Long COVID: mechanisms, risk factors and recovery

Experimental Physiology, Год журнала: 2022, Номер 108(1), С. 12 - 27

Опубликована: Ноя. 22, 2022

Abstract Long COVID, the prolonged illness and fatigue suffered by a small proportion of those infected with SARS‐CoV‐2, is placing an increasing burden on individuals society. A Physiological Society virtual meeting in February 2022 brought clinicians researchers together to discuss current understanding long COVID mechanisms, risk factors recovery. This review highlights themes arising from that meeting. It considers nature exploring its links other post‐viral illnesses such as myalgic encephalomyelitis/chronic syndrome, how research can help us better support suffering all syndromes. started particularly swiftly populations routinely monitoring their physical performance – namely military elite athletes. The high degree diagnosis, intervention success these active suggest management strategies for wider population. We then consider key component populations, cardiopulmonary exercise training, has revealed COVID‐related changes physiology including alterations peripheral muscle function, ventilatory inefficiency autonomic dysfunction. impact dysautonomia are further discussed relation postural orthostatic tachycardia treatment aim combat sympathetic overactivation stimulating vagus nerve. interrogate mechanisms underlie symptoms, focus impaired oxygen delivery due micro‐clotting disruption cellular energy metabolism, before considering indirectly or directly tackle mechanisms. These include remote inspiratory training integrated care pathways combine rehabilitation drug interventions into healthcare access across different populations. Overall, this showcases physiological reveals occur therapeutic being developed tested condition.

Язык: Английский

---

Possible Pathogenesis and Prevention of Long COVID: SARS-CoV-2-Induced Mitochondrial Disorder

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(9), С. 8034 - 8034

Опубликована: Апрель 28, 2023

Patients who have recovered from coronavirus disease 2019 (COVID-19) infection may experience chronic fatigue when exercising, despite no obvious heart or lung abnormalities. The present lack of effective treatments makes managing long COVID a major challenge. One the underlying mechanisms be mitochondrial dysfunction. Severe acute respiratory syndrome 2 (SARS-CoV-2) infections can alter mitochondria responsible for energy production in cells. This alteration leads to dysfunction which, turn, increases oxidative stress. Ultimately, this results loss integrity and cell death. Moreover, viral proteins bind complexes, disrupting function causing immune cells over-react. over-reaction inflammation potentially symptoms. It is important note that roles damage inflammatory responses caused by SARS-CoV-2 development are still being elucidated. Targeting provide promising new clinical approaches long-COVID patients; however, further studies needed evaluate safety efficacy such approaches.

Язык: Английский

---

Delayed induction of type I and III interferons mediates nasal epithelial cell permissiveness to SARS-CoV-2

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Дек. 7, 2021

Abstract The nasal epithelium is a plausible entry point for SARS-CoV-2, site of pathogenesis and transmission, may initiate the host response to SARS-CoV-2. Antiviral interferon (IFN) responses are critical outcome Yet little known about interaction between SARS-CoV-2 innate immunity in this tissue. Here we apply single-cell RNA sequencing proteomics primary cell model human differentiated at air-liquid interface. demonstrates widespread tropism epithelial types. dominated by type I III IFNs interferon-stimulated gene products. This notably delayed onset relative viral expression compared other respiratory viruses. Nevertheless, once established, paracrine IFN begins impact on replication. When provided prior infection, recombinant IFNβ or IFNλ1 induces an efficient antiviral state that potently restricts replication, preserving barrier integrity. These data imply IFN-I/III initiates airway suggest delivery be potential chemoprophylactic strategy.

Язык: Английский

---

Artificial intelligence: machine learning for chemical sciences

Journal of Chemical Sciences, Год журнала: 2021, Номер 134(1)

Опубликована: Дек. 21, 2021

Язык: Английский

---

SARS-CoV-2: A Master of Immune Evasion

Biomedicines, Год журнала: 2022, Номер 10(6), С. 1339 - 1339

Опубликована: Июнь 7, 2022

Viruses and their hosts have coevolved for a long time. This coevolution places both the pathogen human immune system under selective pressure; on one hand, has evolved to combat viruses virally infected cells, while developed sophisticated mechanisms escape recognition destruction by system. SARS-CoV-2, that is causing current COVID-19 pandemic, shown remarkable ability antibody neutralization, putting vaccine efficacy at risk. One of virus’s evasion strategies mitochondrial sabotage: reactive oxygen species (ROS) production, physiology impaired, interferon antiviral response suppressed. Seminal studies identified an intra-cytoplasmatic pathway viral infection, which occurs through construction tunneling nanotubes (TNTs), hence enhancing infection avoiding surveillance. Another method evading monitoring disruption antigen presentation. In this scenario, SARS-CoV-2 reduces MHC-I molecule expression: SARS-CoV-2’s open reading frames (ORF 6 ORF 8) produce proteins specifically downregulate molecules. All these are also exploited other elude detection should be studied in depth improve effectiveness future treatments. Compared Wuhan strain or Delta variant, Omicron mutations impaired its generate syncytia, thus reducing pathogenicity. Conversely, allowed it neutralization preventing cellular recognition, making most contagious evasive variant date.

