SARS-CoV-2 と COVID-19 に関する備忘録 Vol.57

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SARS-CoV-2 と COVID-19 に関するメモ・備忘録

◆Hamsters with long COVID present distinct transcriptomic profiles associated with neurodegenerative processes in brainstem【nature communications　2025年7月22日】

Abstract

Following infection with SARS-CoV-2, patients may experience with one or more symptoms that appear or persist over time. Neurological symptoms associated with long COVID include anxiety, depression, and memory impairment. However, the exact underlying mechanisms are not yet fully understood. Using golden hamsters as a model, we provide further evidence that SARS-CoV-2 is neuroinvasive and can persistently infect the brain, as viral RNA and replicative virus are detected in the brainstem 80 days after the initial infection. Infected hamsters exhibit a neurodegenerative signature in the brainstem, characterized by overexpression of innate immunity genes, and altered expression of genes involved in the dopaminergic and glutamatergic synapses, in energy metabolism, and in proteostasis. These infected animals exhibit persistent depression-like behavior, impaired short-term memory, and late-onset signs of anxiety. Finally, we provide evidence that viral and immunometabolic mechanisms coexist in the brainstem of SARS-CoV-2-infected hamsters, contributing to the manifestation of neuropsychiatric and cognitive symptoms.

◆Accelerated brain ageing during the COVID-19 pandemic【nature communications　2025年7月22日】

Abstract

The impact of SARS-CoV-2 and the COVID-19 pandemic on brain health is recognised, yet specific effects remain understudied. We investigate the pandemic’s impact on brain ageing using longitudinal neuroimaging data from the UK Biobank. Brain age prediction models are trained from hundreds of multi-modal imaging features using a cohort of 15,334 healthy participants. These models are then applied to an independent cohort of 996 healthy participants with two magnetic resonance imaging scans: either both collected before the pandemic (Control groups), or one before and one after the pandemic onset (Pandemic group). Our findings reveal that, even with initially matched brain age gaps (predicted brain age vs. chronological age) and matched for a range of health markers, the pandemic significantly accelerates brain ageing. The Pandemic group shows on average 5.5-month higher deviation of brain age gap at the second time point compared with controls. Accelerated brain ageing is more pronounced in males and those from deprived socio-demographic backgrounds and these deviations exist regardless of SARS-CoV-2 infection. However, accelerated brain ageing correlates with reduced cognitive performance only in COVID-infected participants. Our study highlights the pandemic’s significant impact on brain health, beyond direct infection effects, emphasising the need to consider broader social and health inequalities.

◆Review of organ damage from COVID and Long COVID: a disease with a spectrum of pathology【National Library of Medicine　2024年7月2日】

Abstract

Long COVID, as currently defined by the World Health Organization (WHO) and other authorities, is a symptomatic condition that has been shown to affect an estimated 10 %–30 % of non-hospitalized patients after one infection. However, COVID-19 can also cause organ damage in individuals without symptoms, who would not fall under the current definition of Long COVID. This organ damage, whether symptomatic or not, can lead to various health impacts such as heart attacks and strokes. Given these observations, it is necessary to either expand the definition of Long COVID to include organ damage or recognize COVID-19-induced organ damage as a distinct condition affecting many symptomatic and asymptomatic individuals after COVID-19 infections. It is important to consider that many known adverse health outcomes, including heart conditions and cancers, can be asymptomatic until harm thresholds are reached. Many more medical conditions can be identified by testing than those that are recognized through reported symptoms. It is therefore important to similarly recognize that while Long COVID symptoms are associated with organ damage, there are many individuals that have organ damage without displaying recognized symptoms and to include this harm in the characterization of COVID-19 and in the monitoring of individuals after COVID-19 infections.

◆Immune-Metabolic Programs Drive Disease Trajectories in Paediatric Long COVID【Research Square　2025年7月22日】

Abstract

While most children and adolescents recover uneventfully from SARS-CoV-2 infection, some develop persistent symptoms known as paediatric long COVID (LC). Paediatric LC presents with substantial, multisystem health impairment lasting months to years after SARS-CoV-2 infection. Despite its clinical burden, underpinnings of symptom persistence, heterogeneity, and recovery remain elusive. Here, we demonstrate that severe symptoms in paediatric LC remained stable over two-to-three years, despite unremarkable cardiopulmonary and routine assessments, and were underpinned by temporally shifting immune-metabolic responses. The first year of LC was marked by viral-associated and Th2-like cytokine responses, transitioning into Th17-like and innate responses over time. Neurofilament light chain, an indicator of neuro-axonal injury, rose with LC-severity, but common autoantibodies remained unchanged. Epstein-Barr virus (EBV) exposure emerged as a key modifier linked to broader immune dysfunction, whereas anti-DFS70 autoantibodies correlated with milder haematological alterations. In EBV-naïve LC cases, symptoms became more severe with altered blood viscosity, but less severe with higher IL-12p40, vitamin B1, and basophils, implicating them as protective. The identified LC subgroups displayed metabolically distinct signatures, supporting the existence of biologically coherent endotypes. These findings uncover immune-metabolic axes linked to resilience and persistence in paediatric LC and may provide a basis for biomarker-informed diagnosis and precision intervention.

