Tag: long covid symptoms

The Neurobiology of Long COVID

Abstract:

Persistent neurological and neuropsychiatric symptoms affect a substantial fraction of people after COVID-19 and represent a major component of the post-acute COVID syndrome, also known as long COVID. Here, we review what is understood about the pathobiology of post-acute COVID-19 impacts on the CNS and discuss possible neurobiological underpinnings of the cognitive symptoms affecting COVID-19 survivors. We propose the chief mechanisms that may contribute to this emerging neurological health crisis.
Source: Michelle Monje, Akiko Iwasaki. The Neurobiology of Long COVID. Published:October 06, 2022. DOI: https://doi.org/10.1016/j.neuron.2022.10.006 https://www.cell.com/neuron/pdf/S0896-6273(22)00910-2.pdf (Full text available as PDF file)

Network autonomic analysis of post-acute sequelae of COVID-19 and postural tachycardia syndrome

Abstract:

Background: The autonomic nervous system (ANS) is a complex network where sympathetic and parasympathetic domains interact inside and outside of the network. Correlation-based network analysis (NA) is a novel approach enabling the quantification of these interactions. The aim of this study is to assess the applicability of NA to assess relationships between autonomic, sensory, respiratory, cerebrovascular, and inflammatory markers on post-acute sequela of COVID-19 (PASC) and postural tachycardia syndrome (POTS).

Methods: In this retrospective study, datasets from PASC (n = 15), POTS (n = 15), and matched controls (n = 11) were analyzed. Networks were constructed from surveys (autonomic and sensory), autonomic tests (deep breathing, Valsalva maneuver, tilt, and sudomotor test) results using heart rate, blood pressure, cerebral blood flow velocity (CBFv), capnography, skin biopsies for assessment of small fiber neuropathy (SFN), and various inflammatory markers. Networks were characterized by clusters and centrality metrics.

Results: Standard analysis showed widespread abnormalities including reduced orthostatic CBFv in 100%/88% (PASC/POTS), SFN 77%/88%, mild-to-moderate dysautonomia 100%/100%, hypocapnia 87%/100%, and elevated inflammatory markers. NA showed different signatures for both disorders with centrality metrics of vascular and inflammatory variables playing prominent roles in differentiating PASC from POTS.

Conclusions: NA is suitable for a relationship analysis between autonomic and nonautonomic components. Our preliminary analyses indicate that NA can expand the value of autonomic testing and provide new insight into the functioning of the ANS and related systems in complex disease processes such as PASC and POTS.

Source: Novak P, Giannetti MP, Weller E, Hamilton MJ, Mukerji SS, Alabsi HS, Systrom D, Marciano SP, Felsenstein D, Mullally WJ, Pilgrim DM, Castells M. Network autonomic analysis of post-acute sequelae of COVID-19 and postural tachycardia syndrome. Neurol Sci. 2022 Sep 28:1–12. doi: 10.1007/s10072-022-06423-y. Epub ahead of print. PMID: 36169757; PMCID: PMC9517969. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9517969/ (Full text)

The significance of oxidative stress in the pathophysiology of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

Long COVID is now well accepted as an ongoing post-viral syndrome resulting from infection of a single virus, the pandemic SARS-CoV-2. It mirrors the post-viral fatigue syndrome, Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome, a global debilitating illness arising mainly from sporadic geographically-specific viral outbreaks, and from community endemic infections, but also from other stressors. Core symptoms of both syndromes are post-exertional malaise (a worsening of symptoms following mental or physical activity), pervasive fatigue, cognitive dysfunction (brain fog), and sleep disturbance. Long COVID patients frequently also suffer from shortness of breath, relating to the lung involvement of the SARS-CoV-2 virus.

