SARS-CoV-2 と COVID-19 に関する備忘録 Vol.50

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SARS-CoV-2 と COVID-19 に関するメモ・備忘録

◆Intravenous SARS-CoV-2 Spike protein induces neuroinflammation and alpha-Synuclein accumulation in brain regions relevant to Parkinson’s disease【ScienceDirect　2025年5月20日】

Abstract

Background: Coronavirus disease 2019 (COVID-19) frequently presents with neurological symptoms in human patients and leads to long-lasting brain pathology in a hamster model. There is no overt SARS-CoV-2 virus replication in central neurons. Whether viral proteins are sufficient to cause this pathology requires further investigations. The SARS-CoV-2 Spike-protein S1-subunit (S1-protein) has recently gained interest for causing neuroinflammation and accelerating aggregation of alpha-Synuclein (aSyn) in vitro. Here, we show the impact of S1-protein in a broad spectrum of brain regions after injection via three different application routes in C57/BL6 mice. Methods: S1-protein was administered either intranasally, intravenously or intracerebrally. We quantified aSyn immunoreactivity and phosphorylated aSyn (pS129), microglia and astrocyte reactivity, ACE2/Neuropilin-1 receptor expression, and parvalbumin-positive interneurons in limbic system, basal ganglia, and cortical regions 14 days post-application. Plasma cytokine profiles were assessed 6 days post-injection. Results: While intracerebral injection resulted in decreased aSyn immunoreactivity with increased pS129 in males, intravenous injection led to increased levels of aSyn immunoreactivity and microglia cell density, predominantly in brain regions associated with Parkinson’s disease pathology. Intranasal application of S1-protein induced microgliosis in some brain regions but resulted in sex-dependent alterations of aSyn levels, with increases in females and decreases in males. All routes showed sex-dependent alterations in astrocytic reactivity, receptor expression, and parvalbumin-positive interneurons. Conclusion: Our results demonstrate that S1-protein itself leads to neuroinflammation, altered aSyn homeostasis, and disruption of inhibitory circuits in a route- and sex-dependent manner. These findings indicate the possibility of S1-protein being a crucial agent for both neuroinflammatory processes and altered protein regulation mechanisms. S1-protein trapped in tissue reservoirs could therefore explain symptoms occurring or persisting beyond viral clearance (Post COVID-19 condition).

◆Long-COVID in children and their parents: A prospective cohort study【WILEY Online Library　2025年5月12日】

Abstract

Background

Long-COVID is a significant global health concern, regardless of age. However, few reports have longitudinally evaluated the characteristics, prevalence, and risk factors of long-COVID in children.

Methods

Participants were Japanese children younger than 18 years hospitalized for COVID-19 between November 2021 and October 2022, along with their COVID-19 affected parents. During hospitalization and at 1-, 3-, and 6-month follow-ups, participants completed age-appropriate questionnaires on long-COVID symptoms. The quality of life (QOL) score was assessed in children older than 2 years. The prevalence of long-COVID symptoms by age group was compared. Multivariable logistic regression analysis was conducted to investigate risk factors affecting long-COVID. Analysis of covariance adjusted for potential confounders was conducted to determine which symptoms affect QOL score.

Results

Of 108 children enrolled, the prevalence of long-COVID was 44.9%, 37.8%, and 22.8% at 1, 3, and 6 months, respectively, after SARS-CoV-2 infection. There were no specific risk factors for long-COVID. Cough, fatigue, and sleep disturbance were the most common long-COVID symptoms, with sleep disturbance associated with a change in lower QOL score from admission at all three follow-ups (mean difference 9.25, 20.15, and 19.81; 95% CI, 1.58–16.91, 3.38–36.92, and 5.51–34.11). The prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) symptoms among 0–6 years was significantly lower than among 7–17 years and parents; there was no significant difference between 7 and 17 years and parents.

Conclusion

Even 6 months after SARS-CoV-2 infection, 22.8% of pediatric patients still had long-COVID symptoms. Some of these symptoms were similar to those of ME/CFS, potentially affecting children’s QOL.

