Manifestation of Headache Affecting Quality of Life in Long COVID Patients.

Objectives: The present study aimed to elucidate the characteristics of long COVID patients with headaches. Methods: A single-center retrospective observational study was performed for long COVID outpatients who visited our hospital from 12 February 2021 to 30 November 2022. Results: A total of 482 long COVID patients, after excluding 6, were divided into two groups: the Headache group of patients with complaints of headache (113 patients: 23.4%) and the remaining Headache-free group. Patients in the Headache group were younger (median age: 37 years) than patients in the Headache-free group (42 years), while the ratio of females (56%) in the Headache group was nearly the same as that in the Headache-free group (54%). The proportion of patients in the Headache group who were infected in the Omicron-dominant phase (61%) was larger than the proportions of patients infected in the Delta (24%) and preceding (15%) phases, and that trend was significantly different from the trend in the Headache-free group. The duration before the first visit for long COVID was shorter in the Headache group (71 days) than in the Headache-free group (84 days). The proportions of patients in the Headache group with comorbid symptoms, including general fatigue (76.1%), insomnia (36.3%), dizziness (16.8%), fever (9.7%), and chest pain (5.3%) were larger than the proportions of patients in the Headache-free group, whereas blood biochemical data were not significantly different between the two groups. Interestingly, patients in the Headache group had significant deteriorations of scores indicating depression and scores for quality of life and general fatigue. In multivariate analysis, headache, insomnia, dizziness, lethargy, and numbness were shown to be involved in the quality of life (QOL) of long COVID patients. Conclusions: The manifestation of headaches related to long COVID was found to have a significant impact on social and psychological activities. Alleviation of headaches should be a priority for the effective treatment of long COVID.

Trends in Long COVID Symptoms in Japanese Teenage Patients.

Background: Since the start of the global pandemic of coronavirus disease 2019 (COVID-19), not only adults but also many children have suffered from it. However, the clinical characteristics of long COVID in children remain unclear. Methods: In this retrospective observational study conducted in a single facility, we reviewed the medical records of all long COVID patients who visited Okayama University Hospital from February 2021 to October 2022, and we compared the clinical characteristics of long COVID in teenagers (11 to 18 years of age) with those in adults. Results: Data for 452 long COVID patients including 54 teenagers (11.9%) were analyzed. Fatigue was the most frequent symptom in teenagers (55.6% of the patients) and also in adults. On the other hand, the percentage of teenagers who complained of headache, which was the second most frequent complaint, was significantly higher than the percentage of adults (35.2% vs. 21.9%, p < 0.05). A comparison of the frequencies of symptoms depending on the viral variant showed that fatigue and headache were predominant symptoms in the Omicron variant phase. Of the 50 teenagers who were enrolled in schools, 28 (56.0%) could not attend school due to long COVID symptoms. The most common symptoms as reasons for absence from school were fatigue (85.7% of the patients), headache (42.9%), and insomnia (32.1%). Conclusions: Attention should be paid to the symptoms of fatigue and headache in teenagers with long COVID.

Symptomatic Characteristics of Hypozincemia Detected in Long COVID Patients.

OBJECTIVES: The aim of this study was to determine the characteristics of hypozincemia in long COVID patients. METHODS: This study was a single-center retrospective observational study for outpatients who visited the long COVID clinic established in a university hospital during the period from 15 February 2021 to 28 February 2022. Characteristics of patients with a serum zinc concentration lower than 70 µg/dL (10.7 µmol/L) were compared with characteristics of patients with normozincemia. RESULTS: In a total of 194 patients with long COVID after excluding 32 patients, hypozincemia was detected in 43 patients (22.2%) including 16 male patients (37.2%) and 27 female patients (62.8%). Among various parameters including the background characteristics of the patients and medical histories, the patients with hypozincemia were significantly older than the patients with normozincemia (median age: 50 vs. 39 years). A significant negative correlation was found between serum zinc concentrations and age in male patients (R = -0.39; p < 0.01) but not in female patients. In addition, there was no significant correlation between serum zinc levels and inflammatory markers. General fatigue was the most frequent symptom in both male patients with hypozincemia (9 out of 16: 56.3%) and female patients with hypozincemia (8 out of 27: 29.6%). Patients with severe hypozincemia (serum zinc level lower than 60 µg/dL) had major complaints of dysosmia and dysgeusia, which were more frequent complaints than general fatigue. CONCLUSIONS: The most frequent symptom in long COVID patients with hypozincemia was general fatigue. Serum zinc levels should be measured in long COVID patients with general fatigue, particularly in male patients.