There is no universally accepted pathophysiology, or recognized biomarkers yet for Long COVID or indeed for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Clinical case definitions with very similar characteristics for each have been defined. Chronic inflammation, immune dysfunction, and disrupted energy production in the peripheral system has been confirmed in Long COVID and has been well documented in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Neuroinflammation occurs in the brain in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome as shown from a small number of positron emission tomography and magnetic resonance spectroscopy studies, and has now been demonstrated for Long COVID. Oxidative stress, an increase in reactive oxygen and reactive nitrogen species, and free radicals, has long been suggested as a potential cause for many of the symptoms seen in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, resulting from both activation of the brain’s immune system and dysregulation of mitochondrial function throughout the body. The brain as a high producer of energy may be particularly susceptible to oxidative stress. It has been shown in peripheral immune cells that the balanced production of proteins involved in regulation of the reactive oxygen species in mitochondria is disturbed in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Fluctuations in the chronic low level neuroinflammation during the ongoing course of Long COVID as well as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome have been proposed to cause the characteristic severe relapses in patients.

This review explores oxidative stress as a likely significant contributor to the pathophysiology of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, and the mechanisms by which oxidative stress could cause the symptoms seen in both syndromes. Treatments that could mitigate oxidative stress and thereby lessen the debilitating symptoms to improve the life of patients are discussed.

Source: WALKER, Max Oliver Mackay et al. The significance of oxidative stress in the pathophysiology of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Medical Research Archives, [S.l.], v. 10, n. 9, sep. 2022. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/3050>. Date accessed: 09 oct. 2022. doi: https://doi.org/10.18103/mra.v10i9.3050.

An international study of post-COVID sleep health

Abstract:

Objectives: COVID-19 has infected millions of people worldwide, with growing evidence that individuals with a history of infection may continue to show persistent post-COVID symptoms (long COVID). The aim of this study was to investigate sleep health in an international sample of individuals who reported previously testing positive for COVID-19.

Design: Cross-sectional.

Setting: Online survey distributed online between March and June 2021.

Participants: A total of 1001 individuals who reported a positive diagnosis of COVID-19 across different geographical regions, including North and South America, Sub-Saharan Africa, and Europe.

Measurements: Self-reported sleep health, using the Regulatory Satisfaction Alertness Timing Efficiency Duration scale, as recalled before a COVID-19 diagnosis and also reported currently.

Results: Individuals reported worse overall current sleep health, with lower ratings across the 6 dimensions of sleep health (sleep regularity, satisfaction, alertness, timing, efficiency, and duration) compared to their ratings as recalled before COVID-19 infection. Greater severity of COVID-19 symptoms was the strongest predictor of poor current sleep health (P < .001), independent of demographics, presence of a pre-existing chronic health condition, and time since infection. Poor current sleep health was associated with poorer current quality of life (P < .001).

Conclusions: Poor current sleep health is evident in individuals with a history of COVID-19, particularly those with more severe symptoms at the time of their COVID-19 infection and is associated with a poorer quality of life. Clinicians and researchers should assess sleep health in COVID-19 patients and investigate long-term associations with their mental and physical health, as well as potential benefits of improving sleep in this population.

Source: Alzueta E, Perrin PB, Yuksel D, Ramos-Usuga D, Kiss O, Iacovides S, de Zambotti M, Cortes M, Olabarrieta-Landa L, Arango-Lasprilla JC, Baker FC. An international study of post-COVID sleep health. Sleep Health. 2022 Sep 23:S2352-7218(22)00112-7. doi: 10.1016/j.sleh.2022.06.011. Epub ahead of print. PMID: 36163137; PMCID: PMC9501615. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9501615/ (Full text)

Long COVID symptoms in a population-based sample of persons discharged home from hospital

Abstract:

in English, French

Objectives: The impact of long COVID among persons hospitalized and discharged home is unknown. We aimed to (1) report the prevalence of long COVID in persons hospitalized for COVID-19 and discharged home; (2) estimate the prevalence of physical, sensory, and psychological/mental health impairments; and (3) explore associated factors.

Methods: We conducted a telephone survey of adult residents in Laval, Quebec, who were discharged home ≥ 2 months post-hospitalization for COVID-19. Participants responded to a standard questionnaire regarding persistent symptoms. We calculated the prevalence of long COVID and of persistent types of symptoms and evaluated associated factors using bivariate analysis and multivariable logistic regression.

