SARS-CoV-2 と COVID-19 に関する備忘録 Vol.63

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SARS-CoV-2 と COVID-19 に関するメモ・備忘録

◆Devastating symptoms of long Covid compared to degenerative disease by new study【INDEPENDENT：Vishwam Sankaran　2025年8月26日】

Some patients struggling with long Covid experience long-term fatigue, brain fog, breathlessness and a heavily-reduced quality of life similar to levels seen in Parkinson’s or stroke survivors, researchers find in a new study.

Most people who suffer a Covid-19 infection experience a short illness with a cold, sore throat, or cough and fever for a few days before they get better and fully recover.

However, several who have overcome the novel coronavirus still suffer a myriad of symptoms related to the virus infection in what’s being termed long Covid by the World Health Organisation.

While previous research has established these long Covid symptoms as mainly including fatigue, brain fog and breathlessness, the exact effect of the long-term condition on the daily life of survivors remains unclear.

Now, a new study, published in the Australian Journal of Primary Health, confirms that long Covid isn’t just an inconvenient condition to live with, but it also profoundly limits the daily life of patients.

In the research, scientists assessed 121 adults who contracted Covid-19 sometime between 2020 and mid-2022, and fit the WHO’s description of a long Covid patient in late 2022.

Researchers surveyed participants about their level of disability and functions they had on a daily basis, along with their perceived quality of life.

Participants completed two surveys widely used to measure disability and quality of life: the WHO Disability Assessment Schedule and the Short Form Health Survey.

Researchers found that long Covid is linked to a stark reduction in quality of life, and the ability to do basic life tasks compared to levels seen in the general population.

About 86 per cent of the participants reported “clinically significant disability and participation limitations in daily activities”, scientists wrote.

“Months or years later, they were still struggling with daily activities they once took for granted,” they wrote in The Conversation.

This cohort of 121 individuals with long Covid had “higher levels of disability than 98 per cent of the general population”, according to the study.

“The overall impact may be exacerbated in people with pre-existing comorbidities who are more susceptible to long COVID in the first place,” scientists warned.

Researchers call for stronger efforts to support long Covid patients, prioritising management of their fatigue and getting them to a position where they can perform important daily activities.

“The findings underscore the need for targeted rehabilitation and support services for people living in Australia with long Covid, and further longitudinal research to explore the long-term impact on disability and quality of life, and inform policy and healthcare service delivery,” they wrote.

◆Neurocognitive trajectories in long COVID: Evidence from longitudinal analyses【ScienceDirect　2025年8月19日】

Abstract

Background

Patients frequently report symptoms of cognitive impairment or “brain fog” after acute COVID-19 infection, but the trajectory of these symptoms over time has yet to be determined. We assessed cognitive function over a 42-month period after acute SARS-CoV-2 infection and identified factors associated with the trajectory of cognitive function over this period.

Methods

We analyzed data from participants in the Mount Sinai Health System Post-COVID-19 Registry in New York City, a prospective cohort study of adults followed after acute SARS-CoV-2 infection of any severity. Participants were identified from a list of all patients with COVID-19 who received care at an MSHS facility in New York, recruited beginning April 2020 and followed through January 2024. Cognition was assessed using well-validated in-person measures of attention, working memory, processing speed, executive functioning, language, and memory. We used linear mixed models to investigate the relationships between cognitive scores and time. We also assessed factors (including race, ethnicity, site of acute COVID-19 care, fatigue, depression, anxiety, body mass index, medical comorbidities, and COVID-19 vaccination) that may influence changes in cognitive scores over time.

Findings

We analyzed data from 1553 participants (median age 53 years, 63 % female, 17 % Black, 21 % Hispanic). In adjusted analyses, scores from cognitive measures of attention, working memory, processing speed, executive functions, and verbal learning and memory improved progressively through 42 months post-COVID. However, despite the improvements, on average, measures of processing speed and executive functioning remained ≥1 standard deviation below the normative mean. Having a body mass index of <25 kg/m2 was predictive of a greater improvement in cognitive scores. Interpretation

While cognitive impairment occurring after COVID-19 improved over time in most domains, processing speed and executive functioning remained below the normal range. The cognitive health burden of Long COVID is therefore significant and lasting. Future studies should examine interventions to support rapid recovery, as well as dynamic risk prediction models to determine factors that may impact cognitive recovery longer term.