Differences in Stress Perception of Medical Students Depending on In-Person Communication and Online Communication during the COVID-19 Pandemic: A Japanese Cross-Sectional Survey.

BACKGROUND: Excessive psychological stress in medical students affects their mental health and causes problems such as burnout and depression. Furthermore, changes in the learning environment to online learning due to the COVID-19 pandemic have had a psychological effect on medical students. However, the relationships between medical students' perceived stress and different methods of communication, including in-person and online communication, remain unclear. The purpose of this study was to investigate the differences in stress perception of medical students depending on in-person communication and online communication during the COVID-19 pandemic. METHODS: This study was a cross-sectional study conducted from September to October in 2020. All of the students of Okayama University School of Medicine were asked to participate in a questionnaire survey. The explanatory variables were the frequency and length of communications with others (by in-person or online communication), empathy, and lifestyle. The main outcome measure was perceived stress. Subgroup analysis was conducted for students who preferred to be by themselves and students who preferred to study together and interact with other people. Univariate analysis and multivariate multiple regression analysis were conducted. Gender and grade, which have been shown to be associated with stress in previous studies, were used as covariates for multiple regression analysis. RESULTS: Valid responses to the questionnaire survey were received from 211 (29.4%) of the 717 students. There was no significant association between perceived stress and online communication, but the number of people with which students had in-person communication (1-2 people compared to 0 as a control, regression coefficient [B] = -4.4, 95% confidence interval [CI]; -7.8, -1.1, more than 10 people, B = -12, 95% CI: -18, -5.8) and the length of communication (more than 120 min, B = -4.5, 95% CI: -8.1, -0.92) were associated with a reduction in perceived stress. In subgroup analysis, the number of people with in-person communication and the length of communication had significant associations with stress reduction even in the group of students who had a preference for being by themselves. CONCLUSION: In-person communications rather than online communications were associated with a lower level of perceived stress. In subgroup analysis, this trend was statistically significant in the group of students who had a preference for being by themselves.

Characteristics of Sleep Disturbance in Patients with Long COVID: A Retrospective Observational Study in Japan.

OBJECTIVES: The objective of this study was to determine the clinical and endocrinological features of sleep disturbance in patients with long COVID. METHODS: This study was a single-center retrospective observational study for patients who visited the COVID-19 aftercare outpatient clinic (CAC) established in Okayama University Hospital in Japan during the period from 15 February 2021 to 29 July 2022. The long COVID patients were divided into two groups based on the presence or absence of sleep disturbance, and the clinical and laboratory characteristics of the patients were analyzed. RESULTS: Out of 363 patients with long COVID, after excluding 6 patients, 60 patients (16.5%) (55% males, median age of 38 years) complaining of sleep disturbance were compared with 303 patients (83.5%) (43% males, median age of 40 years) without sleep-related symptoms. Although there were no significant differences in clinical backgrounds and severities of COVID-19 between the two groups by the multivariate analysis, the percentage of long COVID patients with sleep disturbance was significantly increased among patients infected in the Omicron-dominant phase. In addition, the prevalence rate of sleep disturbance in patients when infected in the Omicron phase (24.8%) was two-times higher than that in patients infected in the Delta phase (12.8%). Of note, the percentages of patients with sleep disturbance who also complained of general fatigue, headache, concentration loss, anxiety, low-grade fever, and brain fog symptoms were higher than the percentages of patients without sleep disturbance who had the same complaints. Among the types of sleep disturbance, the percentage of patients who complained of loss of sleep induction (75%) was much higher than the percentage of patients with early-awakening sleep disturbance (6.7%), and many of the patients with mid-awakening types of insomnia had brain fog symptoms. Endocrine examinations revealed that long COVID patients with sleep disturbance had significantly higher levels of plasma adrenocorticotropin and lower levels of serum growth hormone, suggesting the presence of hypothalamic-pituitary stress. CONCLUSION: The prevalence of sleep disturbance has been increasing in long COVID patients infected in the Omicron phase with a certain clinical and endocrine trend.

