Sequelae Of COVID-19 Research Articles

Reduction of long COVID symptoms after stellate ganglion block: A retrospective chart review study

The SARS-CoV-2 pandemic has left millions of individuals with a host of post-viral symptoms that can be debilitating and persist indefinitely. To date there are no definitive tests or treatments for the collection of symptoms known as “Long COVID” or Post-acute sequelae of COVID-19 (PASC). Following our initial case report detailing improvement of Long COVID symptoms after sequential bilateral stellate ganglion blockade (SGB), we performed a retrospective chart analysis study on individuals treated with the same protocol over the course of six months (2021−2022) in our clinic. Patients self-reported symptoms on a 10-point scale as part of optional patient follow-up using an online survey. After one month or more following treatment, patients reported striking reductions in Fatigue, Worsening of Symptoms following Mental and Physical Activity, Memory Problems, Problems Concentrating, Sleep Problems, Anxiety, and Depression. Loss of Taste and Loss of Smell in some individuals did not respond to treatment, likely indicating structural damage following infection. This study suggests that neuromodulation may provide relief of Long COVID symptoms for at least a subset of individuals, and provides support for prospective studies of this potential treatment.

Long COVID and financial outcomes: evidence from four longitudinal population surveys

BackgroundLong-term sequelae of COVID-19 (long COVID) include muscle weakness, fatigue, breathing difficulties and sleep disturbance over weeks or months. Using UK longitudinal data, we assessed the relationship between long COVID...

Incidence, Risk, and Clinical Course of New-Onset Diabetes in Long COVID: Protocol for a Systematic Review and Meta-Analysis of Cohort Studies.

COVID-19, an infectious disease pandemic, affected millions of people globally, resulting in high morbidity and mortality. Causing further concern, significant proportions of COVID-19 survivors endure the lingering health effects of SARS-CoV-2, the pathogen that causes COVID-19. One of the diseases manifesting as a postacute sequela of COVID-19 (also known as "long COVID") is new-onset diabetes. The aim of this study is to examine the incidence of new-onset diabetes in patients with long COVID and assess the excess risk compared with individuals who tested negative for COVID-19. The study also aims to estimate the population-attributable fraction for COVID-19 as a risk factor for new-onset diabetes in long COVID and investigate the clinical course of new-onset diabetes cases. This is a protocol for a systematic review and meta-analysis. PubMed, MEDLINE, Embase, Scopus, and Web of Science databases will be systematically searched to identify articles published between December 2019 and July 2024. A comprehensive search strategy for each database will be developed using a combination of Medical Subject Headings terms, subject headings, and text words to identify eligible studies. Cohort studies and randomized controlled trials (only control arms) involving patients with COVID-19 of any age, with follow-up data on new-onset diabetes in long COVID, will be considered for inclusion. Controls will comprise individuals who tested negative for COVID-19, with or without other respiratory tract infections. Three independent reviewers (AST, NB, and TT) will perform article selection, data extraction, and quality assessment of the studies. A fourth reviewer (ST) will review the identified studies for final inclusion in the analysis. The random-effects DerSimonian-Laird models will be used to estimate the pooled incidence proportion (%), incidence rate of diabetes (per 1000 person-years), and risk ratio (with 95% CIs) for diabetes incidence. A total of 1972 articles were identified through the initial search conducted in August 2023. After excluding duplicates, conducting title and abstract screening, and completing full-text reviews, 41 articles were found to be eligible for inclusion. The search will be updated in July 2024. Currently, data extraction is underway, and the meta-analysis is expected to be completed in August 2024. Publication of the study findings is anticipated by the end of 2024. The study findings should provide valuable insights to inform both clinical practice and public health policies regarding the effective management of new-onset diabetes in patients with long COVID. DERR1-10.2196/54853.

Persistent Neurological Deficits in Mouse PASC Reveal Antiviral Drug Limitations.

