Treatment of long COVID complicated by postural orthostatic tachycardia syndrome-Case series research.

Background: Coronavirus disease 2019 (COVID-19) sequelae, also known as long COVID, can present with various symptoms. Among these symptoms, autonomic dysregulation, particularly postural orthostatic tachycardia syndrome (POTS), should be evaluated. However, previous studies on the treatment of POTS complicated by COVID-19 are lacking. Therefore, this study aimed to investigate the treatment course of long COVID complicated by POTS. Methods: The medical records of patients who complained of fatigue and met the criteria for POTS diagnosis were reviewed. We evaluated the treatment days, methods and changes in fatigue score, changes in heart rate on the Schellong test, and social situation at the first and last visits. Results: Thirty-two patients with long COVID complicated by POTS were followed up (16 males; median age: 28 years). The follow-up period was 159 days, and the interval between COVID-19 onset and initial hospital attendance was 97 days. Some patients responded to ß-blocker therapy. Many patients had psychiatric symptoms that required psychiatric intervention and selective serotonin reuptake inhibitor prescription. Changes in heart rate, performance status, and employment/education status improved from the first to the last visit. These outcomes were believed to be because of the effects of various treatment interventions and spontaneous improvements. Conclusions: Our study suggests that the condition of 94% of patients with POTS complicated by long COVID will improve within 159 days. Therefore, POTS evaluation should be considered when patients with long COVID complain of fatigue, and attention should be paid to psychological symptoms and the social context.

Online search interest in long-term symptoms of coronavirus disease 2019 during the COVID-19 pandemic in Japan: Infodemiology study using the most visited search engine in Japan.

Prolonged symptoms that occur after COVID-19 (long-COVID) vary from mild, which do not interfere with daily life, to severe, which require long-term social support. This study assessed the secular trend in online searches on long-COVID in Japan. We conducted an observational study using data provided by Yahoo! JAPAN on the monthly search volume of query terms related to long-COVID from January 2020 to December 2022, including the search volume of the query "コロナ" (long-COVID in Japanese). The number of new cases of COVID-19 by month was used as a control for search trends, and the symptoms retrieved in conjunction with long-COVID were compared. Trends in online searches for each symptom of long-COVID were analyzed. The symptoms of long-COVID were classified according to "Component 1-Symptoms and Complaints" of the International Classification of Primary Care, 2nd edition (ICPC-2). Interest in long-COVID increased in response to peaks in the number of new cases of COVID-19 in Japan. The most frequent symptom searches with long-COVID were hair loss/baldness (3,530, 21,400, and 33,600 searches in 2020, 2021, and 2022, respectively), cough (340, 7,900 and 138,910 searches in 2020, 2021, and 2022, respectively), disturbance of smell/taste (230, 13,340, and 44,160 searches in 2020, 2021, and 2022, respectively), and headache (580, 6,180, and 42,870 searches in 2020, 2021, and 2022, respectively). In addition, the ranking of interest in "weakness/tiredness, general" in long-COVID increased each year (not in the top 10 in 2020, seventh in 2021, and second in 2022), and the absolute number of searches also increased. To our knowledge, this is the first study to investigate secular trends in online interest in long-COVID in the world. Continued monitoring of online interest in long-COVID is necessary to prepare for a possible increase in the number of patients with long-COVID.

Xiphodynia Caused by a Large Xiphoid Process.

We present the case of a 72-year-old man with a three-month history of epigastric pain. A physical examination revealed a tender, hard mass around the epigastric area. Enhanced CT showed no chest or abdominal abnormalities, except for a large xiphoid process. The diagnosis was xiphodynia caused by a large xiphoid process. Xyphoidynia should be considered a differential diagnosis for epigastric pain.

The relationship between having a usual source of primary care and COVID-19 parental vaccine hesitancy: A nationwide survey among Japanese mothers.

Background: Studies have shown that a usual source of care increases the receipt of child preventive care; however, the relationship between having a usual source of primary care and COVID-19 parental vaccine hesitancy has not been fully investigated. The aims of this study were to elucidate the characteristics of mothers with a primary care physician, and to explore the relationship between having a usual source of primary care and COVID-19 parental vaccine hesitancy among mothers in Japan. Method: This cross-sectional survey-based study included 4516 mothers. Using a chi-square test, the characteristics of mothers with and without a primary care physician were compared. Poisson regression was applied to evaluate the relationship between having a usual source of primary care and parental COVID-19 vaccine hesitancy. Results: Mothers with a usual source of primary care had higher education, lower mental distress, had younger children, and were less hesitant toward the child's COVID-19 vaccination. Vaccine hesitancy was observed in 39.8% of mothers with a usual source of primary care and 45.5% of those without. Poisson regression analysis showed that mothers with a primary care physician were less vaccine-hesitant (IRR = 0.90, 95% CI = 0.84-0.96) after adjusting for potential confounders. Conclusion: This study suggested that having a usual source of primary care may contribute to lower parental COVID-19 vaccine hesitancy. However, the high vaccine hesitancy rate, even among mothers with a usual source of primary care, warrants healthcare providers to be equipped to help parents make informed decisions about vaccination through the continuity of care.