◆Subdomains of Post-COVID Syndrome (PCS) – a population-based study【BMC Infectious Diseases　2025年8月26日】

Abstract

Purpose

‘Post-COVID Syndrome’ (PCS), which encompasses the multifaceted sequelae of COVID-19, can be severity-graded by a previously defined score encompassing 12 different long-term symptom complexes. The PCS score was shown to have two main predictors, namely acute COVID-19 severity and individual resilience. The purpose of the present study was to verify these predictors and to assess their detailed relationship to the symptom complexes constituting the PCS score.

Methods

The study drew upon a largely expanded dataset (n = 3,372) from COVIDOM, the cohort study underlying the original PCS score definition. Classification and Regression Tree (CART) analysis served to resolve the detailed relationship between the predictors and the constituting symptom complexes of the PCS score.

Results

Among newly recruited COVIDOM participants (n = 1,930), the PCS score was again found to be associated with both its putative predictors. Of the score-constituting symptom complexes, neurological symptoms, sleep disturbance, and fatigue were predicted by individual resilience whereas the acute disease severity predicted exercise intolerance, chemosensory deficits, joint or muscle pain, signs of infection, and fatigue. These associations inspired the definition of two novel PCS scores that included the above-mentioned subsets of symptom complexes only. Similar to the original PCS score, both novel scores were found to be inversely correlated with quality of life as measured by the EQ-5D-5L index.

Conclusion

The two newly defined PCS scores may enable a more refined assessment of PCS severity, both in a research context and to delineate distinct PCS subdomains with possibly different therapeutic and interventional needs in clinical practise.

◆Years lived with disability may signal long-COVID risk, global researchers say【University of Minnrsota : CIDRAP : Mary Van Beusekom　2025年8月28日】

Years lived with disability (YLDs) may be an early indicator of long-COVID risk, especially in low-resource communities where persistent symptoms are underreported, per data collected from the height of the pandemic.

For the global analysis, published in Med Research, an international group of researchers used the Global Burden of Disease (GBD) 2021 framework to further analyze 2020-21 data that they published in 2024 on long-COVID’s direct burden.

This study looked at YLDs in 920 locations as a potential signal of future higher risk of long-COVID in 2022 and 2023. The team also assessed patterns of inequality to identify vulnerable groups.

“Among the six key health burden metrics used in the GBD framework, including incidence, prevalence, mortality, DALYs [disability-adjusted life-years], years lived with disability (YLDs), and years of life lost (YLLs), YLDs may be more appropriate for assessing the burden of long COVID, as they are specifically designed to capture nonfatal health losses by accounting for both the prevalence and severity of symptoms,” the study authors wrote.

Even wealthy countries had inequalities

Age-standardized YLD rates were higher in low- and middle-income countries (LMICs)—especially in Sub-Saharan Africa and in regions in South Asia and Eastern Europe where long-COVID research has been sparse. Those nations also lack a strong healthcare system that would enable efficient diagnosis, reporting, and long-COVID management. Examples of such countries include Mozambique, Malawi, Ethiopia, and Iraq.

Of the 10 countries with the highest age-standardized YLD rates in 2021, 80% were in the low, low-middle, and middle Socio-demographic Index categories.

Many higher-income countries had lower overall YLD rates but still had large inequalities in certain areas. For example, long-COVID risk varied widely by US state, with rural and other underserved areas having higher YLD rates. This pattern suggests that national averages may obscure important local vulnerabilities, the researchers said.

“Even within high-income nations, we saw dramatic differences between communities,” co–first author Dan Shan, an independent researcher, said in a news release from Far Publishing Ltd. “The effects of long COVID are not equally distributed, and without granular data, certain subgroups may be overlooked in policy decisions.”

Women aged 20 years and older bore a significantly greater long-COVID burden than men, which the authors said aligns with trends seen in previous studies.

