condition" by the World Health Organization. The multi-systemic impairments caused by this condition include neuropsychiatric symptoms characterized by the presence of fatigue, cognitive and sleep disturbances, and increased rates of mood and anxiety disorders. Despite their high incidence and a significant risk of chronicity, they remain poorly understood. This article provides an overview of the psychiatric aspects of post-COVID-19 condition and their treatment.

Au décours de la pandémie de SARS-CoV-2 sont apparus chez de nombreux patients un ensemble de symptômes persistants et invalidants, communément appelé « Covid long ¼ et défini comme « affection post-Covid-19 ¼ par l'OMS. Les atteintes multisystémiques provoquées par cette affection comprennent des symptômes neuropsychiatriques caractérisés, notamment une fatigue, des troubles cognitifs et des taux élevés de troubles de l'humeur et anxieux. Malgré leur incidence élevée et un risque important de chronicité, ils restent mal connus. Cet article propose une synthèse et une mise à jour des connaissances au sujet des dimensions psychiatriques de l'affection post-Covid-19 et de leurs prises en charge.

Determinants of post-COVID-19 symptoms among adults aged 55 or above with chronic conditions in primary care: data from a prospective cohort in Hong Kong.

Background: Primary care patients, especially those with an older age, are one of the most vulnerable populations for post-COVID-19 symptoms. Identifying predictors of post-COVID symptoms can help identify high-risk individuals for preventive care. Methods: Out of 977 primary care patients aged 55 years or above with comorbid physical and psychosocial conditions in a prospective cohort in Hong Kong, 207 patients infected in the previous 5-24 weeks were included. The three most common post-COVID-19 symptoms (breathlessness, fatigue, cognitive difficulty), which lasted beyond the 4-week acute infection period, were assessed using items from the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS), together with other self-reported symptoms. Multivariable analyses were conducted to identify predictors of post-acute and long COVID-19 symptoms (5-24 weeks after infection). Results: The 207 participants had a mean age of 70.8 ± 5.7 years, 76.3% were female, and 78.7% had ≥2 chronic conditions. In total, 81.2% reported at least one post-COVID symptom (mean: 1.9 ± 1.3); 60.9, 56.5 and 30.0% reported fatigue, cognitive difficulty, and breathlessness respectively; 46.1% reported at least one other new symptom (such as other respiratory-related symptoms (14.0%), insomnia or poor sleep quality (14.0%), and ear/nose/throat symptoms (e.g., sore throat) (10.1%), etc.). Depression predicted post-COVID-19 fatigue. The female sex predicted cognitive difficulty. Receiving fewer vaccine doses (2 doses vs. 3 doses) was associated with breathlessness. Anxiety predicted a higher overall symptom severity level of the three common symptoms. Conclusion: Depression, the female sex, and fewer vaccine doses predicted post-COVID symptoms. Promoting vaccination and providing intervention to those at high-risk for post-COVID symptoms are warranted.

[Prospects and possibilities for the treatment of patients with long COVID-19 syndrome].

AIM: To study the efficacy and safety of a drug product based on the succinic acid complex with trimethylhydrazine used to treat patients with asthenic syndrome after a new coronavirus infection (COVID-19). MATERIALS AND METHODS: A prospective, multicenter, comparative, randomized, double-blind, placebo-controlled study of the safety and efficacy of sequential therapy with Brainmax® enrolled 160 patients 12-16 weeks after coronavirus infection (no more than 12 months). The study was conducted at 6 healthcare centers in different regions of the Russian Federation. At the enrollment, clinical and neurological examination and the following tests were performed: complete blood count, urinalysis, blood chemistry, coagulation test, pulse oximetry, electrocardiography, glomerular filtration rate calculation (according to Cockcroft-Gault formula) were performed. Also, the patients were assessed using the following tools: VAS headache rating scale, MFI-20 asthenia scale, PSQI index, FAS-10 fatigue assessment scale, Dizziness Handicap Inventory (DHI), MoCA-test for cognitive impairment assessment, Beck Anxiety Inventory, Kérdö Autonomic Index. RESULTS: The primary endpoint was the mean reduction in the MFI-20 asthenia scale score after the therapy (Visit 5, 41st day of therapy) compared to data from Visit 0 (beginning of therapy). A clinically significant advantage of the study drug versus the placebo was demonstrated, with a median absolute change in the MFI-20 score of -19.5 [-27; -11] points in the Brainmax® drug group and -3 [-7; 1] score in the placebo group (p<0.001). A significant sleep quality improvement according to the PSQI index was shown in the study group: by -2.5 [-4; -1] points versus no improvement in the placebo group (0 [-3; 0], p<0,001). Significant differences were also noted for the following secondary endpoints: PSQI sleep quality scale, FAS-10 fatigue assessment scale, DHI, and Beck Anxiety and Depression Inventory. There was also a decrease in patients' complaints of cognitive deterioration according to the CGI scale. CONCLUSION: Our study clearly demonstrated the efficacy and high safety profile of Brainmax® in a representative sample of patients with the post-COVID syndrome.