Early-stage antibody kinetics after the third dose of BNT162b2 mRNA COVID-19 vaccination measured by a point-of-care fingertip whole blood testing.

Amid the Coronavirus Disease 2019 pandemic, we aimed to demonstrate the accuracy of the fingertip whole blood sampling test (FWT) in measuring the antibody titer and uncovering its dynamics shortly after booster vaccination. Mokobio SARS-CoV-2 IgM & IgG Quantum Dot immunoassay (Mokobio Biotechnology R&D Center Inc., MD, USA) was used as a point-of-care FWT in 226 health care workers (HCWs) who had received two doses of the BNT162b2 mRNA vaccine (Pfizer-BioNTech) at least 8 months prior. Each participant tested their antibody titers before and after the third-dose booster up to 14-days. The effect of the booster was observed as early as the fourth day after vaccination, which exceeded the detection limit (> 30,000 U/mL) by 2.3% on the fifth day, 12.2% on the sixth day, and 22.5% after the seventh day. Significant positive correlations were observed between the pre- and post-vaccination (the seventh and eighth days) antibody titers (correlation coefficient, 0.405; p < 0.001). FWT is useful for examining antibody titers as a point-of-care test. Rapid response of antibody titer started as early as the fourth day post-vaccination, while the presence of weak responders to BNT162b2 vaccine was indicated.

Hormonal trends in patients suffering from long COVID symptoms.

Symptoms of long COVID are complex and long-lasting, and endocrine dysfunction might be involved in the underlying mechanisms. In this study, to clarify the hormonal characteristics of long COVID patients, laboratory data for patients who visited the outpatient clinic for long COVID were evaluated. A retrospective analysis was performed for patients who visited Okayama University Hospital during the period from Feb 2021 to Dec 2021 with focus on the interrelationships between major symptoms and endocrine data. Information and laboratory data were obtained from medical records for 186 patients. The patients had various symptoms, and the most frequent symptoms were general malaise, dysosmia/dysgeusia, hair loss, headache, dyspnea, and sleeplessness. Patients who were suffering from fatigue and dysosmia/dysgeusia were younger, while hair loss was more frequent in older and female patients. As for the characteristics of patients suffering from general fatigue, the scores of depression and fatigue were positively correlated with serum levels of cortisol and free thyroxin (FT4), respectively. Also, patients suffering from general fatigue had lower levels of serum growth hormone and higher levels of serum FT4, while patients with dysosmia/dysgeusia had a significantly lower level of serum cortisol. Serum thyrotropin (TSH) levels were higher and the ratios of FT4/TSH were lower in the initially severe cases, suggesting occult hypothyroidism. In addition, the ratios of plasma adrenocorticotropin to serum cortisol were decreased in patients with relatively high titers of serum SARS-CoV-2 antibody. Thus, hormonal changes seem to be, at least in part, involved in the persistent symptoms of long COVID.

Transitional Changes in Fatigue-Related Symptoms Due to Long COVID: A Single-Center Retrospective Observational Study in Japan.

