SARS-CoV-2 と COVID-19 に関する備忘録 Vol.45

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SARS-CoV-2 と COVID-19 に関するメモ・備忘録

◆Kidney Function Following COVID-19 in Children and Adolescents【JAMA Network　2025年4月11日】

Abstract

Importance It remains unclear whether children and adolescents with SARS-CoV-2 infection are at heightened risk for long-term kidney complications.

Objective To investigate whether SARS-CoV-2 infection is associated with an increased risk of postacute kidney outcomes among pediatric patients, including those with preexisting kidney disease or acute kidney injury (AKI).

Design, Setting, and Participants This retrospective cohort study used data from 19 health institutions in the National Institutes of Health Researching COVID to Enhance Recovery (RECOVER) initiative from March 1, 2020, to May 1, 2023 (follow-up ≤2 years completed December 1, 2024; index date cutoff, December 1, 2022). Participants included children and adolescents (aged <21 years) with at least 1 baseline visit (24 months to 7 days before the index date) and at least 1 follow-up visit (28 to 179 days after the index date). Exposures SARS-CoV-2 infection, determined by positive laboratory test results (polymerase chain reaction, antigen, or serologic) or relevant clinical diagnoses. A comparison group included children with documented negative test results and no history of SARS-CoV-2 infection.

Main Outcomes and Measures Outcomes included new-onset chronic kidney disease (CKD) stage 2 or higher or CKD stage 3 or higher among those without preexisting CKD; composite kidney events (≥50% decline in estimated glomerular filtration rate [eGFR], eGFR ≤15 mL/min/1.73 m2, dialysis, transplant, or end-stage kidney disease diagnosis), and at least 30%, 40%, or 50% eGFR decline among those with preexisting CKD or acute-phase AKI. Hazard ratios (HRs) were estimated using Cox proportional hazards regression models with propensity score stratification.

Results Among 1 900 146 pediatric patients (487 378 with and 1 412 768 without COVID-19), 969 937 (51.0%) were male, the mean (SD) age was 8.2 (6.2) years, and a range of comorbidities was represented. SARS-CoV-2 infection was associated with higher risk of new-onset CKD stage 2 or higher (HR, 1.17; 95% CI, 1.12-1.22) and CKD stage 3 or higher (HR, 1.35; 95% CI, 1.13-1.62). In those with preexisting CKD, COVID-19 was associated with an increased risk of composite kidney events (HR, 1.15; 95% CI, 1.04-1.27) at 28 to 179 days. Children with acute-phase AKI had elevated HRs (1.29; 95% CI, 1.21-1.38) at 90 to 179 days for composite outcomes.

Conclusions and Relevance In this large US cohort study of children and adolescents, SARS-CoV-2 infection was associated with a higher risk of adverse postacute kidney outcomes, particularly among those with preexisting CKD or AKI, suggesting the need for vigilant long-term monitoring.

◆The influence of SARS-CoV-2 spike protein exposure on retinal development in the human retinal organoids【BMC Cell & Bioscience　2025年4月11日】

Abstract

Background

Pregnant women are considered a high-risk population for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as the virus can infect the placenta and embryos. Recently, SARS-CoV-2 has been widely reported to cause retinal pathological changes and to infect the embryonic retina. The infection of host cells by SARS-CoV-2 is primarily mediated through spike (S) protein, which also plays a crucial role in the pathogenesis of SARS-CoV-2. However, it remains poorly understood how the S protein of SARS-CoV-2 affects retinal development, and the underlying mechanism has not yet been clarified.

Methods

We used human embryonic stem cell-derived retinal organoids (hEROs) as a model to study the effect of S protein exposure at different stages of retinal development. hEROs were treated with 2 μg/mL of S protein on days 90 and 280. Immunofluorescence staining, RNA sequencing, and RT-PCR were performed to assess the influence of S protein exposure on retinal development at both early and late stages.

Results

The results showed that ACE2 and TMPRSS2, the receptors facilitating SARS-CoV-2 entry into host cells, were expressed in hEROs. Exposure to the S protein induced an inflammatory response in both the early and late stages of retinal development in the hEROs. Additionally, RNA sequencing indicated that early exposure of the S protein to hEROs affected nuclear components and lipid metabolism, while late-stages exposure resulted in changes to cell membrane components and the extracellular matrix.

Conclusion

This work highlights the differential effects of SARS-CoV-2 S protein exposure on retinal development at both early and late stages, providing insights into the cellular and molecular mechanisms underlying SARS-CoV-2-induced developmental impairments in the human retina.

