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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Sex differences in symptomatology and immune profiles of Long COVID

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 2, 2024

Summary Strong sex differences in the frequencies and manifestations of Long COVID (LC) have been reported with females significantly more likely than males to present LC after acute SARS-CoV-2 infection 1–7 . However, whether immunological traits underlying differ between sexes, such explain differential symptomology is currently unknown. Here, we performed sex-based multi-dimensional immune-endocrine profiling 165 individuals 8 without an exploratory, cross-sectional study identify key biological LC. We found that female male participants experienced different sets symptoms, distinct patterns organ system involvement, suffering from a higher symptom burden. Machine learning approaches identified immune features characterized males. Males had decreased monocyte DC populations, elevated NK cells, plasma cytokines including IL-8 TGF-β-family members. Females increased exhausted T cytokine-secreting antibody reactivity latent herpes viruses EBV, HSV-2, CMV, lower testosterone levels their control counterparts. Testosterone were associated burden over designation. These findings suggest processes illuminate crucial role dysregulation sex-specific pathology.

Язык: Английский

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Sex Differences in Long COVID

JAMA Network Open, Год журнала: 2025, Номер 8(1), С. e2455430 - e2455430

Опубликована: Янв. 22, 2025

Importance A substantial number of individuals worldwide experience long COVID, or post-COVID condition. Other postviral and autoimmune conditions have a female predominance, but whether the same is true for especially within different subgroups, uncertain. Objective To evaluate sex differences in risk developing COVID among adults with SARS-CoV-2 infection. Design, Setting, Participants This cohort study used data from National Institutes Health (NIH) Researching to Enhance Recovery (RECOVER)–Adult cohort, which consists enrolled prospectively followed up at 83 sites 33 US states plus Washington, DC, Puerto Rico. Data were examined all participants between October 29, 2021, July 5, 2024, who had qualifying visit 6 months more after their initial Exposure Self-reported (male, female) assigned birth. Main Outcomes Measures Development measured using self-reported symptom-based questionnaire scoring guideline first that occurred least Propensity score matching was estimate ratios (RRs) (95% CIs). The full model included demographic clinical characteristics social determinants health, reduced only age, race, ethnicity. Results Among 12 276 experienced infection (8969 [73%] female; mean [SD] age infection, 46 [15] years), associated higher primary (RR, 1.31; 95% CI, 1.06-1.62) 1.44; 1.17-1.77) models. finding observed across groups except 18 39 years 1.04; 0.72-1.49). Female significantly overall when analysis restricted nonpregnant 1.50; 95%: 1.27-1.77). aged 40 54 years, ratio 1.42 0.99-2.03) menopausal 1.45 1.15-1.83) nonmenopausal compared male participants. Conclusions Relevance In this prospective NIH RECOVER-Adult an increased sex, association pregnancy, status dependent. These findings highlight need identify biological mechanisms contributing specificity facilitate stratification, targeted drug development, improved management COVID.

Язык: Английский

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Sex differences in airway disease: estrogen and airway surface liquid dynamics

Biology of Sex Differences, Год журнала: 2024, Номер 15(1)

Опубликована: Июль 18, 2024

Abstract Biological sex differences exist for many airway diseases in which females have either worse or better health outcomes. Inflammatory such as cystic fibrosis (CF) and asthma display a clear male advantage post-puberty while female benefit is observed during the pre-puberty years. The influence of menstrual cycle stage pregnancy on frequency severity pulmonary exacerbations CF point to role steroid hormones, particularly estrogen, underpinning biological these diseases. There are ways by estrogen may aggravate involving disturbances surface liquid (ASL) dynamics, inappropriate hyper-immune allergenic responses, well exacerbation pathogen virulence. deleterious effect function contrasts with characterised edema pneumonia, acute respiratory distress syndrome (ARDS) COVID-19. Airway hypersecretion alveolar flooding hallmarks ARDS COVID-19, contribute morbidity mortality severe forms ASL dynamics encompasses intrinsic features thin lining fluid covering epithelium regulate mucociliary clearance (ciliary beat, height, volume, pH, viscosity, mucins, channel activating proteases) addition innate defence mechanisms (pathogen virulence, cytokines, defensins, specialised pro-resolution lipid mediators, metabolism). Estrogen regulation contributing CF, COVID-19 major focus this review. Graphical

Язык: Английский

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Possible Role of Fibrinaloid Microclots in Postural Orthostatic Tachycardia Syndrome (POTS): Focus on Long COVID

Journal of Personalized Medicine, Год журнала: 2024, Номер 14(2), С. 170 - 170

Опубликована: Янв. 31, 2024

Postural orthostatic tachycardia syndrome (POTS) is a common accompaniment of variety chronic, inflammatory diseases, including long COVID, as are small, insoluble, 'fibrinaloid' microclots. We here develop the argument, with accompanying evidence, that fibrinaloid microclots, through their ability to block flow blood microcapillaries and thus cause tissue hypoxia, not simply correlated but in fact, by preceding it, may be chief intermediary POTS, which body's exaggerated 'physiological' response hypoxia. Similar reasoning accounts for symptoms bundled under term 'fatigue'. Amyloids known membrane disruptors, when targets nerve membranes, this can explain neurotoxicity hence autonomic nervous system dysfunction contributes POTS. Taken together view, we indicate microclots serve link POTS fatigue COVID manner at once both mechanistic explanatory. This has clear implications treatment such diseases.