Systemic vulnerabilities, entrenched health disparities

“These high age-standardized YLD rates may point to systemic vulnerabilities and entrenched structural health disparities, indicating a potential for considerable and enduring long COVID burden that could persist to the present day in the absence of targeted interventions,” the researchers wrote.

The findings highlight that while both advantaged and disadvantaged populations in LMICs need attention, the most disadvantaged groups warrant special attention owing to their severe resource constraints and limited ability to build resilience, they added.

“We found that many communities, especially in low-resource settings, were already experiencing a disproportionately high burden of prolonged symptoms,” Shan said. “Without intervention, this might translate into years of long COVID consequences that go largely untracked.”

The researchers called for urgent expansion of long-COVID care, particularly in lower-resource settings, and for the integration of disability data into early-warning systems. They also urged global health agencies to prioritize vulnerable groups for rehabilitation services, research funding, and surveillance infrastructure. “Ignoring these warning signs risks deepening global health inequalities for years to come,” Shan said.

◆12-Lipoxygenase (12-LOX) Plays a Key Role in Hyperinflammatory Response Caused by SARS-CoV-2【bioRxiv　2025年8月28日】

Abstract

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to significant global morbidity and mortality. The severe disease outcomes are often linked to a hyperinflammatory response known as a “cytokine storm.” The underlying mechanisms responsible for this exaggerated immune response remain incompletely understood. This study aimed to investigate the molecular pathways contributing to the severe inflammatory damage and mortality associated with COVID-19. SARS-CoV-2 hijacks host lipid metabolism, particularly the phospholipase A2 (PLA2) pathway, which leads to the production of the bioactive molecules, including the 12-Lipoxygenase (12-LOX)-derived lipid mediators in platelets, as well as in lung and vascular cells. We hypothesized that 12-LOX drives the hyperinflammatory response and disease severity, and that its inhibition could reduce inflammation and improve outcomes. Analysis of autopsy lung samples from COVID-19 decedents and SARS-CoV-2-infected K18-hACE2 transgenic mice revealed increased 12-LOX expression. We evaluated VLX-1005, a selective small-molecule 12-LOX inhibitor, in infected mice. Treatment initiated 48 hours post-infection significantly improved survival, reduced body weight loss, and decreased lung inflammation compared to controls. Notably, male mice showed higher survival rates than females. VLX-1005 treatment also suppressed key chemokines and cytokines associated with the cytokine storm, and reduced lung damage. These findings identify 12-LOX as a critical mediator of the hyperinflammatory response in severe COVID-19 and support its inhibition as a promising therapeutic strategy to mitigate inflammatory damage and reduce mortality.

Significance This study provides critical insights into the mechanisms underlying severe COVID-19, identifying 12-Lipoxygenase (12-LOX) as a key driver of the hyperinflammatory response that contributes to disease severity and mortality. By demonstrating that SARS-CoV-2 hijacks host lipid metabolism to elevate pro-inflammatory lipid mediators, the research uncovers a novel pathogenic pathway that exacerbates lung inflammation. The use of VLX-1005, a selective 12-LOX inhibitor, significantly improved survival and reduced inflammatory damage in a mouse model, highlighting its therapeutic potential. These findings not only deepen our understanding of COVID-19 pathogenesis but also position 12-LOX as a promising target for intervention, offering a new avenue for mitigating the effects of cytokine storms in severe cases.

◆Long COVID-19: a Four-Year prospective cohort study of risk factors, recovery, and quality of life【BMC Infectious Diseases　2025年8月30日】

Abstract

Purpose
Long COVID-19 is a growing public health concern, but its long-term burden and predictors remain underexplored, particularly in underrepresented populations.

Methods
This four-year prospective cohort study was conducted in Saudi Arabia, enrolling adults with confirmed acute COVID-19 from multiple affiliated healthcare centers between March 2020 and March 2024. Of 1,521 screened patients, 816 were enrolled and followed for up to four years (median: 24 months). Per WHO criteria, participants were classified as having long COVID-19 (n = 238) or resolved infection (n = 578). Demographics, comorbidities, vaccination, reinfection, and acute illness severity were recorded. Health-related quality of life (HRQoL) was assessed using SF-36 and EQ-5D-5 L. Logistic regression identified predictors of long COVID-19, and Cox proportional hazards models evaluated time to recovery.