Post-Acute Sequelae of COVID-19 (PASC) encompasses persistent neurological symptoms, including olfactory and autonomic dysfunction. Here, we report chronic neurological dysfunction in mice infected with a virulent mouse-adapted SARS-CoV-2 that does not infect the brain. Long after recovery from nasal infection, we observed loss of tyrosine hydroxylase (TH) expression in olfactory bulb glomeruli and neurotransmitter levels in the substantia nigra (SN) persisted. Vulnerability of dopaminergic neurons in these brain areas was accompanied by increased levels of proinflammatory cytokines and neurobehavioral changes. RNAseq analysis unveiled persistent microglia activation, as found in human neurodegenerative diseases. Early treatment with antivirals (nirmatrelvir and molnupiravir) reduced virus titers and lung inflammation but failed to prevent neurological abnormalities, as observed in patients. Together these results show that chronic deficiencies in neuronal function in SARS-CoV-2-infected mice are not directly linked to ongoing olfactory epithelium dysfunction. Rather, they bear similarity with neurodegenerative disease, the vulnerability of which is exacerbated by chronic inflammation.

Growth hormone treatment for neurologic symptoms of post-acute sequelae of COVID-19.

Following SARS-CoV-2 infection, some patients develop lingering neurologic symptoms of post-acute sequelae of COVID-19 (PASC) that commonly include fatigue and "brain fog." PASC symptoms are also linked with reduced growth hormone (GH) secretion, but GH treatment has not been tested to relieve symptoms. We enrolled 13 adults with neurologic PASC symptoms and peak stimulated GH secretion less than 10 ng/mL (glucagon stimulation) in a pilot study to receive 9 months of daily GH injections and an additional 3 months of off-treatment assessment. We compared peak stimulated GH secretion at baseline and 12 months and assessed measures of cognition, metabolism, body composition, and physical performance over the first 6 months of treatment. Patient-reported outcomes of fatigue, quality of life, sleep, and mood were recorded at baseline and compared with timepoints at 6, 9, and 12 months. GH treatment was associated with significantly improved scores for Brief Fatigue Inventory, Multidimensional Fatigue Symptom Inventory, Quality of Life Assessment of GrowthHormone Deficiency in Adults, Profile of Mood States, and Beck Depression Inventory-II, with no significant change in Pittsburgh Sleep Quality Index. Six months of adjunct GH treatment was not associated with significant changes in cognition, body composition, resting energy expenditure, or physical performance. Peak stimulated GH secretion was not altered at 12 months following 9 months of GH treatment. GH treatment significantly improved neurologic symptoms in PASC patients but cognition, sleep, and physical performance were not significantly altered.

Long-Term Functional Limitations and Predictors of Recovery After COVID-19: A Multicenter Prospective Cohort Study

BackgroundLimited data exist on post-severe COVID-19 functional trajectory, particularly considering premorbid status. We characterized 1-year functional recovery post-hospitalization for COVID-19, highlighting predictors of long-term recovery. MethodsWe enrolled adult patients with lab-confirmed SARS-CoV-2 infection and hospitalized for COVID-19 sequelae, from five major Ontario, Canada hospitals in a prospective cohort study. Assessments included telephone interviews on admission followed by telephone and in-person assessments at 3-, 6-, 9-, and 12-months post-discharge. The Activity-Measure for Post-Acute Care (AM-PAC) Mobility and Cognition scales were administered at baseline and every 3 months for 1 year. Secondary outcomes included symptoms, spirometry, physical performance, dyspnea, fatigue, distress, anxiety and depression, and quality of life. ResultsA total of 254 patients (57.1% male) with a mean age of 60.0 (±13.1) years and an average hospital stay of 14.3 (±19.7) days agreed to participate. At 12 months, 55.3% demonstrated clinically important deficits in mobility and 38.8% had cognitive deficits compared to premorbid levels. Fatigue was reported in 44.2%, followed by difficulty walking long distances in 35.8% and dyspnea in 33.0%. Almost 40% of patients had an FEV1(% Pred) < 80% at 12 months, 60.3% had impairments in physical performance, and 44.5% had problems with anxiety or depression. Predictors of better mobility at 12 months included higher premorbid mobility status, male sex, shorter hospital stay, fewer comorbidities, and higher FEV1 (% pred) at the 3-month follow-up. ConclusionsOur study provides compelling evidence of the long-term impact of COVID-19 on functional and cognitive status 1-year post-infection.