Evaluating the psychometric properties of the fatigue severity scale using item response theory.

BACKGROUND: Fatigue is a common daily experience and a symptom of various disorders. While scholars have discussed the use of the Fatigue Severity Scale (FSS) using item response theory (IRT), the characteristics of the Japanese version are not yet examined. This study evaluated the psychometric properties of the FSS using IRT and assessed its reliability and concurrent validity with a general sample in Japan. METHODS AND MEASURES: A total of 1,007 Japanese individuals participated in an online survey, with 692 of them providing valid data. Of these, 125 participants partook in a re-test after approximately 18 days and had their longitudinal data analyzed. In addition, the graded response model (GRM) was used to assess the FSS items' characteristics. RESULTS: The GRM's results recommended using seven items and a 6-point scale. The FSS's reliability was acceptable. Furthermore, the validity was adequate from the results of correlation and regression analyses. The synchronous effects models demonstrated that the Multidimensional Fatigue Inventory (MFI) enhanced depression, and depression enhanced FSS. CONCLUSION: This study suggested that the Japanese version of the FSS should be a 7-item scale with a 6-point response scale. Further investigations may reveal the different aspects of fatigue assessed by the analyzed fatigue measures.

Effectiveness of Xiangsha Liujun pills on decreased digestive function in convalescent patients of coronavirus disease 2019: a randomized, double blind, placebo controlled clinical trial.

OBJECTIVE: To evaluate the effectiveness and safety of Xiangsha Liujun pills on the decreased digestive function in patients in the recovery phase of the Coronavirus disease 2019 (COVID-19). METHODS: A randomized, double blind, placebo controlled clinical trial was conducted. A total of 200 COVID-19 patients in the recovery phase were included in our study in Ezhou Hospital of Traditional Chinese Medicine. Totally 200 subjects were randomly divided into a treatment group (Xiangsha Liujun pills) and a control group (placebo), with 100 in each group. Subjects took Xiangsha Liujun pills or placebo orally three times a day for two weeks. Three visits were scheduled at week 0 (baseline), week 1 (the middle of the intervention) and week 2 (the end of the intervention) for each eligible patient. The total efficacy rates for improving the Traditional Chinese Medicine (TCM) symptoms (fatigue, poor appetite, abdominal distension and loose stools) and the disappearance rates of symptoms were observed and compared in the treatment and control groups. Adverse events were recorded during the study period. SAS 9.4 was used to analyze the data. RESULTS: A total of 200 patients were included in this study, among which 4 participants withdrew because the drugs did not work. Three patients were excluded for age. Before the treatment, there was no significant difference between the TCM symptoms scores of subjects. After 1 week of treatment, the full analysis set (FAS) showed that the efficacy rates for abdominal distension and loose stools in the treatment group were significantly higher than the control group ( 0.05). There were no significant differences in the efficacy rates for fatigue and poor appetite between the two groups (0.05). In addition, the disappearance rate of fatigue in the treatment group was significantly higher than the control group (0.05); there were no significant differences between the two groups after treatment in the rates of poor appetite, abdominal distension, and loose stools (>0.05). After 2 weeks of treatment, the efficacy rates for fatigue, poor appetite, abdominal distension, and loose stools in the treatment group were significantly higher than the control group (0.05). The disappearance rate of loose stools in the treatment group was significantly higher than the control group ( 0.05). However, there were no significant differences in the disappearance rates of fatigue, poor appetite, and abdominal distension between the two groups ( 0.05). No severe adverse events were reported by subjects during the study. CONCLUSIONS: This clinical study confirmed that Xiangsha Liujun pills can effectively improve the symptoms related to the decreased digestive function in COVID-19 convalescent patients.