Five cluster classifications of long COVID and their background factors: A cross-sectional study in Japan.

PURPOSE: The long-term symptoms of coronavirus disease 2019 (COVID-19), i.e., long COVID, have drawn research attention. Evaluating its subjective symptoms is difficult, and no established pathophysiology or treatment exists. Although there are several reports of long COVID classifications, there are no reports comparing classifications that include patient characteristics, such as autonomic dysfunction and work status. We aimed to classify patients into clusters based on their subjective symptoms during their first outpatient visit and evaluate their background for these clusters. METHODS: Included patients visited our outpatient clinic between January 18, 2021, and May 30, 2022. They were aged ≥ 15 years and confirmed to have SARS-CoV-2 infection and residual symptoms lasting at least 2 months post-infection. Patients were evaluated using a 3-point scale for 23 symptoms and classified into five clusters (1. fatigue only; 2. fatigue, dyspnea, chest pain, palpitations, and forgetfulness; 3. fatigue, headache, insomnia, anxiety, motivation loss, low mood, and forgetfulness; 4. hair loss; and 5. taste and smell disorders) using CLUSTER. For continuous variables, each cluster was compared using the Kruskal-Wallis test. Multiple comparison tests were performed using the Dunn's test for significant results. For nominal variables, a Chi-square test was performed; for significant results, a residual analysis was conducted with the adjusted residuals. RESULTS: Compared to patients in other cluster categories, those in cluster categories 2 and 3 had higher proportions of autonomic nervous system disorders and leaves of absence, respectively. CONCLUSIONS: Long COVID cluster classification provided an overall assessment of COVID-19. Different treatment strategies must be used based on physical and psychiatric symptoms and employment factors.

Patent Foramen Ovale Complicated With Renal Infarction and Pulmonary Embolism: A Case Report With Literature Review.

A 48-year-old man visited our emergency room after experiencing sudden left back pain, diaphoresis, and nausea. The patient underwent physical and laboratory examinations. Physical examination revealed tenderness in the left costovertebral angle. Laboratory examination revealed a slight elevation in D-dimer levels. Contrast-enhanced computed tomography revealed a bilateral pulmonary embolism and left renal infarction. Back pain was resolved following anticoagulation therapy with heparin. Transesophageal echocardiography revealed a patent foramen ovale (PFO). The patient was discharged on an anticoagulant, apixaban. Identifying the cause of paradoxical embolisms, such as an atrial septal defect or PFO, in cases with an arterial embolism in a young patient with no underlying disease is important.

Effect of Repetitive Transcranial Magnetic Stimulation on Long Coronavirus Disease 2019 with Fatigue and Cognitive Dysfunction.

Objectives: There is no established treatment for chronic fatigue and various cognitive dysfunctions (brain fog) caused by long coronavirus disease 2019 (COVID-19). We aimed to clarify the effectiveness of repetitive transcranial magnetic stimulation (rTMS) for treating these symptoms. Methods: High-frequency rTMS was applied to occipital and frontal lobes in 12 patients with chronic fatigue and cognitive dysfunction 3 months after severe acute respiratory syndrome coronavirus 2 infection. Before and after ten sessions of rTMS, Brief Fatigue Inventory (BFI), Apathy Scale (AS), and Wechsler Adult Intelligence Scale-fourth edition (WAIS4) were determined and N-isopropyl-p-[123I]iodoamphetamine single photon emission computed tomography (SPECT) was performed. Results: Twelve subjects completed ten sessions of rTMS without adverse events. The mean age of the subjects was 44.3 ± 10.7 years, and the mean duration of illness was 202.4 ± 114.5 days. BFI, which was 5.7 ± 2.3 before the intervention, decreased significantly to 1.9 ± 1.8 after the intervention. The AS was significantly decreased after the intervention from 19.2 ± 8.7 to 10.3 ± 7.2. All WAIS4 sub-items were significantly improved after rTMS intervention, and the full-scale intelligence quotient increased from 94.6 ± 10.9 to 104.4 ± 13.0. Hypoperfusion in the bilateral occipital and frontal lobes observed on SPECT improved in extent and severity after ten sessions of rTMS. Conclusions: Although we are still in the early stages of exploring the effects of rTMS, the procedure has the potential for use as a new non-invasive treatment for the symptoms of long COVID.