◆Characterizing Long COVID Symptoms During Early Childhood【JAMA Pediatrics　2025年5月27日】

Abstract

Importance Recent studies have identified characteristic symptom patterns of long COVID (LC) in adults and children older than 5 years. However, LC remains poorly characterized in early childhood. This knowledge gap limits efforts to identify, care for, and prevent LC in this vulnerable population.

Objectives To identify symptoms that had the greatest difference in frequency comparing children with a history of SARS-CoV-2 infection to those without, to identify differences in the types of symptoms by age group (infants/toddlers [0-2 years] vs preschool-aged children [3-5 years]), and to derive an index that can be used in research studies to identify young children with LC.

Design, Setting, and Participants This was a multisite longitudinal cohort study with enrollment from over 30 US health care and community settings, including infants, toddlers, and preschool-aged children with and without SARS-CoV-2 infection history. Study data were analyzed from May to December 2024.

Exposure SARS-CoV-2 infection.

Main Outcomes and Measures LC and 41 symptoms among infants/toddlers and 75 symptoms among preschool-aged children.

Results The study included 472 infants/toddlers (mean [SD] age, 12 [9] months; 278 infected with SARS-CoV-2; 194 uninfected; 234 male [50%]; 73 Black or African American [16%]; 198 Hispanic, Latino, or Spanish [43%]; 242 White [52%]) and 539 preschool-aged children (mean [SD] age, 48 [10] months; 399 infected with SARS-CoV-2; 140 uninfected; 277 female [51%]; 70 Black or African American [13%]; 210 Hispanic, Latino, or Spanish [39%]; 287 White [54%]). The median (IQR) time between first infections and completion of symptom surveys was 318 (198-494) days for infants/toddlers and 520 (330-844) days for preschool-aged children. A research index was derived for each age group based on symptoms most associated with infection history. The index is calculated by summing scores assigned to each prolonged symptom that was present, where higher scores indicate greater magnitude of association with history of SARS-CoV-2 infection: poor appetite (5 points), trouble sleeping (3.5 points), wet cough (3.5 points), dry cough (3 points), and stuffy nose (0.5 points) for infants/toddlers, and daytime tiredness/sleepiness/low energy (6.5 points) and dry cough (3 points) for preschool-aged children. Among infants/toddlers with infection, 40 of 278 (14%) were classified as having probable LC by having an index of at least 4 points. Among preschool-aged children, 61 of 399 (15%) were classified as having probable LC by having an index of at least 3 points. Participants with higher indices often had poorer overall health, lower quality of life, and perceived delays in developmental milestones.

Conclusions and Relevance This cohort study identified symptom patterns and derived research indices that were distinct between the 2 age groups and differed from those previously identified in older ages, demonstrating the need to characterize LC separately across age ranges.

◆Spatial transcriptomics of the epipharynx in long COVID identifies SARS-CoV-2 signalling pathways and the therapeutic potential of epipharyngeal abrasive therapy【nature : scientific reports　2025年5月12日】

Abstract

In this study, the critical role of the epipharynx in managing long-term coronavirus disease 2019 (COVID-19), and in particular, how residual SARS-CoV-2 RNA affects signalling pathways in the epipharynx were investigated via spatial gene expression analysis (Visium HD). Moreover, we hypothesize that epipharyngeal abrasive therapy (EAT) targeting the epipharynx could improve long COVID symptoms by modulating local inflammation and gene expression. We conducted a comparative analysis of the gene expression profiles of three patients with long COVID and two control individuals without COVID-19. Residual SARS-CoV-2 RNA was detected in the epipharynx of patients with long COVID, along with the activation of signalling pathways in epithelial and immune cells. After EAT, the viral RNA was either completely cleared or significantly reduced. T-cell receptor signalling pathways were suppressed; the levels of proinflammatory cytokines, such as interleukin-6 and tumour necrosis factor-α, were reduced; and excessive antibody production was mitigated. Histology showed that EAT effectively eliminated the inflamed, dysfunctional ciliated epithelium. This study clarifies that SARS-CoV-2 has long-term effects on the immune response in the epipharynx, emphasizing the need to focus on chronic epipharyngitis as a potential cause of long COVID. Furthermore, EAT may offer a promising approach to alleviating persistent long COVID symptoms.