◆SARS-CoV-2 spike protein amyloid fibrils impair fibrin formation and fibrinolysis【bioRxiv　2025年7月1日】

Abstract

Long COVID, also known as post-acute sequelae of COVID-19 (PASC) from SARS-CoV-2 infection, is a debilitating and persistent disease of multiple systems and organs. WHO reports a total of 778 million registered SARS-CoV-2 infections as of June 2025. Recent studies indicate that as many as 25% of COVID patients will experience at least one symptom of Long COVID. Long COVID pathophysiology is a complex and not fully established process. One prevailing theory is that the formation of fibrin amyloid microclots (fibrinaloids), due to SARS-CoV-2 infection, can induce persistent inflammation and capillary blockage. An association between the amyloidogenic Spike protein of SARS-CoV-2 and impaired fibrinolysis has previously been made when it was observed that fibrin clots formed in the presence of a mixture of amyloid fibrils from the spike protein displayed a resistance to plasmin-mediated lysis. Here we investigated the molecular processes of impaired fibrinolysis using seven amyloidogenic SARS-COV-2 Spike peptides. Five out of seven Spike amyloid fibrils appeared not to substantially interfere with the fibrinogen-fibrin-fibrinolysis process in vitro, while two spike fibrils were active in different ways. Spike601 amyloid fibrils (sequence 601-620) impaired thrombin mediated fibrin formation by binding and sequestering fibrinogen but did not affect fibrinolysis. On contrary fibrin clots formed in the presence of Spike685 amyloid fibrils (sequence 685-701) exhibited a marked resistance to plasmin mediated fibrinolysis. We conclude that Spike685 amyloid fibrils can induce dense fibrin clot networks, as well as incorporate fibrin into aggregated structures that resist fibrinolysis. These results demonstrate how the Spike protein of SARS-CoV-2 could contribute to the formation fibrinolysis-resistant microclots observed in long COVID.

◆Risk of neuropsychiatric and related conditions associated with SARS-CoV-2 infection: a difference-in-differences analysis【nature communications　2025年7月24日】

Abstract

The COVID-19 pandemic has been associated with increased neuropsychiatric conditions in children and youths, with evidence suggesting that SARS-CoV-2 infection may contribute additional risks beyond pandemic stressors. This study aims to assess the full spectrum of neuropsychiatric conditions in COVID-19 positive children (ages 5–12) and youths (ages 12–20) compared to a matched COVID-19 negative cohort, accounting for factors influencing infection risk. Using EHR data from 25 institutions in the RECOVER program, we conduct a retrospective analysis of 326,074 COVID-19 positive and 887,314 negative participants matched for risk factors and stratified by age. Neuropsychiatric outcomes are examined 28 to 179 days post-infection or negative test between March 2020 and December 2022. SARS-CoV-2 positivity is confirmed via PCR, serology, or antigen tests, while negativity requires negative test results and no related diagnoses. Risk differences reveal higher frequencies of neuropsychiatric conditions in the COVID-19 positive cohort. Children face increased risks for anxiety, OCD, ADHD, autism, and other conditions, while youths exhibit elevated risks for anxiety, suicidality, depression, and related symptoms. These findings highlight SARS-CoV-2 infection as a potential contributor to neuropsychiatric risks, emphasizing the importance of research into tailored treatments and preventive strategies for affected individuals.

◆Long Covid in Year 5: Some Progress, Still Many Questions【Journal of Insurance Medicine　2025年7月24日】

Abstract

Long Covid was first described in 2020. Five years later, progress in disease characterization has been considerable, and definitions continue to evolve. Several disease mechanisms are under study, and evidence for multiple endotypes is accumulating. No clinical biomarker has been identified, nor has an effective therapy been developed. Overlap with other post-infectious syndromes, particularly myalgic encephalomyelitis/chronic fatigue syndrome, is now more evident. For most individuals, symptoms of long Covid progressively disappear over time. Recurrent Covid-19 infections are now an important contributor to the pool of affected individuals. While symptoms limit activity in as many as 20%, inability to work is less common. The anticipated surge of disability claims from insured individuals has not materialized.

◆Association Between COVID-19 Infection and Subjective Cognitive Decline in Adults: A Cross-Sectional Online Survey Study【Sage Journals　2025年7月24日】

Abstract

Background:

Cognitive impairment is the most common residual symptom following COVID infection, reported in approximately 22% of adults diagnosed with COVID-19. Subjective cognitive decline is considered a significant early indicator of the progression of Alzheimer’s disease. There is limited research investigating subjective cognitive decline following COVID-19 infection.
Purpose:
The purpose of this study was to examine the relationship between COVID-19 infection and subjective cognitive decline in adults.

Methods:

In this comparative and cross-sectional study, data were collected via an online survey involving 98 adults diagnosed with COVID-19 and 317 adults never diagnosed with COVID-19. The mean age of participants was 30.2 ± 8.4 years, and 36.6% were female. The revised Everyday Cognition Scale was used to assess subjective cognitive decline. Data analysis included descriptive statistics, one-way analysis of covariance, and hierarchical multiple regression.

Results:

After controlling for covariates, adults diagnosed with COVID-19 experienced significantly greater subjective declines in memory (P = .002), language (P = .002), organizational ability (P = .03), attention (P = .003), and global cognition (P = .007) than those never diagnosed with COVID-19. Furthermore, COVID-19 diagnosis was a significant predictor of worse subjective declines in these domains of cognition.

Conclusion:

Findings highlight the associations between COVID-19 infection and subjective cognitive decline across various domains. These results underscore the need for longitudinal studies to explore the progression of cognitive decline. Early detection and management of cognitive dysfunction can prevent further deterioration of cognitive function.