SARS-CoV-2 と COVID-19 に関する備忘録 Vol.64

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SARS-CoV-2 と COVID-19 に関するメモ・備忘録

◆Prevalence and characterization of post-acute sequelae of SARS-CoV-2 infection (PASC) in Rwanda【ScienceDirect　2025年8月30日】

Abstract

Background

Reliable, population-level estimates of post-acute sequelae of SARS-CoV-2 infection (PASC) remain scarce for sub-Saharan Africa. We aimed to quantify PASC prevalence and identify associated factors among adult COVID-19 survivors in Rwanda.

Methods

A nationally representative cross-sectional telephone survey (August-October 2024) sampled 3143 adults from the national COVID-19 registry. PASC was defined as new or persisting symptoms ≥3 months after acute illness and lasting ≥2 months. The prevalence was calculated, and multivariable logistic regression identified factors independently associated with PASC.

Results

Overall, PASC prevalence was 34%. Leading symptoms were back pain, headache, dizziness, fatigue, and reduced sexual desire. Higher odds of PASC occurred in women, adults ≥35 years, individuals with ≥2 COVID-19 infections, and those screening positive for anxiety. Current alcohol use was linked to lower odds. COVID-19 vaccination showed no association with PASC.

Conclusions

Approximately one-third of adult Rwandan COVID-19 survivors continue to experience persistent symptoms. This burden signals that post-COVID care must become an integral part of routine health services, especially as new variants periodically drive fresh waves of infection. Preventing repeat infections and integrating mental health support emerge as actionable priorities. Harmonized longitudinal studies are needed to clarify PASC causality.

◆Long-Term Influence of Pediatric Long COVID Syndrome on Visual Perception and Neuropsychiatric Symptoms【ScienceDirect　2025年8月28日】

Abstract

Background

Long COVID presents with a wide range of persistent symptoms and durations following coronavirus disease 2019 (COVID-19) infection. However, data on children and adolescents remain limited. This study aims to explore visual perception and neuropsychiatric symptoms in pediatric patients and examine their associations with brain volume differences.

Methods

A total of 60 participants, aged six to 18 years and confirmed COVID-19 antibody positive, were recruited five to eight months after infection. Owing to the diversity of symptoms, each symptom was assigned a weighted score from 0 to 3 based on its severity and relevance to brain function. Participants were then divided into two groups according to symptom severity. All participants underwent magnetic resonance imaging, and the Test of Visual Perceptual Skills-Fourth Edition (TVPS-4) was administered.

Results

The most common neuropsychiatric symptoms were headache or dizziness, along with attention and memory deficits, which persisted for up to six months. Gray matter volumes were significantly increased in the group with severe symptoms, particularly in subcortical and temporal regions. These brain volume differences showed significant correlations with both acute and chronic symptoms. In the TVPS-4 assessment, significant differences were observed in overall standard scores and in the Sequential Memory subtest between participants with visual-related symptoms and healthy control subjects.

Conclusions

Neuropsychiatric symptoms, impaired visual perception, and gray matter volume differences are evident in pediatric long COVID cases. The severity of neuropsychiatric symptoms during the acute phase may predict the degree of chronic-phase brain volume alterations. Longitudinal follow-up studies are essential to validate and expand upon these findings.

◆SARS-CoV-2 Orf6 Triggers MTCH1-Dependent Mitochondrial Dysfunction and Necroptosis in Human Neurons【Research Square　2025年9月7日】

Abstract

The molecular basis of neuronal damage in SARS-CoV-2 infection remains elusive. Here, we identify the viral accessory protein Orf6 as a key driver of necroptotic neuronal death. Through a systematic screen of 22 structural and non-structural SARS-CoV-2 proteins, Orf6 emerged to be the most cytotoxic to human cells. In primary human neurons, Orf6 selectively activates the necroptotic pathway by inducing phosphorylation of RIPK3 and MLKL, without engaging apoptosis, pyroptosis, or autophagy. These findings were corroborated in SARS-CoV-2-infected neurons and in hippocampal brain sections from COVID-19 patients, where elevated necroptosis markers were observed. Mechanistically, Orf6 was found to directly interact with the mitochondrial membrane protein Mitochondrial Carrier Homolog 1 (MTCH1), triggering mitochondrial calcium overload, membrane potential loss, and oxidative stress. Genetic knockdown of MTCH1 or pharmacological inhibition of RIPK3 effectively rescued neurons from Orf6-induced necroptosis and mitochondrial dysfunction. Collectively, our findings reveal a novel, mitochondria-dependent mechanism of viral neuropathogenesis and implicate Orf6-mediated necroptosis as a contributor to long-term neurological sequelae in COVID-19.

◆Effect of Metformin on the Risk of Post-coronavirus Disease 2019 Condition Among Individuals With Overweight or Obese: A Population-based Retrospective Cohort Study【OXFORD ACADEMIC　2025年9月1日】

Abstract

Background

A subgroup analysis of the COVID-OUT trial’s long-term outcome found that starting metformin within 3 days of coronavirus disease 2019 (COVID-19) diagnosis reduced post–COVID-19 condition (PCC) incidence by 63% in overweight or obese individuals. However, its generalizability remains uncertain.

Objectives

To evaluate the effectiveness of metformin in preventing PCC in adults with overweight or obesity who had a recent COVID-19 infection.