◆Impact of SARS-CoV-2 infection on the mitochondrial network in human pluripotent stem cell-derived cardiomyocytes【ScienceDirect　2025年5月20日】

Abstract

Introduction

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has been associated with cardiovascular complications, including cardiac failure, arrhythmias, and acute coronary syndromes, particularly among hospitalized patients. Elevated levels of both troponin and cell-free mitochondrial DNA in the bloodstream have been identified as biomarkers, correlating with the severity of the disease. These markers suggest that SARS-CoV-2 may induce damage to both cardiac cells and mitochondria. Given the crucial role of mitochondria in maintaining the physiological functions of cardiomyocytes, we aim to investigate the impact of SARS-CoV-2 on both cardiac cells and their mitochondrial function.

Objective

We aim to explore whether SARS-CoV-2 can directly infect cardiomyocytes and subsequently examine the extent of mitochondrial network disruptions. Finally, we will investigate the downstream consequences of these mitochondrial alterations, particularly metabolic processes and innate immune responses, which are closely tied to SARS-CoV-2 infection.

Method

We used human pluripotent stem cell-derived cardiomyocytes (HPSC-CMs) as a model to study SARS-CoV-2 infection. Infection was assessed through microscopy and viral RNA detection. We also examined changes in cellular, nuclear, and mitochondrial morphology following infection using advanced imaging techniques. Additionally, we measured alterations in RNA expression of inflammatory markers and mitochondrial genes. Finally, we used a non-cardiac cell line to confirm the ability of SARS-CoV-2 to induce mitochondrial disruptions and to investigate the viral and cellular protein factors involved in this process.

Results

Following SARS-CoV-2 infection, we confirmed viral genome presence in HPSC-CMs and observed Troponin+ and Spike+ cells. We showed that infection led to an increase of inflammation markers and a morphological perturbation of the HPSC-CMs. Both cardiac and non-cardiac cell line showed signs of mitochondrial network perturbation. We identify ORF9b, an antagonist of innate immune response, as a viral candidate for this perturbation.

Conclusion

These findings confirm that SARS-CoV-2 can directly infect cardiomyocytes, triggering an inflammatory response. The virus targets mitochondria, which play a dual role as both the primary energy source and a reservoir of compounds utilized by the virus for replication, as well as a platform for initiating innate immune responses. This interaction may provide a key mechanism underlying the cardiac injuries observed during SARS-CoV-2 infection.

◆In Kashmir, Brain Fog Is the Symptom Nobody Saw Coming――Kashmiri youth are forgetting conversations, missing school, and numbing out. This is what brain fog looks like.【Kashmir Observer : Syed Duha and Mehak Fayaz　2025年5月27日】

Abdul Rashid doesn’t cut wood the way he used to. A carpenter from Saida Kadal, he once shaped furniture by eye. Now he stares at the tape, measures twice, sometimes thrice. Still unsure.

“Maybe I’m getting old,” he says. But he’s only 49. His hands are steady. It’s his mind that wavers.

His 16-year-old son says he forgets mid-sentence. “The words come, then vanish,” he says, glancing at the floor.

Neither of them knows what to call it. But science does. Brain fog.

They’re not the only ones. In Kashmir, memory slips, scattered focus, and mental fatigue have become worryingly common, especially after COVID.

A 2024 global study in Clinical Neurology and Neurosurgery found over 20% of long COVID patients experience cognitive issues. An Indian study confirmed 26.4% of recovered patients face similar problems.

But numbers only tell part of the story. In Kashmir, where life was already fractured by shutdowns, conflict, and constant disconnection, the pandemic didn’t just spread illness. It sank deeper. It clouded minds.

Students were hit hard. A 2021 UNICEF report said 64% of children in Jammu and Kashmir had no access to online learning during lockdown. No classes, no teachers, no friends. Just months of stillness. For many, that pause wasn’t just in their routine, it slowed their thinking, their speech, their growth.

A teenager from Pulwama said he often zones out during conversations. “I try to listen, but halfway through, I’m somewhere else,” he said. Others talked about forgetting easy words, missing steps in tasks, losing track of time.

In Baramulla, a 22-year-old woman described her days as “foggy and tiring.” “Even folding clothes or remembering shopping lists feels like climbing a mountain,” she said. “I wasn’t like this before COVID.”