Effects of diagnosis threat on cognitive complaints after COVID-19.

OBJECTIVE: The term "long-COVID" refers to the persistence of neurological symptoms after being ill with COVID-19 (e.g., headaches, fatigue, and attentional impairment). Providing information about long-COVID (i.e., "diagnosis threat") increased subjective cognitive complaints among recovered COVID-19 patients compared with those exposed to neutral information (Winter & Braw, 2022). Notably, this effect was particularly prominent among more suggestible participants. Our aim in the current study was to validate these initial findings and to explore the impact of additional variables (e.g., suggestibility). METHOD: Recovered patients (n = 270) and controls (n = 290) reported daily cognitive failures after being randomly assigned to either a diagnosis threat (exposure to an article providing information regarding long-COVID) or a control condition. RESULTS: Recovered patients, but not controls, reported more cognitive failures in the diagnosis threat condition compared with the control condition. Diagnosis threat added significantly to the prediction of cognitive complaints based on relevant demographic variables and suggestibility. Diagnosis threat and suggestibility interacted (i.e., suggestible individuals were particularly vulnerable to the impact of a diagnosis threat). CONCLUSIONS: Diagnosis threat may contribute to the persistence of complaints regarding cognitive impairment among recovered COVID-19 patients. Suggestibility may be an underlying mechanism that increases the impact of diagnosis threat. Other factors, such as vaccination status, may be at play though we are only at the initial stages of research concerning their impact. These may be the focus of future research, aiding in identifying risk factors for experiencing COVID-19 symptoms past the resolution of its acute phase. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Safety outcomes associated with the moderna COVID-19 vaccine (mRNA-1273): a literature review.

INTRODUCTION: Current safety data from Phase 3 clinical trials have concluded that apart from transient local and systemic reactions, no safety concerns were identified for the Moderna COVID-19 vaccine (mRNA-1273). However, Phase 3 studies are insufficient to detect rare adverse events (AEs). A literature search of the two major electronic databases, Embase and PubMed, was performed to enable the identification and characterization of all relevant articles from December 2020 to November 2022. AREAS COVERED: This narrative review summarizes the key safety outcomes associated with the mRNA-1273 vaccine to inform healthcare decisions and increase public awareness of mRNA-1273 vaccine safety. The primary adverse events (AEs) reported within a diverse population, receiving the mRNA-1273 vaccine, were; localized injection site pain, fatigue, headache, myalgia, and chills. In addition, the mRNA-1273 vaccine was also associated with; less than a 1-day change in the menstrual cycle, a 10-fold higher risk of myocarditis and pericarditis within young males aged 18-29 years and increased levels of anti-polyethylene glycol (PEG) antibodies. EXPERT OPINION: The transient nature of commonly observed AEs and the rare occurrence of severe events within mRNA-1273 recipients show no significant safety concerns which should prevent vaccination. However, large-scale epidemiological studies with longer follow-up periods are required to surveillance rare safety outcomes.

Fading Fatigue - A Self-Management App for Supporting Long-COVID Patients with Fatigue.

Fatigue is the most prevalent Long-COVID symptom. Individuals who are affected have to learn to organize and manage daily activities according to the subjectively perceived energy reserves. Our objective was to develop an application, Fading Fatigue, that supports patients in their energy management, in particular after an initial therapy guided by health professionals. Fading Fatigue was developed in an iterative approach and implemented as a client-server application. Interviews and a literature search were conducted to identify limitations and challenges of the current treatment. Fading Fatigue offers several tools for energy management: a daily energy planner, a documentation aid for well-being and a progress view. Future work should study usability. Inclusion of additional features increasing the adherence such as providing feedback could be considered.

Post-COVID Symptoms in Occupational Cohorts: Effects on Health and Work Ability.

Post-acute COVID-19 syndrome is frequently observed in workers and has a substantial impact on work ability. We conducted a health promotion program to identify cases of post-COVID syndrome, analyze the distribution of symptoms and their association with work ability. Of the 1422 workers who underwent routine medical examination in 2021, 1378 agreed to participate. Among the latter, 164 had contracted SARS-CoV-2 and 115 (70% of those who were infected) had persistent symptoms. A cluster analysis showed that most of the post-COVID syndrome cases were characterized by sensory disturbances (anosmia and dysgeusia) and fatigue (weakness, fatigability, tiredness). In one-fifth of these cases, additional symptoms included dyspnea, tachycardia, headache, sleep disturbances, anxiety, and muscle aches. Workers with post-COVID were found to have poorer quality sleep, increased fatigue, anxiety, depression, and decreased work ability compared with workers whose symptoms had rapidly disappeared. It is important for the occupational physician to diagnose post-COVID syndrome in the workplace since this condition may require a temporary reduction in work tasks and supportive treatment.

