SARS-CoV-2 と COVID-19 に関する備忘録 Vol.49

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SARS-CoV-2 と COVID-19 に関するメモ・備忘録

◆Evaluation of Retinal and Optic Nerve Parameters in Recovered COVID-19 Patients: Potential Neurodegenerative Impact on the Ganglion Cell Layer【MDPI　2025年5月9日】

Abstract

Background/Objectives: This study aimed to analyze optic nerve parameters, retinal nerve fiber layer thickness (RNFLT), ganglion cell layer thickness (GCLT), and subfoveal choroidal thickness (ChT) in patients who have recovered from coronavirus disease 2019 (COVID-19).
Methods: This comparative study included 78 recovered COVID-19 patients (16 men, 62 women) and 56 age- and sex-matched healthy controls (18 men, 38 women). COVID-19 was confirmed in all patients, either through the detection of viral RNA in nasopharyngeal swabs via reverse transcriptase polymerase chain reaction or by serological testing for SARS-CoV-2 antibodies. Spectral-domain optical coherence tomography (SD-OCT) was used to assess optic nerve parameters, RNFLT, GCLT, and ChT.
Results: The mean age was 35.0 ± 8.3 years in the COVID-19 group and 31.5 ± 8.3 years in the control group, with no statistically significant differences in age or sex distribution between groups (p = 0.41 and p = 0.16, respectively). Optic nerve parameters and RNFLT (overall and across the four peripapillary quadrants) did not differ significantly between the COVID-19 and control groups. However, the mean ganglion cell–inner plexiform layer (GC-IPL) thickness was significantly reduced in all quadrants in the COVID-19 group compared to the controls. No significant difference was observed in mean subfoveal ChT between groups.
Conclusions: A significant reduction in ganglion GCLT was observed in recovered COVID-19 patients compared to healthy controls, suggesting a potential neurodegenerative effect of the disease on the optic nerve.

◆Persistent neuropsychological deficits in recovered COVID-19 patients: Correlations with disease biomarkers【Taylor & Francis Omline　2025年5月12日】

Abstract

Objective

Cognitive impairment, including deficits in attention, memory, executive function, and processing speed, is common in post-COVID-19 conditions, though language performance remains less studied. The present study examined the long-term effects of COVID-19 condition on cognition and language – communication, and its associations with disease severity, Body Mass Index (BMI), inflammatory markers, and quality of life.

Method

Nighty eight Greek participants under 65 years of age were recruited for this study. Forty-seven participants were allocated in the COVID-19 group and 51 served as cognitively healthy controls. The COVID-19 group was categorized by disease severity and long COVID status. Assessments occurred 12 weeks post-infection, with 12 patients reevaluated after another 12 weeks. Neurocognitive tests included ABCD-II, verbal fluency, CCT, SDMT, and Euro QoL EQ-5D. Blood samples were analyzed for inflammatory markers.

Results

Covid-19 survivors experienced significant cognitive deficits compared to healthy controls, particularly in processing speed, memory, and verbal fluency. Long COVID patients showed notably lower scores in processing speed and QoL, compared to those without Long COVID. However, no significant differences were observed between groups on episodic memory and executive functions tasks. Cognitive deficits were associated with biomarkers such as d-dimers and C-Reactive protein, with elevated d-dimers linked to poorer performance on generative drawing and cognitive flexibility. Higher education served as a protective factor, and was associated with higher scores in tasks such as story retelling, confrontation naming, generative drawing and reading comprehension. Older age and higher Body Mass Index were associated with poorer cognitive performance, especially on processing speed. Sex appears to influence language comprehension outcomes, with males exhibiting enhanced performance on the reading comprehension-sentence task. Disease severity negatively affected performance on the Symbol Digit Modalities Test and generative naming, indicating that greater severity was linked to poorer outcomes in these domains. Follow-up evaluations of recovered COVID-19 patients revealed significant improvements in processing speed and recall, suggesting partial recovery in these areas, although some deficits persisted over time.

Conclusion

The study supports findings that the prolonged effects of COVID-19 markedly impaired neurocognitive functions in recovering patients, especially those with severe or long COVID syndrome. Moreover, while several cognitive domains may improve over time, many other domains remain impaired and vulnerable.

◆SARS-CoV-2 damages cardiomyocyte mitochondria and implicates long COVID-associated cardiovascular manifestations【ScienceDirect　2025年5月10日】

Abstract

Introduction

With the COVID-19 pandemic becoming endemic, vigilance for Long COVID-related cardiovascular issues remains essential, though their specific pathophysiology is largely unexplored.

