SARS-CoV-2 と COVID-19 に関する備忘録 Vol.54

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SARS-CoV-2 と COVID-19 に関するメモ・備忘録

◆First episode of psychiatric and neuropsychiatric disease among patients infected with COVID‐19: A scoping review【National Library of Medicine　2025年6月25日】

Abstract

This scoping review aims to examine the frequency and prevalence of neuropsychiatric disorders reported in patients infected with coronavirus disease 2019, and the mechanisms by which these develop during and post infection. A systematic search using relevant search terms and key words was done on six electronic databases of literature on neuropsychiatric conditions post‐coronavirus disease 2019 infection from 2020 to 2023. Data were extracted following Joanna Briggs Institute guidelines, focusing on key findings, intervention details, and outcomes. We included 333 studies in the review. Studies indicated an elevated risk of neuropsychiatric disorders post‐coronavirus disease 2019, with some risks remaining high 2 years after diagnosis. A significant prevalence of depressive, psychotic, and anxiety disorders, as well as post‐traumatic stress symptoms were noted among coronavirus disease 2019 survivors. There was increased prevalence of insomnia and other sleep disturbances, mild to severe cognitive dysfunction, and eating disorders. Coronavirus disease 2019 infection is associated with a significant risk of developing various neuropsychiatric disorders, including schizophrenia, depressive disorders, anxiety, post‐traumatic stress disorder, and cognitive dysfunction. Long‐term monitoring and early interventions are essential to mitigate these risks and improve patient outcomes.

◆Severe Acute Respiratory Syndrome Coronavirus 2 Infection and the Long-Term Risk of Pneumonia in an Urban Population: An Observational Cohort Study up to 46 Months After Infection【OXFORD ACADEMIC　2025年6月25日】

Abstract

Background

Coronavirus disease 2019 (COVID-19) could increase susceptibility to future pulmonary infections. Given the sheer number of individuals infected by severe acute respiratory syndrome coronavirus 2, increased prevalence of future pulmonary infections could be a public health concern.

Methods

We conducted a retrospective study to determine whether COVID-19 is associated with increased incidence of future pneumonia. In an urban population in Montefiore Health System in the Bronx between 1 March 2020 and 31 January 2024, there were 64 376 patients with a history of COVID-19, 1.2 million patients without (controls), and 8468 patients with influenza without COVID-19. Controls were propensity matched. Multivariate Cox adjusted hazard ratios (aHRs) with 95% confidence interval (CIs) accounting for confounders were calculated. Outcomes were also analyzed with respect to comorbid conditions, median incomes, insurance status, and unmet social needs.

Results

Hospitalized (aHR, 3.69 [95% CI, 3.29–4.15]) and nonhospitalized (aHR, 1.40 [1.27–1.55]) patients with COVID-19 had higher risks of future pneumonia than controls. Hospitalized patients with COVID-19 experienced more recurrent pneumonia episodes than nonhospitalized patients with COVID-19 (2.3 vs 1.93 cases per patient, respectively; P < .05), who also had a higher rate of recurrence than the control group (1.71 cases per patient). Individuals on Medicaid (aHR, 1.40 [95% CI, 1.26­–1.55]) or Medicare (2.39 [2.12­–2.69]) (relative to private insurance) and those with unmet social needs (aHR, 1.34 [1.12–1.60]) were at even higher risks of outcomes. Hospitalized patients with COVID-19 had a higher adjusted risk of outcomes than patients with influenza (aHR, 2.89 [95% CI, 2.26–3.69]). Risks of outcomes varied by COVID-19 variants/waves. Conclusions

COVID-19 is associated with a higher risk of new-onset pneumonia. Patients with lower socioeconomic status or unmet needs were at higher risk.

◆Severe Acute Respiratory Syndrome Coronavirus 2 Infection and the Long-Term Risk of Pneumonia in an Urban Population: An Observational Cohort Study up to 46 Months After Infection【WILEY Online Library　2025年3月10日】

Abstract

Background

We hypothesized that disorders of gut-brain interaction (DGBI) increased during the pandemic due to the enteropathic nature of SARS-CoV-2, together with the potential for COVID-19 pandemic-related stress to negatively impact the gut-brain axis. To test our hypothesis, we conducted a series of pre-specified cross-sectional surveys initiated at the beginning of the pandemic to trend the prevalence of Rome IV DGBI over time among a nationally representative sample of more than 160,000 people in the US.

