SARS-CoV-2 と COVID-19 に関する備忘録 Vol.62

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SARS-CoV-2 と COVID-19 に関するメモ・備忘録

◆The silent legacy of COVID-19: exploring genomic instability in long-term COVID-19 survivors【BMC Infectious Diseases　2025年8月19日】

Abstract

Background

Persistent symptoms and complications reported by many patients for more than four weeks after contracting coronavirus disease 2019 (COVID-19) are referred to as post-COVID-19 syndrome. These persistent symptoms can occur in individuals with both mild and severe COVID-19, though the underlying pathophysiological mechanisms remain poorly understood. This study aims to explore post-COVID-19 syndrome from a biological perspective, focusing on genomic instability.

Methods

In this cross-sectional study, the comet assay method was employed in March 2024 to evaluate the level of DNA damage in 29 patients to examine the post-COVID-19 syndrome state at Kausar Semnan Hospital in Iran. Levels of DNA damage were assessed using the alkaline comet assay in patients hospitalized for COVID-19, four weeks after a positive RT-PCR test. Patients were categorized based on pneumonia severity: mild (11 patients in non-ICU), moderate (10 patients in ICU and non-intubated), and severe/critical (8 patients in ICU and intubated). Ten healthy individuals who tested negative for COVID-19 were considered as a control group. Data were analyzed using descriptive and inferential statistical tests at a significance level of p < 0.01 in GraphPad Prism 9 software. Results

Post-COVID-19 patients exhibited significantly higher levels of DNA damage compared to healthy controls. The highest DNA damage was observed in intubated-ICU patients (mean DNA damage: 29.5%), followed by non-intubated-ICU patients (mean: 24.3%), non-ICU patients (mean: 19.1%), and healthy controls (mean: 9.4%). These findings suggest a clear correlation between COVID-19 severity and increased genomic instability.

Conclusion

The results of this study highlight the prevalence of DNA damage in post-COVID-19 patients, which may explain long-term genomic instability and associated health complications. The findings underscore the importance of further research into the pathophysiological mechanisms of post-COVID-19 syndrome, particularly its impact on genomic stability. This study contributes to the growing evidence that post-COVID-19 syndrome is a complex condition with virus-specific abnormalities affecting multiple biological pathways. Future studies should focus on understanding these mechanisms to develop targeted interventions for long-term COVID-19 survivors.

◆Favorable responses to upadacitinib, a JAK1 inhibitor, in long COVID patients with predominant neuropsychiatric symptoms: case reports in 2 autistic patients and one typically developing patient【BMC Neurology　2025年8月20日】

Abstract

The long-term impact of coronavirus disease 2019 (COVID-19) has become evident over the past 3–4 years, with the recognition of post-COVID long-term sequelae, often referred to as long COVID. Neuropsychiatric symptoms are one of the hallmarks of long COVID. In severe cases, it can even present features of encephalopathy. Since some of the neuropsychiatric symptoms associated with long COVID overlap symptoms found in neuropsychiatric disorders, it has been difficult to sort out the effects of long COVID in such subjects. This is especially true in patients diagnosed with autism spectrum disorders (ASD), given their difficult behavioral symptoms and other co-morbid conditions. COVID-19 is thought to affect the onset or progress of encephalopathy symptoms by activation of the immune system through the type 1 interferon (IFN) signaling pathway. In that case, treatment would require an immunomodulating agent that targets such pathways. However, such measures may not be applied to ASD subjects, in whom long COVID may not even be considered as the cause of their symptoms. In this study, we present the beneficial effects of upadacitinib, a JAK (janus kinase) 1 inhibitor, that blocks downstream signaling of type 1 IFNs, on 3 patients, 2 with ASD and one without ASD. In these patients, long COVID was thought to have triggered or aggravated encephalopathy-like symptoms. The beneficial effects of upadacitinib were not only noted by an improvement of their behavioral symptoms but also shown by an improvement of monocyte cytokine profiles (less activated state); peripheral blood monocytes were used as surrogates of microglial cells. These three cases presented highlight a possible use of JAK inhibitors for treating long COVID-associated neuropsychiatric symptoms in both ASD and non-ASD subjects. The presented cases highlight the inherent difficulty of diagnosing long COVID in ASD cases.