◆Risk of celiac disease, type 1 diabetes, and thyroid disease autoimmunity during the SARS-CoV-2 pandemic in South of Sweden: insights from the TRIAD study【Taylor & Francis Online　2025年4月15日】

Abstract

Recent studies have implied an increased incidence of autoimmune diseases following the SARS-CoV-2 pandemic. The objective was to determine if SARS-CoV-2 infections were associated with celiac disease (CD), type 1 diabetes (T1D), and autoimmune thyroid disease (AITD) autoantibodies in a population-based screening when the pandemic hit the South of Sweden during 2021 and 2022. Between August 2021 and June 2022 self-obtained capillary plasma samples were collected from 1088 children at 6–9 years of age and 1185 adolescents at 13–16 years of age, who were randomly invited from the general population to a screening for CD, T1D, AITD, and SARS-CoV-2 antibodies. Among children and adolescents screened for autoantibodies associated with CD, T1D and AITD, the SARS-CoV-2 infection rate was increased in tissue transglutaminase autoantibody (tTGA) positive (13/17; 76.5%) compared with tTGA negative (492/1168; 42.1%) 13–16-year-old individuals (p = 0.0057). There was no association between SARS-CoV-2 infection rate and AITD- or T1D autoantibodies. Our findings indicate a potential association between prior SARS-CoV-2 infection and screening-detected CD autoimmunity in adolescents aged 13–16 years. Further research is needed to elucidate whether ongoing CD autoimmunity increases susceptibility to infection or if SARS-CoV-2 may act as a trigger for CD autoimmunity in genetically and environmentally predisposed individuals.

◆Leading long COVID researcher fears it could become a national epidemic【SPECTRUM NEWS NY1 : Eric Feldman　2025年4月16日】

A leader in Mount Sinai Health System’s efforts to learn more about long COVID fears it could become a national epidemic.

Dr. David Putrino is in charge of rehabilitation innovation at Mount Sinai Health System, and that includes a groundbreaking $10 million clinic that focuses on diagnosing and researching treatments for long COVID.

“We’re not taking any steps to reduce the risks of a nationwide epidemic,” he said in an interview with NY1, saying he is alarmed by the latest data on people diagnosed with long COVID and the lack of awareness of what seems to be happening.

Long COVID is defined as having symptoms from COVID-19 at least three months after being diagnosed. For some people, the symptoms can last much longer, with far more serious consequences.

Symptoms for each person differ, in a list that is 200 long. The latest data from the Centers for Disease Control and Prevention shows that 5% of the population currently has long COVID. And for a quarter of them, it’s debilitating.

“I’m really concerned about the overall effect this is going to have on national health when we’re not following the science,” he said.

Because even though we are out of the pandemic, the risks of long COVID remain.

“Your risk of going on to develop long COVID increases slightly with each infection, even if you recover just fine from the last infection,” he said.

And he has seen this firsthand.

At the Cohen Center for Recovery from Complex Chronic Illness, Putrino and his team see a couple new patients every day that go through a series of tests to see if they have the illness.

And the numbers are only going up — and the waiting list growing longer. Right now, it’s a six-month wait to get seen.

It’s part of their $10 million clinic, as Mount Sinai has become one of the places people turn to from around the country to learn more about long COVID.

“A lot of patients try to see us from California,” he said. “It’s very hard for us to see out-of-state patients.”

Many times, he said patients arrive after seeing other doctors.

“They go to the doctor, they test and they get told good news, everything tested normal, which is not good news for someone who is feeling as terrible as most people with long COVID feel,” he said.

One of those people was Nicole Lopez-Jantzen, who used to run marathons, and now can barely walk her dog.

“I’m tired right now,” she said on a walk with NY1 just across the street from her apartment in Queens. “My energy just goes down, down. And then I have to go lie down.”

Doctors couldn’t figure out what was wrong until she was seen at Mount Sinai and diagnosed with long COVID in 2022.

From neurological to respiratory, her symptoms run the gamut.

That is the purpose of the testing they perform at Mount Sinai. One is a tilt table that will measure a patient’s blood pressure, sweat levels and heart rate in real time as the table moves.

“Seventy percent of people with long COVID have something called autonomic dysfunction, meaning that we have a part of our nervous system, this is the part of your nervous system that controls all the things you don’t usually think about that’s under autonomous control,” he said. “Your blood pressure, your heart rate, whether you’re feeling hot or cold, digesting your food, you don’t need to think about these functions, your body just does these functions for you.”

The goal in the series of tests is to test patients as much as possible to identify what is wrong.

