SARS-CoV-2 と COVID-19 に関する備忘録 Vol.56

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SARS-CoV-2 と COVID-19 に関するメモ・備忘録

◆The predisposing factors to having a coded diagnosis of Long COVID【ScienceDirect　2025年7月1日】

Abstract

Objectives

Long COVID is characterized by a constellation of persistent symptoms following an initial infection with COVID-19 virus. The primary focus of this study was to investigate how the characteristics of people diagnosed with Long COVID differed from those of matched individuals who did not have a diagnosis of Long COVID, after at least one confirmed positive COVID-19 test.

Study design

A retrospective observational cohort study was performed using data collected for the time period, January 1, 2020 to January 31, 2024 from a population database of 2.85 million people.

Methods

The primary outcome was a primary care coded diagnosis, or referral for treatment of Long COVID following an acute COVID-19 infection, to a Long COVID clinic. Twenty six thousand, six hundred and twenty six (26,626) individuals were identified with a diagnosis of Long COVID and at least one previous recorded COVID-19 positive test. These were matched by age and sex with 133,165 individuals (i.e. an approximate ratio of 5 controls to one case) with at least one previous recorded COVID-19 positive test but no recorded diagnosis of Long COVID. Mortality rate was also analysed in relation to having a previous confirmed acute COVID-19 infection.

Results

There was a higher proportion of people with 2, 3, 4 and 5 or more comorbidities in the diagnosed Long COVID group compared to those with one or no comorbidity. Black/ Black British ethnicity (+28 %) and Mixed ethnicity (+37 %) were both associated with a higher likelihood of a Long COVID diagnosis when compared to White ethnicity. Those in the most disadvantaged quintile (as measured by Townsend index) were more than twice as likely to have Long COVID than the most advantaged quintile. The risk of Long COVID increased by 5.7 % per each comorbidity, with modulation by the number of COVID-19 vaccinations. The risk of Long COVID doubled for every additional confirmed positive COVID-19 test. BMI did not have an effect when account was taken of Townsend quintile.

Lastly, we analysed mortality rates following a COVID-19 infection. Female sex was associated with a lower risk of death. More disadvantaged individuals as measured by Townsend quintile were more likely to have died. This risk was nearly doubled for the most deprived quintile compared to least deprived quintile.

Conclusions

In this city region wide study with individuals matched for age and sex, we have determined that being in a socially disadvantaged situation and being Black/Black British or of Mixed ethnicity increased the risk of developing Long COVID. BMI did not have an effect when account was taken of Townsend quintile. These findings can inform public health messages and public health interventions going forward, whether in relation to Long COVID or future pandemic preparedness.

◆Fragments of viral surface proteins modulate innate immune responses via formyl peptide receptors【iScience　2025年6月29日】

Summary

Formyl peptide receptors (FPRs) are pattern recognition receptors well-known for bacterial pathogen sensing. We here identified activator and inhibitor motifs for FPRs that are present on surface proteins of various viral pathogens. Peptides containing these motifs interact with all FPR family members and modulate various important immune functions in innate immune cells. Viral breakdown products comprising these motifs were found in patients with COVID-19. In the spike protein, many activators are found in highly mutagenic regions, whereas the inhibitor motif is located in a conserved domain that also exists in further unrelated viruses. The physiochemical properties of FPR1 activators correlate with the occurrence of protein aggregation hotspots. Such hotspots are present on various surface proteins of unrelated viruses that can also activate FPRs. This points toward a general contribution of FPRs in modulating antiviral immune responses during many distinct viral infections.

◆Cardiovascular Manifestations of Patients with Long COVID【MDPI　2025年7月13日】

Abstract

Background: This study investigates the potential mechanisms behind changes in cardiac structure and function in long COVID patients.
Methods: This study involved 176 consecutive outpatients in follow-up care (average age 55.9 years; 58.5% male) who experienced symptoms for over 12 weeks (average 6.2 ± 2.7 months), following coronavirus infection (COVID-19).
Results: The patients with long COVID and cardiovascular manifestations were significantly more hospitalized (88.5% vs. 75.9%) and had longer hospital stays. Significant echocardiography changes were observed in the left ventricular ejection fraction (LVEF) (59.6 ± 5.4% vs. 62.5 ± 3.8%); longitudinal strain (LS) in the sub-endocardium and intra-myocardium layers (−20.9 vs. −22.0% and −18.6 vs. −19.5%); circumferential strain (CS) in the sub-epicardium layers (−9.6 vs. −10.5%); and CS post-systolic shortening (CS PSS) (0.138 vs. 0.088 s). Additionally, pathological cardiac magnetic resonance (CMR) findings were seen in 58.2% of the group of patients with long COVID and cardiovascular manifestation; 43.3% exhibited positive late gadolinium enhancement (LGE), 21.0% had elevated native T1 mapping, and 22.4% had elevated native T2 mapping.
Conclusions: Most patients with long COVID showed structural and functional changes in their cardiovascular systems, primarily caused by prolonged inflammation. Using multimodality imaging is important for uncovering the mechanisms to predict chronic myocarditis, early-stage heart failure, and pre-ischemic states, which can lead to serious complications. Recognizing the specific cardiovascular phenotypes associated with long COVID is essential in order to provide timely and appropriate treatment.