◆“Have you considered that it could be burnout?”—psychologization and stigmatization of self-reported long COVID or post-COVID-19 vaccination syndrome【BMC Medicine　2025年8月20日】

Abstract

Background

People reporting long COVID (LC) or post-COVID-19 vaccination syndrome (PCVS) not only suffer from their symptoms but also from stigmatization. Despite ample account and characterization of stigma experiences so far, its mechanisms and consequences on health outcomes, and particularly the role of “psychologization” remain unclear.

Methods

In a cross-sectional observational study, we examined a large convenience sample of adults who report having LC or PCVS. We translated and adapted the “Long Covid Stigma Scale” to measure stigmatization. We measured generally perceived and personally experienced psychologization with newly developed scales/items. Outcome measures included disclosure concerns, loss of trust in medicine, life satisfaction, depression, anxiety, self-esteem, and loneliness. We calculated overall prevalences of stigma and psychologization and their correlations with the outcomes. Using mediation analysis with SEM, we tested the hypothesis that psychologization of LC and PCVS syndromes causes harm by increasing stigmatization.

Results

Altogether, N = 2053 individuals (68% reporting LC, 32% reporting PCVS) were included in the analyses. The overall prevalences of stigma experiences were high: 83% of those reporting LC and 90% of those reporting PCVS experienced stigma. Prevalences of perceived psychologization (LC: 87%, PCVS: 91%) and experienced psychologization (LC: 82%, PCVS: 87%) were similarly high. Both stigmatization and psychologization were positively correlated with disclosure concerns, loss of trust in medicine, depression, anxiety, and loneliness as well as negatively correlated with life satisfaction and self-esteem. Mediation analysis indicated that stigmatization mediated a relevant proportion of the relationship between psychologization and negative outcomes.

Conclusions

People reporting LC or PCVS are subject to stigmatization and psychologization. From a patient perspective, psychologization appears to be an important driver of stigmatization and negative outcomes.

◆The Challenge of Long COVID: Is the Pandemic Really Over?【Sage Journals　2025年8月17日】

Abstract

Sequelae of SARS-CoV-2 infection began appearing among patients who had COVID-19 within months of the first wave of the COVID-19 pandemic in 2020. This phenomenon, termed post–COVID-19 condition and also known as long COVID, has been a source of controversy among physicians, as presentation of long COVID has been a somewhat mysterious constellation of signs and symptoms that seem mostly impervious to efficacious treatment. Although a considerable amount has been learned about the pathophysiology and other biomedical features of long COVID, the epidemiologic parameters of long COVID, including incidence and prevalence, are uncertain in the United States and globally. The best estimates are that millions of people have long COVID. Despite the declining incidence of COVID-19, the low case fatality of long COVID suggests that its prevalence is poised to continue to grow. This increasing prevalence of long COVID presents a challenge for the public health sector. Here, we examine the public health implications of long COVID. We offer policy recommendations, including ending congratulatory talk that the pandemic is over, encouraging more focused attention from the United States and global nongovernmental organizations, and establishing a multinational research initiative to better understand and respond to long COVID and other postviral and postinfectious chronic conditions. Although COVID-19 may not be as widespread and disruptive as in the early months of the pandemic, it would be a mistake to presume that, because the acute crisis is behind us, the pandemic is past. Long COVID is an ongoing public health threat and merits our concern.

◆SARS-CoV-2 infection heightens the risk of developing HPV-related carcinoma in situ and cancer【SPRINGER NATURE　2025年8月14日】

Abstract

Objective

This study aims to investigate the impact of SARS-CoV-2 infection on HPV-related cancer and carcinoma in situ.

Method

We utilized data from TriNetX, a database encompassing 106 healthcare organizations spanning 15 countries and comprising information from over 124 million participants. Propensity score matching was utilized to compare two cohorts: SARS-CoV-2 infection and non- SARS-CoV-2 infection groups. The cohorts consisted of females aged 18–90 with no previous history of HPV-related cancers before SARS-CoV-2 infection in 2020 and no HPV vaccine before 2020. We utilized Cox proportional hazard regression analysis to estimate hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs). Subgroup analyses were performed based on age and race to validate the findings.