“Many of the things that we’re measuring with this technology are very dynamic so some days you can be perfectly fine and other days it can be really challenging to do anything related to your daily life and it’s tests like this that really push the limits of someone’s body’s abilities that allows us to identify objectively when something is going wrong so we can identify the problem,” Putrino said.

There’s another test called the Bod Pod that looks like a space capsule. It is a three-minute test to simply see how healthy patients’ blood vessels are while resting.

Someone with long COVID will feel overexerted just from sitting.

“What we saw in people with long COVID is they were burning 20, 30 percent more energy than someone that we would expect for their height, weight, gender and age,” he said. “So even though we were asking them to sit very still and not use any energy at all, their bodies were working really, really hard to maintain that.”

Diagnosing long COVID is one challenge. But getting people actually tested — and getting people educated about the illness — is another one.

Putrino said Mount Sinai was conducting a study on long COVID where they were looking to compare impacts on people with long COVID to those who did not suffer long-term consequences from the virus.

However, Putrino said it was apparent very quickly that there was a problem when his team spoke with the 200 respondents.

He said about a quarter of them described symptoms that could be consistent with long COVID.

“So you know they’d say, ‘Yeah, I fully recovered.’ Then we’d ask questions about their cognition, and they would say, ‘Oh, you know I do find it harder to do my job these days,'” Putrino said. “‘You know I do feel my memory is a little different since I had COVID, but I don’t think I have long COVID. I just think my memory is a bit different.'”

He said all those people had to be removed from the study, but whether they got tested? Ultimately, he cannot know.

That falls in line with an ongoing long COVID survey being taken by the New York City Department of Health and Mental Hygiene.

In exclusive data obtained by NY1, preliminary results from the survey of about 9,000 New Yorkers shows that 31% of respondents who have long-lasting symptoms believe they have long COVID. However, only 6% have been officially diagnosed.

The city is still collecting the survey data, which was announced in January 2024.

The early data raises questions about how much access there is for people who are potentially looking to get tested for long COVID, said Dr. Michelle Morse, the interim commissioner of health at the city DOH.

“It means some of those folks may not have had access to health care or maybe didn’t feel comfortable bringing up their symptoms with their provider,” she said. “This highlights a huge challenge across the city and across the nation. Access to health care.”

She said it could also mean that doctors are not diagnosing long COVID, which is something Nicole Lopez-Jantzen told NY1 was her experience and Putrino said he has heard from his patients at Mount Sinai.

The average age of Mount Sinai’s long COVID patients is 38, which Putrino said shows the illness affects young people.

The city data also points to people with lower socioeconomic status — and people of color — also being at higher risk for developing long COVID.

That would match trends already established about who were more susceptible to catching the virus. Morse does not believe that is a coincidence.

“One of the reasons we think that may be the case that more people of color and more people who are low wealth may have symptoms of long COVID is because they did have a higher burden of COVID during the pandemic,” she said. “So knowing that that trend was also the case with more folks of color and more people of low income were affected by COVID and infected by COVID, then it stands to reason that perhaps more of them may have long COVID symptoms.”

The city survey is federally funded, but Morse said that money has not been pulled, despite reports of cuts throughout the federal government.

Putrino said Mount Sinai’s clinic does not have any federal funding, but has heard about others around the country losing federal dollars. He said that’s one of the reasons why it’s so crucial they continue their work into finding treatments.

Right now, there are none for long COVID. Mount Sinai is currently conducting multiple trials.

One is a headset that has shown promising signs in animal testing to reduce brain inflammation, according to Putrino.

The headset provides magnetic therapy at a rate 100,000 times less than an MRI scan. A researcher demonstrating the device told NY1 that she couldn’t feel anything happening even as the device was turned on.

Brain inflammation can cause indecisiveness and memory loss, both symptoms of long COVID.

Participants take part for 15 minutes two times a week for a month. They underwent cognitive testing before the trial, and will do so again after it’s complete. Half of the participants are getting the treatment, and half are not.

Putrino said the study of several dozen participants will be complete over the summer.

The challenge is that this is for one set of symptoms. And many others remain, as the work to understand long COVID continues.

