Tag: covid-19

Two-Years Follow-Up of Symptoms and Return to Work in Complex Post-COVID-19 Patients

Abstract:

Introduction: Many COVID-19 patients present with severe long-lasting symptoms. They might benefit from a coordination team to manage such complex situations, but late efficacy still needs to be determined.
Population and Methods: Out of 105 contacts, 45 patients had two phone consultations separated by personalized support 15 and 22 months, respectively, after COVID infection. Self-reported symptoms, feelings of improvement and ability to return to work allowed us to determine the efficacy of the therapeutic strategy proposed.
Results: Unlike what was expected, many post-COVID-19 patients directly contacted the coordination team and had significant pre-existing comorbidities. Despite exercise, respiratory, olfactory rehabilitations, cognition/speech therapy and/or psychological support, the more frequent self-reported symptoms (fatigue, neurocognitive disorders, muscles and joint pain) did not resolve. However, dyspnea, anxiety and chest pain were significantly reduced. Finally, 2/3 of the patients felt some degree of improvement and returned to work either partially or fully, but 1/3 remained complaining of symptoms and out of work as late as 22 months after COVID occurrence. All patients greatly appreciated the second phone consultation.
Conclusions: In such complex situations, besides early and adapted rehabilitations and psychological help allowing better symptom management, relatively simple actions such as a phone call might be very useful to reduce patients’ feelings of abandonment.
Source: Van Wambeke E, Bezler C, Kasprowicz A-M, Charles A-L, Andres E, Geny B. Two-Years Follow-Up of Symptoms and Return to Work in Complex Post-COVID-19 Patients. Journal of Clinical Medicine. 2023; 12(3):741. https://doi.org/10.3390/jcm12030741 https://www.mdpi.com/2077-0383/12/3/741 (Full text)

Long-COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Potential neurophysiological biomarkers for these enigmatic entities

Since early in the pandemic, fatigue has been recognized as one of the most common persistent complaints in individuals infected with SARS-CoV-2, and constitutes one main symptom of the so-called long-COVID syndrome. The term fatigue refers to a sustained feeling of tiredness, which can be present at rest; it is not directly related to physical activity, but can be exacerbated disproportionally by exertion.

Survivors of other recent coronavirus outbreaks, such as severe acute respiratory syndrome (SARS) in 2002 and Middle East respiratory syndrome (MERS) in 2012 also developed chronic fatigue. These ‘post-infectious’ fatigue syndromes, including long-COVID, resemble myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a chronic disorder of unknown physiopathology characterized by fatigue, post-exertional malaise, chronic muscle or skeletal pain, and cognitive impairment (‘brain fog’).

Despite it being an extremely disabling symptom, the results of routine examinations are often normal in patients complaining of lingering fatigue, a phenomenon that has also led the medical-scientific community to view this condition with skepticism.

In physiology, fatigue is defined as a decrease in the maximal force-generating capacity of a muscle during exercise. It may result from peripheral processes distal to the neuromuscular junction and from central processes controlling the discharge rate of motoneurons.

Physical fatigue related to both central and peripheral nervous system dysfunction can be assessed with neurophysiological techniques including transcranial magnetic stimulation (TMS) of the motor cortex, electrical stimulation of nerve trunks or intramuscular nerve fibers, and electromyography (EMG) recordings.

In August 2021, the first study showing myopathic changes in quantitative EMG (qEMG) in long-COVID patients with musculoskeletal symptoms was published (). The same authors demonstrated myopathic qEMG features and histopathological changes in skeletal muscle biopsies in 16 patients with complaints of fatigue, myalgia, and/or weakness persisting for up to 14 months after mild to moderate COVID-19 (). The wide variety of histological changes in this study, including muscle fiber atrophy, mitochondrial changes, subsarcolemmal accumulation, inflammation, capillaries alteration, suggests that skeletal muscle may be a major target of SARS-CoV-2.

On the opposite side of the neuroaxis, dysfunction in the activity of the primary motor cortex and reduced corticomotor output may underlie fatigue.

