SARS-CoV-2 と COVID-19 に関する備忘録 Vol.61

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SARS-CoV-2 と COVID-19 に関するメモ・備忘録

◆Three-year assessment of cognitive and olfactory disturbances among COVID-19 convalescent patients grouped by olfactory hallucination status in Armenia: A qualitative and quantitative study【medRxiv　2025年8月13日】

Abstract

Background COVID-19 reinfections have emerged as a critical concern, particularly in relation to post-acute sequelae of SARS-CoV-2 infection, commonly known as long COVID. Long COVID is known to manifest diverse, debilitating symptoms across all demographics. Limited studies have investigated the causal relationship of COVID-19 reinfections and long COVID.

Methods We leveraged demographically diverse electronic health records from the COVID-19 enclave of the National Clinical Cohort Collaborative, part of the RECOVER initiative, to create a matched cohort of reinfected and control adults. All participants had at least one documented COVID-19 infection. We used one-to-one coarsened exact matching on sex, race/ethnicity, age, healthcare utilization, existing comorbidities, site of care, and the timing and severity of first infection. Index dates were assigned to each matched pair as the date of reinfection for the reinfected case. Long COVID was defined using a machine learning computable phenotype trained on clinically diagnosed long COVID cases. Cumulative incidence one year after index was calculated using an Aalen-Johansen estimator. Risk ratios were calculated by taking the ratio of long COVID incidence among reinfected and control cases.

Results We found that reinfection resulted in a significantly higher risk of long COVID compared to not being reinfected (risk ratio, 1.35, 95% CI, 1.32-1.39; risk difference, 0.029, 95% CI, 0.027-0.031). This effect was consistent across most stratifications.

Conclusions We found that COVID-19 reinfection resulted in a roughly 35% increase in the incidence of long COVID in a matched cohort using observational electronic health records.

◆MicroRNAs in long COVID: roles, diagnostic biomarker potential and detection【SPRINGER NATURE　2025年8月13日】

Abstract

Long COVID or Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), marked by persistent symptoms lasting weeks to months after acute SARS-CoV-2 infection, affects multiple organ systems including the respiratory, cardiovascular, neurological, gastrointestinal, and renal systems. These prolonged effects stem from chronic inflammation, immune dysregulation, and direct viral injury. MicroRNAs (miRNAs)—small non-coding RNAs involved in gene regulation—play a pivotal role in this process by modulating immune responses, inflammation, and cellular stress. Altered miRNA expression patterns during and after infection contribute to the pathogenesis of Long COVID. While conventional miRNA detection techniques have been valuable, they face limitations in sensitivity, throughput, and detecting RNA modifications. This review highlights Oxford Nanopore Sequencing (ONS) as a promising alternative, offering real-time, long-read, amplification-free RNA sequencing that preserves native modifications. ONS enables direct sequencing of full-length miRNAs and their precursors, providing novel insights into miRNA processing and regulatory roles. Despite current challenges with short-read accuracy, ongoing technical advances are improving ONS performance. Its integration in miRNA profiling holds significant potential for uncovering novel regulatory interactions and advancing clinical biomarker discovery in Long COVID and other conditions.

◆Digital Biometric Measures in Long COVID
A Secondary Analysis of the STOP-PASC Randomized Clinical Trial【JAMA Network　2025年8月14日】

Key Points

Question What are longitudinal digital wearable biometric measures and trajectory patterns in participants with postacute sequelae of SARS-CoV-2 infection (or long COVID) enrolled in a randomized clinical trial?

Findings In this substudy of a randomized clinical trial involving 50 participants, distinct longitudinal trajectories of digital biometric measures for long COVID were identified, including physical activity and heart rate.

Meaning The findings suggest that physiological and behavioral biometric measures from wearable devices are promising digital biomarkers for use in long COVID clinical trials and research.

Abstract

Importance Digital biometrics can be used to monitor disease, but there is limited research on their applications for assessing postacute sequelae of SARS-CoV-2 (PASC) or long COVID.