Results
Fatigue (57.1%), post-exertional malaise (45.8%), cough (41.2%), and cognitive dysfunction (30.7%) were the most common persistent symptoms. Female sex (adjusted OR 11.11; 95% CI: 4.48–26.24) and diabetes mellitus (adjusted OR 14.3; 95% CI: 7.0–29.4) independently predicted long COVID-19. Delayed recovery was associated with female sex (aHR 3.36; 95% CI: 1.85–6.10), diabetes (aHR 1.57; 95% CI: 1.00–2.46), reinfection (aHR 1.86; 95% CI: 1.05–3.29), and hospitalization (aHR 1.08; 95% CI: 1.01–1.16). HRQoL scores remained significantly lower at 6 and 12 months. In the long COVID-19 group, 38.7% of patients normally resumed work within 12 months, compared to 82.3% in the resolved COVID-19 group.

Conclusions
Nearly 29% of post-acute COVID-19 patients developed long COVID-19 in this Middle Eastern cohort. Female sex, diabetes, reinfection, and hospitalization predicted delayed recovery. Persistent symptoms and impaired HRQoL highlight the need for early risk stratification and structured post-COVID care.

◆SARS-CoV-2 nucleocapsid induces hyperinflammation and vascular leakage through the Toll-like receptor signaling axis in macrophages【bioRxiv　2025年8月28日】

SUMMARY

Tens of thousands of severe COVID-19 cases are hospitalized weekly in the U.S., often driven by an imbalance between antiviral responses and inflammatory signaling, leading to uncontrolled cytokine secretion. The SARS-CoV-2 nucleocapsid (N) protein is a known immune antagonist, but its role in macrophage-driven cytokine storms is unclear. We demonstrate that N functions in a pathway-specific manner, specifically amplifying nuclear factor κB-related transcripts upon Toll-like receptor 7/8 stimulation. Moreover, we show that this is a conserved feature of pathogenic coronaviruses, with the delta variant N being the most pro-inflammatory. Our interaction networks suggest the delta variant N drives inflammation through interactions with several stress granule-related proteins. Profiling of secreted cytokines revealed that supernatants from the delta variant N-expressing macrophages disrupt brain and heart endothelial barriers, implicating N in COVID-19-associated cognitive and cardiac complications. Our findings highlight N-mediated immune imbalance as a driver of severe COVID-19 and identify N as a promising therapeutic target to mitigate hyperinflammation.

◆Age-Related Changes in the Clinical Picture of Long COVID【American Geriatrics Society　2025年9月1日】

Abstract

Background

This study evaluated the impact of aging on the frequency and prevalent symptoms of Long COVID, also termed post-acute sequelae of SARS-CoV-2, using a previously developed Long COVID research index (LCRI) of 41 self-reported symptoms in which those with 12 or more points were classified as likely to have Long COVID.

Methods

We analyzed community-dwelling participants ≥ 60 years old (2662 with prior infection, 461 controls) compared to participants 18–59 years (7549 infected, 728 controls) in the Researching COVID to Enhance Recovery adult (RECOVER-Adult) cohort ≥ 135 days post-onset.

Results

Compared to the Age 18–39 group, the adjusted odds of LCRI ≥ 12 were higher for the Age 40–49 group (odds ratio [OR] = 1.40, 95% confidence intervals [CI] = 1.21–1.61, p < 0.001) and 50–59 group (OR = 1.31, CI = 1.14–1.51, p < 0.001), similar for the Age 60–69 group (OR = 1.09, CI = 0.93–1.27, p = 0.299), and lower for the ≥ 70 group (OR = 0.68, CI = 0.54–0.85, p < 0.001). Participants ≥ 70 years had smaller adjusted differences between infected and uninfected symptom prevalence rates than those aged 18–39 for the following symptoms: hearing loss, fatigue, pain (including joint, back, chest pain and headache), post-exertional malaise, sleep disturbance, hair loss, palpitations, and sexual desire/capacity, making these symptoms less discriminating for Long COVID in older adults than in younger. Symptom clustering, as described in Thaweethai et al. (JAMA 2023) also exhibited age-related shifts: clusters 1 (anosmia and ageusia) and 2 (gastrointestinal, chronic cough and palpitations, without anosmia, ageusia or brain fog) were more likely, and clusters 3 (brain fog, but no loss of smell or taste) and 4 (a mix of symptoms) less likely to be found in older adults (relative risk ratios for clusters 3–4 ranging from 0.10–0.34, p < 0.001 vs. 18–39 year-olds). Conclusions

Within the limits of this observational study, we conclude that in community-dwelling older adults, aging alters the prevalence and pattern of reported Long COVID.