Results

The study included a total of 4,872,295 patients, with 1,281,997 in the SARS-CoV-2 infection group and 3,590,298 in the non-infection group. After propensity score matching, both groups comprised 1,281,997 patients each. Over a 3-year follow-up period, individuals with SARS-CoV-2 infection had significantly higher risks of developing HPV-related cancers compared to those without infection: a 67% increase in cervical cancer, 131% in vaginal cancer, 98% in vulvar cancer, 92% in anal cancer, and 78% in oropharyngeal cancer. Similar trends were observed for carcinoma in situ, with increased risks of 34% for cervical, 61% for vaginal, 74% for vulvar, 96% for anal, and 78% for oropharyngeal carcinoma in situ. Subgroup analyses stratified by age and race demonstrated consistent results.

Conclusion

SARS-CoV-2 infection is associated with elevated risks of HPV-related carcinoma in situ and cancer, irrespective of age or race. The findings underscore the importance of understanding the interplay between viral infections and cancer development, particularly in the context of the COVID-19 pandemic.

◆Extracting post-acute sequelae of SARS-CoV-2 infection symptoms from clinical notes via hybrid natural language processing【nature : npj health systems　2025年8月21日】

Abstract

Accurately and efficiently diagnosing Post-Acute Sequelae of COVID-19 (PASC) remains challenging due to its myriad symptoms that evolve over long- and variable-time intervals. To address this issue, we developed a hybrid natural language processing pipeline that integrates rule-based named entity recognition with BERT-based assertion detection modules for PASC-symptom extraction and assertion detection from clinical notes. We developed a comprehensive PASC lexicon with clinical specialists. From 11 health systems of the RECOVER initiative network across the U.S., we curated 160 intake progress notes for model development and evaluation, and collected 47,654 progress notes for a population-level prevalence study. We achieved an average F1 score of 0.82 in one-site internal validation and 0.76 in 10-site external validation for assertion detection. Our pipeline processed each note at 2.448 ± 0.812 seconds on average. Spearman correlation tests showed ⍴ > 0.83 for positive mentions and ⍴ > 0.72 for negative ones, both with P < 0.0001. These demonstrate the effectiveness and efficiency of our models and its potential for improving PASC diagnosis.

◆Fears of new Covid wave after cases in hospital patients soar by 31% in two weeks【THE i PAPER：Tom Bawden　2025年8月20日】

Concerns about a new Covid wave are mounting after positive tests for the virus among hospital patients jumped by nearly a third in a fortnight.

The proportion of hospital patients with respiratory symptoms testing positive for the virus rose from 5.8 per cent on 26 July to 7.6 per cent on 10 August – a 31 per cent increase in 15 days, according to the UK Health Security Agency (UKHSA).

Known as the “positivity rate”, this infection level is much higher than that found among the general public, as hospital patients with symptoms are not a representative sample of wider society.

The positivity rate is also different from the ‘hospitalisation’ rate, which refers to those people who are admitted to hospital due to Covid – meaning their case is serious.

This increased by 15 per cent in the week to Monday August 10th, from 1.3 per 100,000 of the population to 1.5 – although the level remains lower than it has been for most of the time since Covid began.

By contrast, the positivity rate refers to the number of people in hospital for other reasons, whose Covid cases are typically less serious.

Scientists caution that changes in the numbers over time cannot be taken as a precise indicator of broader trends – which is much better established through widespread random testing outside hospitals, in the general population.

But it is seen as a decent indicator of wider trends and comes against a backdrop of concerns about rising Covid infections.

Immunity given by vaccines and previous infections has waned, while at the same time, a highly contagious new Covid variant XFG, or Stratus, is spreading.

As a result, experts say the sharp rise in positive tests inside hospitals suggests the country is facing a new wave of infections.