At-Admission Prediction of Mortality and Pulmonary Embolism in COVID-19 Patients Using Statistical and Machine Learning Methods: An International Cohort Study (preprint)

By September, 2022, more than 600 million cases of SARS-CoV-2 infection have been reported globally, resulting in over 6.5 million deaths. COVID-19 mortality risk estimators are often, however, developed with small unrepresentative samples and with methodological limitations. It is highly important to develop predictive tools for pulmonary embolism (PE) in COVID-19 patients as one of the most severe preventable complications of COVID-19. Using a dataset of more than 800,000 COVID-19 patients from an international cohort, we propose a cost-sensitive gradient-boosted machine learning model that predicts occurrence of PE and death at admission. Logistic regression, Cox proportional hazards models, and Shapley values were used to identify key predictors for PE and death. Our prediction model had a test AUROC of 75.9% and 74.2%, and sensitivities of 67.5% and 72.7% for PE and all-cause mortality respectively on a highly diverse and held-out test set. The PE prediction model was also evaluated on patients in UK and Spain separately with test results of 74.5% AUROC, 63.5% sensitivity and 78.9% AUROC, 95.7% sensitivity. Age, sex, region of admission, comorbidities (chronic cardiac and pulmonary disease, dementia, diabetes, hypertension, cancer, obesity, smoking), and symptoms (any, confusion, chest pain, fatigue, headache, fever, muscle or joint pain, shortness of breath) were the most important clinical predictors at admission. Our machine learning model developed from an international cohort can serve to better regulate hospital risk prioritisation of at-risk patients.

Long-Term Effects of COVID-19 on Sleep Patterns (preprint)

Objectives: To examine the long term impact of COVID-19 on sleep patterns and development of sleep disorders. Methods: Using the centralized Massachusetts General Brigham (MGB) Research Patient Data Registry (RPDR), SARS-CoV2 positive patients were surveyed about their sleep patterns before and after the viral infection. Information related to co-morbid conditions and medications were obtained through chart review. Results: Two hundred and forty five completed surverys were analysed. Average age was 53.3 ± 16.3 years, and participants were predominantly Non-Hispanic White (84.1%) and female (74.3%). Average BMI (kg/m2) was 29.9 ± 6.9, and a greater proportion was non-smokers (63.2%). After COVID-19, there was an increase in the percentage of participants reporting difficulty initiating (31 ± 46% vs. 39 ± 49%, P=0.01), and maintaining sleep (43 ± 49% vs. 57 ± 49%, P<0.001), and use of sleep aids (24 ± 43% vs. 30 ± 45% P=0.003) with an incidence rate of 24.3%, 37.4%, and 12.3% respectively. In addition, there was an increase in daytime fatigue and the need for napping (58 ± 49% vs. 36 ± 48%, P <0.0001) with an incidence of 8% and 23% respectively. The sleep symptoms persisted beyond 12 months among 28% of the participants and were predominantly seen among women. Conclusions: Infection with SARS-CoV2 has negative effects on sleep, and a significant proportion of adults experience insomnia and daytime sleepiness beyond 12 months after recovering from the initial infection.

Long COVID: Plasma levels of neurofilament light chain in mild COVID-19 patients with neurocognitive symptoms (preprint)