◆Characterization of Postural Orthostatic Tachycardia Syndrome in Long COVID: Self-reported Data From the LISTEN Study【JACC Journals　2025年8月27日】

Abstract

Background

Postural orthostatic tachycardia syndrome (POTS) has emerged as a significant cardiovascular phenotype among individuals experiencing postacute COVID-19 syndrome, commonly referred to as long COVID.
Objectives
The purpose of this study was to describe the experience of people reporting long COVID-associated POTS.

Methods

We collected data from individuals aged ≥18 years with self-reported long COVID who participated in the Yale Listen to Immune, Symptom and Treatment Experiences Now (LISTEN) cohort, an online observational study. The study included participants surveyed from May 2022 to July 2023. POTS status was determined by self-reported diagnosis of POTS. We compared the demographics, symptoms, associated conditions, and health status of people with and without self-reported POTS.

Results

Of the 578 individuals included, 167 (28.9%) reported new-onset POTS and 411 (71.1%) did not report POTS as one of their long COVID-associated conditions. Seventy-eight percent of participants with self-reported POTS were women (range, 18-74 years). Participants with self-reported POTS were younger, had more financial difficulties, more social isolation, more suicidal thoughts, worse health status measured by the EuroQoL visual analog scale, and reported higher rates of rapid heart rate after standing up, dizziness, palpitations, persistent chest pain, sudden chest pain, excessive fatigue, exercise intolerance, heat intolerance, brain fog, tinnitus, migraine, internal tremors, skin discoloration, and dry eyes, as well as new-onset myalgic encephalomyelitis/chronic fatigue syndrome and mast cell disorders.

Conclusions

Individuals with self-reported long COVID-associated POTS experienced substantial health burdens in various domains compared with those without self-reported POTS, highlighting the urgency for further research to understand the mechanism, characterize the physiological derangements, and target treatments so we can help these individuals.

◆Characterization of Postural Orthostatic Tachycardia Syndrome in Long COVID: Self-reported Data From the LISTEN Study【JACC Journals　2025年8月27日】

Abstract

Long COVID (LC) includes persistent behavioral and cognitive deficits, impacting quality of life. Neuroinflammation plays a key role in these alterations, with genetic factors influencing susceptibility. The MnSOD Val16Ala SNP is associated with neuroinflammation and cognitive dysfunction, but its role in LC remains unclear. This study investigated the relationship between the SOD2 Val16Ala polymorphism and neurocognitive alterations in young adults post-SARS-CoV-2 infection. Neurocognitive performance was assessed using the Neupsilin test in individuals with and without prior COVID-19. Blood samples were collected for the quantification of cytokines (IL-1, IL-6, TNF-α, and IFN-γ) and for the genotyping of the SOD2 Val16Ala polymorphism. The COVID-19 group showed worse cognitive performance and higher cytokine levels than controls, particularly in memory and executive function. Val allele carriers (Val/Ala and Val/Val) exhibited increased pro-inflammatory cytokine levels compared to Ala/Ala carriers. These findings suggest a potential interaction between genetic susceptibility and inflammatory response in post-COVID neurocognitive alterations. Young adults post-COVID-19 presented an exacerbated neuroinflammatory response, likely influencing cognition. The presence of the Val allele was associated with greater susceptibility to inflammatory events, suggesting a genetic component in LC-related neurological dysfunction. These results reinforce the role of neuroinflammation in LC and highlight the importance of genetic factors in determining cognitive outcomes. Understanding these mechanisms may help identify individuals at higher risk and support future therapeutic strategies.