COVID-19 sequelae on transthoracic echocardiography findings in pediatric patients with septal congenital heart disease: A retrospective comparative analysis

COVID-19 sequelae on transthoracic echocardiography findings in pediatric patients with septal congenital heart disease: A retrospective comparative analysis

SARS-CoV-2 Spike Protein 1 Causes Aggregation of α-Synuclein via Microglia-Induced Inflammation and Production of Mitochondrial ROS: Potential Therapeutic Applications of Metformin.

Abnormal aggregation of α-synuclein is the hallmark of neurodegenerative diseases, classified as α-synucleinopathies, primarily occurring sporadically. Their onset is associated with an interaction between genetic susceptibility and environmental factors such as neurotoxins, oxidative stress, inflammation, and viral infections. Recently, evidence has suggested an association between neurological complications in long COVID (sometimes referred to as 'post-acute sequelae of COVID-19') and α-synucleinopathies, but its underlying mechanisms are not completely understood. In this study, we first showed that SARS-CoV-2 Spike protein 1 (S1) induces α-synuclein aggregation associated with activation of microglial cells in the rodent model. In vitro, we demonstrated that S1 increases aggregation of α-synuclein in BE(2)M-17 dopaminergic neurons via BV-2 microglia-mediated inflammatory responses. We also identified that S1 directly affects aggregation of α-synuclein in dopaminergic neurons through increasing mitochondrial ROS, though only under conditions of sufficient α-Syn accumulation. In addition, we observed a synergistic effect between S1 and the neurotoxin MPP+ S1 treatment. Combined with a low dose of MPP+, it boosted α-synuclein aggregation and mitochondrial ROS production compared to S1 or the MPP+ treatment group. Furthermore, we evaluated the therapeutic effects of metformin. The treatment of metformin suppressed the S1-induced inflammatory response and α-synucleinopathy. Our findings demonstrate that S1 promotes α-synucleinopathy via both microglia-mediated inflammation and mitochondrial ROS, and they provide pathological insights, as well as a foundation for the clinical management of α-synucleinopathies and the onset of neurological symptoms after the COVID-19 outbreak.

Association between COVID-19 and the Risk of Vascular Dementia: A Mendelian Randomisation Study of the Potential Cognitive Sequela of COVID-19.

A growing body of observational studies and Mendelian Randomisation analyses suggest an increased risk of Alzheimer's disease and dementia following COVID-19 infection. However, evidence on the potential association between COVID-19 and vascular dementia, which is plausible given the vascular complications of COVID-19 infection, is still limited. In this study, we conducted a two-sample Mendelian Randomisation analysis to examine the potential causal relationship between COVID-19 phenotypes and the risk of vascular dementia, using summary data from large-scale GWASs. The two-sample Mendelian Randomisation analysis did not detect any significant associations of COVID-19 infection, COVID-19 hospitalisation, or critical COVID-19 with the risk of vascular dementia, with weighted average β values of -0.29 (95% CI: -0.84, 0.26; p = 0.301), -0.12 (95% CI: -0.36, 0.13; p = 0.345), and -0.07 (95% CI: -0.23, 0.09; p = 0.374), respectively. Our findings do not support the hypothesis that vascular dementia is one of the long-term sequelae of COVID-19.

SPIKENET: An Evidence-Based Therapy for Long COVID.