Kashmir’s healthcare system wasn’t built to catch this kind of illness. There’s roughly one psychiatrist for every 180,000 people. Mental health wasn’t discussed much before. Now, even when people want to talk, they don’t know where to go.

And while the mind slows, life speeds up.

The economy hasn’t recovered. The Kashmir Chamber of Commerce and Industry recorded losses of over ₹17,000 crore during the pandemic. One in four small businesses shut down or shrank. That kind of stress isn’t just financial. It eats into confidence, routine, and hope.

At the same time, drug use is rising. The Institute of Mental Health and Neurosciences (IMHANS) reported a 23% jump in drug-related cases after COVID. These aren’t all thrill-seekers. Many are simply looking for a way out of the fog. “It’s not about getting high,” said a 19-year-old in rehab. “It’s about not feeling broken all the time.”

So what now?

Mental health experts say the region needs a system that listens. Not just at hospitals, but in schools, mohallas, homes. District wellness centres with trained counselors. Mental health check-ins in classrooms. Teachers, community workers, and ASHA staff trained to spot early signs, like sudden silence, memory lapses, or confusion.

And most importantly, experts say, families need to slow down. When a child forgets something again and again, the answer isn’t scolding. It’s listening. It’s asking what’s going on inside. It’s giving space, not shame.

Because brain fog doesn’t make a scene. It creeps in quietly, dulling attention, memory, and emotion, and blunts the edges of everyday life. In the valley, where stillness already weighs heavy, this kind of silence is dangerous.

Abdul Rashid is still working. Still cutting wood. His son is still trying to speak without stumbling. They are not giving up. But they need more than willpower. They need recognition, care, tools.

The fog may be invisible, but it is real. And it is everywhere, settling not just on minds, but on futures.

◆Renal Long COVID: A Scoping Review【ScienceDirect　2025年5月29日】

Abstract

Rationale & Objective

Whether long coronavirus disease (long COVID) affects the kidneys remains to be understood. In this scoping review, we described the evidence of renal long COVID.

Study Design

A scoping review was conducted according to the Joanna Briggs Institute and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines by searching MEDLINE, Embase, and other databases from inception until February 2025.

Setting & Study Populations

We included evidence on kidney-related outcomes in adult survivors of coronavirus disease 2019 (COVID-19) with data on long COVID.

Selection Criteria for Studies

Cohorts from all settings.

Data Extraction

We extracted data related to longitudinal kidney outcomes.

Analytical Approach

Data were synthesized and presented in tables and figures.

Results

We screened 6,203 studies and included 37 in this review (38 reports), comprising 1,308,265 individuals with follow-up data. The majority were retrospective (61%) and from Europe (37%). All reports included hospitalized patients and 34% also included the community setting. Acute kidney injury (AKI) during acute COVID-19 phase was assessed in 58% of the reports. Chronic kidney disease (CKD) development was assessed in 29% of the reports, with wide variation in its frequency, ranging from 0.4%-45%. Progression of CKD (7 studies, 18%) ranged from 8%-49%. Studies reporting higher frequencies of AKI found larger rates of renal long COVID. Overall, there was high heterogeneity in how kidney-related outcomes were reported during follow-up. Most studies presented data on crude kidney function biomarkers (eg, serum creatinine or estimated glomerular filtration rate), while a few (13%) reported major adverse kidney events. Data on proteinuria or urinary biomarkers were scarce.

Limitations

Lack of studies with pre-COVID-19 data.

Conclusions

This scoping review highlighted that renal long COVID, characterized by CKD development and/or progression, may occur. Available evidence suggests that AKI may be associated with renal long COVID. Therefore, long-term kidney function monitoring is advisable after COVID-19 recovery to enable early diagnosis and timely intervention for CKD.

Plain-Language Summary

Kidney complications may persist after coronavirus disease 2019 (COVID-19) recovery, but their long-term impact remains unclear. Our review analyzed data from over 1 million patients and found that those who experienced acute kidney injury during COVID-19 had a higher risk of developing or worsening chronic kidney disease. However, the studies showed significant variation in how often renal long COVID occurred, highlighting the need for more research. Given these findings, regular kidney function monitoring after COVID-19 recovery is essential for early detection and intervention to prevent long-term complications. This study underscores the importance of recognizing renal long COVID as a potential consequence in the post-COVID era.