Antibody Avidity Maturation Following Recovery From Infection or the Booster Vaccination Grants Breadth of SARS-CoV-2 Neutralizing Capacity.

BACKGROUND: Cross-neutralizing capacity of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is important in mitigating (re-)exposures. Role of antibody maturation, the process whereby selection of higher affinity antibodies augments host immunity, to determine SARS-CoV-2 neutralizing capacity was investigated. METHODS: Sera from SARS-CoV-2 convalescents at 2, 6, or 10 months postrecovery, and BNT162b2 vaccine recipients at 3 or 25 weeks postvaccination, were analyzed. Anti-spike IgG avidity was measured in urea-treated ELISAs. Neutralizing capacity was assessed by surrogate neutralization assays. Fold change between variant and wild-type neutralization inferred the breadth of neutralizing capacity. RESULTS: Compared with early-convalescent, avidity indices of late-convalescent sera were significantly higher (median, 37.7 [interquartile range 28.4-45.1] vs 64.9 [57.5-71.5], P < .0001). Urea-resistant, high-avidity IgG best predicted neutralizing capacity (Spearman r = 0.49 vs 0.67 [wild-type]; 0.18-0.52 vs 0.48-0.83 [variants]). Higher-avidity convalescent sera better cross-neutralized SARS-CoV-2 variants (P < .001 [Alpha]; P < .01 [Delta and Omicron]). Vaccinees only experienced meaningful avidity maturation following the booster dose, exhibiting rather limited cross-neutralizing capacity at week 25. CONCLUSIONS: Avidity maturation was progressive beyond acute recovery from infection, or became apparent after the booster vaccine dose, granting broader anti-SARS-CoV-2 neutralizing capacity. Understanding the maturation kinetics of the 2 building blocks of anti-SARS-CoV-2 humoral immunity is crucial.

Serum gasdermin D levels are associated with the chest computed tomography findings and severity of COVID-19.

BACKGROUND: The role of programmed cell death, especially pyroptosis and apoptosis, in unfavorable immune responses in COVID-19 remains to be elucidated. METHODS: We conducted a cross-sectional analysis to investigate the association between the serum gasdermin D (GSDMD) levels, a pyroptotic marker, and caspase-cleaved cytokeratin 18 fragment (M30), an apoptotic marker, and the clinical status and abnormal chest computed tomography (CT) findings in patients with COVID-19. RESULTS: In this study, 46 patients diagnosed with COVID-19 were divided into the following three groups according to the disease severity: mild to moderate group (n = 10), severe group (n = 14), and critical group (n = 22). The serum GSDMD levels were higher in the critical group than in the mild to moderate group (P = 0.016). In contrast, serum M30 levels were lower in the critical group than in the severe group (P = 0.048). Patients who required mechanical ventilation or died had higher serum GSDMD levels than those who did not (P = 0.007). Area of consolidation only and of ground glass opacity plus consolidation positively correlated with serum GSDMD levels (r = 0.56, P < 0.001 and r = 0.53, P < 0.001, respectively). CONCLUSION: Higher serum GSDMD levels are associated with critical respiratory status and the consolidation area on chest CT in patients with COVID-19, suggesting that excessive activation of pyroptosis may affect the clinical manifestations in patients with COVID-19.

Nerve Identification Procedures Are Necessary for Complete Recovery From Recurrent Cases of Anterior Cutaneous Nerve Entrapment Syndrome: A Case Report.

Anterior cutaneous nerve entrapment syndrome (ACNES) involves pain in the abdominal wall due to nerve compression or ischemia. The diagnosis of ACNES is challenging with the pain often inclined to be diagnosed as psychological in origin. A 20-year-old woman presenting with abdominal pain was initially diagnosed with mesenteric lymphadenitis and prescribed pain relievers. However, following worsened pain, she was hospitalized. Blood examinations, abdominal and gynecological ultrasonography, and gastrocolonoscopy yielded no abnormal findings, leading to suspicions of psychological factors. As the patient experienced sharp abdominal pain on movement, but not at rest, which was temporarily relieved by lidocaine injections, she was diagnosed with ACNES. Rectus abdominal resection was performed but the pain relapsed. Laparoscopic surgery was performed to cut the nerve that caused the pain. After three surgeries, the patient was completely symptom-free. ACNES should be considered as a differential diagnosis for intractable abdominal pain. For recurrent relapses, the triggering nerves must be carefully identified for the successful treatment of ACNES.