“We are looking like we are on the cusp of a summer wave – which would be in keeping with previous summers,” Simon Williams, a behavioural scientist and public health expert at Swansea University, told The i Paper.

“However, how much and to what extent we will see rises remains to be seen – waves are much smaller and flatter than in early years of Covid.”

Professor Lawrence Young, a virologist at Warwick University, told The i Paper “the rise in Covid positivity is a concern”. He added that it “reinforces the fact that the virus is still circulating and is capable of spreading”.

“A particular concern is the impact on infection levels as people return to work and school after the holiday season and the effect of cooler weather. This coupled with new virus variants and restricted access to free vaccines over the autumn period is worrying.”

Nearly 13 million fewer people will be offered an autumn booster for Covid this year, fuelling concerns we could be heading for a new wave of the virus.

The Government said that pensioners aged 65 to 74 will no longer be able to go for a free jab.

Meanwhile, 6.9 million people in “clinical risk” groups such as pregnant women and people with chronic heart and liver disease will also be excluded for the first time.

However, Professor Young said he is encouraged by the fact that “hospitalisation rates are low” in the latest UKHSA data.

Hospitalisation rates refer to people who are admitted to hospital due to Covid – as opposed to the positivity rate which refers to the number of people in hospital for all reasons.

The latest positivity rate of 7.6 per cent remains lower than it has been for much of the pandemic despite the recent sharp rise – but it is much higher than it was in January, when it was 2.2 per cent.

However, it hit 16.6 per cent last July and 14.6 per cent last October, according to UKHSA data.

Professor Sheena Cruickshank, of Manchester University, says “although the latest positivity rate seems a jump from the previous week it’s still at a very low level”.

But she cautions that “when schools come back and university terms restart its possible that activity may get higher as more people mix indoors”.

“We are seeing a smallish wave in the States and whether something similar happens here later in the autumn remains to be seen,” she told The i Paper.

Dr Alex Allen, Consultant Epidemiologist, UKHSA: “The latest weekly data shows that Covid-19 continues to circulate at baseline levels, although activity has increased slightly across indicators.

“Based on the available information so far, there is no evidence to suggest that the vaccines in current use will be less effective than the dominant strains”.

◆Cardiorenal outcomes after herpes zoster reactivation in COVID-19 survivors from a global TriNetX study【nature : scientific reports　2025年8月17日】

Abstract

Herpes zoster (HZ) has emerged as a post-viral complication in COVID-19 survivors, but its long-term clinical impact remains uncertain. This retrospective cohort study utilized the TriNetX Global Collaborative Network to evaluate whether HZ reactivation after COVID-19 is associated with increased risks of mortality, cardiovascular, and renal outcomes. Adults diagnosed with HZ within one year of COVID-19 were propensity score–matched 1:1 with controls without HZ. A total of 48,442 matched patients were followed for three years. Compared with controls, HZ patients had significantly higher risks of major adverse cardiovascular events (HR: 1.38, 95% CI: 1.30–1.46), acute kidney injury (HR: 1.67, 95% CI: 1.55–1.80), and renal function decline defined by eGFR < 60 mL/min/1.73 m² (HR: 1.28, 95% CI: 1.20–1.37). Although no significant difference in overall all-cause mortality was observed across the full follow-up period, time-stratified analysis revealed a biphasic pattern: patients with HZ had lower mortality risk during the first 90 days but showed significantly higher mortality from day 91 to three years post-COVID-19 (HR: 1.33, 95% CI: 1.24–1.44). Subgroup analyses consistently identified older age, chronic comorbidities, impaired renal function, and systemic inflammation as risk enhancers across outcomes. These findings suggest that HZ reactivation after COVID-19 signals a vulnerable subgroup predisposed to cardiorenal complications. Targeted follow-up and risk-based interventions are warranted in this population.