It is well known the potential of severe acute respiratory coronavirus type 2 (SARS-CoV-2) infection to induce post-acute sequelae, a condition called Long COVID. This syndrome includes several symptoms, but the central nervous system (CNS) main one is neurocognitive dysfunction. Recently it has been demonstrated the relevance of plasma levels of neurofilament light chain (pNfL), as a biomarker of early involvement of the CNS in COVID-19. The aim of this study was to investigate the relationship between pNfL in patients with post-acute neurocognitive symptoms and the potential of NfL as a prognostic biomarker in these cases. A group of 63 long COVID patients ranging from 18 to 59 years-old were evaluated, submitted to a neurocognitive battery assessment, and subdivided in different groups, according to results. Plasma samples were collected during the long COVID assessment and used for measurement of pNfL with the Single molecule array (SIMOA) assays. Levels of pNfL were significantly higher in long COVID patients with neurocognitive symptoms when compared to HC (p = 0.0031). Long COVID patients with cognitive impairment and fatigue symptoms presented higher pNfL levels when compared to long COVID patients without these symptoms, individually and combined (p = 0.0263, p = 0.0480, and 0.0142, respectively). Correlation analysis showed that levels of cognitive lost and exacerbation of fatigue in the neurocognitive evaluation had a significative correlation with higher pNfL levels (p = 0.0219 and 0.0255, respectively). Previous reports suggested that pNfL levels are related with higher risk of severity and predict lethality of COVID-19. Our findings demonstrate that SARS-CoV-2 infection seems to have a long-term impact on the brain, even in patients who presented mild acute disease. NfL measurements might be useful to identify CNS involvement in long COVID associated with neurocognitive symptoms and to identify who will need continuous monitoring and treatment support.

"There is no one who helps you with it." Experiences of people with long COVID regarding medical care, therapeutic measures, and barriers in the German healthcare system: results of a qualitative study with four focus groups (preprint)

Background Many people experience long-term symptoms such as fatigue, cognitive problems, or shortness of breath after an acute infection with COVID-19. This emerging syndrome, known as long COVID, is new and complex in many aspects. This study aims to collect the experiences of people with long COVID with ambulatory healthcare structures. Methods Four focus groups were conducted with a total of 23 adults with long COVID in June and July 2022. These discussions were audio-recorded, subsequently transcribed, and analyzed using the qualitative content analysis of Mayring and Kuckartz. Results Fourteen out of 19 participants who had a primary care encounter regarding their long COVID symptoms did not perceive it as helpful. Many respondents reported that their general practitioners did not take their long COVID symptoms seriously and did not refer them to specialists or made therapeutic recommendations. However, some participants reported that they were prescribed non-pharmaceutical therapies (e.g., group meetings supported by psychotherapists, occupational therapy, etc.) that improved their condition. 14 of 23 respondentsperceived care barriers such as providers' lack of awareness of long COVID, poor access to specialists, a lack of specialized care (e.g., long COVID clinics), or high bureaucratic hurdles for specific healthcare services. To improve medical care, participants suggested campaigns to raise awareness of long COVID among healthcare providers and the general population, increase research and government investments regarding the development of treatment structures for long COVID, expanding existing therapeutic services, and establishing one-stop shops for integrated specialist healthcare for people with long COVID. Conclusions Several implications for healthcare professionals and policymakers can be derived from this study: (1) general practitioners should take the symptoms of long COVID seriously, assume a care coordinating role, make referrals, and establish contact with long COVID clinics; (2) care planners should focus on developing interprofessional evidence-based care and treatment approaches for long COVID; (3) existing care structures such as long COVID outpatient clinics should be expanded. Trial registration: The study is registered in the German register for clinical trials (DRKS00026007).

Effect of Inadequate Sleep on Clinician Performance.

The negative impacts of sleep deprivation and fatigue have long been recognized. Numerous studies have documented the ill effects of impaired alertness associated with the disruption of the sleep-wake cycle; these include an increased incidence of human error-related accidents, increased morbidity and mortality, and an overall decrement in social, financial, and human productivity. While there are multiple studies on the impact of sleep deprivation and fatigue in resident physicians, far fewer have examined the effects on attending physicians, and only a handful addresses the accumulated effects of chronic sleep disturbances on acute sleep loss during a night call-shift. Moreover, the rapid and unprecedented spread of coronavirus disease 2019 (COVID-19) pandemic significantly increased the level of anxiety and stress on the physical, psychological, and the economic well-being of the entire world, with heightened effect on frontline clinicians. Additional studies are necessary to evaluate the emotional and physical toll of the pandemic in clinicians, and its impact on sleep health, general well-being, and performance.

Gender-Specificity of Fatigue and Concerns Related to the COVID-19 Pandemic-A Report on the Polish Population.