The COVID-19 pandemic has been one of the most impactful events in our lifetime, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple SARS-CoV-2 variants were reported globally, and a wide range of symptoms existed. Individuals who contract COVID-19 continue to suffer for a long time, known as long COVID or post-acute sequelae of COVID-19 (PASC). While COVID-19 vaccines were widely deployed, both unvaccinated and vaccinated individuals experienced long-term complications. To date, there are no treatments to eradicate long COVID. We recently conceived a new approach to treat COVID in which a 15-amino-acid synthetic peptide (SPIKENET, SPK) is targeted to the ACE2 receptor binding domain of SARS-CoV-2, which prevents the virus from attaching to the host. We also found that SPK precludes the binding of spike glycoproteins with the receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) of a coronavirus, murine hepatitis virus-1 (MHV-1), and with all SARS-CoV-2 variants. Further, SPK reversed the development of severe inflammation, oxidative stress, tissue edema, and animal death post-MHV-1 infection in mice. SPK also protects against multiple organ damage in acute and long-term post-MHV-1 infection. Our findings collectively suggest a potential therapeutic benefit of SPK for treating COVID-19.

Symptoms and Conditions in Children and Adults up to 90 Days after SARS-CoV-2 Infection: A Retrospective Observational Study Utilizing the Common Data Model.

Background/Objectives: There have been widespread reports of persistent symptoms in both children and adults after SARS-CoV-2 infection, giving rise to debates on whether it should be regarded as a separate clinical entity from other postviral syndromes. This study aimed to characterize the clinical presentation of post-acute symptoms and conditions in the Korean pediatric and adult populations. Methods: A retrospective analysis was performed using a national, population-based database, which was encoded using the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). We compared individuals diagnosed with SARS-CoV-2 to those diagnosed with influenza, focusing on the risk of developing prespecified symptoms and conditions commonly associated with the post-acute sequelae of COVID-19. Results: Propensity score matching yielded 1,656 adult and 343 pediatric SARS-CoV-2 and influenza pairs. Ninety days after diagnosis, no symptoms were found to have elevated risk in either adults or children when compared with influenza controls. Conversely, at 1 day after diagnosis, adults with SARS-CoV-2 exhibited a significantly higher risk of developing abnormal liver function tests, cardiorespiratory symptoms, constipation, cough, thrombophlebitis/thromboembolism, and pneumonia. In contrast, children diagnosed with SARS-CoV-2 did not show an increased risk for any symptoms during either acute or post-acute phases. Conclusions: In the acute phase after infection, SARS-CoV-2 is associated with an elevated risk of certain symptoms in adults. The risk of developing post-acute COVID-19 sequelae is not significantly different from that of having postviral symptoms in children in both the acute and post-acute phases, and in adults in the post-acute phase. These observations warrant further validation through studies, including the severity of initial illness, vaccination status, and variant types.

Long COVID symptoms after 8-month recovery: persistent static lung hyperinflation associated with small airway dysfunction

BackgroundLimited research has investigated the relationship between small airway dysfunction (SAD) and static lung hyperinflation (SLH) in patients with post-acute sequelae of COVID-19 (PASC) especially dyspnea and fatigue.Methods64 patients with PASC were enrolled between July 2020 and December 2022 in a prospective observational cohort. Pulmonary function tests, impulse oscillometry (IOS), and symptom questionnaires were performed two, five and eight months after acute infection. Multivariable logistic regression models were used to test the association between SLH and patient-reported outcomes.ResultsSLH prevalence was 53.1% (34/64), irrespective of COVID-19 severity. IOS parameters and circulating CD4/CD8 T-cell ratio were significantly correlated with residual volume to total lung capacity ratio (RV/TLC). Serum CD8 + T cell count was negatively correlated with forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) with statistical significance. Of the patients who had SLH at baseline, 57% continued to have persistent SLH after eight months of recovery, with these patients tending to be older and having dyspnea and fatigue. Post-COVID dyspnea was significantly associated with SLH and IOS parameters R5-R20, and AX with adjusted odds ratios 12.4, 12.8 and 7.6 respectively. SLH was also significantly associated with fatigue.ConclusionSAD and a decreased serum CD4/CD8 ratio were associated with SLH in patients with PASC. SLH may persist after recovery from infection in a substantial proportion of patients. SAD and dysregulated T-cell immune response correlated with SLH may contribute to the development of dyspnea and fatigue in patients with PASC.