Background and Objectives: Changes in post COVID-19 condition (PCC) characteristics caused by viral variants have yet to be clarified. We aimed to characterize the differences between clinical backgrounds and manifestations in long COVID patients who were infected with the Delta variant and those who were infected with the Omicron variants. Materials and Methods: This study was a single-center retrospective observational study for patients who visited our COVID-19 aftercare outpatient clinic (CAC) established in Okayama University Hospital (Japan) during the period from 15 February 2021 to 15 July 2022. We classified the onset of COVID-19 in the patients into three groups, the preceding, Delta-dominant, and Omicron-dominant periods, based on the prevalent periods of the variants in our prefecture. Results: In a total of 353 patients, after excluding 8 patients, 110, 130, and 113 patients were classified into the preceding, Delta-dominant, and Omicron-dominant periods, respectively. Patients infected in the Omicron-dominant period had significantly fewer hospitalizations, milder illnesses, more vaccinations and earlier visit to the CAC than did patients infected in the Delta-dominant period. Patients infected in the Omicron-dominant period had significantly lower frequencies of dysosmia (12% vs. 45%, ** p < 0.01), dysgeusia (14% vs. 40%, ** p < 0.01) and hair loss (7% vs. 28%, ** p < 0.01) but had higher frequencies of fatigue (65% vs. 50%, * p < 0.05), insomnia (26% vs. 13%, * p < 0.05) and cough (20% vs. 7%, ** p < 0.01) than did patients infected in the Delta-dominant period. Conclusions: The transitional changes in long COVID symptoms caused by the two variants were characterized.

Effects of Yoga and Mindfulness Programs on Self-Compassion in Medical Professionals during the COVID-19 Pandemic: An Intervention Study.

Stress among healthcare workers (HCWs) increased during the coronavirus disease 2019 pandemic. We aimed to determine whether a yoga and mindfulness program could alleviate burnout and other psychological and physical distress in HCWs, and how this might affect their empathy for patients. A weekly one-hour yoga and mindfulness program was conducted for three months in 2021. Participants were 18 consenting HCWs and, the final analysis included 13 participants. They responded to online questionnaires before and after the program. We measured salivary cortisol levels before and after the program on the first and last days. Self-measured pulse rates (PRs) were taken before and after each session, which decreased significantly in both cases (before, after the first program: 72, 65 bpm, p < 0.05; before, after the last program: 75, 66, p < 0.05), but salivary cortisol levels did not change. No significant changes were observed in Patient Health Questionnaire-9, Maslach Burnout Inventory, Sense of Coherence, Connor-Davidson Resilience Scale, Self-compassion Scale, or Jefferson Scale of Empathy. However, common humanity, a subscale of self-compassion, increased significantly (before the first program: 5.6, after the last program: 6.5, p < 0.05), and over-identification decreased significantly (7.9, 6.7, p < 0.01). Yoga and mindfulness programs may help improve the sense of common humanity and reduce over-identification in HCWs.

[Central Nervous System and Psychiatric Complications in Long Coronavirus Disease 2019].

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has prevailed worldwide since early 2020 and has caused the global coronavirus disease 2019(COVID-19)pandemic. A considerable number of patients suffer from various sequela after SARS-CoV-2 infection, which is known as post COVID-19 condition(PCC). Amid the COVID-19 pandemic, we opened a COVID-19 aftercare clinic in February 2021 in Okayama University Hospital, where we specifically consult PCC patients. While examining such patients, three Cs are essential: complexity, continuity, and collaboration. Neurological and psychiatric manifestations are particularly important from the wide range of PCC symptoms. Indeed, a recent meta-analysis demonstrated that PCC patients suffer from brain fog(32%), memory loss(27%), attention disorder(22%), dyssomnia(31%), anxiety(23%), and depression(12%). The pathophysiology and treatment strategies for these conditions are yet to be developed, and further research is required. We have corroborated that endocrinological impairments may underlie the onset and deterioration of PCC. Through our continuous consultation at the COVID-19 aftercare clinic, we intend to conduct research on the pathophysiology of and treatment strategies for PCC.

Examining the association between vaccine reactogenicity and antibody titer dynamics after the third dose of BNT162b2 vaccine using a mixed-effects model