The first TMS study on motor cortex physiology was conducted on 12 patients with long-term fatigue and ‘brain fog’ after severe COVID-19 (). It showed disruption of the physiological mechanism of post-contraction depression, i.e., the transient decrease in the amplitude of motor evoked potentials and prolongation of the cortical silent period after a fatiguing motor task, which depends on cortical inhibitory mechanisms and has the protective purpose of preventing muscle overload. Impairment of intracortical GABAergic activity, as indicated by disrupted long-interval intracortical inhibition, together with reduced excitability of the primary motor cortex was subsequently demonstrated in 67 patients with fatigue and cognitive difficulties after mild COVID-19 (). These patients also presented selective deficits in executive functions. Based on these findings, the authors proposed that fatigue depends on altered excitability and neurotransmission within the motor cortex at rest, and on abnormal reactivity to muscular exercise. In addition, reduced executive control may contribute to exacerbating poor physical performance and fatigue tolerance ().

These objective neurophysiological and histopathological findings showed for the first time that fatigue may due both to pathological processes in the muscle (the effector of the motor command) and/or at the site of motor command processing. The mechanisms of chronic dysfunction of neural and muscle cells may be sustained by inflammation or dysimmunity, triggered by SARS-COV-2 in predisposed individuals.

Immune-inflammatory and neuroendocrine mechanisms have also been implicated in ME/CFS. In particular, increased production of autoantibodies against CNS and autonomic nervous system targets, such as the ß2 adrenergic receptor (ß2AdR), have been documented (). As ß2AdR are important vasodilators, their functional disturbance may result in vasoconstriction and hypoxemia with chronic muscular and cerebral hypoperfusion.

The COVID-19 pandemic is likely to greatly increase the incidence of ME/CFS, so that the intense research on the pathophysiological mechanisms of fatigue in long-COVID can help to shed light on a poorly understood and underestimated syndrome.

Source: Versace V, Tankisi H. Long-COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Potential neurophysiological biomarkers for these enigmatic entities. Clin Neurophysiol. 2023 Jan 13;147:58-59. doi: 10.1016/j.clinph.2023.01.001. Epub ahead of print. PMID: 36657309; PMCID: PMC9838078. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9838078/ (Full text)

Vascular “Long COVID”: A New Vessel Disease?

Abstract:

Vascular sequelae following (SARS-CoV-2 coronavirus disease) (COVID)-19 infection are considered as “Long Covid (LC)” disease, when occurring 12 weeks after the original infection. The paucity of specific data can be obviated by translating pathophysiological elements from the original Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2) infection (In a microcirculatory system, a first “endotheliitis,” is often followed by production of “Neutrophil Extracellular Trap,” and can evolve into a more complex leukocytoklastic-like and hyperimmune vasculitis. In medium/large-sized vessels, this corresponds to endothelial dysfunction, leading to an accelerated progression of pre-existing atherosclerotic plaques through an increased deposition of platelets, circulating inflammatory cells and proteins. Associated dysregulated immune and pro-coagulant conditions can directly cause thrombo-embolic arterial or venous complications. In order to implement appropriate treatment, physicians need to consider vascular pathologies observed after SARS-Cov-2 infections as possible “LC” disease.

Source: Zanini G, Selleri V, Roncati L, Coppi F, Nasi M, Farinetti A, Manenti A, Pinti M, Mattioli AV. Vascular “Long COVID”: A New Vessel Disease? Angiology. 2023 Jan 18:33197231153204. doi: 10.1177/00033197231153204. Epub ahead of print. PMID: 36652923. https://pubmed.ncbi.nlm.nih.gov/36652923/

Epidemiology, symptomatology, and risk factors for long COVID symptoms: Multi-centre study

Abstract:

Background: Long COVID induces a substantial global burden of disease. The pathogenesis, complications, epidemiological and clinical characteristics of COVID-19 patients in the acute phase have been evaluated, while few studies have characterized the epidemiology, symptomatology and risk factors of long COVID symptoms. Its characteristics among coronavirus disease 2019 (COVID-19) patients in the general population remain unaddressed.