Objective To better understand digital biometric patterns in long COVID using wearable device technology and whether there are any differences between the nirmatrelvir-ritonavir and placebo-ritonavir intervention arms.

Design, Setting, and Participants This secondary analysis is an exploratory substudy of a placebo-controlled randomized clinical trial (Selective Trial of Paxlovid for PASC [STOP-PASC]) that was conducted from November 2022 to September 2023 at Stanford University. Trial participants were randomized, and a subset enrolled into the prespecified substudy.

Intervention Participants were randomized 2:1 to receive oral nirmatrelvir (300 mg) and ritonavir (100 mg) or placebo-ritonavir twice daily for 15 days. Substudy participants were provided with a smartwatch and asked to wear it for 24 hours a day, 7 days a week for the 15-week study.

Main Outcomes and Measures Mean changes in digital biometric measures in physical activity, heart rate, and oxygen saturation tracked by a smartwatch. Biometric measures were summarized by treatment arm for each of 5 different time frames: baseline, treatment period, and 3 subsequent time intervals. Summary measure trajectories were clustered and demographics and clinical characteristics were compared among clusters using absolute standardized differences expressed in units of SDs.

Results Of the 94 participants enrolled in the substudy, 50 (37 in nirmatrelvir-ritonavir and 13 in placebo-ritonavir) met the analysis eligibility criteria based on wear time and data completeness. These participants had a mean (SD) age of 42.7 (13.2) years and included 29 females (58.0%). Using mixed models for repeated measures, no significant differences were detected between the intervention arms in the change in biometric measures over time, consistent with the patient-reported outcomes in the STOP-PASC trial. In the overall substudy cohort, latent class mixed models and cluster analysis identified distinct longitudinal trajectories of long COVID over the 15-week study that tracked with different symptoms. Participants with lower daytime physical activity reported more severe fatigue (9 of 9 [100%] vs 21 of 23 [91.3%]; absolute standardized difference [ASD], 0.30), shortness of breath (9 of 9 [100%] vs 7 of 23 [30.4%]; ASD, 1.31), and cardiovascular symptoms (8 of 9 [88.9%] vs 12 of 23 [52.2%]; ASD, 0.70). Those with higher nighttime physical activity reported more gastrointestinal symptoms (2 of 3 [66.7%] vs 11 of 35 [31.4%]; ASD, 0.50). Additionally, participants with higher median daytime heart rates reported less fatigue (7 of 9 [77.8%] vs 39 of 40 [97.5%]; ASD, 0.63) and shortness of breath (3 of 9 [33.3%] vs 23 of 40 [57.5%]; ASD, 0.50) compared with those with lower heart rates.

Conclusions and Relevance This secondary analysis identified distinct longitudinal trajectories of physiological and behavioral digital biometric measures captured from wearable devices that reflect the heterogeneity and track with different symptoms of long COVID. Digital biometric measures from wearable devices have promising utility for long COVID research.

◆Accelerated vascular ageing after COVID-19 infection: the CARTESIAN study【OXFORD ACADEMIC：European Heart Journal　2025年8月17日】

Abstract

Background and Aims

Increasing evidence suggests that COVID-19 survivors experience long-term cardiovascular complications possibly through development of vascular damage. The study aimed to investigate whether accelerated vascular ageing occurs after COVID-19 infection, and if so, identify its determinants.

Methods

This prospective, multicentric, cohort study, included 34 centres in 16 countries worldwide, in 4 groups of participants—COVID-19-negative controls (ⅰ) and three groups of individuals with recent (6 ± 3 months) exposure to SARS-CoV-2: not hospitalized (ⅱ), hospitalized in general wards (ⅲ), and hospitalized in intensive care units (ⅳ). The main outcome was carotid-femoral pulse wave velocity (PWV), an established biomarker of large artery stiffness.