Low SARS-CoV-2 antibody titers may be associated with poor clinical outcomes for patients with severe COVID-19.

Recently, immune response to coronavirus disease (COVID-19) has attracted attention where an association between higher antibody titer and worsening disease severity has been reported. However, our experiences with severe COVID-19 patients with low antibody titers led to hypothesizing that suppressed humoral immune response may be associated with poorer prognosis in severe COVID19. In this study, antibody titers in severe COVID19 patients were measured at 7, 10, 12, and 14 days after onset. Patients were divided into survivors and non-survivors. SARS-CoV-2 IgM in survivors and non-survivors were 0.06 AU and 0.02 AU (P = 0.048) at 10 days, 0.1 AU and 0.03 AU (P = 0.02) at 12 days, and 0.17 AU and 0.06 AU (P = 0.02) at 14 days. IgG in survivors and non-survivors were 0.01 AU and 0.01 AU (P = 0.04) at 7 days, 0.42 AU and 0.01 AU (P = 0.04) at 12 days, and 0.42 AU and 0.01 AU (P = 0.02) at 14 days. Multivariate analysis showed better survival among patients with IgM positivity at 12 days (P = 0.04), IgG positivity at 12 days (P = 0.04), IgM positivity at 14 days (P = 0.008), and IgG positivity at 14 days (P = 0.005). In severe COVID-19, low antibody titers on days 12 and 14 after onset were associated with poorer prognosis.

Factors associated with preferred place of death among older adults: a qualitative interview study in Tama City, Tokyo, Japan.

OBJECTIVES: To analyse the cognitive processes involved in the decision-making of older adults who are not in the end-of-life stage regarding the selection of a preferred place of death. DESIGN: A qualitative cross-sectional study based on semistructured in-depth interviews. The interview scripts were sectioned by context, then summarised, conceptualised and categorised. Post-categorisation, the relationships between the conceptual factors were examined. SETTING: Tama City, Tokyo, Japan, from November 2015 to March 2016. PARTICIPANTS: 20 long-term care users and their families or care providers were interviewed about their preferred places of death and the factors behind their decisions. RESULTS: Three categories based on the preferred place of end-of-life care and death were extracted from the interview transcripts: (A) discouraging the decision of a preferred place of death, (B) enhancing the desire for home death and (C) enhancing the desire for a hospital/long-term care facility death. Category A consists of concerns about the caregiver's health, anxiety about solitary death, and constraints of and concerns about the household budget. Both categories B and C consist of subcategories of reinforcing and inhibiting factors of whether to desire a home death or a hospital/long-term care facility death. If their previous experiences with care at home, a hospital or a care facility were positive, they preferred the death in the same setting. If those experiences were negative, they tend to avoid the death in the same setting. CONCLUSIONS: One's mindset and decision regarding a preferred place of death include the consideration of economic factors, concerns for caregivers, and experiences of care at home or in a hospital/long-term care facility. Furthermore, health professionals need to be aware of the ambivalence of senior citizens to support their end-of-life decisions.

Relationship between changes in symptoms and antibody titers after a single vaccination in patients with Long COVID.

Coronavirus disease 2019 (COVID-19) is spreading worldwide; there is a need to address its sequelae known as Long COVID. This study evaluated postvaccination changes in symptoms and antibody titers in patients with Long COVID. Patients visiting the outpatient department specializing in Long COVID at our hospital were enrolled. Changes in symptoms were evaluated before and 14-21 days after first vaccination. Antibody titers were measured using ARCHITECT SARS-CoV-2 IgG II Quant at the same time. This study included 42 patients (median age: 45 years; 17 [40.5%] men). Median pre- and postvaccination antibody titers were 456 and 28,963 AU/ml, respectively. Postvaccination symptoms (fatigue, joint pain, and taste and olfactory abnormalities) were relieved, worsened, and unchanged in 7 (16.7%), 9 (21.4%), and 26 (61.9%) patients, respectively. Ratios of pre- and postvaccination antibody titers were 53, 40, and 174 in the unchanged, relief, and worsened groups, respectively. The worsened group had the significantly highest antibody titer ratio (p = 0.02). The higher increased rate of the antibody titer in the worsened group than in the nonworsened group suggests an excessive immune response to vaccination associated with worsening of sequelae. Although patients with Long COVID should be vaccinated, additional concerns should be addressed.

Diagnostic error rates and associated factors for lower gastrointestinal perforation.