Methods

From May 2020 to May 2022, we performed a series of cross-sectional online surveys among a representative sample of adults ≥ 18 years old in the US. We administered Rome IV gastroduodenal and bowel DGBI questionnaires (e.g., chronic idiopathic constipation [CIC], functional bloating, functional dyspepsia, irritable bowel syndrome [IBS]) along with sociodemographic and comorbidity questions. Multivariable logistic regression was used to adjust for time and potential confounders.

Results

Overall, 160,154 people completed the surveys. During the COVID-19 pandemic, the prevalence of IBS (6.1% [May 2020] to 11.0% [May 2022]; +0.188%/month; adjusted p < 0.001) and CIC (6.0% [May 2020] to 6.4% [May 2022]; +0.056%/month; adjusted p < 0.001) increased over time. Among those with IBS, the largest prevalence increase was seen in mixed IBS (+0.085%/month), followed by IBS with constipation (+0.041%/month) and IBS with diarrhea (+0.037%/month). No changes in prevalence were seen for the other examined gastroduodenal and bowel DGBI. Conclusions

During the COVID-19 pandemic, we observed significant increases over time in the prevalence of IBS and CIC. Further research exploring pathophysiologic mechanisms underlying these findings and whether these trends persist beyond the pandemic is warranted.


A national survey of > 160,000 people from May 2020–May 2022 found significant increases in the prevalence of irritable bowel syndrome and chronic idiopathic constipation during the COVID-19 pandemic. This highlights the growing burden of disorders of gut-brain interaction, emphasizing the need for further efforts to effectively diagnose and manage these complex conditions.

◆Functional brain abnormalities in post COVID-19 condition and their relationship with cognition【nature : scientific reports　2025年7月1日】

Abstract

After COVID-19 infection, some patients develop a post-COVID condition (PCC) that is popularly referred to as long COVID. Among its symptoms is persistent cognitive dysfunction that is potentially linked to altered brain functional connectivity (FC). While research has explored functional reorganization in patients with PCC, the intra- and inter- network connectivity and its relationship with cognitive status and clinical outcomes remain unclear. In this study, we recruited 121 individuals with PCC (67 with, and 54 without, cognitive impairment), 20 months after infection, along with 37 non-infected healthy controls from the NAUTILUS Project (ClinicalTrials.gov IDs: NCT05307549 and NCT05307575). Participants underwent resting-state functional magnetic resonance imaging and comprehensive neuropsychological assessment. Resting-state networks were characterized using independent component analyses, dual regression and network modelling for individual FC characterization. Group differences in intra- and inter-network FC, and their associations with clinical and neuropsychological data, were studied. Significance was set at a corrected p-value of < 0.05. Patients with PCC showed increased intra-network FC in 10 cognitively relevant networks, including the default mode, salience, executive control, auditory and basal ganglia networks, correlating positively with general cognition (Montreal Cognitive Assessment scores), time since infection, fatigue and subjective memory failures. Increased inter-network FC between default mode and sensorimotor networks was also observed. Increases in FC may reflect an inefficient compensatory mechanism in patients with PCC, associated with fatigue, subjective memory complaints and persistence of PCC.

◆Biochemical insight into gut microbial imbalance in Covid-19 and post vaccination heart attacks【SPRINGER NATURE　2025年6月25日】

Abstract

Gut dysbiosis (GD) influences myocardial infarction (MI), by promoting inflammation. Investigating compositional shifts in proinflammatory versus beneficial bacterial taxa may reveal novel biomarkers and therapeutic interventions. This study analysed stool samples from 30 patients who experienced myocardial infarction following COVID-19 infection or vaccination, and 20 healthy controls, using 16S rRNA sequencing to investigate gut microbial imbalances. OTUs were identified, and microbial differences were examined via PCA and PLS-DA to explore biomarkers and interventions. MI patients exhibited reduced Prevotella (17.19% vs. 30% in controls) and elevated Escherichia (16.11% vs.0. 28%), Salmonella (2.58% vs. 0.08%), and Bacteroides (15.91% vs. 8.18%), indicating proinflammatory Microbiota. At phylum level, Firmicutes increased (45.80% vs. 40.87%), Proteobacteria rose (13.27% vs. 9.91%), and beneficial Actinobacteria declined (2.78% vs. 3.67%). PCA showed distinct clustering, confirmed by Partial Least Squares Discriminant Analysis, highlighting heightened inflammation-driving taxa. Although Faecalibacterium appeared variably, it was overall diminished in MI patients, likely fueling immune activation. However, Bifidobacterium (2.06% vs. 2.57%) and Lactobacillus (0.63% v. 0.99%) decreased, compromising intestinal barrier integrity. Females had higher Fusobacterium (1.85% vs. ~ 0%) and Streptococcus (2.28% vs. 0.16%), whereas males exhibited increased Desulfovibrio (1.60% vs. 0.08%) and Akkermansia (1.02% vs. 0.04%). Finally, Enterobacteriaceae surged from 0.41% to 10.04%, exacerbating inflammatory cascades and underscoring dysbiosis in MI pathophysiology. Findings highlights pivotal role of dysbiosis in MI, with elevated proinflammatory bacteria (Escherichia, Salmonella, Proteobacteria) and reduced beneficial SCFA-producing taxa (Bifidobacterium, Lactobacillus) worsening inflammation. Sex-specific microbial alterations, characterized by an enrichment of Fusobacterium and Streptococcus in females and elevated levels of Desulfovibrio and Akkermansia in males, underscore their potential utility as clinical biomarkers for risk stratification. Targeted microbiota therapies can enhance cardiac care outcomes.