◆Rise in COVID cases has one CA leader recommending masks【SAN：Dan Levin, Lauren Keenan　2025年9月4日】

A rise in COVID-19 cases and hospitalizations in California has prompted at least one state leader to recommend that people wear masks indoors. The state currently has high coronavirus levels in sewage, according to the CDC.

COVID in wastewater

Wastewater surveillance is a tool used by public health officials to track the presence of viruses like coronavirus.

“Wastewater has been a great breakthrough for us in public health surveillance since the start of the pandemic,” Matt Willis, former Marin County health officer, told Straight Arrow News. “It’s really the best way to see how active the virus is in a given community.”

That tool has shown a recent increase in the virus.

“Overall wastewater concentrations of SARS-CoV-2 are currently increasing, and it is not yet clear when wastewater activity will peak this summer,” the California Department of Public Health said in a statement to Straight Arrow News.

California is one of 21 states with “high” or “very high” levels of coronavirus in wastewater. However, it has still not reached the same levels as the last couple of summers when the virus usually peaks.

“Current wastewater concentrations are about 20 percent lower than peak concentrations during the 2023 summer wave (which peaked in late August), and current concentrations are about 50 percent lower than peak concentrations during the 2024 summer wave (which peaked in early August),” the department said.

The department also told SAN they’re continually seeing an increase in the latest variant known as XFG or “Stratus,” which is now the “dominant variant.”

This variant is the latest in a string of variants since the pandemic.

“It’s important for us to have the ability to do the molecular testing to diagnose new variants when they emerge, in case those actually are more variant, meaning that they might cause more severe illness or more transmissible, meaning more people would get infected,” Willis said. “But for the general public, I’m not seeing a lot of reason why people need to be too concerned about one variant or the next.”

The highest levels of coronavirus in wastewater can be found in the West and the South.

COVID cases rising

The same can be said for the number of COVID-19 cases, with the CDC saying California’s epidemic trend is “likely growing.”

For the week ending Aug. 23, 12% of COVID-19 tests in California came back positive. That’s up from 6% just one month earlier.

“COVID-19 looks like it’s not just seasonal,” Willis said. “It’s actually twice a year. And if you look back at the last like three years, there’s pretty clear waves in the summertime and in the wintertime, which is different than, say, like RSV or influenza virus, which are clearly winter seasonal viruses where it’s incredibly quiet and flat during the summertime.”

Some of the state’s largest cities in counties saw similar rates of increase, with Los Angeles County’s positive test rate up nearly 6%, Orange County up 9% and San Francisco up 2% over a recent four-week period.

Meanwhile, hospital admissions in California from coronavirus remain low but have increased in recent weeks.

The CDPH shows 3.6 COVID-19 hospital admissions per 100,000 people for the week ending Aug. 23. That’s up 0.5 from the week before.

The number of deaths from the virus remains very low.

“It’s important to see this in perspective,” Willis said. “We’ve obviously come a long way since 2020. Even in my community, in Marin County where I was health officer, we were seeing dozens of deaths every month. It’s been a while since we’ve seen any in our community. At the same time, we’re still seeing people coming into the hospital. We’re still seeing emergency room visits increasing for our youngest residents, so it’s still a threat to us.”

Mask request

While the numbers are nowhere close to pandemic levels, some public officials have called on people to once again wear masks indoors.

Officials in Yolo County, which includes part of Sacramento, want people to take extra precautions to prevent transmission.

“California is experiencing a summer COVID wave,” Dr. Aimee Sisson, Yolo County Health Officer, said in a statement. “Based on current wastewater levels of the virus that causes COVID-19, I recommend that everybody in West Sacramento wear a mask when they are around others in indoor public spaces. I also recommend that people in the rest of Yolo County wear masks when they are around others indoors if they are 65 or older, have a weakened immune system, have an underlying medical condition that puts them at a greater risk of severe COVID-19, or spend time around people who fall into these categories.”

Masks became very politicized during the pandemic, and Willis said wearing one is a personal choice, but science is science.

“The fact is that as a tool, a mask is an effective way of preventing infection, period,” Willis said.