◆Fatigue, Brain Fog And A Racing Heart — What Doctors Are Learning About Post-COVID Neurodivergence【Forbes : Nancy Doyle　2025年7月15日】

Have you ever made people gasp by bending your knees backwards or touching your thumb back to your arm? Does your pulse race when you stand up? Do you have a history of gastric issues or irritable bowel syndrome? Are you also neurodivergent, by any chance?

There is emerging, but compelling, evidence that the overlap between neurodivergence, hypermobility syndromes, mast cell activation syndrome, postural orthostatic tachycardia and dysautonomia is not a coincidence, and has a lot to do with COVID.

The impact of these conditions can be severe on their own, though hard to diagnose and lacking in conclusive biomarkers. They lead to chronic fatigue, serious gastro-intestinal distress, brain fog and concentration difficulties, anxiety and depression. People drop out of the labor force, education and careers are curtailed. Prevalence rates are very hard to come by reliably, but estimates range up to 20% of the population affected by one or more of these conditions. Some physicians have noticed that these symptoms and diagnoses are also rising exponentially since COVID, which appears to trigger or exacerbate symptoms.

An Invisible Problem Hiding In Plain Sight

A special meeting at the Royal Society of Medicine (RSM) in London has proposed that neurodivergent people, who are more likely to have hypermobility, connective tissue and autoimmune conditions, have been disproportionately impacted by COVID, and that this is having a significant impact on our ability to go to school and work. The rise in neurodivergence since 2020 that is placing so much strain on education and health services, the tax payer and not forgetting the individuals themselves and their families, is indeed partly due to increased awareness and more accessible diagnostic criteria – as has already been argued. However, this does not explain why these high rates of diagnosis are accompanied by such vastly increased rates of school absence and inability to work. If neurodivergent people have always existed, why are we only now so unwell that we can’t work?

The presentations to the RSM suggested that the effects of COVID on the brain could be contributing to the skyrocketing ADHD and Autism diagnosis waiting lists and to the absence epidemic. Since COVID we’ve needed to ask for help, whereas before we could fly under the radar.

Some people have dropped out of work or school altogether and are now battling to have their illness recognized. Others are still attending, but battling their own bodies, trying to force themselves to work through increasing difficulties with memory, unpredictable energy levels, pain, unstable pulse rates and various allergic inflammation. Their capacity for their work has been drastically reduced, they don’t know why and try as they might to get better, it’s not working. They are likely to be prescribed anxiety or depression medication in primary care and go looking for psychological answers to physical problems. Indeed, many of the markers we look for in diagnosing anxiety are, in fact, expressions of our nervous system – pounding heart rate, dizziness, hot / cold flushes. It is too easy to assign symptoms to stress and very difficult to identify the connections across the whole system.

A Solution Is Also Hiding In Plain Sight

A mixed group of medical experts in immunology, rheumatology, cardiology, urology, psychiatry and neuro-gastroenterology are trying to connect the dots. At the RSM, they presented preliminary data indicating that for people with this overlapping group of conditions, neurocognitive and emotional symptoms have indeed increased. Physical symptoms that were triggered by COVID infections have lowered our tolerance for sensory sensitivity in noise, smell, temperature, texture, light, food allergens, mould and all the toxicity in our environment. People who were neurodivergent a decade ago but coping in education and careers are now too ill to do so, and the effects of neuroinflammation could tip a sub-clinical neurotype into diagnosis territory.