Objective: We examined the prevalence of long COVID symptoms, its symptom patterns, and its risk factors. we aimed to fill the knowledge gaps by evaluating the prevalence of long COVID symptoms in four major Chinese cities.

Methods: We performed a population-based, multi-centre survey by a representative sampling strategy via the Qualtrics platform in Beijing, Shanghai, Guangzhou and Hong Kong (June 2022). We included 2,712 community-dwelling, COVID-19 patients, and measured the prevalence of long COVID symptoms defined by the WHO, and their risk factors. The primary outcomes were the symptoms of long COVID with various levels of impact. A descriptive analysis was conducted on the prevalence and distribution of the long COVID symptoms according to disease severity. A sensitivity analysis of increasing the number of long COVID symptoms was also conducted. A univariate and multivariate regression analysis was performed to examine the risk factors of severe long COVID symptoms, including age, gender, marital status, current occupation, educational level, living status, smoking habits, monthly household income, self-perceived health status, presence of chronic diseases, use of chronic medication, COVID-19 vaccination status, and severity of COVID-19.

Results: The response rate was 63.6%. The prevalence of long COVID, moderate or severe long COVID, and severe long COVID was 90.4%, 62.4%, and 31.0%, respectively. Fatigue (33.7%), cough (31.9%), sore throat (31.0%), difficulty in concentration (30.5%), feeling of anxiety (30.2%), myalgia (29.9%), and arthralgia (29.9%) were the most common severe long COVID symptoms. From multivariate regression analysis, female gender (adjusted odds ratio [aOR]=1.49, 95% C.I.=1.13-1.95), engagement in transportation, logistics, or discipline workforce (aOR=2.52, 95% C.I.=1.58-4.03), living with domestic workers (aOR=2.37, 95% C.I.=1.39-4.03), smoking (aOR=1.55, 95% C.I.=1.17-2.05), poor self-perceived health status (aOR 5.06 to 15.38), chronic diseases (aOR 1.92 to 2.71), chronic medication use (aOR=4.38, 95% C.I.=1.66-11.53), and critical severity of COVID-19 (aOR=1.52, 95% C.I.=1.07-2.15) were associated with severe long COVID. Prior vaccination for ≥2 doses of COVID-19 was a protective factor (aOR=0.35-0.22, 95% C.I.=0.08-0.90).

Conclusions: We have examined the prevalence of long COVID symptoms in four Chinese cities according to the severity of COVID-19. We also evaluated the pattern of long COVID symptoms, and their risk factors. These findings may inform early identification of COVID-19 patients at risk of long COVID and planning of rehabilitative services.

Source: Wong MC, Huang J, Wong NY, Wong GL, Yip TC, Chan RN, Chau SW, Ng SC, Wing YK, Chan FK. Epidemiology, symptomatology, and risk factors for long COVID symptoms: Multi-centre study. JMIR Public Health Surveill. 2023 Jan 12. doi: 10.2196/42315. Epub ahead of print. PMID: 36645453. https://pubmed.ncbi.nlm.nih.gov/36645453/

Can Baseline IL-6 Levels Predict Long COVID in Subjects Hospitalized for SARS-CoV-2 Disease?

Abstract:

The immune response to infection plays a crucial role in the pathogenesis of COVID-19, but several patients develop a wide range of persistent symptoms, which is becoming a major global health and economic burden. However, reliable indicators are not yet available to predict the persistence of symptoms typical of the so-called long COVID. Our study aims to explore an eventual role of IL-6 levels as a marker of long COVID. Altogether, 184 patients admitted to the COVID Medicine Unit of the University Hospital in Palermo, Italy, from the 1st of September 2020, were analyzed.