Effects of pulmonary rehabilitation on functional and psychological parameters in post-acute sequelae of SARS-CoV-2 infection (PASC) patients

BackgroundCOVID-19 survivors may develop long-term symptoms of fatigue, dyspnea, mental health issues, and functional limitations: a condition termed post-acute sequelae of COVID-19 (PASC). Pulmonary rehabilitation (PR) is a recommended treatment for PASC; however, there is a lack of data regarding PR’s effect on multiple health indices and the factors that influence patient outcomes. The aim of our study is to evaluate the impact of pulmonary rehabilitation on functional and psychological parameters in patients diagnosed with Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), thereby offering insights into the efficacy of such interventions in improving the quality of life and clinical outcomes for these individuals.MethodsWe extracted patient demographic, comorbidity, and outcome data from Allegheny Health Network’s electronic medical records. Functionality test results were compared before and after PR, including 6-minute walk test (6MWT), chair rise repetitions (CR reps), timed up and go test (TUG), gait speed (Rehab gait), modified medical research council scale (MMRC), shortness of breath questionnaire (SOBQ), hospital anxiety and depression scale (HADS) and chronic obstructive pulmonary disease assessment test (CAT) scores. Multiple regression analysis was done to evaluate the effect of comorbidities and patient factors on patient responses to PR.ResultsThe 55 patients included in this study had a mean time of 4 months between the initial COVID-19 diagnosis and the subsequent PASC diagnosis. Following pulmonary rehabilitation (PR), significant improvements were observed across various metrics. The distance covered in the 6-minute walk test (6MWT) increased markedly from a pre-rehabilitation average of 895 feet (SD 290) to 1,300 feet (SD 335) post-rehabilitation, with a mean change of 405 feet (95% CI [333, 477]). Chair rise repetitions (CR reps) saw an increase from 9 (SD 3) reps to 13 (SD 3) reps, with a change of 4 reps (95% CI [3.7, 4.9]). The timed up and go test (TUG) time decreased significantly from 13 s (SD 5) to 10 s (SD 2), reflecting a mean reduction of 3 s (95% CI [-4.5, -2.5]). Rehabilitation gait speed improved from 1.0 m/s to 1.3 m/s, changing by 0.3 m/s (95% CI [0.2, 0.3]). The Modified Medical Research Council (MMRC) dyspnea scale showed a notable decrease from a mean of 2 (SD 1) to 1 (SD 1), a change of -1 (95% CI [-1.5, -1]). The Shortness of Breath Questionnaire (SOBQ) scores reduced significantly from 51 (SD 21) to 22 (SD 18), with a change of -29 (95% CI [-34, -23]). The Hospital Anxiety and Depression Scale (HADS) scores decreased from 11 (SD 7) to 8 (SD 7), a reduction of -4 (95% CI [-5, -2]). Lastly, the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) scores significantly dropped from 18 (SD 7) to 9 (SD 7), changing by -10 (95% CI [-11, -8]). However, the presence of hypertension, diabetes, chronic lung diseases, outpatient status, and receipt of specific pharmacologic treatments (decadron, decadron + remdesivir, and decadron + remdesivir + tocilizumab) were identified as factors associated with a poor response to PR.ConclusionOur study supports PR as an integrated model of care for PASC patients to improve several physical and mental health indices. The long-term effects of PR on patients’ functional status should be investigated in the future.

