Long COVID science, research and policy

Nature Medicine, Год журнала: 2024, Номер 30(8), С. 2148 - 2164

Опубликована: Авг. 1, 2024

Long COVID represents the constellation of post-acute and long-term health effects caused by SARS-CoV-2 infection; it is a complex, multisystem disorder that can affect nearly every organ system be severely disabling. The cumulative global incidence long around 400 million individuals, which estimated to have an annual economic impact approximately $1 trillion-equivalent about 1% economy. Several mechanistic pathways are implicated in COVID, including viral persistence, immune dysregulation, mitochondrial dysfunction, complement endothelial inflammation microbiome dysbiosis. devastating impacts on individual lives and, due its complexity prevalence, also has major ramifications for systems economies, even threatening progress toward achieving Sustainable Development Goals. Addressing challenge requires ambitious coordinated-but so far absent-global research policy response strategy. In this interdisciplinary review, we provide synthesis state scientific evidence assess human health, systems, economy metrics, forward-looking roadmap.

Язык: Английский

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Long COVID: a clinical update

The Lancet, Год журнала: 2024, Номер 404(10453), С. 707 - 724

Опубликована: Июль 31, 2024

Язык: Английский

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Mechanisms of long COVID and the path toward therapeutics

Cell, Год журнала: 2024, Номер unknown

Опубликована: Сен. 1, 2024

Язык: Английский

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Mitochondrial dysfunction in long COVID: mechanisms, consequences, and potential therapeutic approaches

GeroScience, Год журнала: 2024, Номер 46(5), С. 5267 - 5286

Опубликована: Апрель 26, 2024

Abstract The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has introduced medical community to phenomenon of long COVID, a condition characterized persistent symptoms following resolution acute phase infection. Among myriad reported COVID sufferers, chronic fatigue, cognitive disturbances, and exercise intolerance are predominant, suggesting systemic alterations beyond initial viral pathology. Emerging evidence pointed mitochondrial dysfunction as potential underpinning mechanism contributing persistence diversity symptoms. This review aims synthesize current findings related in exploring its implications for cellular energy deficits, oxidative stress, immune dysregulation, metabolic endothelial dysfunction. Through comprehensive analysis literature, we highlight significance health pathophysiology drawing parallels with similar clinical syndromes linked post-infectious states other diseases where impairment been implicated. We discuss therapeutic strategies targeting function, including pharmacological interventions, lifestyle modifications, exercise, dietary approaches, emphasize need further research collaborative efforts advance our understanding management COVID. underscores critical role calls multidisciplinary approach address gaps knowledge treatment options those affected this condition.

Язык: Английский

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Fibrin drives thromboinflammation and neuropathology in COVID-19

Nature, Год журнала: 2024, Номер 633(8031), С. 905 - 913

Опубликована: Авг. 28, 2024

Abstract Life-threatening thrombotic events and neurological symptoms are prevalent in COVID-19 persistent patients with long COVID experiencing post-acute sequelae of SARS-CoV-2 infection 1–4 . Despite the clinical evidence 1,5–7 , underlying mechanisms coagulopathy its consequences inflammation neuropathology remain poorly understood treatment options insufficient. Fibrinogen, central structural component blood clots, is abundantly deposited lungs brains COVID-19, correlates disease severity a predictive biomarker for post-COVID-19 cognitive deficits 1,5,8–10 Here we show that fibrin binds to spike protein, forming proinflammatory clots drive systemic thromboinflammation COVID-19. Fibrin, acting through inflammatory domain, required oxidative stress macrophage activation lungs, whereas it suppresses natural killer cells, after infection. Fibrin promotes neuroinflammation neuronal loss infection, as well innate immune brain independently active A monoclonal antibody targeting domain provides protection from microglial injury, lung Thus, drives fibrin-targeting immunotherapy may represent therapeutic intervention acute COVID.