◆SARS-CoV-2 Is Linked to Brain Volume Loss in Multiple Sclerosis【WILEY Online Library　2025年5月29日】

Abstract

Objective

The impact of SARS-CoV-2 infection on brain and spinal cord pathology in patients with multiple sclerosis (pwMS) remains unclear. We aimed to describe changes in brain lesion activity and brain and spinal cord volumes following SARS-CoV-2 infection.

Methods

We included 177 pwMS (570 MRI scans) diagnosed with and tested positive for SARS-CoV-2 infection between August 2020 and May 2021. All patients were free of clinical disease activity, disease-modifying therapy changes, and corticosteroids during the study. MRI scans were performed using a standardized protocol on a 3-Tesla scanner. We analyzed the effect of SARS-CoV-2 on brain lesion load accrual and brain and spinal cord volume measures using adjusted mixed-effect models.

Results

During SARS-CoV-2 infection, patients had a median disease duration of 14.2 years, a median age of 44.9 years, and a median Expanded Disability Status Scale of 2.0. SARS-CoV-2 infection did not lead to any changes in the number or volume of T1 or T2 lesions in the brain. However, SARS-CoV-2 was associated with an increased whole brain (B = −0.17; SE = 0.08; p = 0.028), grey matter (B = −0.25; SE = 0.12; p = 0.040), and cortical grey matter volume loss (B = −0.32; SE = 0.13; p = 0.014). Greater ventricular enlargement following SARS-CoV-2 infection was evident only in individuals over the age of 40 (interaction of age vs. ventricular enlargement: B = 0.17; SE = 0.05; p = 0.0003). Only patients with more severe SARS-CoV-2 infection showed a reduction in mean upper cervical cord area (MUCCA) (B = 1.14; SE = 0.52; p = 0.030).

Interpretation

SARS-CoV-2 infection in clinically stable pwMS was linked to increased neuronal tissue loss.

◆Cognition and Memory after Covid-19 in a Large Community Sample【The NEW ENGLAND JOURNAL of MEDICINE　2024年2月28日】

Abstract

Background

Cognitive symptoms after coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are well-recognized. Whether objectively measurable cognitive deficits exist and how long they persist are unclear.

Methods

We invited 800,000 adults in a study in England to complete an online assessment of cognitive function. We estimated a global cognitive score across eight tasks. We hypothesized that participants with persistent symptoms (lasting ≥12 weeks) after infection onset would have objectively measurable global cognitive deficits and that impairments in executive functioning and memory would be observed in such participants, especially in those who reported recent poor memory or difficulty thinking or concentrating (“brain fog”).

Results

Of the 141,583 participants who started the online cognitive assessment, 112,964 completed it. In a multiple regression analysis, participants who had recovered from Covid-19 in whom symptoms had resolved in less than 4 weeks or at least 12 weeks had similar small deficits in global cognition as compared with those in the no–Covid-19 group, who had not been infected with SARS-CoV-2 or had unconfirmed infection (−0.23 SD [95% confidence interval {CI}, −0.33 to −0.13] and −0.24 SD [95% CI, −0.36 to −0.12], respectively); larger deficits as compared with the no–Covid-19 group were seen in participants with unresolved persistent symptoms (−0.42 SD; 95% CI, −0.53 to −0.31). Larger deficits were seen in participants who had SARS-CoV-2 infection during periods in which the original virus or the B.1.1.7 variant was predominant than in those infected with later variants (e.g., −0.17 SD for the B.1.1.7 variant vs. the B.1.1.529 variant; 95% CI, −0.20 to −0.13) and in participants who had been hospitalized than in those who had not been hospitalized (e.g., intensive care unit admission, −0.35 SD; 95% CI, −0.49 to −0.20). Results of the analyses were similar to those of propensity-score–matching analyses. In a comparison of the group that had unresolved persistent symptoms with the no–Covid-19 group, memory, reasoning, and executive function tasks were associated with the largest deficits (−0.33 to −0.20 SD); these tasks correlated weakly with recent symptoms, including poor memory and brain fog. No adverse events were reported.