Multilevel taxonomic analysis of proinflammatory gut microbiota in first-time myocardial infarction patients post-COVID-19 vaccination. Using 16S rRNA sequencing, this study identifies microbial signatures at various taxonomic levels, highlighting gut dysbiosis and its potential role in cardiovascular inflammation and myocardial infarction pathophysiology.

◆Fatal SARS-CoV-2 Reactivation After Allogeneic Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia【Cureus　2025年7月1日】

Abstract

SARS-CoV-2 has been reported to potentially remain in the lower respiratory tract for some time after it is no longer detectable in the upper respiratory tract, and this could be a source of reactivation. Reactivation of latent viral infections, such as cytomegalovirus and Epstein-Barr virus, after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is often a clinical problem. COVID-19 is caused by SARS-CoV-2 infection and has a high mortality rate in allo-HSCT recipients. However, little is known about SARS-CoV-2 reactivation following allo-HSCT. In this report, a patient with severe aplastic anemia first developed mild COVID-19 (day 0) with negative antigen test results on day 27. Three months later (day 97), the patient underwent allo-HSCT. Two months post-transplantation (day 157, i.e., five months after the initial infection), the patient developed rapidly progressive respiratory failure and was diagnosed with severe COVID-19. Since the patient was hospitalized and there was no obvious route of infection, we have concluded that reactivation of SARS-CoV-2, which had infected the patient five months earlier, occurred under an immunosuppressive state after allo-HSCT. Regarding allo-HSCT in patients who have previously developed COVID-19, careful monitoring using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to detect SARS-CoV-2 could be useful for detecting SARS-CoV-2 reactivation and providing early treatment to prevent fatal COVID-19.

◆Mapping brain changes in post-COVID-19 cognitive decline via FDG PET hypometabolism and EEG slowing【nature : scientific reports　2025年7月2日】

Abstract

Cognitive decline is a common symptom of post-COVID-19 syndrome. However, the mechanisms underlying this deficit remain poorly understood. This study aims to investigate the relationship between brain metabolic and neurophysiological alteration patterns in patients with persistent subjective cognitive decline after mild COVID-19 using joint FDG-PET and EEG analyses. The study was conducted on 28 post-COVID-19 patients with cognitive decline, who underwent comprehensive clinical evaluation including cognitive testing, FDG-PET imaging, and EEG acquisition. Voxelwise statistical analysis of PET images was performed by comparing post-COVID-19 patients with healthy controls (p-voxel < 0.005 uncorrected, p-cluster < 0.005 FWE-corrected, K > 599 voxels). EEG spectral powers were extracted and compared with age and sex-matched controls. The results showed significant hypometabolism in the bilateral frontal, temporal, and parietal lobes, as well as in the left occipital lobe, along with predominantly frontal EEG slowing in post-COVID-19 patients compared to healthy controls. In particular, the EEG alterations were characterized by a significant increase in relative power in the delta and theta bands, accompanied by a marked reduction in alpha band power in the frontal, temporal, and central regions. The observed PET hypometabolism and EEG slowing patterns in anterior brain regions, may help to elucidate the pathophysiological mechanisms underlying cognitive decline in post-COVID-19 patients.

◆Many children suffering ongoing Covid symptoms【University of Otago : Many children suffering ongoing Covid symptoms　2025年7月3日】

More than 20 per cent of children and young people in Aotearoa New Zealand are experiencing significant persistent health symptoms following Covid-19 infection, according to a new Otago-led study.