Lower gastrointestinal perforation is rare and challenging to diagnose in patients presenting with an acute abdomen. However, no study has examined the frequency and associated factors of diagnostic errors related to lower gastrointestinal perforation. This large-scale multicenter retrospective study investigated the frequency of diagnostic errors and identified the associated factors. Factors at the level of the patient, symptoms, situation, and physician were included in the analysis. Data were collected from nine institutions, between January 1, 2015 and December 31, 2019. Timely diagnosis was defined as diagnosis at the first visit in computed tomography (CT)-capable facilities or referral to an appropriate medical institution immediately following the first visit to a non-CT-capable facility. Cases not meeting this definition were defined as diagnostic errors that resulted in delayed diagnosis. Of the 439 cases of lower gastrointestinal perforation identified, delayed diagnosis occurred in 138 cases (31.4%). Multivariate logistic regression analysis revealed a significant association between examination by a non-generalist and delayed diagnosis. Other factors showing a tendency with delayed diagnosis included presence of fever, absence of abdominal tenderness, and unavailability of urgent radiology reports. Initial misdiagnoses were mainly gastroenteritis, constipation, and small bowel obstruction. In conclusion, diagnostic errors occurred in about one-third of patients with a lower gastrointestinal perforation.

Serological Testing Reveals the Hidden COVID-19 Burden among Health Care Workers Experiencing a SARS-CoV-2 Nosocomial Outbreak.

We describe the results of testing health care workers, from a tertiary care hospital in Japan that had experienced a coronavirus disease 2019 (COVID-19) outbreak during the first peak of the pandemic, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody seroconversion. Using two chemiluminescent immunoassays and a confirmatory surrogate virus neutralization test, serological testing revealed that a surprising 42% of overlooked COVID-19 diagnoses (27/64 cases) occurred when case detection relied solely on SARS-CoV-2 nucleic acid amplification testing (NAAT). Our results suggest that the NAAT-positive population is only the tip of the iceberg and the portion left undetected might potentially have led to silent transmissions and triggered the spread. A questionnaire-based risk assessment was further indicative of exposures to specific aerosol-generating procedures (i.e., noninvasive ventilation and airway suctioning) having mediated transmission and served as the origins of the outbreak. Our observations are supportive of a multitiered testing approach, including the use of serological diagnostics, in order to accomplish exhaustive case detection along the whole COVID-19 spectrum. IMPORTANCE We describe the results of testing frontline health care workers, from a hospital in Japan that had experienced a COVID-19 outbreak, for SARS-CoV-2-specific antibodies. Antibody testing revealed that a surprising 42% of overlooked COVID-19 diagnoses occurred when case detection relied solely on PCR-based viral detection. COVID-19 clusters have been continuously striking the health care system around the globe. Our findings illustrate that such clusters are lined with hidden infections eluding detection with diagnostic PCR and that the cluster burden in total is more immense than actually recognized. The mainstays of diagnosing infectious diseases, including COVID-19, generally consist of two approaches, one aiming to detect molecular fragments of the invading pathogen and the other to measure immune responses of the host. Considering antibody testing as one trustworthy option to test our way through the pandemic can aid in the exhaustive case detection of COVID-19 patients with variable presentations.

Back to normal; serological testing for COVID-19 diagnosis unveils missed infections.

BACKGROUND: The gold standard for coronavirus disease (COVID-19) diagnosis has been the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA by nucleic acid amplification testing (NAAT). On the other hand, serological testing for COVID-19 may offer advantages in detecting possibly overlooked infections by NAAT. METHODS: To evaluate seroconversion of NAAT-negative pneumonia patients, immunoglobulin M (IgM) and IgG targeting the spike protein of SARS-CoV-2 were semiquantified by an immunofluorescence assay. Seroconversion was confirmed by another serological method, targeting the nucleocapsid protein. RESULTS: Eight suspected but unconfirmed COVID-19 pneumonia patients (median age, 39 years; range, 21-55) were included. The median period between symptom onset and NAAT sample collection was 6 days (2-27 days). None of them had tested positive for SARS-CoV-2 by NAAT. In contrast, all eight patients revealed seropositivity with the two serological methods, indicating actual seroconversion against SARS-CoV-2. The median period between onset and blood sampling was 26.5 days (7-51 days). CONCLUSION: Eight patients with COVID-19 pneumonia, initially tested negative for SARS-CoV-2 by NAAT, were finally confirmed of the diagnosis by serological testing. To cover the whole spectrum of this heterogenous infectious disease, serology testing should be implemented to the multitiered diagnostic algorithm for COVID-19.