Background To mitigate the COVID-19 pandemic, many countries have recommended the use of booster vaccinations. The relationship between the degree of adverse vaccine reactions and elevated antibody titers is of interest;however, no studies have investigated the temporal changes in antibody titers based on repeated measurements after a third dose of the BNT162b2 vaccine. Methods This prospective longitudinal cohort study was conducted with 62 healthcare workers who received a third dose of the BNT162b2 at Okayama University Hospital, Japan. Venous blood draw and fingertip whole blood test sample collection were conducted at the early (3–13 days) and 1-month time points;only FWT sample collection was conducted at the 2-month time point. Information on adverse reactions within 1 week after vaccination was also obtained. The association between fever of 37.5 °C or higher and antibody titers after the third dose of BNT162b2 was examined using a mixed-effects model and Poisson regression with robust variance. Results A trend toward higher antibody titers in the early period after vaccination was observed in the febrile individuals, but the differences were not significant at 1 and 2 months post-vaccination (the partial regression coefficient for fever was 8094.3 [-1910.2, 18,098.8] at 1 month after vaccination, and 1764.1 [-4133.9, 7662.1] at 2 months after vaccination in the adjusted models). Conclusion The findings suggest that the presence of fever after the third vaccine does not predict a sustained elevation in serum antibody titers.

Clinical Characteristics of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Diagnosed in Patients with Long COVID

Background and Objectives: COVID-19 can be serious not only in the acute phase but also after the acute phase and some patients develop ME/CFS. There have been few studies on patients with long COVID in whom ME/CFS was diagnosed by physicians based on standardized criteria after examinations and exclusion diagnosis and not based on only subjective symptoms. The purpose of this study was to elucidate the detailed characteristics of ME/CFS in patients with long COVID. Materials and Methods: A retrospective descriptive study was performed for patients who visited a COVID-19 aftercare clinic established in Okayama University Hospital during the period was from February 2021 to April 2022. Results: Clinical data were obtained from medical records for 281 patients, and 279 patients who met the definition of long COVID were included. The overall prevalence rate of ME/CFS diagnosed by three sets of ME/CFS criteria (Fukuda, Canadian and IOM criteria) was 16.8% (48.9% in male and 51.1% in females). The most frequent symptoms in ME/CFS patients were general fatigue and post-exertional malaise (89.4% of the patients), headache (34.0%), insomnia (23.4%), dysosmia (21.3%) and dysgeusia (19.1%). Dizziness, chest pain, insomnia and headache were characteristic symptoms related to ME/CFS. The male to female ratio in ME/CFS patients was equal in the present study, although ME/CFS was generally more common in women in previous studies. Given that patients with ME/CFS had more severe conditions in the acute phase of COVID-19, the severity of the acute infectious state might be involved in the pathophysiology of ME/CFS. Conclusions: The prevalence rate of ME/CFS and the characteristic sequelae in the long COVID condition were revealed in this study.

Prevalence of psychological distress on public health officials amid COVID-19 pandemic.

OBJECTIVES: While the coronavirus disease 2019 (COVID-19) pandemic has led to increased burnout among frontline healthcare workers (HCWs), little research has been done regarding the potential psychological burden among public health officials who have worked tirelessly to tackle the pandemic from an administrative perspective. This study aimed to determine the prevalence of burnout, depression, and job-related stress in Japanese public health officers amid the COVID-19 pandemic. METHODS: We conducted an anonymous, self-administered web-based cross-sectional survey including basic demographics, work-related questions, the Maslach Burnout Inventory, Patient Health Questionnaire-9, Utrecht Work Engagement Scale-3, and Brief Job Stress Questionnaire. 100 public health officers working in the public health centers (PHCs) in Okayama, Japan, answered the survey in December 2021 when the 5th surge in the number of COVID-19 was over. RESULTS: The prevalence of burnout, depression, and job-related stress was 27%, 43%, and 62%, respectively. The multivariate logistic analysis demonstrated that females, public health nurses, and those who suffered from a lack of support from their workplaces were significantly associated with psychological distress. CONCLUSIONS: While we tend to focus on mitigation plans to help alleviate burnout of frontline HCWs, more focus is needed to help public health officers, and public health nurses, in particular, to alleviate their psychological distress and job-related stress to prevent further staff shortages and secure sustainable health systems.

Candida dubliniensis fungemia in a patient with severe COVID-19: A case report.