Results

2390 individuals (age 50 ± 15 years, 49.2% women) were recruited. After adjustment for confounders, all COVID-19-positive groups showed higher PWV (+0.41, +0.37, and +0.40 m/s for groups 2–4, P < .001, P = .001 and P = .003) vs. controls [PWV 7.53 (7.09; 7.97) m/s adjusted mean (95% CI)]. In sex-stratified analyses, PWV differences were significant in women [PWV (+0.55, +0.60, and +1.09 m/s for groups 2–4, P < .001 for all)], but not in men. Among COVID-19 positive women, persistent symptoms were associated with higher PWV, regardless of disease severity and cardiovascular confounders [adjusted PWV 7.52 (95% CI 7.09; 7.96) vs. 7.13 (95% CI 6.67; 7.59) m/s, P < .001]. A stable or improved PWV after 12 months was found in the COVID+ groups, whereas a progression was observed in the COVID− group. Conclusions

COVID-19 is associated with early vascular ageing in the long term, especially in women.

◆SARS-CoV-2 damages cardiomyocyte mitochondria and implicates long COVID-associated cardiovascular manifestations【ScienceDirect　2025年5月10日】

Abstract

Introduction

With the COVID-19 pandemic becoming endemic, vigilance for Long COVID-related cardiovascular issues remains essential, though their specific pathophysiology is largely unexplored.

Objectives

Our study investigates the persistent cardiovascular symptoms observed in individuals long after contracting SARS-CoV-2, a condition commonly referred to as “Long COVID”, which has significantly affected millions globally.

Methods

We meticulously describe the cardiovascular outcomes in five patients, encompassing a range of severe conditions such as sudden cardiac death during exercise, coronary atherosclerotic heart disease, palpitation, chest tightness, and acute myocarditis.

Results

All five patients were diagnosed with myocarditis, confirmed through endomyocardial biopsy and histochemical staining, which identified inflammatory cell infiltration in their heart tissue. Crucially, electron microscopy revealed widespread mitochondrial vacuolations and the presence of myofilament degradation within the cardiomyocytes of these patients. These findings were mirrored in SARS-CoV-2-infected mice, suggesting a potential underlying cellular mechanism for the cardiac effects associated with Long COVID.

Conclusion

Our findings demonstrate a profound impact of SARS-CoV-2 on mitochondrial integrity, shedding light on the cardiovascular implications of Long COVID.

◆Why scientists are rethinking the immune effects of SARS-CoV-2【the BMJ　2025年8月19日】

“Immunity debt,” a theory to explain the global surge in non-covid infections since pandemic restrictions were lifted, is increasingly being challenged by emerging evidence. Nick Tsergas reports

Mycoplasma pneumoniae is a bacterial infection not known to cause widespread hospital admissions. “I can count on my two hands the number of times I’d ever seen mycoplasma pneumoniae before 2023,” says Samira Jeimy, clinical immunologist at the University of Western Ontario. “All of a sudden I feel like everybody has it.”

Over the past three years similar reports have circulated of rising bacterial infections, flare-ups of old viruses becoming more common, and children landing in hospital with diseases not usually seen in young, healthy people. One explanation offered by public health leaders has been “immunity debt”—the idea that precautions taken in the covid pandemic suppressed routine exposures to circulating pathogens, leaving people more vulnerable to them when restrictions were lifted.

The theory landed in the public consciousness at the right moment. A simple idea that sounded like science, it soothed a public seeking answers just as the world was returning to a semblance of normality. And it served a policy function, allowing governments to focus on economic recovery.

But its explanatory power has faded as the number of non-covid infections has kept rising each year. A 2024 analysis by the US Centers for Disease Control and Prevention found that invasive group A strep infections saw their most dramatic year-on-year increase from 2021 to 2022, well after most precautions had been lifted in the US. Rates have been abnormally high since then, raising questions about what might be behind the trend.

A growing number of scientists believe that the SARS-CoV-2 virus may instead be subtly altering our immune systems. If correct, their hypothesis will change how we understand everything from respiratory syncytial virus (RSV) to shingles to sepsis.