◆Sex and other predictors of mortality in long-term follow-up of patients with cardiovascular disease and COVID-19: a single-center retrospective study【nature : scientific reports　2025年4月17日】

Abstract

Male sex is a well-known predictor of short-term prognosis in patients with coronavirus disease (COVID-19). Data, however, on long-term outcomes are scarce. We aimed to assess the differences in mortality between sexes and find other important predictors of survival from a long-term perspective. Data from all patients retrieved from a database of COVID-19 patients hospitalized at University Hospital in Krakow, Poland, between February 13, 2020, and May 10, 2021, were analyzed for clinical in-hospital data and after a 42 months follow-up period. Of the 4071 COVID-19 patients hospitalized, 2183 were men (53.6%). Males were on average younger and more likely to have concomitant chronic obstructive pulmonary disease, heart failure, coronary artery disease (including acute and chronic coronary syndrome) compared to women. In terms of laboratory findings, more advanced inflammatory markers and troponin I were predominantly observed in male patients than in female patients. Males were found to have a greater predisposition for relevant cardiovascular comorbidities and were more likely to have died during the 42 months follow-up. Additionally, higher levels of troponin I, N-terminal pro B-type natriuretic peptide and D-dimer were associated with a greater risk of death. Kaplan–Meier survival analyses revealed a worse 42 months survival for men up to the age of 65 years. Cardiovascular comorbidities, male sex and older age, as well as higher concentrations of markers indicating a thrombotic state and myocardial injury, were associated with poorer long-term prognosis in patients with COVID-19.

◆Studies across 14 nations show 25% to 30% rate of long COVID【University of Minnesota CIDRAP　2025年4月18日】

A new study in BMJ Global Health across 13 middle- and high-income countries reveals that 25% of patients reported symptoms of long COVID after symptomatic COVID-19, and long COVID is significantly more prevalent in participants from less wealthy nations and in patients of Arab or North African ethnicity.

A second study published in BMC Public Health showed that, among 3,693 COVID-19 patients in China, 30.2% reported at least one persistent long-COVID symptom, and 10.7% noted symptoms affecting daily life.

Higher rate in those of Arab/North African ethnicity

The first study involved 6,528 adult patients with symptomatic COVID-19 in Argentina, Brazil, Canada, Colombia, Ecuador, Egypt, India, Nepal, Pakistan, Philippines, Russia, Saudi Arabia, South Africa, and the United Arab Emirates.

Long COVID was defined as the presence of patient-reported symptoms 180 days after COVID-19, the authors said.

Among the 25.1% of participants who said they experienced long-COVID symptoms, 12.8% reported sleeping disorders, 9.8% reported joint pain, 8.7% had fatigue, and 8.1% noted headaches. Almost a third of participants (29.8%) from lower middle-income countries said they had long COVID, compared with 14.4% in high-income countries (adjusted odds ratio [aOR] 1.53; 95% confidence interval [CI], 1.10 to 2.14).

The highest long-COVID prevalence was seen in patients with Arab/North African ethnicity (36.1%), and hospitalized patient were also at increased risk of long COVID (aOR, 2.04; 95% CI, 1.63 to 2.54).

“Our results thus suggest that the burden to health and healthcare-related costs may fall disproportionately on countries with the least capacity to carry them, and most frequently affect individuals that may be under-represented in clinical trials of interventions aimed to combat long COVID,” the authors wrote.

Older age, re-infection tied to higher risk

In the second study, people with COVID-19 were asked to complete a survey on symptoms 180 days after infection in March 2023 through June 2023.

Older age, female sex, and COVID re-infection were all associated with increased risk for self-reported long COVID. Reported use of Chinese medicine and more than three vaccine doses were protective factors.

◆Anti-nucleocapsid and anti-spike antibody trajectories in people with post-covid condition versus acute-only infections: a nested longitudinal case-control study within the Virus Watch prospective cohort【nature communications　2025年4月17日】

Abstract

People with Post-Covid Condition (PCC) may demonstrate aberrant immune responses post-infection; however, serological follow-up studies are limited. We aim to compare SARS-CoV-2 serological responses to infection and vaccination in people who develop PCC versus those with an acute infection only. Participants (n = 2010) are a sub-cohort of the Virus Watch community cohort in England who provided monthly finger-prick serological samples. We compare the likelihood of post-infection seroconversion using logistic mixed models and the trajectories of anti-nucleocapsid (anti-N) and anti-spike (anti-S) antibodies using linear mixed models. Participants who developed PCC (n = 394) have 1.8x the odds of post-infection seroconversion for anti-N antibodies compared to those with an acute infection only (n = 1616) (odds ratio= 1.81 (95% confidence interval (CI) 1.16-2.90); however, these results are moderated by vaccination status and variant – with differences observed in pre-Omicron, unvaccinated participants. Anti-N levels, however, were elevated within 200 days post-infection in people with PCC compared to those without, after accounting for variant and vaccination status. Vaccination response (anti-S) pre- or post-infection did not systematically differ between groups. People with PCC demonstrate persistently higher anti-N antibody levels following primary infection compared to those with an acute infection only. These findings extend emerging evidence around infection-related immune activation and PCC.

