Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments

Infectious Diseases, Год журнала: 2021, Номер 53(10), С. 737 - 754

Опубликована: Май 22, 2021

Long COVID or post-COVID-19 syndrome first gained widespread recognition among social support groups and later in scientific medical communities. This illness is poorly understood as it affects COVID-19 survivors at all levels of disease severity, even younger adults, children, those not hospitalized. While the precise definition long may be lacking, most common symptoms reported many studies are fatigue dyspnoea that last for months after acute COVID-19. Other persistent include cognitive mental impairments, chest joint pains, palpitations, myalgia, smell taste dysfunctions, cough, headache, gastrointestinal cardiac issues. Presently, there limited literature discussing possible pathophysiology, risk factors, treatments COVID, which current review aims to address. In brief, driven by long-term tissue damage (e.g. lung, brain, heart) pathological inflammation from viral persistence, immune dysregulation, autoimmunity). The associated factors female sex, more than five early symptoms, dyspnoea, prior psychiatric disorders, specific biomarkers D-dimer, CRP, lymphocyte count), although research required substantiate such factors. preliminary evidence suggests personalized rehabilitation training help certain cases, therapeutic drugs repurposed other similar conditions, myalgic encephalomyelitis chronic syndrome, postural orthostatic tachycardia mast cell activation also hold potential. sum, this hopes provide understanding what known about COVID.

Язык: Английский

---

Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms

Frontiers in Microbiology, Год журнала: 2021, Номер 12

Опубликована: Июнь 23, 2021

The novel virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic of disease 2019 (COVID-19). Across the globe, subset patients who sustain an SARS-CoV-2 infection are developing wide range persistent symptoms that do not resolve over course many months. These being given diagnosis Long COVID or Post-acute sequelae COVID-19 (PASC). It is likely individual with PASC have different underlying biological factors driving their symptoms, none which mutually exclusive. This paper details mechanisms by RNA viruses beyond just be connected to long-term health consequences. also reviews literature on and other virus-initiated chronic syndromes such as post-Ebola myalgic encephalomyelitis/chronic fatigue (ME/CFS) discuss scenarios for symptom development. Potential contributors include consequences from injury one multiple organs, reservoirs in certain tissues, re-activation neurotrophic pathogens herpesviruses under conditions immune dysregulation, interactions host microbiome/virome communities, clotting/coagulation issues, dysfunctional brainstem/vagus nerve signaling, ongoing activity primed cells, autoimmunity due molecular mimicry between pathogen proteins. individualized nature suggests therapeutic approaches may required best manage care specific diagnosis.

Язык: Английский

---

Long-Term Respiratory and Neurological Sequelae of COVID-19

Medical Science Monitor, Год журнала: 2020, Номер 26

Опубликована: Ноя. 1, 2020

Since the initial reports of coronavirus disease 2019 (COVID-19) in China late 2019, infections from severe acute respiratory syndrome 2 (SARS-CoV-2) have spread rapidly, resulting a global pandemic that has caused millions deaths. Initially, large number infected people required direction healthcare resources to provide supportive care for acutely ill population an attempt reduce mortality. While clinical trials safe and effective antiviral agents are ongoing, vaccine development programs being accelerated, long-term sequelae SARS-CoV-2 infection become increasingly recognized concerning. Although upper lower tracts main sites entry into body, COVID-19 pneumonia as most common presentation, lung damage may be followed by pulmonary fibrosis chronic impairment function, with impaired quality life. Also, increasing shown involves central nervous system (CNS) peripheral (PNS) directly or indirectly damages neurons, leading neurological sequelae. This review aims update on mechanisms involved 3 areas injury, neuronal neurodegenerative diseases, including Alzheimer disease, Parkinson multiple sclerosis, highlights need patient monitoring following stage rationale prevention, diagnosis, management these potential

Язык: Английский

---

Neuroinvasion and Encephalitis Following Intranasal Inoculation of SARS-CoV-2 in K18-hACE2 Mice