◆Comparative Analysis of Long COVID and Post-Vaccination Syndrome: A Cross-Sectional Study of Clinical Symptoms and Machine Learning-Based Differentiation【medRxiv　2025年8月16日】

Abstract

Importance Long COVID is a well-documented post-viral syndrome, while post-vaccination syndrome (PVS) remains poorly characterized. Understanding their similarities and differences is essential for refining diagnostic criteria and developing targeted interventions. This study systematically compares the symptomatology of long COVID and PVS following COVID-19 vaccination, highlighting key distinctions that could inform clinical practice and research.

Objective To assess the clinical characteristics of long COVID and PVS and identify key distinguishing features between the conditions.

Design, Setting and Participants This cross-sectional analysis used questionnaire data from the decentralized Yale Listen to Immune, Symptom and Treatment Experiences Now (LISTEN) Study, collected from May 2022 to July 2023. Data analysis occurred between July 2023 and May 2024. A convenience sample of adults (age ≥18 years) with either long COVID or PVS was included.

Main Outcomes and Measures Symptom data were analyzed using clustering techniques to identify groups with shared symptom patterns. A gradient-boosted machine learning model was used to determine the most distinguishing symptoms between long COVID and PVS.

Results The long COVID group (n = 441) and PVS group (n = 241) had similar demographic profiles (median age 46 years; 74% vs 80% female, respectively). Participants with long COVID most commonly reported brain fog, altered sense of smell and taste, shortness of breath, fatigue, memory problems, and difficulty speaking. Participants with PVS more frequently reported burning sensations, neuropathy, and numbness. Clustering analysis identified three symptom-based subgroups: one enriched for neurological symptoms and PVS; one characterized by multi-system symptoms and predominantly long COVID; and one dominated by psychiatric and sleep symptoms, also primarily long COVID. The machine learning model achieved an AUC of 0.79 (95% CI, 0.75–0.82) and highlighted altered sense of smell, cough, burning sensations, and brain fog as key differentiators.

Conclusions and Relevance Although long COVID and PVS share overlapping symptoms, they have distinct clinical profiles, suggesting the possibility of different underlying biological mechanisms. These distinctions may help refine diagnostic criteria, guide personalized treatment strategies, and inform further research into their respective pathophysiology.

◆Long COVID Claims Still Impact California’s Workers Comp System, Report Shows【INSURANCE JOURNAL　2024年10月21日】

The impact and surge of long-term COVID on the California workers’ compensation system since 2020 has been prevalent, including long-term impacts on disability and long-term patterns of medical cost and treatment on long COVID claims.

That’s from a report by the Workers’ Compensation Insurance Rating Bureau of California.

The WCIRB report finds long Covid is still prevalent, with roughly 30% of California adults having reported activity limitations from long COVID, and there is an even higher prevalence in healthcare, manufacturing and retail industries.

The report’s findings include:

  • More than one-in-seven COVID-19 claims with medical payments filed between April 2020 and July 2021 were estimated to involve long COVID over a 30-month post-acute care period.
  • 5% of all COVID-19 claims filed between April 2020 and July 2021, including indemnity-only claims, were estimated to involve long COVID.
  • Roughly 40% of COVID-19 claims involving hospitalization were estimated to involve long COVID over a 30-month post-acute care period.
  • Long COVID claims incurred higher indemnity and medical losses than other COVID-19 claims, mostly driven by a higher share of permanent disability claims.

According to the report, long COVID claims compared to other COVID-19 claims have a higher share of indemnity claims and higher average incurred indemnity losses at roughly 30 months after policy inception, driven by a longer average duration (27 weeks) of temporary disability benefits, and a higher share of claims (35 claim average) involving permanent disability benefits.

Long COVID PD claims averaged $79,828 compared with $31,230 for COVID claims, and long COVID TD claims averaged $19,694 compared with $3,711 for COVID claims, the report shows.

Long COVID claims were also more likely to involve litigation and have higher ALAE payments, according to the report.