◆Comparison of the association between COVID-19 and new onset diabetes in a regional and national dataset【ScienceDirect　2025年4月17日】

Abstract

Aims

This study examined new onset diabetes following COVID-19 infection in large datasets.

Methods

A retrospective cohort study design was used in three distinct databases: data from a large academic medical center (University of Kentucky Healthcare, UKHC), claims data from privately insured patients in the Merative MarketScan (MarketScan) database, and a subset of the MarketScan database with lab tests. Control groups included patients from the prepandemic timeframe (prepandemic cohort), as well as COVID-era patients without documented COVID infection (COVID − cohort).

Results

Incident diabetes in COVID infected patients was higher in all datasets. In the UKHC and MarketScan datasets, the adjusted Hazard ratios (HR) were 3.46 and 2.13 in UKHC and MarketScan. Incident diabetes was elevated even in patients who were treated in the outpatient setting and much higher in patients who were treated in the inpatient setting, especially those who required inpatient interventions. In MarketScan, the HR for developing type 1 diabetes was 1.61.

Conclusions

Persons infected with COVID-19 during the initial 18 months of the pandemic demonstrated a higher incidence of new onset diabetes, which was evident in all populations. Diabetes incidence was especially high in an academic center population with higher health disparities, and in patients with a more severe infection with the virus.

◆Long COVID clinical evaluation, research and impact on society: a global expert consensus【SPRINGER NATURE　2025年4月20日】

Abstract

Background

Long COVID is a complex, heterogeneous syndrome affecting over four hundred million people globally. There are few recommendations, and no formal training exists for medical professionals to assist with clinical evaluation and management of patients with Long COVID. More research into the pathology, cellular, and molecular mechanisms of Long COVID, and treatments is needed. The goal of this work is to disseminate essential information about Long COVID and recommendations about definition, diagnosis, treatment, research and social issues to physicians, researchers, and policy makers to address this escalating global health crisis.

Methods

A 3-round modified Delphi consensus methodology was distributed internationally to 179 healthcare professionals, researchers, and persons with lived experience of Long COVID in 28 countries. Statements were combined into specific areas: definition, diagnosis, treatment, research, and society.

Results

The survey resulted in 187 comprehensive statements reaching consensus with the strongest areas being diagnosis and clinical assessment, and general research. We establish conditions for diagnosis of different subgroups within the Long COVID umbrella. Clear consensus was reached that the impacts of COVID-19 infection on children should be a research priority, and additionally on the need to determine the effects of Long COVID on societies and economies. The consensus on COVID and Long COVID is that it affects the nervous system and other organs and is not likely to be observed with initial symptoms. We note, biomarkers are critically needed to address these issues.

Conclusions

This work forms initial guidance to address the spectrum of Long COVID as a disease and reinforces the need for translational research and large-scale treatment trials for treatment protocols.

◆Persistent immune dysregulation and metabolic alterations following SARS-CoV-2 infection【medRxiv　2025年4月17日】

Abstract

SARS-CoV-2 can cause a variety of post-acute sequelae including Long COVID19 (LC), a complex, multisystem disease characterized by a broad range of symptoms including fatigue, cognitive impairment, and post-exertional malaise. The pathogenesis of LC is incompletely understood. In this study, we performed comprehensive cellular and transcriptional immunometabolic profiling within a cohort that included SARS-CoV-2-naïve controls (NC, N=30) and individuals with prior COVID-19 (∼4-months) who fully recovered (RC, N=38) or went on to experience Long COVID symptoms (N=58). Compared to the naïve controls, those with prior COVID-19 demonstrated profound metabolic and immune alterations at the proteomic, cellular, and epigenetic level. Specifically, there was an enrichment in immature monocytes with sustained inflammasome activation and oxidative stress, elevated arachidonic acid levels, decreased tryptophan, and variation in the frequency and phenotype of peripheral T-cells. Those with LC had increased CD8 T-cell senescence and a distinct transcriptional profile within CD4 and CD8 T-cells and monocytes by single cell RNA sequencing. Our findings support a profound and persistent immunometabolic dysfunction that follows SARS-CoV-2 which may form the pathophysiologic substrate for LC. Our findings suggest that trials of therapeutics that help restore immune and metabolic homeostasis may be warranted to prevent, reduce, or resolve LC symptoms.