BACKGROUND: The COVID-19 pandemic, which is now going on its third year, and its consequences experienced in almost every sphere of life may eventually lead to pandemic fatigue. Previous research indicates that one of the important determinants of the negative consequences of the pandemic is gender. Based on the WHO's definition of pandemic fatigue, a study was undertaken to determine the level of pandemic fatigue and concerns expressed in relation to the pandemic in Poland. METHODS: A survey among 1064 respondents was conducted using the CATI technique during the fourth wave of the COVID-19 pandemic in Poland. Questionnaires adopted: the Polish adaptation of the Pandemic Fatigue Scale (PFS), Subjective Fatigue Symptoms (SFS), and the COVID-19 Concerns Checklist (CCC) and sociodemographic questions. The following statistical methods were employed: ANOVA analysis of variance, Mann-Whitney U test or Kruskal-Wallis test, and Chi-square test. RESULTS: The analysis showed that women received higher overall PFS, information PFS, SFS, and pandemic-related concerns scores. Other factors that were associated with pandemic fatigue were age, treatment for chronic diseases, receipt of the COVID-19 vaccine, and COVID-19 survivor status. CONCLUSIONS: Women in Poland are experiencing pandemic fatigue, subjective fatigue symptoms, and concerns associated with the COVID-19 pandemic at a higher rate than men. Along with implementing interventions focused on public health safety, it seems reasonable to put in place strategies to assist people who are less capable of coping with prolonged stressful situations.

Third dose mRNA vaccination against SARS-CoV-2 reduces medical complaints seen in primary care: a matched cohort study.

BACKGROUND: SARS-CoV-2 mRNA vaccination has been associated with both side effects and a reduction in COVID-related complaints due to the decrease in COVID-19 incidence. We aimed to investigate if individuals who received three doses of SARS-CoV-2 mRNA vaccines had a lower incidence of (a) medical complaints and (b) COVID-19-related medical complaints, both as seen in primary care, when compared to individuals who received two doses. METHODS: We conducted a daily longitudinal exact one-to-one matching study based on a set of covariates. We obtained a matched sample of 315,650 individuals aged 18-70 years who received the 3rd dose at 20-30 weeks after the 2nd dose and an equally large control group who did not. Outcome variables were diagnostic codes as reported by general practitioners or emergency wards, both alone and in combination with diagnostic codes of confirmed COVID-19. For each outcome, we estimated cumulative incidence functions with hospitalization and death as competing events. RESULTS: We found that the number of medical complaints was lower in individuals aged 18-44 years who received three doses compared to those who received two doses. The differences in estimates per 100,000 vaccinated were as follows: fatigue 458 less (95% confidence interval: 355-539), musculoskeletal pain 171 less (48-292), cough 118 less (65-173), heart palpitations 57 less (22-98), shortness of breath 118 less (81-149), and brain fog 31 less (8-55). We also found a lower number of COVID-19-related medical complaints: per 100,000 individuals aged 18-44 years vaccinated with three doses, there were 102 (76-125) fewer individuals with fatigue, 32 (18-45) fewer with musculoskeletal pain, 30 (14-45) fewer with cough, and 36 (22-48) fewer with shortness of breath. There were no or fewer differences in heart palpitations (8 (1-16)) or brain fog (0 (- 1-8)). We observed similar results, though more uncertain, for individuals aged 45-70 years, both for medical complaints and for medical complaints that were COVID-19 related. CONCLUSIONS: Our findings suggest that a 3rd dose of SARS-CoV-2 mRNA vaccine administered 20-30 weeks after the 2nd dose may reduce the incidence of medical complaints. It may also reduce the COVID-19-related burden on primary healthcare services.

Prevalence of long COVID complaints in persons with and without COVID-19.

We studied the prevalence and patterns of typical long COVID complaints in ~ 2.3 million individuals aged 18-70 years with and without confirmed COVID-19 in a Nation-wide population-based prospective cohort study in Norway. Our main outcome measures were the period prevalence of single-occurring or different combinations of complaints based on medical records: (1) Pulmonary (dyspnea and/or cough), (2) Neurological (concentration problems, memory loss), and/or (3) General complaints (fatigue). In persons testing positive (n = 75 979), 64 (95% confidence interval: 54 to 73) and 122 (111 to 113) more persons per 10 000 persons had pulmonary complaints 5-6 months after the test compared to 10 000 persons testing negative (n = 1 167 582) or untested (n = 1 084 578), respectively. The corresponding difference in prevalence of general complaints (fatigue) was 181 (168 to 195) and 224 (211 to 238) per 10 000, and of neurological complaints 5 (2 to 8) and 9 (6-13) per 10 000. Overlap between complaints was rare. Long COVID complaints were only slightly more prevalent in persons with than without confirmed COVID-19. Still, long COVID may pose a substantial burden to healthcare systems in the future given the lasting high incidence of symptomatic COVID-19 in both vaccinated and unvaccinated individuals.