Viruses, Год журнала: 2021, Номер 13(1), С. 132 - 132

Опубликована: Янв. 19, 2021

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can cause neurological disease in humans, but little is known about the pathogenesis of SARS-CoV-2 central nervous system (CNS). Herein, using K18-hACE2 mice, we demonstrate that neuroinvasion and encephalitis associated with mortality these mice. Intranasal mice 105 plaque-forming units resulted 100% by day 6 after infection. The highest virus titers lungs were observed on 3 declined days 5 By contrast, very high levels infectious uniformly detected brains all animals 6. Onset severe infected correlated peak viral brain. SARS-CoV-2-infected exhibited hallmarks characterized production cytokines chemokines, leukocyte infiltration, hemorrhage neuronal cell death. was also found to productively infect cells within nasal turbinate, eye olfactory bulb, suggesting entry into brain this route intranasal Our data indicate direct CNS together induced inflammatory response

Язык: Английский

---

Neurological manifestations of long-COVID syndrome: a narrative review

Therapeutic Advances in Chronic Disease, Год журнала: 2022, Номер 13

Опубликована: Янв. 1, 2022

Accumulating evidence points toward a very high prevalence of prolonged neurological symptoms among coronavirus disease 2019 (COVID-19) survivors. To date, there are no solidified criteria for 'long-COVID' diagnosis. Nevertheless, is conceptualized as multi-organ disorder with wide spectrum clinical manifestations that may be indicative underlying pulmonary, cardiovascular, endocrine, hematologic, renal, gastrointestinal, dermatologic, immunological, psychiatric, or disease. Involvement the central peripheral nervous system noted in more than one-third patients antecedent severe acute respiratory syndrome 2 (SARS-CoV-2) infection, while an approximately threefold higher incidence recorded observational studies including patient-reported data. The most frequent encompass fatigue; 'brain fog'; headache; cognitive impairment; sleep, mood, smell, taste disorders; myalgias; sensorimotor deficits; and dysautonomia. Although limited exists to date on pathophysiological mechanisms implicated manifestation 'long-COVID', neuroinflammatory oxidative stress processes thought prevail propagating sequelae. In this narrative review, we sought present comprehensive overview our current understanding features, risk factors, Moreover, propose diagnostic therapeutic algorithms aid prompt recognition management causes persist beyond resolution COVID-19. Furthermore, causal treatments currently unavailable, approaches symptom-oriented symptoms. addition, emphasize collaborative research initiatives urgently needed expedite development preventive strategies

Язык: Английский

---

Cognitive impact of COVID-19: looking beyond the short term

Alzheimer s Research & Therapy, Год журнала: 2020, Номер 12(1)

Опубликована: Дек. 1, 2020

COVID-19 is primarily a respiratory disease but up to two thirds of hospitalised patients show evidence central nervous system (CNS) damage, predominantly ischaemic, in some cases haemorrhagic and occasionally encephalitic. It unclear how much the ischaemic damage mediated by direct or inflammatory effects virus on CNS vasculature secondary extracranial cardiorespiratory disease. Limited data suggest that causative SARS-CoV-2 may enter via nasal mucosa olfactory fibres, haematogenous spread, capable infecting endothelial cells, pericytes probably neurons. Extracranially, targets cells pericytes, causing cell dysfunction, vascular leakage immune activation, sometimes leading disseminated intravascular coagulation. remains be confirmed whether cerebral are similarly targeted. Several aspects likely impact cognition. Cerebral white matter particularly vulnerable also critically important for cognitive function. There accumulating hypoperfusion accelerates amyloid-β (Aβ) accumulation linked tau TDP-43 pathology, inducing phosphorylation α-synuclein at serine-129, ischaemia increase risk development Lewy body Current therapies understandably focused supporting function, preventing thrombosis reducing activation. Since angiotensin-converting enzyme (ACE)-2 receptor SARS-CoV-2, ACE inhibitors angiotensin blockers predicted ACE-2 expression, it was initially feared their use might exacerbate COVID-19. Recent meta-analyses have instead suggested these medications protective. This perhaps because entry deplete ACE-2, tipping balance towards II-ACE-1-mediated classical RAS activation: exacerbating promoting inflammation. relevant APOE ε4 individuals, who seem increased COVID-19, lowest activity. leave an unexpected legacy long-term neurological complications significant number survivors. Cognitive follow-up will important, especially develop cerebrovascular during acute illness.