Results: In our sample (n = 398), 70% reported physical symptoms, 58% psychological problems, and 16% sensory impairments. 31.5% reported being troubled by persistent symptoms (long COVID). Factors associated with long COVID were a greater number of symptoms (odds ratio (OR) = 1.97, 95% confidence interval (CI) = 1.69-2.28) and increased hospital stay (OR = 1.03, 95% CI = 1.01-1.06). Other factors associated with physical and psychological symptoms were female sex (OR = 2.17, 95% CI = 1.27-3.71 and OR = 2.06, 95% CI = 1.25-3.39; respectively), higher education level (OR = 2.10, 95% CI = 1.20-3.68 and OR = 2.43, 95% CI = 1.44-4.14; respectively), and obesity (OR = 1.95, 95% CI = 1.15-3.34 and OR = 1.70, 95% CI = 1.05-2.77; respectively).

Conclusion: In this population-based study of persons hospitalized for COVID-19 and discharged home, nearly one third were troubled by symptoms for 2 months or more post-discharge. There was a high proportion with persistent physical and psychological/mental health symptoms. Further research will assess the specific needs of these patients to inform health policy makers on service requirements for these persons.

Source: Feldman DE, Boudrias MH, Mazer B. Long COVID symptoms in a population-based sample of persons discharged home from hospital. Can J Public Health. 2022 Sep 21:1–10. doi: 10.17269/s41997-022-00695-9. Epub ahead of print. PMID: 36131218; PMCID: PMC9491248. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9491248/ (Full text)

Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long-COVID symptoms

Abstract:

Background: Autoimmunity has been reported in patients with severe COVID-19. We investigated whether antinuclear/extractable-nuclear antibodies (ANAs) were present up to a year after infection, and if they were associated with the development of clinically relevant Post-Acute Sequalae of COVID-19 (PASC) symptoms.

Methods: A rapid assessment line immunoassay was used to measure circulating levels of ANA/ENAs in 106 convalescent COVID-19 patients with varying acute phase severities at 3, 6, and 12 months post-recovery. Patient-reported fatigue, cough, and dyspnea were recorded at each timepoint. Multivariable logistic regression model and receiver-operating curves (ROC) were used to test the association of autoantibodies with patient-reported outcomes and pro-inflammatory cytokines.

Results: Compared to age- and sex-matched healthy controls (n=22) and those who had other respiratory infections (n=34), patients with COVID-19 had higher detectable ANAs at 3 months post-recovery (p<0.001). The mean number of ANA autoreactivities per individual decreased from 3 to 12 months (3.99 to 1.55) with persistent positive titers associated with fatigue, dyspnea, and cough severity. Antibodies to U1-snRNP and anti-SS-B/La were both positively associated with persistent symptoms of fatigue (p<0.028, AUC=0.86) and dyspnea (p<0.003, AUC=0.81). Pro-inflammatory cytokines such as tumour necrosis factor alpha (TNFα) and C-reactive protein predicted the elevated ANAs at 12 months. TNFα, D-dimer, and IL-1β had the strongest association with symptoms at 12 months. Regression analysis showed TNFα predicted fatigue (β=4.65, p=0.004) and general symptomaticity (β=2.40, p=0.03) at 12 months.

Interpretation: Persistently positive ANAs at 12 months post-COVID are associated with persisting symptoms and inflammation (TNFα) in a subset of COVID-19 survivors. This finding indicates the need for further investigation into the role of autoimmunity in PASC.