Язык: Английский

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Increased fibrinaloid microclot counts in platelet-poor plasma are associated with Long COVID

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 5, 2024

Abstract Outcomes following SARS-CoV-2 infection are variable; whilst the majority of patients recover without serious complications, a subset develop prolonged illness termed Long COVID or post-acute sequelae (PASC). The pathophysiology underlying remains unclear but appears to involve multiple mechanisms including persistent inflammation, coagulopathy, autoimmunity, and organ damage. Studies suggest that microclots, also known as fibrinaloids, play role in COVID. In this context, we developed method quantify microclots investigated relationship between microclot counts We show cohort, platelet-poor plasma from samples had higher count compared control groups retained wide distribution counts. Recent COVID-19 infections were seen be associated with than equivalent subsequent time-dependent reduction Our findings could potential biomarker disease and/or treatment target some patients.

Язык: Английский

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Clinical Spectrum of Long COVID: Effects on Female Reproductive Health

Viruses, Год журнала: 2024, Номер 16(7), С. 1142 - 1142

Опубликована: Июль 16, 2024

The COVID-19 pandemic caused by SARS-CoV-2 has presented numerous health challenges, including long-term COVID, which affects female reproductive health. This review consolidates the current research on impact of menstrual cycle, ovarian function, fertility, and overall gynecological study emphasizes role angiotensin-converting enzyme receptors in viral entry subsequent tissue-specific pathological effects. It also explores potential influence long COVID hormonal balance immune responses, contributing to irregularities impaired function. findings indicate a higher prevalence among women, highlighting substantial implications for need sex-sensitive longitudinal studies. Enhanced surveillance targeted are essential develop effective interventions that prioritize women's well-being following infection. advocates sex-informed approach ongoing healthcare strategies, aiming provide up-to-date pertinent data providers general public, ultimately improving outcomes females affected COVID.

Язык: Английский

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Comorbidities and neurosurgical interventions in a cohort with connective tissue disorders

Frontiers in Neurology, Год журнала: 2025, Номер 15

Опубликована: Янв. 22, 2025

Background Connective tissue disorders (CTDs) are a heterogeneous group of often presenting with variety comorbidities including musculoskeletal, autonomic, and immune dysfunction. Some CTDs such as hypermobile Ehlers-Danlos syndrome (hEDS), which is one the most common, have been associated neurological requiring surgical intervention. The frequency these in populations their subsequent requirement for neurosurgical intervention remains unclear. Methods Based on our initial experience this population, we investigated presentation rates specific interventions cohort individuals referred to institution evaluation management issues secondary diagnosed or suspected from 2014 2023. Primary diagnoses were made by referring physicians institutions based clinical standard-of-care criteria. We evaluated relationships between multivariate correlation intersection plots using UpSetR package. Results Of 759 individuals, excluded 42 incomplete data. From remaining (total cohort, N = 717), 460 (64%) hEDS, 7 CTD other than 250 lacked formal diagnosis. found that hEDS had higher certain comorbidities, Mast Cell Activation Disorder Postural Orthostatic Tachycardia Syndrome, compared without diagnosis (unaffected). total 426 (59%) Chiari I Malformation, shared significant overlap hEDS. those who elected undergo surgery ( n 612), 61% required craniocervical fusion (CCF). Notably, 404 chose intervention, which, 73% CCF instability. Conclusion In retrospective study potentially defined commonly encountered revealed rate at they

Язык: Английский

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Postacute Sequelae of COVID (PASC or Long COVID): An Evidenced-Based Approach

Open Forum Infectious Diseases, Год журнала: 2024, Номер 11(9)

Опубликована: Авг. 27, 2024

Abstract While the acute manifestations of infectious diseases are well known, in some individuals, symptoms can either persist or appear after period. Postviral fatigue syndromes recognized with other viral infections and described coronavirus disease 2019 (COVID-19). We have a growing number individuals that for weeks, months, years. Here, we share evidence regarding abnormalities associated postacute sequelae COVID-19 (PASC) therapeutics. describe physiological biochemical seen reporting PASC. several evidence-based interventions to offer patients. It is expected this understanding mechanisms driving PASC benefits certain therapeutics may not only lead better outcomes those but also potential treating postinfectious sequelae.

Язык: Английский

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Potential Beneficial Effects of Naringin and Naringenin on Long COVID—A Review of the Literature

Microorganisms, Год журнала: 2024, Номер 12(2), С. 332 - 332

Опубликована: Фев. 4, 2024

Coronavirus disease 2019 (COVID-19) caused a severe epidemic due to acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Recent studies have found that patients do not completely recover from infections, but instead, suffer variety of post-acute sequelae SARS-CoV-2 infection, known as long COVID. The effects COVID can be far-reaching, with duration up six months and range symptoms such cognitive dysfunction, immune dysregulation, microbiota dysbiosis, myalgic encephalomyelitis/chronic fatigue syndrome, myocarditis, pulmonary fibrosis, cough, diabetes, pain, reproductive thrombus formation. However, recent shown naringenin naringin palliative on various COVID-19 sequelae. Flavonoids naringenin, commonly in fruits vegetables, positive effects, including reducing inflammation, preventing viral providing antioxidants. This article discusses the molecular mechanisms clinical treating above diseases. It proposes them potential drugs for treatment COVID, it inferred exhibit extended medications, future likely serving nutraceuticals or supplements comprehensive alleviation manifestations complications.

Язык: Английский

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