Candida dubliniensis phenotypically mimics Candida albicans in its microbiological features; thus, its clinical characteristics have yet to be fully elucidated. Here we report the case of a 68-year-old Japanese man who developed C. dubliniensis fungemia during treatment for severe coronavirus disease 2019 (COVID-19). The patient was intubated and received a combination of immunosuppressants, including high-dose methylprednisolone and two doses of tocilizumab, as well as remdesivir, intravenous heparin, and ceftriaxone. A blood culture on admission day 11 revealed Candida species, which was confirmed as C. dubliniensis by mass spectrometry. An additional sequencing analysis of the 26S rDNA and ITS regions confirmed that the organism was 100% identical to the reference strain of C. dubliniensis (ATCC MYA-646). Considering the simultaneous isolation of C. dubliniensis from a sputum sample, the lower respiratory tract could be an entry point for candidemia. Although treatment with micafungin successfully eradicated the C. dubliniensis fungemia, the patient died of COVID-19 progression. In this case, aggressive immunosuppressive therapy could have caused the C. dubliniensis fungemia. Due to insufficient clinical reports on C. dubliniensis infection based on definitive diagnosis, the whole picture of the cryptic organism is still unknown. Further accumulation of clinical and microbiological data of the pathogen is needed to elucidate their clinical significance.

Clinical Characteristics of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Diagnosed in Patients with Long COVID.

Background and Objectives: COVID-19 can be serious not only in the acute phase but also after the acute phase and some patients develop ME/CFS. There have been few studies on patients with long COVID in whom ME/CFS was diagnosed by physicians based on standardized criteria after examinations and exclusion diagnosis and not based on only subjective symptoms. The purpose of this study was to elucidate the detailed characteristics of ME/CFS in patients with long COVID. Materials and Methods: A retrospective descriptive study was performed for patients who visited a COVID-19 aftercare clinic established in Okayama University Hospital during the period was from February 2021 to April 2022. Results: Clinical data were obtained from medical records for 281 patients, and 279 patients who met the definition of long COVID were included. The overall prevalence rate of ME/CFS diagnosed by three sets of ME/CFS criteria (Fukuda, Canadian and IOM criteria) was 16.8% (48.9% in male and 51.1% in females). The most frequent symptoms in ME/CFS patients were general fatigue and post-exertional malaise (89.4% of the patients), headache (34.0%), insomnia (23.4%), dysosmia (21.3%) and dysgeusia (19.1%). Dizziness, chest pain, insomnia and headache were characteristic symptoms related to ME/CFS. The male to female ratio in ME/CFS patients was equal in the present study, although ME/CFS was generally more common in women in previous studies. Given that patients with ME/CFS had more severe conditions in the acute phase of COVID-19, the severity of the acute infectious state might be involved in the pathophysiology of ME/CFS. Conclusions: The prevalence rate of ME/CFS and the characteristic sequelae in the long COVID condition were revealed in this study.

Interest in Infectious Diseases specialty among Japanese medical students amidst the COVID-19 pandemic: A web-based, cross-sectional study.

INTRODUCTION: The emergence of the novel coronavirus disease of 2019 (COVID-19) has led to huge disruptions in the medical field and society. The significance of training and education for experts has been increasingly acknowledged in Japan, where the number of infectious disease (ID) specialists is reportedly insufficient. In this paper, we report the results of a web-based survey that was conducted to reveal the ways in which the COVID-19 pandemic has influenced medical students' awareness of ID specialists and future career choices. METHOD: This cross-sectional descriptive study was conducted in March 2021 and targeted 717 medical students belonging to Medical School of Okayama University, Japan. The questionnaire consisted of four questions meant to assess students' knowledge and future intentions of becoming ID specialists. RESULTS: We obtained 328 eligible questionnaires (response rate: 45.7%). Of 227 (69.2%) students who were aware of ID specialists, 99 (43.6%) answered that they came to know about them only after the pandemic, 12 (3.7%) answered that their interest in being an ID specialist arose during the pandemic, while 36 (11.0%) responded that they would rather not become ID specialists. At the time of the survey, 5 students (1.5%) were aiming to become ID specialists. CONCLUSION: We observed a very low rate of interest to be an ID specialist among medical students. The experience of the pandemic does not seem to have influenced Japanese medical students to choose ID as a specialty for their careers. Continuous efforts to increase the number of ID specialists are necessary in Japan as a countermeasure against the coming pandemic.