◆An Amyloidogenic Fragment of the Spike Protein from SARS-CoV-2 Virus Stimulates the Aggregation and Toxicity of Parkinson’s Disease Protein Alpha-Synuclein【ACS Publications　2025年8月22日】

Abstract

Emerging evidence suggests that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may have long-term deleterious effects on the central nervous system and even contribute to post-COVID neurological syndromes. Interestingly, inflammation-induced proteolytic processing of the Spike protein of SARS-CoV-2 leads to the generation of peptides capable of aggregating into amyloid fibrils in vitro. Herein, we investigate the in vitro effect of a fibrillogenic fragment of the Spike protein [Spike 194–203 (S194)] on the aggregation and toxicity of the Parkinson’s disease (PD) protein α-synuclein (αSyn). Our results indicate that S194 fibrils stimulate in a concentration-dependent manner the fibrillation of αSyn monomer, resulting in aggregates with increased capacity of inducing lipid vesicle leakage and toxicity to neuroblastoma cells, in comparison with either αSyn or S194 alone. Bidimensional NMR (1H–15N-HSQC) suggests that S194 fibrils cause a higher perturbation in both the N-terminal region (sequence: 19–68) and the hydrophobic central domain of the αSyn monomer (sequence: 71–95), which is corroborated by protein–peptide docking and molecular dynamics simulations. In contrast with fibrils from wild-type αSyn, aggregates from the PD variant A30P exhibited a remarkable accelerative effect on S194 fibrillation. Similarly, fibrils from amyloid-β peptides, which are linked to Alzheimer’s disease, exhibited a pro-aggregating effect on the S194 monomer. Taken together, these findings might contribute to a broader understanding of the potential connections between SARS-CoV-2 infection and amyloid-related neurodegenerative disorders, highlighting areas that may warrant further investigation.

◆Pediatric Long COVID Is Characterized by Myeloid CCR6 Suppression and Immune Dysregulation【bioRxiv　2025年8月22日】

Abstract

The biological mechanisms underlying long COVID in the pediatric population are poorly understood. Our study aimed to characterize the immune pathophysiology of long COVID in children and young people (CYP). We analyzed major immune cell compartments in PBMCs, as well as specific SARS-CoV-2 antibody response in CYP with (n=99) and without (n=18) long COVID at three months following acute infection. Our findings indicate that pediatric long COVID is associated with a dysregulated immune response characterized by altered innate immunity and overactivated T-, B- and NK-cell responses. Furthermore, CYP with long COVID had an impaired humoral response to SARS-CoV-2 marked by a dysregulated B-cell compartment and lower levels of anti-RBD IgG and IgA. This correlated with reduced neutralizing capacity against SARS-CoV-2. Random forest analysis identified CCR6 expression on myeloid cells as the most relevant biomarker that distinguishes long COVID from control individuals with 79% accuracy.

◆Longitudinal and socio-demographic trends in Long COVID and associated activity limitations: Results from the New York City Community Health Survey 2021 – 2023【medRxiv　2025年8月24日】

Abstract

Introduction In this study we describe the longitudinal and socio-demographic trends of Long COVID among adults in New York City using data from a large, population-based annual health survey.

Methods Data from the 2021-2023 Community Health Survey included self-report long-term health effects of COVID-19. Survey-weighted prevalence of lifetime Long COVID (2021-2023), current Long COVID (2022-2023), and current Long COVID with activity limitations (2022-2023) were estimated by year and socio-demographic characteristics among the general adult population and among adults with prior COVID-19. Statistical significance was assessed at the p < 0.05 level. Results The prevalence of lifetime Long COVID increased in the general population during the study period (5.9% -14.3%, p < 0.001) but decreased as a share of adults with prior COVID-19 (34.6% - 26.3%, p < 0.001). In 2023 the population prevalence of current Long COVID was 11.6% and prevalence of related activity limitations was 7.6%, an increase from prior years affecting an estimated 501,000 - 766,000 New Yorkers. Inequities were observed by race/ethnicity, gender, education, and household poverty, and were more pronounced among adults with confirmed or suspected prior COVID-19. Discussion By 2023, 1 in 7 adults in New York City had experienced long-term health effects of COVID-19, half of whom reported current activity limitations. The prevalence and impact of Long COVID present an ongoing and important public health concern, especially given the disproportionate burden among people of color, cisgender women, transgender adults, and individuals with lower socio-economic status.