Patients were divided into two groups according to the IL-6 serum levels (normal or elevated), considering the serum IL-6 levels measured during the first four days of hospitalization. In our study, higher serum IL-6 levels were associated with a doubled higher risk of long COVID (OR = 2.05; 95% CI: 1.04-4.50) and, in particular, they were associated with a higher incidence of mobility decline (OR = 2.55; 95% CI: 1.08-9.40) and PTSD (OR = 2.38; 95% CI: 1.06-8.61). The analysis of our case series confirmed the prominent role of IL-6 levels in response to SARS-CoV-2 infection, as predictors not only of COVID-19 disease severity and unfavorable outcomes, but also long COVID development trends.

Source: Giannitrapani L, Mirarchi L, Amodeo S, Licata A, Soresi M, Cavaleri F, Casalicchio S, Ciulla G, Ciuppa ME, Cervello M, Barbagallo M, Veronese N, The Comepa Group. Can Baseline IL-6 Levels Predict Long COVID in Subjects Hospitalized for SARS-CoV-2 Disease? Int J Mol Sci. 2023 Jan 15;24(2):1731. doi: 10.3390/ijms24021731. PMID: 36675242. https://www.mdpi.com/1422-0067/24/2/1731 (Full text)

Cortical Grey matter volume depletion links to neurological sequelae in post COVID-19 “long haulers”

Abstract:

Objective: COVID-19 (SARS-CoV-2) has been associated with neurological sequelae even in those patients with mild respiratory symptoms. Patients experiencing cognitive symptoms such as “brain fog” and other neurologic sequelae for 8 or more weeks define “long haulers”. There is limited information regarding damage to grey matter (GM) structures occurring in COVID-19 “long haulers”. Advanced imaging techniques can quantify brain volume depletions related to COVID-19 infection which is important as conventional Brain MRI often fails to identify disease correlates. 3-dimensional voxel-based morphometry (3D VBM) analyzes, segments and quantifies key brain volumes allowing comparisons between COVID-19 “long haulers” and normative data drawn from healthy controls, with values based on percentages of intracranial volume.

Methods: This is a retrospective single center study which analyzed 24 consecutive COVID-19 infected patients with long term neurologic symptoms. Each patient underwent Brain MRI with 3D VBM at median time of 85 days following laboratory confirmation. All patients had relatively mild respiratory symptoms not requiring oxygen supplementation, hospitalization, or assisted ventilation. 3D VBM was obtained for whole brain and forebrain parenchyma, cortical grey matter (CGM), hippocampus, and thalamus.

Results: The results demonstrate a statistically significant depletion of CGM volume in 24 COVID-19 infected patients. Reduced CGM volume likely influences their long term neurological sequelae and may impair post COVID-19 patient’s quality of life and productivity.

Conclusion: This study contributes to understanding effects of COVID-19 infection on patient’s neurocognitive and neurological function, with potential for producing serious long term personal and economic consequences, and ongoing challenges to public health systems.

Source: Rothstein TL. Cortical Grey matter volume depletion links to neurological sequelae in post COVID-19 “long haulers”. BMC Neurol. 2023 Jan 17;23(1):22. doi: 10.1186/s12883-023-03049-1. PMID: 36647063; PMCID: PMC9843113. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9843113/ (Full text)

Long COVID: Is There a Role for Antidepressants?

Abstract:

Two years into this historic pandemic, the scientific and healthcare communities continue to learn a great deal regarding COVID-19. The most urgent and immediate focus has been on vaccine development for disease prevention/mitigation and on identification of effective therapeutic interventions for acute phase of illness. However, attention is increasingly being placed on formulating treatment strategies for individuals who are post-COVID-19 and experiencing a syndrome of persistent symptoms that is being referred to as long COVID.

One strategy is to repurpose drugs which have been approved for other conditions and subsequently assess their safety and efficacy when applied to COVID-19. In this light, antidepressant medications have garnered attention amidst evidence supporting anti-inflammatory and anti-viral properties.

In this article, we present purported anti-inflammatory mechanisms of antidepressants, review studies appearing in the literature to date regarding antidepressants and acute COVID-19, and discuss the utility of antidepressants as a potential therapeutic resource for long COVID.