Objectives

Our study investigates the persistent cardiovascular symptoms observed in individuals long after contracting SARS-CoV-2, a condition commonly referred to as “Long COVID”, which has significantly affected millions globally.

Methods

We meticulously describe the cardiovascular outcomes in five patients, encompassing a range of severe conditions such as sudden cardiac death during exercise, coronary atherosclerotic heart disease, palpitation, chest tightness, and acute myocarditis.

Results

All five patients were diagnosed with myocarditis, confirmed through endomyocardial biopsy and histochemical staining, which identified inflammatory cell infiltration in their heart tissue. Crucially, electron microscopy revealed widespread mitochondrial vacuolations and the presence of myofilament degradation within the cardiomyocytes of these patients. These findings were mirrored in SARS-CoV-2-infected mice, suggesting a potential underlying cellular mechanism for the cardiac effects associated with Long COVID.

Conclusion

Our findings demonstrate a profound impact of SARS-CoV-2 on mitochondrial integrity, shedding light on the cardiovascular implications of Long COVID.

◆‘Much-needed grit’ to be fostered in England’s schoolchildren, say ministers【The Guardian : Jamie Grierson　2025年5月16日】

Increased mental health support for young people will give them resilience, say education and health secretaries

Schoolchildren will be helped to develop “much-needed grit” for life beyond school with increased mental health support, the education and health secretaries have said.

Writing in the Telegraph, Bridget Phillipson and Wes Streeting said they would expand mental health support in schools to nearly 1 million extra children in England.

Asked what she meant by “grit” on BBC Radio 4’s Today programme, Phillipson said: “It’s about having the grit, the resilience, the ability to cope with life’s ups and downs, about the challenges that are thrown at you.

“And young people today face many challenges, very different to the some of the challenges that I faced, and what I’m announcing today with the health secretary is that a million more young people will be able to access mental health support teams in schools.

“That’s about getting in there early when young people are struggling, making sure they’ve got access to trained, qualified professionals who can help them manage all of this.”

The support will include helping teachers to identify which children need extra help, running group sessions to tackle anxiety and low mood and bringing in one-to-one support for those who need it but do not meet an NHS referral threshold.

The support will help curb low school attendance, which can ultimately lead to lower incomes later in life, the secretaries of state argue.

“By deploying NHS-led, evidence-based intervention during children’s formative years, we will not only halt the spiral towards crisis but cultivate much-needed grit amongst the next generation – essential for academic success and life beyond school, with all its ups and downs,” they write.

“Children today, who have been brought up in an increasingly digitised 21st century, are facing new and complex challenges in their childhoods that simply didn’t exist when we were younger. Negotiating your school days in the face of this is having a serious impact on some children’s mental health.”

About 20% of young people in England experience some type of mental health issue in any given year, up from 14% in 2017, the ministers write.

Research published by the government last week illustrated the direct, escalating impact that poor mental health had on children’s school attendance, they said. Children with poor attendance earn £10,000 less by age 28 on average, compared with those who had near-perfect attendance as pupils.

◆Hyper-reactivity of CD8+ T cells and high expression of IL-3 correlates with occurrence and severity of Long-COVID【ScienceDirect　2025年4月24日】

Abstract

Following SARS-CoV-2 infection, some individuals develop Long-COVID-syndrome lasting for more than 3 months. We analyzed blood samples from patients with Long-COVID, controls without persistent symptoms following SARS-CoV-2-infection and non-infected donors without a history of infection. Long-COVID patients showed clear signs of T cell hyper-activation predominantly in the CD8+ T cell subset with a 4-fold higher expression of CD25 and 2-fold more effector-memory T cells. Following polyclonal T cell stimulation, we found a 2-fold stronger upregulation of CD25 and a 7-fold higher release of IL-3 in Long-COVID. Intracellular staining revealed 5-fold more IL-3-expressing CD8+ T cells in Long-COVID, while GM-CSF, IFN-γ and IL-2 were much less upregulated. These changes correlated with the severity of Long-COVID and persisted for up to 18 months after infection. Our data reveal a pronounced and long-lasting CD8+ T cell hyper-activation and hyper-reactivity in Long-COVID and speak for a trial of T cell-immunosuppression in patients with Long-COVID.