Conclusions

Participants with resolved persistent symptoms after Covid-19 had objectively measured cognitive function similar to that in participants with shorter-duration symptoms, although short-duration Covid-19 was still associated with small cognitive deficits after recovery. Longer-term persistence of cognitive deficits and any clinical implications remain uncertain. (Funded by the National Institute for Health and Care Research and others.)

◆Gut Microbial Signatures in Long COVID: Potential Biomarkers and Therapeutic Targets【SPLINGER NATURE　2025年6月1日】

Abstract

Introduction

Following severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, symptoms can persist for more than 12 weeks in over 10% of patients in a condition known as long coronavirus disease (COVID). Gut microbiota dysbiosis is correlated with long COVID, but the specific relationship between long COVID and the gut microbiome remains unclear. Here, we aimed to investigate connections between the gut microbiota and long COVID severity.

Methods

Fecal samples were collected from 31 patients with long COVID, 14 with COVID-19 but not long COVID, and 23 healthy controls. The mean interval between COVID-19 diagnosis and sample collection was 65.5 (range: 13.0–110.3) weeks for patients with long COVID and 74.8 (range: 50.7–110.4) weeks for positive control group. Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Patient-reported outcomes were used to comprehensively assess long COVID symptom severity.

Results

Symptom severity was higher in patients with severe initial infections and significantly correlated with serum triglyceride, fasting blood glucose, and high-density lipoprotein-cholesterol levels. Results showed distinct microbial profiles in patients with long COVID. Leuconostoc, Actinomyces, and Granulicatella were significantly enriched, and they accurately distinguished patients with long COVID from controls, indicating their potential as long COVID biomarkers. Particular gut bacteria were significantly correlated with certain systemic, gastrointestinal, otolaryngologic, and visual symptoms. Parabacteroides, Eubacterium ventriosum group, and Rothia abundance was correlated with blood biomarkers that influence long COVID development, including total and low-density lipoprotein cholesterol and basophil levels.

Conclusions

The gut microbial signature of patients with long COVID differed from that of healthy controls. Certain microbial genera showed significant differences between patients with long COVID and controls, suggesting potential as preliminary biomarkers and therapeutic targets for long COVID pending validation in larger studies.

◆Ischaemic endothelial necroptosis induces haemolysis and COVID-19 angiopathy【nature　2025年6月4日】

Abstract

Microangiopathy is a major complication of SARS-CoV-2 infection and contributes to the acute and chronic complications of the disease1. Endotheliopathy and dysregulated blood coagulation are prominent in COVID-19 and are considered to be major causes of microvascular obstruction1,2. Here we demonstrate extensive endothelial cell (EC) death in the microvasculature of COVID-19 organs. Notably, EC death was not associated with fibrin formation or platelet deposition, but was linked to microvascular red blood cell (RBC) haemolysis. Importantly, this RBC microangiopathy was associated with ischaemia–reperfusion injury, and was prominent in the microvasculature of humans with myocardial infarction, gut ischaemia, stroke, and septic and cardiogenic shock. Mechanistically, ischaemia induced MLKL-dependent EC necroptosis and complement-dependent RBC haemolysis. Deposition of haemolysed RBC membranes at sites of EC death resulted in the development of a previously unrecognized haemostatic mechanism preventing microvascular bleeding. Exaggeration of this haemolytic response promoted RBC aggregation and microvascular obstruction. Genetic deletion of Mlkl from ECs decreased RBC haemolysis, microvascular obstruction and reduced ischaemic organ injury. Our studies demonstrate the existence of a RBC haemostatic mechanism induced by dying ECs, functioning independently of platelets and fibrin. Therapeutic targeting of this haemolytic process may reduce microvascular obstruction in COVID-19, and other major human diseases associated with organ ischaemia.

◆Long COVID in Young Children, School-Aged Children, and Teens【JAMA Pediatrics　2025年5月27日】

Abstract

Long COVID happens when a child continues to have symptoms lasting at least 3 months after a SARS-CoV-2 infection.