Cardiovascular Dysautonomy as a Sequel of SARS COV 2. Case Series

The impact of COVID-19, caused by the SARS-CoV-2 virus, a pandemic that originated in Wuhan, China, can lead to serious complications, in addition to mild symptoms, with special interest in the autonomic nervous system (ANS). Damage to the ANS by SARS-CoV-2 can cause dysautonomia, an imbalance between the sympathetic and parasympathetic system, with unclear mechanisms such as cytokine storm, excessive inflammation, and virus neurotropism. A significant sequelae of COVID-19 is cardiac dysautonomia, which affects heart rate, blood pressure and other autonomic reflexes, causing postural tachycardia, orthostatic hypotension, arrhythmias and fatigue. There is decreased heart rate variability (HRV) in patients, suggesting dysautonomia. Long COVID syndrome can also include cardiac dysautonomia. To diagnose cardiac autonomic neuropathy, at least two of six criteria must be met, such as an SDNN less than 50 ms and an RMSSD less than 15 ms. The cases of cardiac dysautonomia below present several of these criteria met. Methods to evaluate cardiac dysautonomia include the COMPASS 31 scale and the orthostatic hypotension questionnaire (OHQ), but more research is still needed, especially in Mexico. The case study shows that those who followed non-pharmacological recommendations such as cardiovascular exercise, increased water intake and BMI control had improvement, while cases that did not follow these recommendations did not show significant improvements. Cardiac dysautonomia is a post-COVID-19 sequelae with high prevalence, highlighting the importance of non-invasive methods for its diagnosis. Even without symptoms, people can have this sequelae, so it is important to suspect cardiovascular disorders. The need for early intervention and monitoring of hygienic-dietary measures is emphasized to avoid the worsening and chronicity of cardiac dysautonomia, with the hope of preventing the development of chronic diseases and fatal outcomes.

Factors influencing cardiovascular system-related post-COVID-19 sequelae: A single-center cohort study.

COVID-19 sequelae are long-term symptoms of COVID-19. Cardiovascular disease is not only a risk factor for the occurrence of COVID-19 sequelae but also a potential result directly or indirectly caused by COVID-19 infection. The aim of this study is to investigate the cardiovascular system-related symptoms of outpatients and inpatients of the Cardiovascular Department of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine after recovery from novel coronavirus infection, analyze the influencing factors, and symptom characteristics of related symptoms, and thereby provide a basis for further formulating a reasonable diagnosis and treatment plan. From January 15, 2023 to February 15, 2023, 452 recovered patients with novel coronavirus infection who were admitted to the Cardiovascular Department of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine due to symptoms of the cardiovascular system (complaints of chest pain and palpitations) were involved in this study. A unified questionnaire was used to record the general information, past medical history, characteristics of chest pain or palpitations, and other COVID-19-related sequelae of the selected patients. All data were statistically analyzed by SPSS 26.0 statistical software. A total of 226 patients with cardiovascular symptoms and 226 patients without cardiovascular symptoms were included in this study. After univariate and multivariate logistic regression analysis, women (OR 2.081, 95% CI = 1.358-3.189) and young people (OR 2.557, 95% CI = 1.44-4.54) had a higher risk of cardiovascular symptoms; prehypertension (OR 1.905, 95% CI = 1.091-3.329) and hypertension (OR 2.287, 95% CI = 1.433-3.649) increased the risk of cardiovascular symptoms; patients with history of previous cardiovascular disease (OR 1.862, 95% CI = 1.16-2.988) and history of diabetes (OR 2.138, 95% CI = 1.058-4.319) had a higher risk of developing cardiovascular symptoms. The main symptoms related to COVID-19 sequelae reported by all 452 patients were fatigue (76.8%), shortness of breath (54.2%), dry mouth and bitter mouth (46.0%), gastrointestinal symptoms (42.7%), sleep disturbances (37.4%), sweating (31.9%), chills (29%), dizziness (25.7%), confusion of brain fog (25.2%), and tinnitus (14.6%). Compared with patients without cardiovascular symptoms, patients with cardiovascular symptoms were more likely to have shortness of breath (OR 3.521, 95% CI = 2.226-5.472), gastrointestinal symptoms (OR 2.039, 95% CI = 1.226-3.393), and dry mouth and bitter mouth (OR 1.918, 95% CI = 1.229-2.992). The differences were statistically significant (P < 0.05). In this new coronavirus infection, women, young people, the elderly, people with prehypertension, hypertension, and patients with a history of cardiovascular disease and diabetes have a higher risk of developing cardiovascular symptoms, and patients with cardiovascular symptoms are more likely to develop other COVID-19 sequelae.