◆Measuring the fitted filtration efficiency of cloth masks, medical masks and respirators【PLOS One　2025年4月21日】

Abstract

Importance

Masks reduce transmission of SARS-CoV2 and other respiratory pathogens. Comparative studies of the fitted filtration efficiency of different types of masks are scarce.

Objective

To describe the fitted filtration efficiency against small aerosols (0.02–1 µm) of medical and non-medical masks and respirators when worn, and how this is affected by user modifications (hacks) and by overmasking with a cloth mask.

Design

We tested a 2-layer woven-cotton cloth mask of a consensus design, ASTM-certified level 1 and level 3 masks, a non-certified mask, KF94s, KN95s, an N95 and a CaN99.

Setting

Closed rooms with ambient particles supplemented by salt particles.

Participants

12 total participants; 21–55 years, 68% female, 77% white, NIOSH 1–10.

Main Outcome and Measure

Using standard methods and a PortaCount 8038, we counted 0.02–1 µm particles inside and outside masks and respirators, expressing results as the percentage filtered by each mask. We also studied level 1 and level 3 masks with earguards, scrub caps, the knot-and-tuck method, and the effects of braces or overmasking with a cloth mask.

Results

Filtration efficiency for the cloth mask was 47–55%, for level 1 masks 52–60%, for level 3 masks 60–77%. A non-certified KN95 look-alike, two KF94s, and three KN95s filtered 57–77%, and the N95 and CaN99 97–98% without fit testing. External braces and overmasking with a well-fitting cloth mask increased filtration, but earguards, scrub caps, and the knot-and-tuck method did not.

◆Dynamic brain glymphatic changes and cognitive function in COVID-19 recovered patients: a DTI-ALPS prospective cohort study【Frontiers in Psychology　2025年4月22日】

Abstract

Objective: This study aimed to evaluate brain glymphatic function in COVID-19 recovered patients using the non-invasive Diffusion Tensor Imaging-Analysis Along the Perivascular Space (DTI-ALPS) technique. The DTI-ALPS technique was employed to investigate changes in brain glymphatic function in these patients and explore correlations with cognitive function and fatigue.

Materials and methods: Follow-up assessments were conducted at 1, 3, and 12 months post-recovery. A total of 31 patients completed follow-ups at all three time points, with 30 healthy controls (HCs) for comparison.

Results: Compared to HCs, COVID-19 recovered patients showed a significant decline in MoCA scores at 3 months post-recovery (p < 0.05), which returned to near-normal levels by 12 months. Mental fatigue, measured by the Fatigue Assessment Scale (FAS), was significantly higher in COVID-19 patients at all follow-up points compared to HCs (p < 0.05). The DTI-ALPS index in both hemispheres showed significant differences at 3 months post-recovery compared to HCs (p < 0.001), indicating increased glymphatic activity. Longitudinal analysis revealed a peak in the DTI-ALPS index at 3 months post-recovery, which then decreased by 12 months. Correlation analysis showed a significant negative correlation between the Bilateral brain hemisphere DTI-ALPS index and MoCA scores (right side: r = −0.373, p = 0.003; left side: r = −0.255, p = 0.047), and a positive correlation with mental fatigue (right side: r = 0.275, p = 0.032; left side: r = 0.317, p = 0.013). Conclusion: This study demonstrates dynamic changes in brain glymphatic function in COVID-19 recovered patients, with a peak in activity at 3 months post-recovery. These changes are associated with cognitive function and mental fatigue, suggesting potential targets for addressing neurological symptoms of long COVID. The non-invasive DTI-ALPS technique proves to be a valuable tool for assessing brain glymphatic function in this population.

◆Impact of pre-existing comorbidities and multimorbidities, demography and viral variants on post-acute sequelae of COVID-19 (‘Long COVID’) in Dutch primary care: A retrospective cohort study【International Journal of Infectious Dideases　2025年4月19日】

Abstract

Introduction

Post-acute sequelae of COVID-19 (PASC), or Long COVID, involves persistent symptoms following acute infection, posing a global health challenge. While a growing number of studies have investigated potential predictors and risk factors, uncertainties remain regarding their consistency and clinical applicability. This study investigates PASC prevalence, comorbidities, demographics and viral variants using Dutch primary care electronic healthcare records (EHR).

Methods

A retrospective cohort study used EHR data from 59 general practices in the Northern Netherlands, including 19,638 SARS-CoV-2 PCR-positive patients from January 1, 2020, to December 31, 2021. PASC was identified via World Health Organization and CDC guidelines, a Dutch Word2Vec model, and clinical assessments. Relative risk (RR) calculations analysed comorbidities, demographics and viral variants.