Язык: Английский

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Persistent symptoms and clinical findings in adults with post-acute sequelae of COVID-19/post-COVID-19 syndrome in the second year after acute infection: A population-based, nested case-control study

PLoS Medicine, Год журнала: 2025, Номер 22(1), С. e1004511 - e1004511

Опубликована: Янв. 23, 2025

Background Self-reported health problems following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are common and often include relatively non-specific complaints such as fatigue, exertional dyspnoea, concentration or memory disturbance sleep problems. The long-term prognosis of post-acute sequelae COVID-19/post-COVID-19 (PCS) is unknown, data finding correlating organ dysfunction pathology with self-reported symptoms in patients non-recovery from PCS scarce. We wanted to describe clinical characteristics diagnostic findings among persisting for >1 year assessed risk factors persistence versus improvement. Methods This nested population-based case-control study included subjects aged 18–65 years ( n = 982) age- sex-matched control without 576) according an earlier questionnaire (6–12 months after infection, phase 1) consenting provide follow-up information undergo comprehensive outpatient assessment, including neurocognitive, cardiopulmonary exercise, laboratory testing four university centres southwestern Germany (phase 2, another 8.5 [median, range 3–14 months] 1). mean age the participants was 48 years, 65% were female. At 67.6% at 1 developed persistent PCS, whereas 78.5% recovered remained free related PCS. Improvement associated mild index previous full-time employment, educational status, no specialist consultation not attending a rehabilitation programme. development new initially intercurrent secondary SARS-CoV-2 status. Patients less frequently never smokers (61.2% 75.7%), more obese (30.2% 12.4%) higher values body mass (BMI) fat, had lower status (university entrance qualification 38.7% 61.5%) than continued recovery. Fatigue/exhaustion, neurocognitive disturbance, chest symptoms/breathlessness anxiety/depression/sleep predominant symptom clusters. Exercise intolerance post-exertional malaise (PEM) >14 h compatible myalgic encephalomyelitis/chronic fatigue reported by 35.6% 11.6% patients, respectively. In analyses adjusted sex-age class combinations, centre qualification, significant differences between those recovery observed performance three different tests, scores perceived stress, subjective cognitive disturbances, dysautonomia, depression anxiety, quality, quality life. handgrip strength (40.2 [95% confidence interval (CI) [39.4, 41.1]] 42.5 CI [41.5, 43.6]] kg), maximal oxygen consumption (27.9 [27.3, 28.4]] 31.0 [30.3, 31.6]] ml/min/kg weight) ventilatory efficiency (minute ventilation/carbon dioxide production slope, 28.8 [28.3, 29.2]] 27.1 [26.6, 27.7]]) significantly reduced relative group adjustment centre, education, BMI, smoking use beta blocking agents. There measures systolic diastolic cardiac function rest, level N-terminal brain natriuretic peptide blood levels other measurements (including complement activity, markers Epstein–Barr virus [EBV] reactivation, inflammatory coagulation markers, serum cortisol, adrenocorticotropic hormone dehydroepiandrosterone sulfate). Screening viral (PCR stool samples spike antigen plasma) subgroup negative. Sensitivity (pre-existing illness/comorbidity, obesity, medical care infection) revealed similar findings. PEM pain worse results almost all tests. A limitation that we objective on exercise capacity cognition before infection. addition, did unable attend clinic whatever reason illness, immobility social deprivation exclusion. Conclusions this study, majority working recover second their illness. Patterns essentially similar, dominated complaints. Despite signs deficits capacity, there major investigations, our do support persistence, EBV adrenal insufficiency increased turnover pathophysiologically relevant history disease might help stratify cases severity.

Язык: Английский

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Cerebromicrovascular mechanisms contributing to long COVID: implications for neurocognitive health

GeroScience, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

Abstract Long COVID (also known as post-acute sequelae of SARS-CoV-2 infection [PASC] or post-COVID syndrome) is characterized by persistent symptoms that extend beyond the acute phase infection, affecting approximately 10% to over 30% those infected. It presents a significant clinical challenge, notably due pronounced neurocognitive such brain fog. The mechanisms underlying these effects are multifactorial, with mounting evidence pointing central role cerebromicrovascular dysfunction. This review investigates key pathophysiological contributing cerebrovascular dysfunction in long and their impacts on health. We discuss how endothelial tropism direct vascular trigger dysfunction, impaired neurovascular coupling, blood–brain barrier disruption, resulting compromised cerebral perfusion. Furthermore, appears induce mitochondrial enhancing oxidative stress inflammation within cells. Autoantibody formation following also potentially exacerbates injury, chronic ongoing compromise. These factors collectively contribute emergence white matter hyperintensities, promote amyloid pathology, may accelerate neurodegenerative processes, including Alzheimer’s disease. emphasizes critical advanced imaging techniques assessing health need for targeted interventions address complications. A deeper understanding essential advance treatments mitigate its long-term consequences.