In-vitro and in-vivo assessment of nirmatrelvir penetration into CSF, central nervous system cells, tissues, and peripheral blood mononuclear cells

Three years after SARS-CoV-2 emerged as a global infectious threat, the virus has become endemic. The neurological complications such as depression, anxiety, and other CNS complications after COVID-19 disease are increasing. The brain, and CSF have been shown as viral reservoirs for SARS-CoV-2, yielding a potential hypothesis for CNS effects. Thus, we investigated the CNS pharmacology of orally dosed nirmatrelvir/ritonavir (NMR/RTV). Using both an in vitro and an in vivo rodent model, we investigated CNS penetration and potential pharmacodynamic activity of NMR. Through pharmacokinetic modeling, we estimated the median CSF penetration of NMR to be low at 18.11% of plasma with very low accumulation in rodent brain tissue. Based on the multiples of the 90% maximal effective concentration (EC90) for SARS-CoV-2, NMR concentrations in the CSF and brain do not achieve an exposure level similar to that of plasma. A median of only 16% of all the predicted CSF concentrations in rats were > 3xEC90 (unadjusted for protein binding). This may have implications for viral persistence and neurologic post-acute sequelae of COVID-19 if increased NMR penetration in the CNS leads to decreased CNS viral loads and decreased CNS inflammation.

A murine model of post-acute neurological sequelae following SARS-CoV-2 variant infection.

Viral variant is one known risk factor associated with post-acute sequelae of COVID-19 (PASC), yet the pathogenesis is largely unknown. Here, we studied SARS-CoV-2 Delta variant-induced PASC in K18-hACE2 mice. The virus replicated productively, induced robust inflammatory responses in lung and brain tissues, and caused weight loss and mortality during the acute infection. Longitudinal behavior studies in surviving mice up to 4 months post-acute infection revealed persistent abnormalities in neuropsychiatric state and motor behaviors, while reflex and sensory functions recovered over time. In the brain, no detectable viral RNA and minimal residential immune cell activation was observed in the surviving mice post-acute infection. Transcriptome analysis revealed persistent activation of immune pathways, including humoral responses, complement, and phagocytosis, and gene expression levels associated with ataxia telangiectasia, impaired cognitive function and memory recall, and neuronal dysfunction and degeneration. Furthermore, surviving mice maintained potent systemic T helper 1 prone cellular immune responses and strong sera neutralizing antibodies against Delta and Omicron variants months post-acute infection. Overall, our findings suggest that infection in K18-hACE2 mice recapitulates the persistent clinical symptoms reported in long-COVID patients and provides new insights into the role of systemic and brain residential immune factors in PASC pathogenesis.

SARS-CoV-2, periodontal pathogens, and host factors: The trinity of oral post-acute sequelae of COVID-19.

COVID-19 as a pan-epidemic is waning but there it is imperative to understand virus interaction with oral tissues and oral inflammatory diseases. We review periodontal disease (PD), a common inflammatory oral disease, as a driver of COVID-19 and oral post-acute-sequelae conditions (PASC). Oral PASC identifies with PD, loss of teeth, dysgeusia, xerostomia, sialolitis-sialolith, and mucositis. We contend that PD-associated oral microbial dysbiosis involving higher burden of periodontopathic bacteria provide an optimal microenvironment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. These pathogens interact with oral epithelial cells activate molecular or biochemical pathways that promote viral adherence, entry, and persistence in the oral cavity. A repertoire of diverse molecules identifies this relationship including lipids, carbohydrates and enzymes. The S protein of SARS-CoV-2 binds to the ACE2 receptor and is activated by protease activity of host furin or TRMPSS2 that cleave S protein subunits to promote viral entry. However, PD pathogens provide additional enzymatic assistance mimicking furin and augment SARS-CoV-2 adherence by inducing viral entry receptors ACE2/TRMPSS, which are poorly expressed on oral epithelial cells. We discuss the mechanisms involving periodontopathogens and host factors that facilitate SARS-CoV-2 infection and immune resistance resulting in incomplete clearance and risk for 'long-haul' oral health issues characterising PASC. Finally, we suggest potential diagnostic markers and treatment avenues to mitigate oral PASC.