Published in the International Journal of Paediatrics and Child Health, the study led by researchers from University of Otago, Wellington – Ōtākou Whakaihu Waka, Pōneke is one of the most comprehensive assessments of the effects of Covid-19 on youth health in New Zealand to date.

Researchers surveyed more than 4200 children and young adults aged 3–20 years between November 2022 and April 2023, following New Zealand’s first widespread Covid-19 community transmission in early 2022.

More than 70 per cent of participants reported a confirmed Covid-19 infection.

One in four reported experiencing more frequent coughs, colds, and stomach bugs since infection, while one in five reported ongoing symptoms such as headaches (21.7 per cent), fatigue (20.6 per cent), stomach aches (14.6 per cent), and new anxiety (13.1 per cent).

Prior to Covid-19’s widespread arrival, 82.6 per cent of children rated their health as “very good” or “excellent” — that number dropped to 66.9 per cent after the Omicron variant waves.

Children who had Covid-19 were significantly more likely to rate their health as “fair” or “poor” compared to those who did not.

Children with pre-existing health conditions, such as asthma or ADHD, were more likely to develop post-Covid symptoms. However, many previously healthy children also reported new difficulties, including fatigue, persistent coughs, concentration issues, and sleep disturbances.

Lead author Associate Professor Julie Bennett, from the Department of Public Health, emphasises the importance of preventing Covid-19 infections, as long-term symptoms can affect children’s ability to participate in daily activities and attend school.

“Reducing infections to key to preventing Long Covid. Simple steps like opening windows to improve ventilation in classrooms, workplaces and at home helps reduce the spread of Covid-19 to others.”

Associate Professor Bennett says common symptoms reported in New Zealand children include headaches, fatigue, stomach aches, anxiety and more frequent coughs and colds.

“If a child has Covid, ensure they are able to rest during and after infection to prevent post-viral complications such as Long Covid.”

Co-author Larisa Hockey, of Long Covid Kids New Zealand, says the findings show that Covid-19 has had a measurable and ongoing impact on many children’s health in New Zealand.

“There is strong evidence that preventing infection is key to preventing Long Covid,” she says.

“Children deserve every opportunity to grow up healthy and thrive — and that includes protecting them from preventable long-term illness.

“Long Covid is having a significant impact on children’s lives, and those of family members.”

“Both previously healthy children and those with existing health conditions reported new symptoms that affected school attendance, concentration, and overall wellbeing.

◆Protective role of anti-SARS-CoV-2 antibody responses against vital organ related long COVID symptoms【nature : scientific reports　2025年7月3日】

Abstract

COVID-19 pandemic continues to challenge the world with a major public health problem, long COVID (LC), which is estimated to affect over 400 million people worldwide. Many unknowns remain regarding the mechanisms involved in LC. We investigated the impact of anti-SARS-CoV-2 antibody and IFN-γ responses on the development of LC and its various phenotypes. We studied a cohort of 137 convalescents following predominantly mild COVID-19 during the first pandemic wave (2020) and up to one-year post-infection. We found 45% of LC cases that were associated with a greater number and duration of acute-phase symptoms. Cardiovascular and/or gastrointestinal symptoms in the acute phase were associated to protection against LC development, while pulmonary, otorhinolaryngological, musculoskeletal and other symptoms were associated with increased risk of LC development. Regarding LC phenotypes, we observed risk associations and potentially deleterious effects of anti-SARS-CoV-2 antibodies for LC symptoms classified as general or other. In contrast, for vital organ-related LC symptoms, we found only protective associations, particularly for cardiovascular symptoms, which indeed had a low prevalence in LC (16%). Collectively, our data suggest that anti-SARS-CoV-2 antibodies play a protective role against vital organ-related LC symptoms, especially cardiovascular symptoms, but are insufficient in preventing or limiting other highly prevalent LC symptoms, such as neurological, psychiatric and pulmonary.

◆Quality of life and mental health in children with long COVID【nature : communications medicine　2025年7月3日】

Abstract

Background

Pediatric Long COVID (PLC) is a heterogeneous condition, which can have a substantial impact on daily life of children and adolescents. This study aimed to evaluate health related quality of life (HRQoL), and mental and social health of children with PLC, in relation to children with other chronic health conditions (CHC) and from the general population (GP) during the pandemic.