COVID vaccination

The county’s Health and Human Services Agency also recommends vaccination as the most effective way to prevent severe disease and death.

“High vaccination rates translate to lower mortality at the community level, and for an individual, it’s the same,” Willis said. “If you’re vaccinated, you’re much less likely to end up in a hospital and that’s just been proven over and over again. That is not a political statement. That is just a scientific reality.”

This all comes at a time when federal health officials continue to voice their opposition to Health and Human Services Secretary Robert F. Kennedy and his views on vaccinations.

“I think it’s very concerning and discouraging that somehow someone who is a vaccine skeptic was able to find his way to the highest position of power in our science infrastructure nationally,” Willis said.

◆Latent Transition Analysis for Longitudinal Studies of Post-Acute Infection Syndromes: A Multinational Investigation of Post-COVID-19 Condition【medRxiv　2025年9月2日】

Abstract

Post-Acute Infectious Syndromes (PAISs) refer to the symptoms persisting for months after an initial infection. PAISs are multi-systemic conditions, and thus clinical research studies often collect rich, multi-modal datasets – including demographic information, patients’ comorbidities, acute-phase presentation, and observations over extended periods that can include clinical data, patient-reported outcomes (PROMs) or experimental data. Yet, the complexity of the datasets and lack of the precise clinical case definition pose difficulties in comprehensive and meaningful analyses of such datasets. Studies on Post-COVID-19 condition (PCC) represent the most prominent example of this challenge.

In this work, we outline a flexible and interpretable framework for modelling and analysing data from longitudinal studies of PAIS using Latent Transition Analysis (LTA). The framework enables the identification of distinct disease phenotypes and the patient-level analysis of transitions between them, without relying on predefined clinical categorisations. Furthermore, we introduce a method for incorporating covariate information, which enables exploration of how patient characteristics influence disease trajectories.

We apply this methodology to the ORCHESTRA dataset, composed of individuals affected by SARS-CoV-2 infection from multiple European centres. Longitudinal data were collected at SARS-CoV-2 infection, and at 6, 12, 18, and 24 months of follow-up from patients in France, Italy, Spain, and the Netherlands. In total, 5,094 patients were clinically assessed, reporting symptoms and quality-of-life information. Our model identifies distinct PCC phenotypes and uncovers complex transition patterns among them. We found that advanced age and pre-existing chronic respiratory conditions significantly increased the likelihood of transitioning to more severe PCC states in later timepoints. Conversely, male sex and exposure to later SARS-CoV-2 variants were associated with a higher probability of complete recovery.

Our study highlights how LTA can enhance the interpretability of complex, time-resolved clinical data, support personalized patient monitoring and management, and accelerate therapeutic development — not only for PCC but also for other PAISs in both pandemic and inter-pandemic settings.

◆Wearable-derived Sleep Measurements are Associated with Long-COVID in the RECOVER Adult Cohort【Research Square　2025年9月2日】

Abstract

Wearables yield a wide array of sleep-related measures that are relevant to Long COVID. We leveraged wearables-derived sleep measures (WDSM) to identify differences between individuals with Long COVID (LC) versus individuals with possible or no LC in the RECOVER adult cohort. We found significant associations between LC and reduced heart rate variability measured during sleep and increased nightly variability in sleep duration after adjusting for confounders. Moreover, LC was independently associated with lower sleep efficiency, greater variability of nighttime sleep timing, higher resting heart rate, lower respiratory rate during rapid eye movement (REM) sleep, prolonged REM sleep onset latency, worse global physical and mental health. Cluster analysis identified distinct multidimensional patterns of WDSM that are associated with LC and quality of life. Together, the strong association between WDSM, or WDSM clusters, with LC provides a potential biomarker for future validation efforts to detect LC and monitor treatment effectiveness.