Emerging trends in management of long COVID with a focus on pulmonary rehabilitation: A review.

Long COVID, or post-acute sequelae of COVID-19 (PASC), represents a complex condition with persistent symptoms following SARS-Cov-2 infection. The symptoms include fatigue, dyspnoea, cognitive impairment, decreased quality of life in variable levels of severity. Potential mechanisms behind long COVID include vascular damage, immune dysregulation and viral persistence. Diagnosing long COVID involves medical evaluation by multidisciplinary team and assessment of persistent symptoms with scoring systems in development. Treatment strategies are symptom-focused, encompassing multidisciplinary care, rehabilitation and tailored exercise programmes. Pulmonary rehabilitation, an effective and critical component of long COVID management, has shown promise, particularly for patients with respiratory symptoms such as dyspnoea. These programmes, which combine exercise, breathing techniques, education and psychological support, improve symptoms, quality of life and overall recovery. Innovative technologies, such as telemedicine, wearable devices, telerehabilitation, are transforming long COVID management. Telemedicine facilitates consultations and interventions, eliminating healthcare access barriers. Wearable devices enable remote and continuous monitoring of patients during their rehabilitation activities. Telerehabilitation has proven to be safe and feasible and to have high potential for COVID-19 recovery. This review provides a concise overview of long COVID, encompassing its definition, prevalence, mechanisms, clinical manifestations, diagnosis and management approaches. It emphasizes the significance of multidisciplinary approach in diagnosis and treatment of long COVID, with focus on pulmonary rehabilitation and innovative technology advances to effectively address the management of long COVID.

Long-Term Effect of Post-Covid-19 Syndrome on Respiratory Parameters in Iraqi People

Background: The long-term sequelae of COVID-19 are thought to be a novel area of research due to variances in the epidemiology and therapy. Nevertheless, the follow-up time interval (6 or 12 months) was excessively long, and the time point of the follow-up period varied from 3 to 24 months in the prior research. More research is required to understand better COVID-19's effects, including their long-term effects on the lungs and how they may affect pulmonary function. Therefore, this study aims to investigate the long-term impact of post-COVID-19 syndrome on pulmonary function tests. Methods: This research was a case-control study conducted from 13 October 2023 to 13 November 2023 at the Al-Sader Teaching Hospital in Maysan City. There are fifty-eight patients and fifty-eight controls included. This study comprised patients who visited a pulmonary consulting clinic and had COVID-19 symptoms, matched by controls who were chosen at random. The controls had to meet the same criteria as the cases, with the exception that they did not have COVID-19 disease. The most popular kind of breathing or pulmonary function test is spirometry, spirometry was used to measure: FVC, FEV, and FEV1/FVC ratio. Result: Sixty-six post COVID-19 syndrome with ages (34.1 ± 9.8) years and sixty-seven controls were enrolled. The results of FVC and FEV parameters indicate a significant difference (P&lt;0.05) between cases and control groups. However, no significant differences existed between groups for the FEV1/FVC ratio. In the comparison of lung function tests between cases and control across different age groups (18-29, 30-39, 50-65) years, we found that mean FVC is significantly lower for the age group 18-29 years than for 30-39 and 50-65 years, and the mean FEV is significantly lower for the age group 18-29 years than for 30-39. Conclusion: After COVID-19, a significant number of patients continue to have symptoms, with respiratory symptoms accounting for the majority of complaints. Patients with continuing symptoms were younger and presented a significantly lower FVC and FEV.