Results

PASC prevalence was 5.8% (95% CI: 5.4-6.1%). Comorbidities significantly increasing PASC risk included lung disease (RR: 1.95), cardiovascular disease (RR: 1.73), diabetes (RR: 1.82), kidney disease (RR: 1.98) and mental illness (RR: 1.29). Females and individuals aged ≥45 had increased risk. Multivariate regression revealed higher odds of prolonged PASC for ages 45-59 (adjusted odds ratios [AOR]: 3.02), 60-74 (AOR: 3.25) and 75+ (AOR: 2.44). Combined mental illness and lung disease further increased risk (AOR: 2.55).

Conclusion

Chronic conditions, multimorbidity and demographics significantly influence PASC onset and duration. Targeted interventions may mitigate its long-term impact.

◆Cardiovascular post-acute sequelae of SARS-CoV-2 in children and adolescents: cohort study using electronic health records【nature communications　2025年4月11日】

Abstract

The risk of cardiovascular outcomes following SARS-CoV-2 infection has been reported in adults, but evidence in children and adolescents is limited. This paper assessed the risk of a multitude of cardiac signs, symptoms, and conditions 28-179 days after infection, with outcomes stratified by the presence of congenital heart defects (CHDs), using electronic health records (EHR) data from 19 children’s hospitals and health institutions from the United States within the RECOVER consortium between March 2020 and September 2023. The cohort included 297,920 SARS-CoV-2-positive individuals and 915,402 SARS-CoV-2-negative controls. Every individual had at least a six-month follow-up after cohort entry. Here we show that children and adolescents with prior SARS-CoV-2 infection are at a statistically significant increased risk of various cardiovascular outcomes, including hypertension, ventricular arrhythmias, myocarditis, heart failure, cardiomyopathy, cardiac arrest, thromboembolism, chest pain, and palpitations, compared to uninfected controls. These findings were consistent among patients with and without CHDs. Awareness of the heightened risk of cardiovascular disorders after SARS-CoV-2 infection can lead to timely referrals, diagnostic evaluations, and management to mitigate long-term cardiovascular complications in children and adolescents.

◆Decoding post-mortem infection dynamics of SARS-CoV-2, IAV and RSV: New insights for public health and emerging infectious diseases management【Journal of Infectious　2025年4月21日】

Summary

Objectives

The persistence and infectivity of respiratory viruses in cadavers remain poorly characterized, posing significant biosafety risks for forensic and healthcare professionals. This study systematically evaluates the post-mortem stability and transmission potential of SARS-CoV-2, influenza A virus (IAV), and respiratory syncytial virus (RSV) under varying environmental conditions, providing critical insights into viral kinetics.

Methods

To assess the post-mortem stability of SARS-CoV-2, tissue samples were collected from infected cadavers at 4 ℃, room temperature (RT, 20–22 ℃), and 37 ℃ over a predetermined timeframe. Viral kinetics were analyzed using quantitative assays, while histopathology and immunohistochemistry characterized tissue-specific distribution. Additionally, comparative analyses were conducted both in vitro and in cadaveric tissues to characterize the survival dynamics of IAV and RSV under identical conditions.

Results

SARS-CoV-2 exhibited prolonged post-mortem infectivity, persisting for up to 5 days at RT and 37 ℃ and over 7 days at 4 ℃, with the highest risk of transmission occurring within the first 72 h at RT and 24 h at 37 ℃. In contrast, RSV remained viable for 1–2 days, while IAV persisted for only a few hours post-mortem. Viral decay rates were temperature-dependent and varied across tissues, demonstrating distinct post-mortem survival kinetics.

Conclusions

This study presents the first comprehensive analysis of viral persistence in cadavers, revealing prolonged SARS-CoV-2 stability compared to IAV and RSV. These findings underscore the need for enhanced post-mortem biosafety protocols to mitigate occupational exposure risks in forensic and clinical settings. By elucidating viral decay dynamics across environmental conditions, this research establishes a critical foundation for infection control strategies, informing biosafety policies for emerging respiratory pathogens.

◆Global prevalence of long COVID and its most common symptoms among healthcare workers: a systematic review and meta-analysis【BMJ Public Health　2025年4月17日】

Abstract

Objectives Long COVID, a condition where symptoms persist after the acute phase of COVID-19, is a significant concern for healthcare workers (HCWs) due to their higher risk of infection. However, there is limited knowledge regarding the prevalence, symptoms and clustering of long COVID in HCWs. We aimed to estimate the pooled prevalence and identify the most common symptoms of long COVID among HCWs who were infected with SARS-CoV-2 virus globally, and investigate any differences by geographical region and other factors.