Язык: Английский

---

Persistent Brainstem Dysfunction in Long-COVID: A Hypothesis

ACS Chemical Neuroscience, Год журнала: 2021, Номер 12(4), С. 573 - 580

Опубликована: Фев. 4, 2021

Long-COVID is a postviral illness that can affect survivors of COVID-19, regardless initial disease severity or age. Symptoms long-COVID include fatigue, dyspnea, gastrointestinal and cardiac problems, cognitive impairments, myalgia, others. While the possible causes long-term tissue damage, viral persistence, chronic inflammation, review proposes, perhaps for first time, persistent brainstem dysfunction may also be involved. This hypothesis split into two parts. The tropism damage in COVID-19. As has relatively high expression ACE2 receptor compared with other brain regions, SARS-CoV-2 exhibit therein. Evidence exists neuropilin-1, co-receptor SARS-CoV-2, expressed brainstem. Indeed, autopsy studies have found RNA proteins highly prone to from pathological immune vascular activation, which been observed COVID-19 cases. second part concerns functions overlap symptoms long-COVID. contains numerous distinct nuclei subparts regulate respiratory, cardiovascular, gastrointestinal, neurological processes, linked neurons do not readily regenerate, long-lasting and, thus, implicated similar disorders, such as pain migraine myalgic encephalomyelitis fatigue syndrome.

Язык: Английский

---

The neuroinvasiveness, neurotropism, and neurovirulence of SARS-CoV-2

Trends in Neurosciences, Год журнала: 2022, Номер 45(5), С. 358 - 368

Опубликована: Март 3, 2022

Язык: Английский

---

Hyperinflammatory Immune Response and COVID-19: A Double Edged Sword

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Сен. 30, 2021

The coronavirus disease-19 (COVID-19) elicited by the severe acute respiratory syndrome 2 (SARS-CoV-2) has caused devastating health, economic and social impact worldwide. Its clinical spectrum ranges from asymptomatic to failure multi-organ or death. pathogenesis of SARS-CoV-2 infection is attributed a complex interplay between virus host immune response. It involves activation multiple inflammatory pathways leading hyperinflammation cytokine storm, resulting in tissue damage, distress (ARDS) failure. Accumulating evidence raised concern over long-term health effects COVID-19. Importantly, neuroinvasive potential may have consequences brain. This review provides conceptual framework on how tricks system induce cause disease. We also explore key differences mild COVID-19 its short- effects, particularly human

Язык: Английский

---

Neurological complications and infection mechanism of SARS-CoV-2

Signal Transduction and Targeted Therapy, Год журнала: 2021, Номер 6(1)

Опубликована: Ноя. 23, 2021

Abstract Currently, SARS-CoV-2 has caused a global pandemic and threatened many lives. Although mainly causes respiratory diseases, growing data indicate that can also invade the central nervous system (CNS) peripheral (PNS) causing multiple neurological such as encephalitis, encephalopathy, Guillain-Barré syndrome, meningitis, skeletal muscular symptoms. Despite increasing incidences of clinical complications SARS-CoV-2, precise neuroinvasion mechanisms have not been fully established. In this review, we primarily describe associated with discuss potential through which invades brain based on current evidence. Finally, summarize experimental models were used to study neuroinvasion. These form basis for studies significance infection in brain.

Язык: Английский

---