Source: Son K, Jamil R, Chowdhury A, Mukherjee M, Venegas C, Miyasaki K, Zhang K, Patel Z, Salter B, Yuen ACY, Lau KS, Cowbrough B, Radford K, Huang C, Kjarsgaard M, Dvorkin-Gheva A, Smith J, Li QZ, Waserman S, Ryerson CJ, Nair P, Ho T, Balakrishnan N, Nazy I, Bowdish DM, Svenningsen S, Carlsten C, Mukherjee M. Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long-COVID symptoms. Eur Respir J. 2022 Sep 22:2200970. doi: 10.1183/13993003.00970-2022. Epub ahead of print. PMID: 36137590. https://pubmed.ncbi.nlm.nih.gov/36137590/

Neurological post-acute sequelae of SARS-CoV-2 infection (PASC)

Abstract:

The novel corona virus infectious disease, COVID-19, caused by SARS-CoV-2, can have two phases: acute (generally 4 weeks after onset) and chronic (> 4 weeks after onset). Both phases include a wide variety of signs and symptoms including neurological and psychiatric symptoms. The signs and symptoms that are considered sequelae of COVID-19 are termed post-COVID condition, long COVID-19, and post-acute sequelae of SARS-CoV-2 infection (PASC).

PASC symptoms include fatigue, dyspnea, palpitation, dysosmia, sub-fever, hypertension, alopecia, sleep problems, loss of concentration, amnesia, numbness, pain, gastrointestinal symptoms, depression, and anxiety. Because the specific pathophysiology of PASC has not yet been clarified, there are no definite criteria of the condition, hence the World Health Organization’s definition is quite broad. Consequently, it is difficult to correctly diagnose PASC.

Approximately 50% of patients may show at least one PASC symptom up to 12 months after COVID-19 infection; however, the exact prevalence of PASC has not been determined. Despite extensive research in progress worldwide, there are currently no clear diagnostic methodologies or treatments for PASC.

In this review, we discuss the currently available information on PASC and highlight the neurological sequelae of COVID-19 infection. Furthermore, we provide clinical suggestions for diagnosing and caring for PASC patients based on our outpatient clinic experience.

Source: Takao M, Ohira M. Neurological post-acute sequelae of SARS-CoV-2 infection (PASC). Psychiatry Clin Neurosci. 2022 Sep 23. doi: 10.1111/pcn.13481. Epub ahead of print. PMID: 36148558. https://pubmed.ncbi.nlm.nih.gov/36148558/

Lactoferrin as Possible Treatment for Chronic Gastrointestinal Symptoms in Children with Long COVID: Case Series and Literature Review

Abstract:

Long COVID is an emergent, heterogeneous, and multisystemic condition with an increasingly important impact also on the pediatric population. Among long COVID symptoms, patients can experience chronic gastrointestinal symptoms such as abdominal pain, constipation, diarrhea, vomiting, nausea, and dysphagia.
Although there is no standard, agreed, and optimal diagnostic approach or treatment of long COVID in children, recently compounds containing multiple micronutrients and lactoferrin have been proposed as a possible treatment strategy, due to the long-standing experience gained from other gastrointestinal conditions. In particular, lactoferrin is a pleiotropic glycoprotein with antioxidant, anti-inflammatory, antithrombotic, and immunomodulatory activities. Moreover, it seems to have several physiological functions to protect the gastrointestinal tract.
In this regard, we described the resolution of symptoms after the start of therapy with high doses of oral lactoferrin in two patients referred to our post-COVID pediatric unit due to chronic gastrointestinal symptoms after SARS-CoV-2 infection.
Source: Morello R, De Rose C, Cardinali S, Valentini P, Buonsenso D. Lactoferrin as Possible Treatment for Chronic Gastrointestinal Symptoms in Children with Long COVID: Case Series and Literature Review. Children. 2022; 9(10):1446. https://doi.org/10.3390/children9101446 (Full text)

Post-COVID myalgic encephalomyelitis in chronic heart disease patient: A case series

Abstract

Purpose of Study: Myalgic encephalomyelitis (ME), also called chronic fatigue syndrome, is a condition characterized by severe fatigue that impairs a patient’s ability to perform common daily activities.

Criteria for ME include 6 months of fatigue-limited daily activities, unrefreshing sleep, and symptom exacerbation following physical or mental strain, and orthostatic intolerance.

New reports indicate that ME incidence may be higher in specific patient populations. This study was designed to investigate the association between ME and Cardiovascular disease in patients recovering from COVID-19 infection.