◆Burden of Selected Chronic Conditions Among Adults of Prime Working Age (25–54) by 2022 Self-Reported COVID-19 and Long COVID History Compared to 2019 Pre-Pandemic Baseline Prevalence: Behavioral Risk Factor Surveillance System【WILEY Online Library　2025年5月20日】

Abstract

Introduction

Prior research has observed increased risks for numerous chronic conditions among individuals with Long COVID. Chronic conditions have been associated with employment limitations and increased economic hardships. Data from the Behavioral Risk Factor Surveillance System (BRFSS) present an opportunity to examine changes by employment status in the prevalence of a range of chronic conditions between 2019 (pre-pandemic) and, in 2022, by self-reported COVID-19 or Long COVID.

Methods

We assessed the prevalence of chronic conditions in 2022 by employment status and self-reported COVID-19 and Long COVID history using data from BRFSS for adults of prime working age (25–54 years) who were employed for wages, self-employed, unemployed less than 1 year, unemployed 1 year or more, or unable to work. For each chronic condition (coronary heart disease and myocardial infarction [combined], stroke, ever and current asthma, chronic obstructive pulmonary disease, kidney disease, diabetes, and arthritis), we generated adjusted prevalence ratios (aPRs) comparing 2022 prevalence by COVID-19/Long COVID category to prevalences among respondents in that employment status before the pandemic (2019).

Results

The prevalence of both asthma and diabetes increased significantly between 2019 and 2022 among respondents in all included employment categories and COVID-19/Long COVID histories combined. Among employed respondents with Long COVID in 2022, aPRs using 2019 prevalence figures for all employed respondents as a baseline for comparison had statistically significant elevations for every chronic condition assessed.

Conclusions

The increased prevalence of a range of chronic conditions between 2019 and 2022 among adults with Long COVID may present a burden for individuals, the workplace, the healthcare system, and the economy. Additional research in a longitudinal context could better quantify these associations. Efforts to prevent, identify, and treat Long COVID can reduce this burden.

◆Gastrointestinal Barrier Disruption in Post-COVID Syndrome Fatigue Patients【WILEY Online Library　2025年5月15日】

Abstract

Background

Post-COVID Syndrome (PCS) is the term for a condition with persistent symptoms in a proportion of COVID-19 patients after asymptomatic, mild, or severe disease courses. Numbers vary, but the current estimate is that after COVID-19 approximately 10% develop PCS. The aim of our study was to evaluate the impact of SARS-CoV-2 infection on the gastrointestinal (GI) tract and associations with the development of PCS with fatigue, post-exertional malaise (PEM), orthostatic dysregulation, autonomous dysregulation, and/or neurocognitive dysregulation.

Methods

By combining medical record data from a prospective observational study with symptom analysis before, during, and after SARS-CoV-2 infection, we aimed to identify potential risk factors and predictive markers for PCS. Additionally, we analyzed blood, saliva, and stool samples from this well-characterized PCS patient cohort to biologically validate our findings.

Results

We identified significant associations between pre-existing GI complaints and the development of PCS Fatigue. PCS patients showed higher LBP/sCD14 ratios, lower IL-33 levels, and higher IL-6 levels compared to control groups. Our results highlight the critical role of the GI tract in PCS development of post-viral Fatigue.

Conclusion

We propose that the viral infection disrupts pathways related to the innate immune response and GI barrier function, evidenced by intestinal low-grade inflammation and GI barrier leakage. Monitoring GI symptoms and markers before, during, and after SARS-CoV-2 infection is crucial for identifying predictive clinical phenotypes in PCS. Understanding the interaction between viral infections, immune responses, and gut integrity could lead to more effective diagnostic and treatment strategies, ultimately reducing the burden on PCS patients.


Gastrointestinal (GI) barrier disruption in the context of SARS-CoV-2 infection is associated with the development of Post-COVID Syndrome (PCS) Fatigue. Pre-existing GI complaints may predispose to fatigue development. Monitoring GI symptoms and markers before, during, and after SARS-CoV-2 infection is crucial for identifying predictive clinical phenotypes in PCS Fatigue. COVID-19, coronavirus disease 2019; EBV, Epstein-Barr virus; GI, gastrointestinal tract; IL, interleukin; LBP/sCD14, the ratio of lipopolysaccharide binding protein to soluble CD14; ME/CFS, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome; PCS, Post-COVID Syndrome; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

◆Spike proteins of coronaviruses activate mast cells for degranulation via stimulating Src/PI3K/AKT/Ca2+ intracellular signaling cascade【ASM Journals : Journal of Virology　2025年4月30日】