Design

A retrospective cohort study using a sequential target trial emulation framework.

Data Sources

The United Kingdom primary care data from the Clinical Practice Research Datalink Aurum database from March 2020 to July 2023.

Participants

Adults with overweight or obesity (body mass index ≥ 25 kg/m²) and a record of severe acute respiratory syndrome coronavirus 2 infection were included. Exclusions included metformin use in the prior year or metformin contraindications.

Measurements

The outcome was PCC, defined by a PCC diagnostic code or at least 1 World Health Organization–listed symptoms between 90 and 365 days after diagnosis, with no prior history of the symptom within 180 days before infection. The pooled hazard ratio and risk difference for the incidence of PCC were adjust for baseline characteristics.

Results

Among 624 308 patients, 2976 initiated metformin within 90 days of COVID-19 diagnosis. The 1-year risk difference for PCC in the intention-to-treat analysis was −12.58% (hazard ratio 0.36; 95% CI, 0.32–0.41), with consistent results in subgroup analyses.

Limitations

Findings may not apply to individuals with a normal body mass index.

Conclusions

Early metformin treatment in overweight or obese individuals may reduce PCC risk. Further research is needed to confirm causality and clarify metformin’s role in PCC management.

◆CSF immune cell alterations in women with neuropsychiatric Long COVID【OXFORD ACADEMIC　2025年9月8日】

Abstract

Background

Women are disproportionately affected by neuropsychiatric symptoms following recovery from acute COVID-19. However, whether there are central nervous system-specific changes in gene expression in women with neuropsychiatric Long COVID (NP-Long COVID) remains unknown.

Methods

Twenty-two women with and ten women without NP-Long COVID were enrolled from New Haven, CT, and the surrounding region and consented to a blood draw and large volume lumbar puncture. Total RNA was extracted from cerebrospinal fluid (CSF) cells and peripheral blood mononuclear cells (PBMC). Polyadenylated RNA was sequenced, and differential expression analyses were performed.

Results

Both CSF and PBMC samples showed differential gene expression associated with Long COVID status. There were CSF-specific differentially expressed genes (DEGs) in people with Long COVID, including in genes related to oxidative stress, reactive oxygen species, and P53 response, indicating compartment-specific immune responses. Some pathways were dysregulated in both the CSF and PBMC of Long COVID compared to controls, including those related to androgen response, MTORC1 signaling, and lipid metabolism.

Conclusions

Women with NP-long COVID show compartment-specific, transcriptional profiles in the CSF with evidence of enrichment in cellular stress pathways. These results underscore the importance of examining CSF-specific molecular profiles to better understand post-viral neurological syndromes.

◆Association of acute COVID-19 severity and long COVID fatigue and quality of life: Prospective cohort multicenter observational study【Medicine LWW 　2025年9月5日】

Abstract

Long COVID, or post-COVID-19 condition, is characterized by symptoms persisting beyond 12 weeks after severe acute respiratory syndrome coronavirus 2 infection, affecting individuals regardless of acute disease severity. Fatigue – often linked with depression and anxiety – is among its most debilitating manifestations. However, the associations between fatigue subtypes (physical vs mental), mental health symptoms, and acute disease severity on long-term health-related quality of life (HRQoL) remain unclear. This study examines the relationships between long COVID fatigue, depression, anxiety, acute disease severity, and HRQoL in a post-COVID-19 cohort. This prospective observational cohort study was conducted across 5 Portuguese hospitals between November 2020 and June 2022. Adults (≥18 years) with confirmed severe acute respiratory syndrome coronavirus 2 infection ≥6 months prior and fulfilling World Health Organization criteria for long COVID were included. Acute Coronavirus disease 2019 (COVID-19) severity was classified per World Health Organization definitions. The sampling strategy included patients across the severity spectrum. At 3 months postinfection (T1), patients received physician-led clinical assessments. At 6 months (T2), they attended in-person follow-up visits, completing standardized forms and validated questionnaires assessing post-acute sequelae. Fatigue was reported both binarily (yes/no) and via the chalder fatigue scale (11-item version). Anxiety and depression were assessed using the hospital anxiety and depression scale; post-traumatic stress disorder symptoms with the 14-item post-traumatic stress scale; and HRQoL with the EuroQol-5 dimensions. Descriptive statistics, analysis of variance, chi-square, and correlation analyses (Pearson’s or Spearman’s) were used to evaluate associations. Analyses were performed using SPSS (v27; IBM Corp., Amonk). Among 208 patients, fatigue was significantly associated with anxiety and depression (P < .001). Physical fatigue correlated more strongly with depression (r = 0.65, P < .001) and anxiety (r = 0.58, P < .001) than mental fatigue (r = 0.50 and R = 0.48, respectively; P < .001). Surprisingly, severe acute COVID-19 cases reported lower fatigue (CFQ: 13.3 ± 8.4) than mild (17.7 ± 7.2) or moderate (17.4 ± 8.0) cases (P < .005), and higher HRQoL (EuroQol visual analog scale: 74.3 ± 20.3, P = .002). Anxiety symptoms were more common in mild cases (P < .001); post-traumatic stress disorder symptoms did not differ by severity. Long COVID fatigue – especially physical – is strongly linked to depression and anxiety. Mild/moderate acute COVID-19 cases show greater fatigue and lower HRQoL than severe cases, highlighting the need for tailored long-term care regardless of initial severity.