Design Systematic review and meta-analysis (PROSPERO CRD42022312781).

Data sources We searched MEDLINE, CINAHL, EMBASE, PsycINFO and the grey literature from 31 December 2019 until 18 February 2022.

Eligibility criteria We included studies reporting primary data on long COVID prevalence and symptoms in adult HCWs who had SARS-CoV-2 infection.

Data extraction and synthesis Methodological quality was assessed using the Joanna Briggs Institute checklist. Meta-analysis was performed for prevalence data of long COVID following SARS-CoV-2 infection.

Results Out of 5737 articles, 28 met the inclusion criteria, with a combined sample size of 6 481 HCWs. 15 articles scored equal to or above the median score for methodological quality. The pooled prevalence of long COVID among HCWs who had SARS-CoV-2 infection was 40% (95% CI: 29% to 51%, I2: 97.2%; 12 studies), with a mean follow-up period of 22 weeks. The most prevalent symptoms reported were fatigue (35%), neurologic symptoms (25%), loss/decrease of smell and/or taste (25%), myalgia (22%) and shortness of breath (19%).

Conclusion This review highlights the substantial burden of long COVID among HCWs worldwide. However, limitations in data quality and inconsistent definitions of long COVID impact the generalisability of these findings. To improve future interventions, we recommend enhanced cohort study designs for better characterisation of long COVID prevalence and symptoms in HCWs.

◆Neurotoxic Implications of Human Coronaviruses in Neurodegenerative Diseases: A Perspective from Amyloid Aggregation【ACS Chemical Biology　2025年4月24日】

Abstract

Human coronaviruses (HCoVs) include seven species: HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, MERS-CoV, SARS-CoV-1, and SARS-CoV-2. The last three, classified as Betacoronaviruses, are highly transmissible and have caused severe pandemics. HCoV infections primarily affect the respiratory system, leading to symptoms such as dry cough, fever, and breath shortness, which can progress to acute respiratory failure and death. Beyond respiratory effects, increasing evidence links HCoVs to neurological dysfunction. However, distinguishing direct neural complications from preexisting disorders, particularly in the elderly, remains challenging. This study examines the association between HCoVs and neurodegenerative diseases like Alzheimer disease, Parkinson disease, Lewy body dementia, amyotrophic lateral sclerosis, and Creutzfeldt-Jakob disease. It also presents the long-term neurological effects of HCoV infections and their differential impact across age groups and sexes. A key aspect of this study is the investigation of the sequence and structural similarities between amyloidogenic and HCoV spike proteins, which can provide insights into potential neuropathomechanisms.

◆Long-term clinical outcome and exercise capacity in SARS-CoV-2-positive elite athletes【SPRINGER NATURE　2025年2月21日】

Abstract

Aims

This study aimed to explore the epidemiological circumstances, long-term clinical outcomes, and perceived impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on elite athletes’ sports performance. A secondary objective was to determine the sports-specific (contact vs. noncontact) prevalence of SARS-CoV‑2 among 65 SARS-CoV-2-positive athletes from the Olympic Training Center Rhineland (OSP; n = 599).

Methods

In all, 65 SARS-CoV-2-positive athletes from the German Olympic Training Center (OSP; 66% males—age: 23 ± 4 years; 34% females—age: 23 ± 5 years) participated in the panel study. Data collection occurred between June 2020 and October 2021 at two test times (t0: after a negative polymerase chain reaction [PCR] test, t1: 16 weeks after t0) through questionnaires and clinical assessments.

Results

The SARS-CoV‑2 prevalence was nearly identical in noncontact and contact-sport athletes (10.8% vs. 11.3%); 37% experienced symptoms lasting > 4 weeks. Over 50% of athletes paused their training for 4–8 weeks. At t1, 40% still experienced reduced perceived performance capacity (PPC) compared to their pre-COVID-19 level, while 64% reported ongoing limitations in sports participation, with mental and physical fatigue as the most prominent limiting factor, followed by shortness of breath and joint and muscle pain.

Conclusion

The long-term management of SARS-CoV-2-positive elite athletes should involve a comprehensive, multidimensional psychophysiological approach to address persistent sport-restricting symptoms. This approach will assist in developing tailored training protocols that allow a gradual increase in intensity and volume.