Abstract

Mast cells (MCs) are strategically located at the interface between host and environment. The non-allergic functions of MCs in immunosurveillance against pathogens have been recently underscored. However, the activation of MCs by pathogens may beneficially or detrimentally regulate immune inflammation to combat or promote pathogen invasion. We and others have conclusively demonstrated that MCs serve as a crucial mediator in the induction of hyperinflammation initiated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), leading to substantial tissue damage across multiple organs in murine and nonhuman primate models. Whereas the precise mechanism underlying virus-induced MC activation and degranulation remains largely elusive, our previous findings have indicated that the binding of the Spike proteins to cellular receptors is sufficient to elicit MC activation for rapid degranulation. This study aims to corroborate the ubiquity of coronavirus-induced MC degranulation and elucidate the intracellular signaling pathways that mediate the activation of MCs upon Spike protein binding to the cellular receptors. Our transcriptome analysis revealed MC activation upon the stimulations with a range of Spike/RBD proteins and viral particles of coronavirus. Notably, the interaction between these Spike/RBD proteins and cellular receptors triggered the activation of src kinase, a member of Src Family Kinases (SFKs). This activation, in turn, stimulated the PI3K/AKT signaling pathway, resulting in an accumulation of intracellular calcium ions. These calcium ions subsequently facilitated microtubule-dependent granule transport, ultimately promoting MC degranulation. In summary, this study elucidates the mechanism underlying virus-triggered activation of MCs and has the potential to aid in the development of MC-targeted antiviral therapeutic strategies.

◆Long COVID: A Systematic Review of Preventive Strategies【MDPI　2025年5月21日】

Abstract

Background: Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, long COVID (LC) has become a significant global health burden. While knowledge about LC is accumulating, studies on its prevention are still lacking.
Methods: We conducted a systematic review following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to investigate prevention options for LC. We identified fifteen articles on vaccines, seven on antivirals, and six on other interventions after searching for articles in the PubMed/MEDLINE database using the MeSH terms.
Results: Most vaccine-related studies demonstrated a protective effect of COVID-19 vaccines against developing LC. Our review found an equivocal effect of antivirals, while metformin had a protective effect in outpatients and corticosteroids were protective in hospitalized patients against LC. Conversely, COVID-19 convalescent plasma and multiple micronutrient supplement did not confer any protection against LC.
Conclusions: COVID-19 vaccination is vital as it not only prevents COVID-19 but also reduces the severity of illness and may help prevent LC. Further studies are warranted to shed light on preventive strategies for long COVID.

◆Genome-wide association study of long COVID【nature genetics　2025年5月21日】

Abstract

Infections can lead to persistent symptoms and diseases such as shingles after varicella zoster or rheumatic fever after streptococcal infections. Similarly, severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection can result in long coronavirus disease (COVID), typically manifesting as fatigue, pulmonary symptoms and cognitive dysfunction. The biological mechanisms behind long COVID remain unclear. We performed a genome-wide association study for long COVID including up to 6,450 long COVID cases and 1,093,995 population controls from 24 studies across 16 countries. We discovered an association of FOXP4 with long COVID, independent of its previously identified association with severe COVID-19. The signal was replicated in 9,500 long COVID cases and 798,835 population controls. Given the transcription factor FOXP4’s role in lung physiology and pathology, our findings highlight the importance of lung function in the pathophysiology of long COVID.

◆Cognitive Slowing, Dysfunction in Verbal Working Memory, Divided Attention and Response Inhibition in Post COVID-19 Condition in Young Adults【MDPI　2025年5月21日】

Abstract

After COVID-19 infection, about 30% of people have clinically persisting symptoms, characterized as Post COVID-19 Condition (PCC). One of the most reported symptoms in PCC is cognitive dysfunction, yet there are only a few studies investigating long-term effects on different domains of cognitive function. A total of 107 young adults, university students aged 18–34 years, participated. In total, 68.2% had contracted SARS-CoV-2; 21.9% showed PCC. Three groups were compared: no-C19 (COVID-19-negative controls), C19 (COVID-19-recovered without PCC) and PCC. Attention and executive function were measured with the Vienna Test System (Schuhfried®, Mödling, Austria). In verbal working memory, the PCC group had a significantly lower performance with a moderate effect. The rate of below-average performance was higher in PCC (56.2%) compared to no-C19 (20.6%) and C19 (15.8%). In divided attention and response inhibition, PCC also showed lower performance, 62.5% and 37.5%, respectively, than no-C19 and C19. The co-occurrence of decreased cognitive functions was pronounced in PCC. The present study revealed significant long-lasting cognitive dysfunction in PCC in young adults, two years after COVID-19 infection. Verbal working memory was significantly impaired, and a lower performance was found in divided attention and response inhibition. In addition, there was an increased reaction time in most cognitive tasks, demonstrating cognitive slowing in young people with PCC.