The meeting further presented the extraordinary evidence that effective treatments for these issues may already be available, such as anti-histamines, probiotics, mast cell stabilisers – simple, cheap, low risk medications which have made the difference between someone working and not working. One of the presenters, Dr Stephanie Barrett, MBChB, MD, FRCP, a Consultant Rheumatologist, has found that non pharmacological and non-invasive treatment such as repeated transcranial magnetic stimulation (rTMS) has also been found to be beneficial. She reports:

“RTMS (neuromodulation) was an extraordinary breakthrough for the treatment of depression. Now using a different protocol, we have shown that we can treat severe fibromyalgia with associated fatigue and dysautonomia, in patients who are stuck for decades in the pain/ fatigue prison.

The additional challenge for our patients is 80% prevalence of neurodivergence. All the complex physical conditions and associations are treatable but they need to be recognised first. We could set up hubs with the government, at low cost to treat all these conditions and return people of all ages to education and the workforce.”

Each specialist presented various statistics, using many of the same treatments, indicating that a clear majority of their patients who were neurodivergent and unable to work before treatment are now back in work following an affordable protocol. Careers resumed, stories of people who feel they have “got their life back”.

Believe People When They Say They Are Ill

In a country where productivity has dived since the financial crisis, and the health of the nation has not recovered from COVID, The Royal Society of Medicine are trying to understand the root causes, rather than paper over the end results. Neurodivergent people are at risk of losing their support from welfare payments due to changes to the benefits system, which could underrate the presence of multiple, mid-level symptoms, even though these all add up to a significant drain. Whilst political circles are arguing over the extent to which the population is malingering versus “genuinely” ill, this group of physicians have come above the squabbling with a potential lever to tip the system from decline to healing. Following their proposed protocols, we can believe people who say that they can’t cope, treat them and support their recovery to living a full life again.

We are at risk of a lost generation of working age people who cannot understand their fatigue, who are trying their hardest but just cannot get moving, the more they try the harder it is (see: post-exertion malaise). Many have internalized the idea that they just need to try harder and are trapped in a cycle of self-blame and worsening symptoms.

If you think you might be affected by any of these conditions, take an inventory of your symptoms, however disjointed they are, and talk to your primary care physician. Even if they can’t refer you to a specialist, they owe you an explanation for your difficulties, so remember to be clear about what’s happening. If your capacity has changed, and you feel like it’s increasingly hard to cope with work you previously enjoyed or found easy, then this could be a physiological problem and you should speak to your doctor.

Is COVID to blame for the rise in neurodivergence? The answer is complex. We have higher levels of awareness and improved diagnostic criteria. For children, we have failing schools where rigid curricula and draconian discipline disproportionately disadvantage neurodivergent children. In workplaces we have increasing demands for productivity rises and endless escalation of technology and surveillance. All this undoubtedly contributes to the absence epidemic, but all of it started before the pandemic. Further, rises in diagnosis alone don’t fully explain the stark differences before and after COVID. Some studies showing that school absence has doubled from 2017 to 2023. The Royal Society of Medicine took some time to come at this problem from a less obvious angle, and in doing so have brought a cost effective solution into the light.

It’s time to stop assuming that people are lazy and time to stop putting multi-system health issues in the “too difficult box.” As employers, as a country and as individuals with families to support, we can’t afford to ignore the rising absence any longer.

◆Wearing a mask while exercising indoors improves lung function【University of Alberta : Michael Brown　2025年2月5日】

Not only does the COVID-pandemic practice of wearing a mask while exercising indoors help protect us from viruses, it can improve lung function, according to a University of Alberta study that unmasks the surprising effects of increased exertion in dry environments.

“One of the questions that surfaced during COVID was, ‘When you wear a mask for protection from viruses, does a mask affect physical activity effort for breathing and overall intensity?’” says Michael Kennedy, an exercise physiology professor in the Faculty of Kinesiology, Sport, and Recreation. “We wanted to understand whether a basic cloth mask had any negatives or benefits beyond reducing virus transmission and contagion risks during exercise.”

For the study, Kennedy’s team had study participants run on a treadmill because this is by far the most popular type of aerobic exercise in a fitness centre. The researchers measured lung function using handheld spirometers — devices participants blow into — during and after exercise, both with and without masks.

The data revealed that mask wearers experienced less reduction in forced expiratory volume (FEV1), which is the amount of air a person can forcibly exhale from their lungs within the first second of exhaling, compared with their unmasked counterparts. This indicated less constriction in the airway, called bronchoconstriction, which can occur with high breathing rates in dry air.

“The findings suggest masks may be beneficial during indoor exercise in dry environments, as they improved lung function and also reduced post-exercise symptoms like cough, wheezing and tightness in the throat,” Kennedy says, noting that none of the participants had an extensive history of asthma or exercise-induced asthma, so these findings are applicable to most people who exercise.