Source: Rivas-Vázquez R, Carrazana EJ, Blais MA, Rey GJ, RivasVázquez E, Quintana AA. Long COVID: Is There a Role for Antidepressants? Neurol Curr Res. 2022;2(3):1019. https://www.medtextpublications.com/open-access/long-covid-is-there-a-role-for-antidepressants-1249.pdf (Full text)

Novel clinical and immunological features associated with persistent post-acute sequelae of COVID-19 after six months of follow-up: a pilot study

Abstract:

Background: Currently, there is scant information regarding the features associated to the persistence of post-COVID-19 syndrome, which is the main aim of the present study.

Methods: A cohort study of 102 COVID-19 patients was conducted. The post-COVID-19 symptoms were assessed by a standardised questionnaire. Lymphocyte immunophenotyping was performed by flow cytometry and chemokines/cytokines, neutrophil extracellular traps, the tripartite motif 63, anti-cellular, and anti-SARS-CoV-2 IgG antibodies were addressed in serum. The primary outcome was the persistence of post-COVID-19 syndrome after six months follow-up.

Results: Thirteen patients (12.7%) developed the primary outcome and had a more frequent history of post-COVID-19 syndrome 3 months after infection onset (p = .044), increased levels of IL-1α (p = .011) and IP-10 (p = .037) and increased CD57 expression in CD8+ T cells (p = .003). There was a trend towards higher levels of IFN-γ (p = .051), IL-1β (p = .062) and IL-6 (p = .087). The history of post COVID-19 in the previous 3 months, obesity, baseline serum MIP-1α and IP-10, and CD57 expression in CD8+ T cells were independently associated with the persistence of post-COVID-19 syndrome.

Conclusion: Our data suggest an important relationship between a pro-inflammatory state mediated through metabolic pathways related to obesity and increased cellular senescence as a key element in the persistence of post-COVID-19 syndrome at six months of follow-up.

Source: Torres-Ruiz J, Lomelín-Gascón J, Lira Luna J, Vargas-Castro AS, Pérez-Fragoso A, Nuñez-Aguirre M, Alcalá-Carmona B, Absalón-Aguilar A, Balderas-Miranda JT, Maravillas-Montero JL, Mejía-Domínguez NR, Núñez-Álvarez C, Llorente L, Romero-Ramírez S, Sosa-Hernández VA, Cervantes-Díaz R, Juárez-Vega G, Meza-Sánchez D, Rull-Gabayet M, Martínez-Juárez LA, Morales L, López-López LN, Negrete-Trujillo JA, Falcón-Lezama JA, Valdez-Vázquez RR, Gallardo-Rincón H, Tapia-Conyer R, Gómez-Martín D. Novel clinical and immunological features associated with persistent post-acute sequelae of COVID-19 after six months of follow-up: a pilot study. Infect Dis (Lond). 2023 Jan 13:1-12. doi: 10.1080/23744235.2022.2158217. Epub ahead of print. PMID: 36637466. https://www.tandfonline.com/doi/full/10.1080/23744235.2022.2158217 (Full text)

Towards evidence-based and inclusive models of peer support for long covid: A hermeneutic systematic review

Highlights:

• Co-produced peer support can help people living with Long COVID.
• Increasing the use of effective peer support may reduce health inequalities.
• Inclusive peer support can benefit ‘hardly reached’ Long Covid cohorts.
• Linking biomedical, relational and socio-political styles are most effective.

Abstract:

Since the first wave of COVID-19 in March 2020 the number of people living with post-COVID syndrome has risen rapidly at global pace, however, questions still remain as to whether there is a hidden cohort of sufferers not accessing mainstream clinics. This group are likely to be constituted by already marginalised people at the sharp end of existing health inequalities and not accessing formal clinics. The challenge of supporting such patients includes the question of how best to organise and facilitate different forms of support.

As such, we aim to examine whether peer support is a potential option for hidden or hardly reached populations of long COVID sufferers with a specific focus on the UK, though not exclusively. Through a systematic hermeneutic literature review of peer support in other conditions (57 papers), we evaluate the global potential of peer support for the ongoing needs of people living with long COVID.