Язык: Английский

---

Pathophysiological involvement of host mitochondria in SARS-CoV-2 infection that causes COVID-19: a comprehensive evidential insight

Molecular and Cellular Biochemistry, Год журнала: 2022, Номер 478(6), С. 1325 - 1343

Опубликована: Окт. 29, 2022

SARS-CoV-2 is a positive-strand RNA virus that infects humans through the nasopharyngeal and oral route causing COVID-19. Scientists left no stone unturned to explore targetable key player in COVID-19 pathogenesis against which therapeutic interventions can be initiated. This article has attempted review, coordinate accumulate most recent observations support of hypothesis predicting altered state mitochondria concerning mitochondrial redox homeostasis, inflammatory regulations, morphology, bioenergetics antiviral signalling infection. Mitochondria extremely susceptible physiological as well pathological stimuli, including viral infections. Recent studies suggest pathogeneses alter integrity, turn modulate cellular response M protein inhibited (MAVS) aggregation hinders innate response. Viral open reading frames (ORFs) also play an instrumental role altering regulation immune Notably, ORF-9b ORF-6 impair MAVS activation. In aged persons, NLRP3 inflammasome over-activated due impaired function, increased reactive oxygen species (mtROS), and/or circulating free DNA, resulting hyper-response classically activated macrophages. tries understand how fission–fusion dynamics affected by virus. review comprehends overall attribute prognosis patients infected with taking into account pertinent vitro, pre-clinical clinical data encompassing subjects broad range severity morbidity. endeavour may help exploring novel non-canonical strategies disease associated complications.

Язык: Английский

---

Immunosenescence and inflamm-ageing in COVID-19

Ageing Research Reviews, Год журнала: 2022, Номер 84, С. 101818 - 101818

Опубликована: Дек. 11, 2022

Язык: Английский

---

Deciphering the Relationship between SARS-CoV-2 and Cancer

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(9), С. 7803 - 7803

Опубликована: Апрель 25, 2023

Some viruses are known to be associated with the onset of specific cancers. These microorganisms, oncogenic or oncoviruses, can convert normal cells into cancer by modulating central metabolic pathways hampering genomic integrity mechanisms, consequently inhibiting apoptotic machinery and/or enhancing cell proliferation. Seven promote tumorigenesis in humans: human papillomavirus (HPV), hepatitis B and C (HBV, HCV), Epstein-Barr virus (EBV), T-cell leukemia 1 (HTLV-1), Kaposi sarcoma-associated herpesvirus (KSHV), Merkel polyomavirus (MCPyV). Recent research indicates that SARS-CoV-2 infection COVID-19 progression may predispose recovered patients accelerate development. This hypothesis is based on growing evidence regarding ability modulate pathways, promoting chronic low-grade inflammation causing tissue damage. Herein, we summarize main relationships date between cancer, providing a summary proposed biochemical mechanisms behind cellular transformation. Mechanistically, DNA (such as HPV, HBV, EBV, MCPyV) encode their oncogenes. In contrast, RNA (like HCV, HTLV-1) oncogenes trigger host through cis-/-trans activation leading different types cancer. As for SARS-CoV-2, its role an seems occur inhibition oncosuppressors controlling autophagy infected cells. However, these effects could significant particular scenarios like those linked severe long COVID. On other hand, looking at SARS-CoV-2─cancer relationship from opposite perspective, oncolytic anti-tumor immune response were triggered some cases. summary, our work aims recall comprehensive attention scientific community elucidate and, more general, β-coronavirus susceptibility prevention supporting therapeutic approaches.

Язык: Английский

---

Metabolic Alterations in SARS-CoV-2 Infection and Its Implication in Kidney Dysfunction

Frontiers in Physiology, Год журнала: 2021, Номер 12

Опубликована: Фев. 25, 2021

Clinical strategies focusing on pathogen elimination are expected in an infectious-disease outbreak, such as the severe coronavirus disease 2019 (COVID-19), to avoid organ dysfunction. However, understanding host response viral infection is crucial develop effective treatment optimize patient’s conditions. The pathogenic viruses can promote metabolic changes during infection, favoring its survival, altering cell phenotype and function, causing sustained inflammation tissue injury. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), etiological agent of COVID-19, provokes systemic possibly lipid glucose metabolism. Besides syndrome (SARS), SARS-CoV-2 cause kidney injury, which has been associated with severity disease. Although it not clear mechanisms whereby induces dysfunction, known that virus presents tropism, namely, podocytes proximal tubular epithelial cells. Changes renal metabolism disorders important events injury progression. Here, we explored interface raised perspective disturbances a critical event dysfunction COVID-19.

Язык: Английский

---

Coronavirus disease 2019 (COVID‐19) update: From metabolic reprogramming to immunometabolism

Journal of Medical Virology, Год журнала: 2022, Номер 94(10), С. 4611 - 4627

Опубликована: Июнь 11, 2022

The field of immunometabolism investigates and describes the effects metabolic rewiring in immune cells throughout activation fates these cells. Recently, it has been appreciated that plays an essential role progression viral infections, cancer, autoimmune diseases. Regarding COVID-19, aberrant response underlying diseases establishes two major respiratory pathologies, including acute distress syndrome (ARDS) or pneumonia-induced lung injury (ALI). Both innate adaptive immunity (T cell-based) were impaired course severe coronavirus 2 (SARS-CoV-2) infection. Current findings have deciphered macrophages (innate cells) are involved inflammatory seen COVID-19. It demonstrated system can change reprogramming some conditions, diseases, infectious disease, growing on COVID-19 allow exploration metabolites with immunomodulatory properties as future therapies to combat this hyperinflammatory response. elucidation exact mechanism reprograming could help apply more precise approaches initial diagnosis, prognosis, in-hospital therapy. This report discusses latest from host immunometabolic responses.

Язык: Английский

---