COVID-19 Sequelae and Their Implications on Social Services.

BACKGROUND: The impact of persistent coronavirus disease 2019 (COVID-19) symptoms on quality of life remains unclear. This study aimed to describe such persistent symptoms and their relationships with quality of life, including clinical frailty and subjective health status. METHODS: A prospective longitudinal 3-month follow-up survey monitored symptoms, health quality, support needs, frailty, and employment. RESULTS: A total of 82 patients with a mean age of 52 years (ranging from 23-84 years) were enrolled, including 48 (58.6%) men, and 34 (41.5%) women. The fully active status decreased from 87.8% before admission to 78.1% post discharge. Two patients (2.4%) were ambulatory and capable of all self-care but unable to carry out any work-related activities 12 weeks after discharge. Clinical frailty scale (CFS) levels 1, 2, 3 and 4 changed drastically between admission and 12 weeks later after discharge. Just after admission, the median EuroQol visual analogue scales (EQ-VAS) was 82.23 (± 14.38), and it decreased to 78.10 (± 16.02) 12 weeks after discharge; 62 (75.6%) of patients reported at least one symptom 12 weeks after discharge. The most frequent symptom was fatigue followed by smell disorder, anxiety, sleep disorder, headache, depressive mood, dyspnea, and taste disorder. CFS was definitively associated with fatigue. Decreased EQ-VAS was associated with fatigue and palpitation, cough, taste disorder, and chest pain. EQ-VAS was worse in women (28%) than in men. Compared with regular outpatient clinic visits before admission, 21 patients (25.6%) reported increased outpatient clinic visits, one (1.4%) reported readmission, and one (1.4%) reported emergency room visits. Six of the 54 (77.1%) patients who were employed before admission lost their jobs. And most vulnerable type was self-employed, because three self-employed job workers were not working at 12 weeks after discharge. CONCLUSION: COVID-19 sequelae should not be underestimated. We find a decrease in health quality and increase in psychological problems in discharged COVID-19 patients, and some patients experience unemployment. The number of patients suffering from COVID-19 sequelae would not be negligible considering there are more than one million COVID-19 infection cases in Korea. Hence, the government should start a systematic monitoring system for discharged patients and prepare timely medical and social interventions accordingly.

Identifying responders to elamipretide in Barth syndrome: Hierarchical clustering for time series data.

BACKGROUND: Barth syndrome (BTHS) is a rare genetic disease that is characterized by cardiomyopathy, skeletal myopathy, neutropenia, and growth abnormalities and often leads to death in childhood. Recently, elamipretide has been tested as a potential first disease-modifying drug. This study aimed to identify patients with BTHS who may respond to elamipretide, based on continuous physiological measurements acquired through wearable devices. RESULTS: Data from a randomized, double-blind, placebo-controlled crossover trial of 12 patients with BTHS were used, including physiological time series data measured using a wearable device (heart rate, respiratory rate, activity, and posture) and functional scores. The latter included the 6-minute walk test (6MWT), Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue score, SWAY Balance Mobile Application score (SWAY balance score), BTHS Symptom Assessment (BTHS-SA) Total Fatigue score, muscle strength by handheld dynamometry, 5 times sit-and-stand test (5XSST), and monolysocardiolipin to cardiolipin ratio (MLCL:CL). Groups were created through median split of the functional scores into "highest score" and "lowest score", and "best response to elamipretide" and "worst response to elamipretide". Agglomerative hierarchical clustering (AHC) models were implemented to assess whether physiological data could classify patients according to functional status and distinguish non-responders from responders to elamipretide. AHC models clustered patients according to their functional status with accuracies of 60-93%, with the greatest accuracies for 6MWT (93%), PROMIS (87%), and SWAY balance score (80%). Another set of AHC models clustered patients with respect to their response to treatment with elamipretide with perfect accuracy (all 100%). CONCLUSIONS: In this proof-of-concept study, we demonstrated that continuously acquired physiological measurements from wearable devices can be used to predict functional status and response to treatment among patients with BTHS.