The reason a mask — whether cloth or surgical — helps reduce lung constriction, according to Kennedy, is that it traps moisture, which can be used to humidify the air on the next breath. Kennedy explains that with every breath, the lungs must warm the air to body temperature (37 C) and humidify it to 100 per cent.

“If we’re going to have gas exchange occur and get oxygen into our bodies, the air has to be both humidified and warm,” he says. “With a mask on, you’re able to humidify the air more effectively, which reduces stress on the lungs and minimizes constriction.”

Kennedy adds, “Even though we think indoor temperatures are fairly warm and comfortable for exercise, our lungs still have to do a lot of work to humidify the air, because Edmonton and Alberta are so dry.”

The team also examined whether wearing a mask reduced exercise-induced asthma. They focused on the 20 to 30 minutes after exercise, when the lungs tend to constrict the most and adverse symptoms emerge.

Though the benefits were clear, Kennedy notes there was an intensity threshold beyond which most participants began to feel that the mask was constricting. However, this limit occurred at the higher end of the intensity spectrum. For example, activities like brisk walking, hiking, indoor biking or spin classes, and aerobics would all fall within the comfort zone.

“What we would call hard or vigorous exercise — where your breathing rate increases and becomes noticeable — is where some participants started to feel the mask might be constricting, such as a really hard hockey shift or intense indoor soccer game,” he says.

Kennedy’s previous research has focused on the effects of cold air on the lungs. In earlier studies, he found that exercising without a mask or scarf in temperatures below -10 C puts undue stress on your lungs.

He explains that when temperatures drop, the air becomes devoid of moisture, forcing the lungs to work extra hard to humidify each breath. Over time, lung function can gradually deteriorate, especially during exercise, so watching your exercise intensity and wearing a mask both indoors — if you are prone to airway constriction, wheezing or coughing — and outdoors in extremely cold air can help you “love your lungs,” Kennedy says.

◆Life expectancy didn’t return to baseline after COVID pandemic, data suggest【University of Minnesota : Mary Van Beusekom　2025年7月16日】

While life expectancy in California edged up after plunging in 2021 amid the height of the COVID-19 pandemic, it hasn’t fully rebounded, a Northwestern University-led study suggests.

The research team analyzed death data for 2019 to 2024 from the California Comprehensive Death Files and population counts from the American Community Survey, publishing their findings last week in JAMA.

The researchers calculated life expectancy—the estimated lifespan of a hypothetical group of newborns based on current age-specific death rates—for the state. They also calculated life expectancy by quartile based on median income in census tracts and by the four racial groups (Hispanic, Asian, Black, and White) recorded on death certificates.

“US life expectancy plummeted during the COVID-19 pandemic and increased in 2022-2023,” the study authors wrote. “Although estimates for 2024 have not been reported for the US, vital statistics through 2024 are available for California.”

Drug overdoses accounted for large deficits in 2021-2023

Life expectancy in California rose slightly in the years leading up to the pandemic but fell sharply after 2019, bottoming out in 2021. Life expectancy regained lost ground thereafter but was still 0.86 year lower in 2024 than in 2019.

While people living in the lowest-income census tract quartile (Q1) lost more life expectancy than the highest-income group (Q4; eg, 4. vs 1.75 years in 2021), the gap between Q1 and Q4 in 2024 was similar to that in 2019 (5.77 vs 5.63 years).

Life-expectancy deficits relative to 2019 were greater in Hispanic and Black people than in their Asian and White counterparts (eg, 5.18, 4.04, 2.73, and 2.18 years in 2021, respectively). The Hispanic population recovered from losses in 2020-2021, when its life expectancy was lower than that of White people, but the advantage over the White population was lower in 2024 than in 2019 (1.17 vs 1.98 years). The life-expectancy gap between Black and White people was higher in 2024 than in 2019 (6.52 vs 5.67 years).

Relative to 2019, in 2021, COVID-19 accounted for 1.22 years (61.6%) of the life-expectancy deficit, after which non-COVID conditions became a larger contributor. Drug overdoses and cardiovascular disease made up 20.4% of the deficit in 2020 and 49.9% in 2023. Drug overdoses were a larger contributor in Q1 than in Q4 (36.6% vs 12.7% in 2023), while cardiovascular disease made a smaller contribution (11.5% vs 26.2%).