◆SARS-CoV-2 infection drives local inflammation of the intestinal epithelium in immunocompromised patients with cancer【Cell : iScience　2025年8月25日】

SUMMARY

Cancer patients undergoing transplantation-based treatments can develop graft-versus-host disease (GVHD), an inflammatory condition that increases mortality risk. In this study, we analyzed three cancer patients with severe inflammatory disorders following SARS-CoV-2 infection using high-resolution microscopy and spatial transcriptomics on pre- and post-infection GI biopsies. We found that up to 49 days after infection, the duodenal epithelium retained COVID viral elements, showed increased expression of viral receptors, inflammatory genes, and interferon activity, and exhibited tissue scarring. Notably, SERPINA1 was a persistent marker of infection and inflammation, also present in ∼600 GI tumor samples, suggesting its role as a broader inflammation marker. These findings indicate that the GI epithelium can serve as a long-term COVID reservoir, potentially driving inflammatory syndromes similar to GVHD. This persistent viral presence may pose additional risks for cancer patients undergoing transplantation, highlighting the need for further investigation into post-COVID inflammatory complications in cancer patients.

◆The numbers that suggest a new Covid wave is already gripping the UK【THE i PAPER：Tom Bawden　2025年8月25日】

Ever since the highly contagious Stratus Covid variant starting spreading rapidly in the UK in April, scientists have feared a new wave.

But while Stratus has spread rapidly to become the country’s dominant Covid variant, the overall infection rate did not take off as predicted – which is not to say there wasn’t a clear increase in numbers, just a much smaller one than many had feared.

This is because, to a large extent, the Stratus variant – formally known as XFG – was supplanting the other variants (keeping overall Covid cases more or less steady when they may overwise have fallen), rather than sending them soaring.

The latest data from the UK Health Security Agency (UKHSA) suggests that may be changing and that a long-anticipated “summer” wave could finally be upon us.

The data shows that the proportion of hospital patients with respiratory symptoms testing positive for Covid jumped by 22 per cent in just over a week, from 7.2 per cent on 6 August to 8.8 per cent on Friday 15 August.

In less than three weeks, the increase in positive hospitals tests had risen to 44 per cent by 15 August.

As such, the figure (known as the positivity rate) is now four times as high as it was in early January. However, it is still less than half what it was at last year’s peak, in July.

With children set to go back to school – in many cases after international travel, which can turbocharge virus circulation – there are fears that the recent rises could continue and we could find ourselves in a new wave – a period of increased transmission of the virus – if we are not already in it.

Cooling weather will add further pressure as people spend more time indoors, often in poorly-ventilated rooms.

It is important to stress that, because the numbers are based on hospital patients with respiratory symptoms, the resulting Covid positivity rate is much higher than for the public as a whole.

But in the absence of population wide surveillance, which does not happen in the summer, the UKHSA statistics are the best indicator of trends that we have, scientists say.

“Test positivity rates, while not directly estimating the number of Covid infections in the general population, can be a valuable indicator of the infection trend,” says Bob Hawkins, a data scientist who works with Independent Sage.

His analysis has shown that the UKHSA positivity data and winter surveillance data for the general public show similar trends – indicating that the positivity rate is a reliable, if rough, sign to what is happening more widely.

Scientists say waning immunity from vaccines and previous infections is a key reason for the recent rise in infections.

At the same time, the XFG variant is more contagious than the other variants and may be better at evading vaccines designed for earlier variants (although the latest version of the vaccine is still considered to offer good protection – especially against serious illness).

Against this backdrop, there are some concerns that the Government’s decision to offer the autumn booster to 13 million fewer people this year including pregnant women and heart disease patients, could push up cases further.

The decision is based on expert advice from the Joint Committee on Vaccination and Immunisation (JCVI) which continuously monitors and evaluates emerging scientific evidence on Covid vaccines but, there are plenty of scientists who think it is a bad idea.

So if we are not already in the grip of a new Covid wave, the data for the last few weeks combined with waning immunity, “back to school” traffic and cooling weather strongly suggests we may soon be.