Methods

Dutch children (8-18 years) with PLC (n = 106, 31% male) were included between May 2021 and March 2023. Reference data was available from a CHC-cohort (n = 90, 56% male) and GP-cohort (n = 844, 47% male) during the first wave of the pandemic (April–May, 2020). Participants completed the Pediatric Quality of Life Inventory (PedsQL) 4.0 and Patient-Reported Outcomes Measurement Information System (PROMIS) instruments (Anxiety, Anger, Depressive symptoms, Sleep-Related Impairment (SRI), and Peer Relationships). Mean scores were analyzed using adjusted ANCOVA. Relative risks (RR (95% CI)) were calculated for impaired HRQoL and severe PROMIS scores.

Results

Children with PLC report high proportions of impaired HRQoL (84%, RR = 3.67 (2.35–5.74)), and have significantly lower PedsQL scores than children with CHC. Children with PLC also exhibit worse PROMIS T-scores of Anxiety, Depressive Symptoms, and SRI than children from the CHC- and GP-cohorts (mean difference range 2.2–9.8 (95%CI 0.6–11.7)), and significantly higher risks of severe anxiety (17%), depressive symptoms (18%), and SRI (17%).

Conclusions

PLC can severely impact HRQoL and mental and social health in children. Screening of these outcomes and individualized management of children with PLC should be a vital part of clinical care for these highly burdened patients.

◆SARS-CoV-2 induces Alzheimer’s disease–related amyloid-β pathology in ex vivo human retinal explants and retinal organoids【Science Advances　2025年7月4日】

Abstract

While the etiology of Alzheimer’s disease remains unknown, there is growing support for the amyloid-β antimicrobial hypothesis. Amyloid-β, the main component of amyloid plaques in Alzheimer’s disease, has been shown to be generated in the presence of microbes. Entrapment of microbes by aggregated amyloid-β may serve as an innate immune response to pathogenic infections. To understand the association of amyloid-β plaques and pathogenic infections in the central nervous system, we obtained viable short-interval postmortem human retinal tissue and generated human retinal organoids that contain electrophysiologically active neurons. Here, we demonstrate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces amyloid-β extracellular protein aggregates in human retinal explants and retinal organoids. Last, pharmacological inhibition of neuropilin-1 resulted in reduced amyloid-β deposition in human retinal explants treated with SARS-CoV-2 Spike 1 protein. These results suggest that Spike 1 protein, during infection with SARS-CoV-2, can induce amyloid-β aggregation, which may be associated with the neurological symptoms experienced in COVID-19.

◆Comprehensive molecular characterization of post-COVID condition: Immunoglobulin suppression and persistent SARS-CoV-2 antigens as key pathophysiological drivers【ScienceDirect　2025年7月日】

Abstract

Background

Post-COVID condition (PCC), or long COVID, affects a significant proportion of individuals following SARS-CoV-2 infection, yet its molecular framework remains poorly understood. This study aimed to define the molecular profile of PCC by integrating broad proteomic analysis using Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH-MS) with targeted antigen quantification through targeted mass spectrometry (MRM/SRM).

Methods

Plasma and pellet fractions from 65 PCC patients, classified as symptomatic or asymptomatic, were analyzed using SWATH-MS with updated SARS-CoV-2 protein libraries (v2022 and v2024), enabling a comprehensive profiling of immune- and viral-related proteins. The presence of viral antigens, specifically spike and nucleocapsid proteins, was quantified using MRM/SRM. A protein-concentration-based severity metric using clustering analysis and dimensionality reduction methods was proposed to assess correlations between proteomic alterations and clinical symptoms.

Results

A key finding in PCC patients, particularly in symptomatic cases, was a pronounced downregulation of immunoglobulins, including kappa and lambda light chains. SWATH-MS analysis identified six proteins (corresponding to UniProt entries Q8N5F4, LV147, KV311, KVD20, A0A5C2G1U0, and KV315) that strongly correlated with disease severity (R² > 0.9), highlighting their potential as biomarkers. In pellet samples, the protein G1SG72 (ABCE1) emerged as a marker associated with severity, suggesting possible alterations in antiviral responses. The severity metric proposed showed a strong correlation with clinical symptoms, providing a quantifiable measure of PCC severity and enabling effective patient stratification. Additionally, MRM/SRM analysis detected the persistent presence of SARS-CoV-2 antigens, specifically the Spike and Nucleocapsid proteins, in symptomatic PCC patients.

Conclusions

This study defines a molecular profile of PCC, marked by immunoglobulin downregulation and the persistence of SARS-CoV-2 antigens, which may contribute to ongoing immune alterations in PCC. The severity metric derived from proteomic profiling provides a tool for categorizing PCC patients based on symptom severity and could support future studies aimed at targeted interventions.