The increasing contribution of drug overdoses to life-expectancy losses in 2021-2023 affected all four racial groups but was strongest among Black people. Overdoses accounted for 0.99 years of the deficit in Black people in 2023, versus 0.42 years in Hispanic and White people and 0.08 years in Asians. Overdoses had a smaller role in life-expectancy declines in 2024 than in 2023 across California (0.17 vs 0.40 years).

Role of exposure to fentanyl, obesity

“Although a prior analysis of California data reported that the life expectancy–income gradient increased during 2020-2021, by 2024 the gap between Q1 and Q4 returned to prepandemic levels,” the researchers wrote. “Life expectancy in the Black population was much lower than in other racial and ethnic populations, and Black and Hispanic populations experienced the largest deficits.”

The near-doubling of the contribution of drug overdoses to the life-expectancy deficit from 2020 to 2023, which had a disproportionate effect on low-income and Black Californians, likely reflected greater exposure to the synthetic opioid fentanyl, the authors said. The substantial contribution of cardiovascular disease to deficits throughout the study, especially in high-income areas, which the researchers said is consistent with the state’s rising obesity rates.

“Study limitations include potential misclassification of causes of death, preliminary 2024 death and population counts, reliance on place (census tract–based rather than individual-level income), and the inability to quantify the contribution of long COVID,” the team wrote. “Results for California may not be generalizable to other states.”

◆Viral mitochondriopathy in COVID-19【ScienceDirect　2025年7月17日】

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), disrupts cellular mitochondria, leading to widespread chronic inflammation and multi-organ dysfunction. Viral proteins cause mitochondrial bioenergetic collapse, disrupt mitochondrial dynamics, and impair ionic homeostasis, while avoiding antiviral defenses, including mitochondrial antiviral signaling. These changes drive both acute COVID-19 and its longer-term effects, known as “long COVID”. This review examines new findings on the mechanisms by which SARS-CoV-2 affects mitochondria and for the impact on chronic immunity, long-term health risks, and potential treatments.

◆Mitochondrial respiration is necessary for CD8+ T cell proliferation and cell fate【nature immunology　2025年7月16日】

Abstract

Mitochondrial electron transport chain (ETC) function is linked to the generation of ATP, signaling molecules including reactive oxygen species (ROS), pyrimidines and tricarboxylic acid cycle metabolites. Mitochondrial electron transport is required for T cell proliferation. However, which mitochondrial ETC functions are necessary for each dynamic state of CD8+ T cell responses is unknown. Here we report that impairing mitochondrial complex III function, which diminishes respiration, proton pumping linked to ATP production and superoxide production, decreases peripheral naive numbers, antigen-induced CD8+ T cell proliferation and memory formation. Acute stimulation of mitochondrial complex III-deficient CD8+ T cells induced an exhausted-like phenotype. Expression of Ciona intestinalis alternative oxidase (AOX) in mitochondrial complex III-deficient CD8+ T cells restores respiration without generating ROS or proton pumping, and rescues proliferation and the exhausted phenotype but not naive or memory formation. Thus, T cell development, proliferation and memory formation have distinct requirements for mitochondrial complex III ROS.

◆Exposure to COVID-19 virus-like particles modulates firing patterns of cortical neurons in the mouse brain【nature : communications biology　2025年7月3日】

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes a systemic infection that affects the central nervous system. However, its high infectivity makes comprehensive research with the active virus challenging. Here, we use virus-like particles (VLPs) to explore how exposure to SARS-CoV-2 proteins affects brain activity patterns in wild-type mice and in mice that express the human tau protein. VLP exposure elicits changes in corticosterone and distinct chemokine levels. Longitudinal two-photon microscopy recordings in primary somatosensory and motor cortices reveal substantial short-term increases in cortical activity in VLP-injected mice, with increased stimulus-evoked activity in both genotypes and elevated spontaneous activity in the human tau genotype only. Vehicle-injected human tau mice also show increases in cortical activity patterns. Over the following weeks, activity metrics partially subside but do not completely return to baseline levels. Overall, our data suggest that exposure to SARS-CoV-2 VLPs leads to strong short-term disruption of cortical activity patterns in mice with long-term residual effects. Middle-aged human tau mice, which have a more vulnerable genetic background and overexpression of the tau protein, exhibit more severe pathobiology and may be at risk for more adverse outcomes.