Язык: Английский

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Red blood cell distribution width to albumin ratio (RAR) is associated with low cognitive performance in American older adults: NHANES 2011–2014

BMC Geriatrics, Год журнала: 2025, Номер 25(1)

Опубликована: Март 7, 2025

The red blood cell distribution width to albumin ratio (RAR) is a novel comprehensive biomarker of inflammation and nutrition, which has emerged as reliable prognostic indicator for adverse outcomes mortality in patients with various diseases. However, the association between RAR low cognitive performance older adults remains unclear. This study aims investigate relationship among United States. study, retrospective analysis, included 2,765 participants aged 60 years from National Health Nutrition Examination Survey (NHANES) conducted 2011 2014. Low was assessed using word learning subset Consortium Establish Registry Alzheimer's Disease (CERAD), Digit Symbol Substitution Test (DSST), Animal Fluency (AFT). defined scores below lowest quartile each test. evaluated weighted multivariable logistic regression, restricted cubic splines (RCS), subgroup analyses. After adjusting all potential confounders, independently linearly positively associated both DSST AFT performance. Specifically, compared first RAR, those fourth had adjusted ORs (95% CIs) 1.81 (1.03, 3.20) 1.68 (1.05, 2.67) Subgroup analysis did not reveal significant interactions stratification variables. significantly Maintaining lower may be crucial strategy mitigating risk decline elderly population.

Язык: Английский

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Blood-brain barrier disruption: a culprit of cognitive decline?

Fluids and Barriers of the CNS, Год журнала: 2024, Номер 21(1)

Опубликована: Авг. 7, 2024

Cognitive decline covers a broad spectrum of disorders, not only resulting from brain diseases but also systemic diseases, which seriously influence the quality life and expectancy patients. As highly selective anatomical functional interface between circulation, blood-brain barrier (BBB) plays pivotal role in maintaining homeostasis normal function. The pathogenesis underlying cognitive may vary, nevertheless, accumulating evidences support BBB disruption as most prevalent contributing factor. This mainly be attributed to inflammation, metabolic dysfunction, cell senescence, oxidative/nitrosative stress excitotoxicity. However, direct evidence showing that causes is scarce, interestingly, manipulation opening alone exert beneficial or detrimental neurological effects. A overview present literature shows close relationship decline, risk factors disruption, well cellular molecular mechanisms disruption. Additionally, we discussed possible leading by potential therapeutic strategies prevent enhance repair. review aims foster more investigations on early diagnosis, effective therapeutics, rapid restoration against would yield better outcomes patients with dysregulated function, although their causative has yet been completely established.

Язык: Английский

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Engineered Wnt7a ligands rescue blood–brain barrier and cognitive deficits in a COVID-19 mouse model

Brain, Год журнала: 2024, Номер 147(5), С. 1636 - 1643

Опубликована: Фев. 2, 2024

Abstract Respiratory infection with SARS-CoV-2 causes systemic vascular inflammation and cognitive impairment. We sought to identify the underlying mechanisms mediating cerebrovascular dysfunction following mild respiratory infection. To this end, we performed unbiased transcriptional analysis brain endothelial cell signalling pathways dysregulated by mouse adapted MA10 in aged immunocompetent C57Bl/6 mice vivo. This revealed significant suppression of Wnt/β-catenin signalling, a critical regulator blood–brain barrier (BBB) integrity. therefore hypothesized that enhancing activity would offer protection against BBB permeability, neuroinflammation, neurological signs acute Indeed, found delivery cerebrovascular-targeted, engineered Wnt7a ligands protected integrity, reduced T-cell infiltration brain, microglial activation Importantly, strategy also mitigated induced deficits novel object recognition assay for learning memory pole descent task bradykinesia. These observations suggest enhancement or its downstream effectors could be potential interventional strategies restoring health viral infections.

Язык: Английский

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