Methods: Used The patient population used for this study includes 19 patients that were referred to the Amarillo Heart Group in Amarillo, TX who also tested positive for Covid-19 at least 6 months prior to September 1, 2021.

The patients that fit this timeline were asked a series of standardized questions and rate the severity of their symptoms on a scale of 0 to 5, with 0 being the absence of symptoms and 5 being the most severe. Two sets of questions were created and named Life Spheres Criteria (4 questions) and Symptoms Criteria (3 questions) based on the 2015 IOM Diagnostic Criteria for CFS. Rating more than 1 Life Spheres question as a 3 or higher or rating all 3 Symptoms Criteria questions as a 3 or higher indicated Chronic Fatigue Syndrome. Information from the survey, including time since infection, demographics, and question scores, were analyzed.

Summary of Results: Our study included 10 women and 10 men, with the average amount of time since Covid-19 infection being 328.17 ± 41.36 days. Worsening of symptoms with mild exertion was the most commonly endorsed criteria (3.58 ± 1.64) and the least common criterion was fatigue reducing activity in school (2.00 ± 1.94).

Women scored higher in every category except reduced activity in school when compared to men. However, there was no significant difference in symptom scores between the two groups with the Combined Fatigue Score being 2.89 ± 1.47 for women and 2.67 ± 1.59 for men.

Nearly all symptom scores significantly positively correlated with one another, meaning if one category was high it was likely for other categories to be high as well.

Ultimately, when looking at the Cumulative Pearson Correlation Scores, reduced social life, difficulty concentrating, and symptoms worsening with mild exertion were found to be most predictive of a high Combined Fatigue Score.

Conclusions: In this case series, over 80% of patients met the criteria for Post-COVID Myalgic Encephalomyelitis. While the link between ME and both COVID-19 and cardiovascular disease has been established, little is known about the severity of ME in patients who have a history of both cardiovascular disease and COVID-19 infection.

To our knowledge, this is the first study to examine ME in patients with both of these predisposing conditions. A high degree of clinical suspicion for ME should be used when screening and treating cardiac patients who have been infected with COVID-19.

Source: Holder, K. G.; Vemulapalli, V.; Daines, B.; Kankam, A.; Galvan, B.; Nambiar, R. Post-COVID myalgic encephalomyelitis in chronic heart disease patient: A case series. Journal of Investigative Medicine ; 70(2):475, 2022. https://pesquisa.bvsalud.org/global-literature-on-novel-coronavirus-2019-ncov/resource/pt/covidwho-1705710

Tunneling nanotubes provide a route for SARS-CoV-2 spreading

Abstract:

Neurological manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection represent a major issue in long coronavirus disease. How SARS-CoV-2 gains access to the brain and how infection leads to neurological symptoms are not clear because the principal means of viral entry by endocytosis, the angiotensin-converting enzyme 2 receptor, are barely detectable in the brain.

We report that human neuronal cells, nonpermissive to infection through the endocytic pathway, can be infected when cocultured with permissive infected epithelial cells. SARS-CoV-2 induces the formation of tunneling nanotubes (TNTs) and exploits this route to spread to uninfected cells. In cellulo correlative fluorescence and cryo-electron tomography reveal that SARS-CoV-2 is associated with TNTs between permissive cells. Furthermore, multiple vesicular structures such as double-membrane vesicles, sites of viral replication, are observed inside TNTs between permissive and nonpermissive cells.

Our data highlight a previously unknown mechanism of SARS-CoV-2 spreading, likely used as a route to invade nonpermissive cells and potentiate infection in permissive cells.

Source: Pepe A, Pietropaoli S, Vos M, Barba-Spaeth G, Zurzolo C. Tunneling nanotubes provide a route for SARS-CoV-2 spreading. Sci Adv. 2022 Jul 22;8(29):eabo0171. doi: 10.1126/sciadv.abo0171. Epub 2022 Jul 20. PMID: 35857849; PMCID: PMC9299553.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299553/ (Full text)