Through our analysis, we highlight three key peer support perspectives in healthcare reflecting particular theoretical perspectives, goals, and understandings of what is ‘good health’, we call these: biomedical (disease control/management), relational (intersubjective mutual support) and socio-political (advocacy, campaigning & social context). Additionally, we identify three broad models for delivering peer support: service-led, community-based and social media. Attention to power relations, social and cultural capital, and a co-design approach are key when developing peer support services for disadvantaged and underserved groups.

Models from other long-term conditions suggest that peer support for long COVID can and should go beyond biomedical goals and harness the power of relational support and collective advocacy. This may be particularly important when seeking to reduce health inequalities and improve access for a potentially hidden cohort of sufferers.

Source: Mullard JCR, Kawalek J, Parkin A, Rayner C, Mir G, Sivan M, Greenhalgh T. Towards evidence-based and inclusive models of peer support for long covid: A hermeneutic systematic review. Soc Sci Med. 2023 Jan 14:115669. doi: 10.1016/j.socscimed.2023.115669. Epub ahead of print. PMCID: PMC9840228. https://www.sciencedirect.com/science/article/pii/S0277953623000242 (Full text)

A Systematic Review of Trials Currently Investigating Therapeutic Modalities for Post-Acute COVID-19 Syndrome and Registered on World Health Organization International Clinical Trials Platform

Abstract:

Background: Post-acute coronavirus 2019 (COVID-19) syndrome (PACS) is a well-recognized complex systemic disease that is associated with substantial morbidity. There is a paucity of established interventions to treat patients with this syndrome.

Objectives: To systematically review registered trials currently investigating therapeutic modalities for PACS.

Data sources: Search was conducted up to the 16th of September 2022 using the COVID-19 section of the World Health Organization (WHO) Internal Clinical Trials Registry Platform.

Study eligibility criteria, participants, and interventions: Interventional clinical trials of any sample size examining any therapeutic modality targeting persistent symptoms among individuals after diagnosis with COVID-19.

Methods: Data on trial characteristics and intervention characteristics were collected and summarized.

Results: After screening 17125 trials, 388 trials from 42 countries were eligible. 331 trials tested mono-therapeutic strategies, while 39 trials included a combination of interventions. Among the 824 primary outcomes identified, there were more than 300 different outcomes. Rehabilitation was the most employed class of intervention with 169 trials. We encountered 76 trials examining pharmacological agents of various classes with the most common agent being colchicine. Complementary and alternative medicine encompassed 64 trials exploring Traditional Chinese Medicine, Ayurveda, homeopathic medications, naturopathic medications, vitamins, dietary supplements, and botanicals. Psychotherapeutic and educational interventions were also employed with 12 and 4 trials, respectively. Other interventions including transcranial current direct stimulation, transcutaneous auricular vagus nerve stimulation, general electrical stimulation, cranial electrotherapy stimulation, various stem cell interventions, and oxygen therapy interventions were also employed.

Conclusion: We identified 388 registered trials with a high degree of heterogeneity exploring 144 unique interventions for PACS. Most target general alleviation of symptoms. There is a need for further high-quality and methodologically robust PACS treatment trials conducted with standardization of outcomes while following WHO’s recommendation for uniform evaluation and treatment.

Source: Fawzy NA, Shaar BA, Taha R, Arabi TZ, Sabbah BN, Alkodaymi MS, Omrani OA, Makhzoum T, Almahfoudh NE, Al-Hammad QA, Hejazi W, Obeidat Y, Osman N, Al-Kattan KM, Berbari EF, Tleyjeh IM. A Systematic Review of Trials Currently Investigating Therapeutic Modalities for Post-Acute COVID-19 Syndrome and Registered on World Health Organization International Clinical Trials Platform. Clin Microbiol Infect. 2023 Jan 12:S1198-743X(23)00009-5. doi: 10.1016/j.cmi.2023.01.007. Epub ahead of print. PMID: 36642173; PMCID: PMC9837206. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9837206/ (Full text)