◆Oxidative stress is a shared characteristic of ME/CFS and Long COVID【PNAS　2025年7月8日】

Significance

More than 65 million individuals worldwide are estimated to have Long COVID (LC), wherein individuals after infection report persistent fatigue, postexertional malaise, and other symptoms resembling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). With no clinically approved treatments or diagnostic markers for these conditions, there is an urgent need to define the molecular underpinnings. By studying bioenergetic characteristics of immune cells in healthy controls, ME/CFS, and LC donors, we find lymphocytes from ME/CFS and LC donors exhibit elevated oxidative stress. Due to excess oxidative stress and consequent mitochondrial damage, ME/CFS and LC donor lymphocytes consume excess host energy, contributing to debilitating fatigue and other sequelae.

Abstract

Over 65 million individuals worldwide are estimated to have Long COVID (LC), a complex multisystemic condition marked by fatigue, post-exertional malaise, and other symptoms resembling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). With no clinically approved treatments or reliable diagnostic markers, there is an urgent need to define the molecular underpinnings of these conditions. By studying bioenergetic characteristics of peripheral blood lymphocytes in 25 healthy controls, 27 ME/CFS, and 20 LC donors, we find both ME/CFS and LC donors exhibit signs of elevated oxidative stress, especially in the memory subset. Using a combination of flow cytometry, RNA-seq, mass spectrometry, and systems chemistry analysis, we observed aberrations in reactive oxygen species (ROS) clearance pathways including elevated glutathione levels, decreases in mitochondrial superoxide dismutase protein levels, and glutathione peroxidase 4–mediated lipid oxidative damage. Strikingly, these redox pathways changes show sex-specific trends. While ME/CFS females exhibit higher total ROS and mitochondrial calcium levels, males have normal ROS levels, with pronounced mitochondrial lipid oxidative damage. In females, these higher ROS levels correlate with T cell hyperproliferation, consistent with the known role of elevated ROS in initiating proliferation. This hyperproliferation can be attenuated by metformin, suggesting this Food and Drug Administration (FDA)-approved drug as a possible treatment, as also suggested by a recent clinical study of LC patients. Moreover, these results suggest a shared mechanistic basis for the systemic phenotypes of ME/CFS and LC, which can be detected by quantitative blood cell measurements, and that effective, patient-tailored drugs might be discovered using standard lymphocyte stimulation assays.

◆The SARS-CoV-2 main protease causes mitochondrial dysfunction in a yeast model【nature : scientific reports　2025年7月18日】

Abstract

Saccharomyces cerevisiae has proven to be an invaluable model organism for studying mitochondrial function owing to its genetic tractability and the high conservation of mitochondrial processes among eukaryotes, including humans. Yeasts are easy to culture and manipulate genetically, which allows rapid generation of mutant strains and detailed dissection of mitochondrial pathways. In addition, the ability of yeasts to survive without functional mitochondria allows the study of mutations that are lethal to organisms that are dependent on aerobic metabolism. Taking advantage of these benefits, we investigated the toxicity of SARS-CoV-2 main protease (Mpro) expression in yeast under conditions that enforce mitochondria-dependent aerobic metabolism. Our results showed that Mpro expression was highly toxic and significantly impaired yeast growth. Pronounced changes in the morphology and mitochondrial function were observed, indicating that mitochondrial pathways are exceptionally sensitive to Mpro activity. These results provide insights that may be relevant for understanding the effects of Mpro in more complex eukaryotic systems.

◆Chronic inflammation in Long COVID relationship to autoimmune diseases【ScienceDirect　2025年7月17日】

Abstract

The new coronavirus pandemic has been ongoing for nearly five years. In addition to the severe symptoms in the acute phase, it is accompanied by long-term complications and sequelae involving the respiratory, neurological, immune, circulatory, and gastrointestinal systems for several months or even years, which is called the Long COVID. Many studies have suggested that systemic chronic inflammation caused by residual viral components may be one of the pathophysiologic mechanisms of Long COVID. In this paper, we will review the autoimmune diseases caused by chronic inflammation. In particular, cytokine storminess, pro-inflammatory responses of inflammatory vesicles, mast cell activation syndrome, changes in the gut microbiota, molecular mimicry, reactivation of latent viruses, and coagulation abnormalities are among the pathways that contribute to autoimmune diseases, including Systemic Lupus Erythematosus, Guillain-Barré syndrome, rheumatoid arthritis. We intervene in the treatment of the disease with probiotics, immunoglobulins, the RECOVER clinical trial model, and immunomodulatory drugs. The aim is to enhance understanding of the pathophysiological mechanism of Long COVID and to provide a reference for the immunotherapy of patients.