Some children have COVID-19 symptoms that do not go away, while others might feel better but later develop new symptoms. Sometimes, symptoms can come and go. Long COVID can affect any child, even if they had mild or no symptoms when they had COVID-19.

Long COVID is common, affecting up to 10% to 20% of children with a history of COVID-19. With almost 6 million US children potentially affected, this is higher than the number of children with asthma, the most common chronic health problem in children.

What Symptoms Should I Look for?

Long COVID can impact many body parts, and its symptoms can last for months or years. It can severely affect daily activities and emotional well-being, such as playing or attending school.

Long COVID has many common features but can look different across ages. Infants, toddlers, and preschool-aged children are more likely to have symptoms parents can observe, such as poor appetite, sleepiness, and respiratory symptoms (eg, a cough). School-aged children are more likely to have neurologic symptoms, eg, trouble focusing, trouble sleeping, or feeling lightheaded. They may also have back or neck pain, headache, stomach pain, or vomiting. Sometimes, they have behavioral changes. Adolescents are more likely to have a change or loss in smell or taste, pain, fatigue-related symptoms, trouble with memory, and lightheadedness. Postexertional malaise (PEM) has been reported in children and adults with long COVID. PEM is a flare of symptoms and/or the appearance of new symptoms even after minimal exertion, including physical activity, mental exertion, and sensory overload. Often presenting 24 hours after the triggering event, PEM is different from just being more tired than normal after an activity or feeling muscle soreness.

How Should Parents Track Their Child’s Symptoms?

Parents can track their child’s symptoms by noting when symptoms start, how long they last, and their severity. Record if symptoms are constant or come and go and what might improve or worsen them. Recording daily can help identify patterns and support discussions with your child’s pediatrician.

How Is Long COVID Diagnosed and Treated?

There are no specific blood tests for long COVID. It is diagnosed based on prolonged symptoms or new or worsening conditions. A past positive COVID-19 test is not needed for diagnosis. Parents can observe and document symptoms to discuss with their child’s pediatrician.

There is no cure for long COVID, but researchers are working hard to find treatment. Health care professionals may recommend medicine to help with some symptoms as well as guidance on how to avoid symptom flares. They can also help collaborate with schools if your child with long COVID needs to change their education plan.

◆The impact of long COVID on physical and cardiorespiratory parameters: A systematic review【PLOS One　2025年6月4日】

Abstract

Background

Since the emergence of COVID-19, millions worldwide have continued to experience persistent symptoms months after infection. Among these, physical and cardiorespiratory impairments are frequently reported, but remain poorly understood. This systematic review aimed to identify and synthesize evidence regarding physical and cardiorespiratory impairments in individuals with long COVID, defined as symptoms persisting for at least three months post-infection.

Methods and findings

A structured search was conducted across the MEDLINE, Embase, CINAHL, and Web of Science databases to identify cross-sectional and longitudinal cohort studies on physical and cardiorespiratory deficits in adults with long COVID. Twenty-two studies involving 3,041 adults with long COVID were included. Critical appraisal using the JBI-APT indicated that most studies had clear inclusion criteria (17/22), well-defined study populations (17/22), and valid exposure measurements (16/22), though confounding factors were often unaddressed (9/22 unclear or not reported). Findings indicate that while adults with long COVID displayed normal pulmonary function at rest, including Forced Vital Capacity (FVC), Forced Expiratory Volume (FEV1), Total Lung Capacity (TLC), and resting Arterial oxygen saturation (SpO2), significant impairments in exercise capacity were identified. Notably, all studies assessing the 6-minute walk test (6MWT) reported reduced distances, consistently falling below the 50th percentile of normative values. Additionally, VO₂peak was decreased in most studies (7/10), falling below 80% of the predicted value, indicating impaired aerobic capacity. Lower Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) values were observed in three out of six studies, with values below 75% of predicted, suggesting impaired gas exchange efficiency during exertion.

Conclusion

Despite preserved resting lung function, these findings highlight significant physical deconditioning in Long COVID adults, with substantial reduction in exercise capacity. Routine assessments should include more sensitive measures, such as the 6MWT and VO₂peak, to detect subtle exercise limitations, even in patients with normal resting SpO₂, to better inform rehabilitation interventions.