◆Long COVID and the kidney【nature reviews nephrology　2025年9月4日】

Abstract

Long coronavirus disease (COVID) — commonly defined as symptoms and/or long-term effects that persist for at least 3 months after acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and cannot be explained by an alternative diagnosis — is a complex, multifaceted and heterogeneous disease that affects many organ systems, including the kidney. COVID-19 can cause acute kidney injury, and several studies have reported an increased risk of chronic kidney disease (CKD) following COVID-19, suggesting that CKD can be a manifestation of long COVID. Furthermore, patients with CKD are at an increased risk of severe COVID-19 and of long COVID. COVID-19 has also been associated with the development of COVID-19-associated nephropathy, which is a collapsing form of focal segmental glomerulosclerosis, and an increased incidence of new-onset vasculitis. Some early reports described associations of COVID-19 and/or SARS-CoV-2 vaccines with relapse or new-onset of other glomerular diseases, but this link was not confirmed in large population-based studies. SARS-CoV-2 vaccination reduces the risk of COVID-19 and long COVID and is particularly important for protecting vulnerable populations such as patients with CKD. Structured long-term follow-up of patients with COVID-19 and post-infectious sequelae is needed to provide further insight into the trajectory of long COVID and enable identification of those at risk of CKD.

◆Respiratory viral infections prime accelerated lung cancer growth【bioRxiv　2025年9月3日】

SUMMARY

The COVID-19 pandemic has highlighted long-term health concerns of viral pneumonia, yet its potential impact on cancer development and growth remains poorly understood. Here, we demonstrate that prior infection with SARS-CoV-2 or influenza virus promoted lung tumor progression by reprogramming the local immune landscape. Retrospective clinical analysis revealed that patients hospitalized with COVID-19 exhibited increased lung cancer incidence. Using multiple murine lung cancer models, we show that prior severe respiratory viral infections accelerated tumor growth and reduced survival. Mechanistically, prior viral pneumonia epigenetically remodeled the lung to establish a pro-tumor microenvironment, including the local accumulation of SiglecFhi tumor-associated neutrophils, a transcriptionally reprogrammed, immunosuppressive population whose signature predicted poor prognosis in human lung adenocarcinoma. In parallel, epithelial compartments exhibited altered differentiation trajectories, with persistence of injury-associated alveolar intermediates positioned along tumorigenic lineages. We observe sustained chromatin remodeling at key cytokine loci in immune and structure cells, linking inflammatory memory to persistent immune suppression. Therapeutically, combined inhibition of neutrophil recruitment via CXCR2 and PD-L1 signaling restored CD8⁺ T cell infiltration and suppressed tumor growth. Together, our findings establish a direct causal relationship between viral pneumonia, including COVID-19, and lung tumorigenesis, highlighting the urgent need to monitor survivors for elevated cancer risk and to develop targeted interventions and therapies aimed at preventing potential cancer bursts in COVID-19 convalescents.

◆Post-COVID syndrome in symptomatic COVID-19 patients: a retrospective cohort study【BMC Infectious Diseases　2025年9月3日】

Abstract

Background

Although post-COVID symptoms have been documented in the literature, the risk factors and time required for full recovery remain unclear. We conducted a retrospective analysis of medical records of COVID-19 patients to investigate the prevalence of symptoms after an acute episode of COVID-19 and the risk factors for persistence of symptoms.

Methods

This retrospective cohort study analysis examined hospital records of post-COVID individuals with previously confirmed or probable SARS-CoV-2 infection and endurring symptom continuation for at least 3 months post-infection or presenting new symptoms persisting for at least 2 months. Follow-up was conducted during at least six months to access longer-term outcomes. The majority of patients received specialized examination and at least two medical examinations. Descriptive and logistic regression analysis was applied to determine the prevalence and risk factors for post-COVID syndrom.

Result

The mean age of the 319 patients was 47.74 ± 11.61 years, and 225 (70.1%) were female. Of the 250/319 patients for whom information on acute infection was available; fever (60.8%), smell disorder (60.8%), asthenia (60.4%) and headache (59.2%) were the most frequent symptoms. The most frequent persisting symptoms were neurological (84.6%), asthenia (80.9%) and cardiac-respiratory symptoms (67.4%). About 80–81% patients reported symptom improvement at six to twelve months of follow-up. Being male and having fever or taste disorders during the acute phase of COVID-19 were independent risk factors for the persistence of long COVID symptoms.

Conclusion

These results could possibly serve to identify patients at a higher risk for the persistence of long COVID symptoms and target them for reinforced therapeutic measures.