Search

Long COVID-19, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), involves symptoms or effects that persist for more than 4 weeks after the initial SARS-CoV-2 infection. One contributing factor to this condition is the disruption in the expression of the antioxidant enzyme Nuclear Factor Erythroid-2 (Nrf2) induced by the COVID-19 infection. Apigenin and related flavonoids, known for their diverse pharmacological activities, including potent antioxidant properties, have emerged as promising candidates for Long COVID-19 therapy. These compounds, particularly apigenin, are recognized for their ability to modulate oxidative stress and inflammation, making them potential activators of the Nrf2 pathway. This study aims to predict the activity of apigenin and its related flavonoids as Nrf2 activators using molecular modeling and molecular dynamics (MD) techniques, providing insights into their therapeutic potential in managing Long COVID-19. The findings from the molecular modeling analysis indicate that apigenin has a favorable affinity, with a free energy value (ΔG) of −6.40 kcal/mol. Additionally, MD simulation results demonstrate the strong stability of the Keap1-apigenin complex, with an average Root Mean Square Deviation (RMSD) value below 0.20 nm and the lowest average Root Mean Square Fluctuation (RMSF) value of 0.86 nm. Using the Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) calculation method, the binding affinity of the Keap1-apigenin complex yields a lower free energy value (ΔG) of −67.039 kJ/mol, consistent with the molecular modeling results. Apigenin also exhibits the ability to inhibit the binding of Nrf2 to the hydrophobic surface of Keap1, with a total energy value of 993.266 kcal/mol and binding affinity value of −1.162 kJ/mol through peptide−receptor docking. In conclusion, the comprehensive results suggest that apigenin has the potential to be a lead compound for developing Nrf2 activators specifically designed for Long COVID-19 therapy. [ABSTRACT FROM AUTHOR]

Background and Objectives: Long COVID-19 syndrome may cause difficulties in functionality during daily life in young people. Our objective was to investigate the respiratory and functional sequelae in young adults with asymptomatic or mild COVID-19 compared with healthy peers 3–6 months and 6–12 months after COVID-19 infection. Materials and Methods: Participants aged 18–25 who had COVID-19 within the last 3–6 months (Post-COVID Group 1, n = 25) and 6–12 months (Post-COVID Group 2, n = 25) and age–gender-matched healthy controls (n = 25) were included in this study. Respiratory functions and muscle strength were measured. Physical function was assessed with 6 min walking test (6MWT) and an Incremental Shuttle Walk Test (ISWT). The 1 min sit-to-stand test (1-MSTST) and hand grip strength (HGS) were used to assess muscle performance. Fatigue and dyspnea severity were questioned. Results: The FVC%pred (p = 0.023) and MEP (p = 0.034) were higher, and 1-MSTST repetitions were lower in Post-COVID Group-1 compared to Post-COVID Group-2 (p = 0.029). The PEF%pred (p = 0.025), MEP (p = 0.001), and ISWT distance were lower in Post-COVID Group-2 compared to healthy controls. The number of 1-MSTST repetitions and 6MWT distance were lower in Post-COVID Group-1 (p = 0.003, p = 0.001) and Post-COVID Group-2 (p = 0.003, p = 0.017) than in healthy controls. Exercise-induced blood lactate change during the ISWT, HGS, fatigue, and dyspnea were not significantly different between post-COVID groups and healthy controls. Conclusions: Young adults who pass asymptomatic or mild SARS-CoV-2 infection exhibit a decline in FVC%pred, PEF%pred, lower extremity muscle performance, and physical function within 3–6 months. In addition, the deterioration in respiratory and physical functions becomes apparent within 6–12 months. [ABSTRACT FROM AUTHOR]

Backgrounds: Although COVID-19 is primarily known as a respiratory disease, there is growing evidence of neurological complications, such as ischemic stroke, in infected individuals. This study aims to evaluate the impact of COVID-19 on acute ischemic stroke (AIS) using radiomic features extracted from brain MR images and machine learning methods. Methods: This retrospective study included MRI data from 57 patients diagnosed with AIS who presented to the Department of Radiology at Hacettepe University Hospital between March 2020 and September 2021. Patients were stratified into COVID-19-positive (n = 30) and COVID-19-negative (n = 27) groups based on PCR results. Radiomic features were extracted from brain MR images following image processing steps. Various feature selection algorithms were applied to identify the most relevant features, which were then used to train and evaluate machine learning classification models. Model performance was evaluated using a range of classification metrics, including measures of predictive accuracy and diagnostic reliability, with 95% confidence intervals provided to enhance reliability. Results: This study assessed the performance of dimensionality reduction and classification algorithms in distinguishing COVID-19-negative and COVID-19-positive cases using radiomics data from brain MR scans. Without feature selection, ANN achieved the highest AUC of 0.857 (95% CI: 0.806–0.900), demonstrating strong discriminative power. Using the Boruta method for feature selection, the k-NN classifier attained the best performance, with an AUC of 0.863 (95% CI: 0.816–0.904). LASSO-based feature selection showed comparable results across k-NN, RF, and ANN classifiers, while SVM exhibited excellent specificity and high PPV. The RFE method yielded the highest overall performance, with the k-NN classifier achieving an AUC of 0.882 (95% CI: 0.838–0.924) and an accuracy of 79.1% (95% CI: 73.6–83.8). Among the methods, RFE provided the most consistent results, with k-NN and the ANN identified as the most effective classifiers for COVID-19 detection. Conclusions: The proposed radiomics-based classification model effectively distinguishes AIS associated with COVID-19 from brain MRI. These findings demonstrate the potential of AI-driven diagnostic tools to identify high-risk patients, support optimized treatment strategies, and ultimately improve clinical implications. [ABSTRACT FROM AUTHOR]

The COVID-19 outbreak, caused by the SARS-CoV-2 virus, was linked to significant neurological and psychiatric manifestations. This review examines the physiopathological mechanisms underlying these neuropsychiatric outcomes and discusses current management strategies. Primarily a respiratory disease, COVID-19 frequently leads to neurological issues, including cephalalgia and migraines, loss of sensory perception, cerebrovascular accidents, and neurological impairment such as encephalopathy. Lasting neuropsychological effects have also been recorded in individuals following SARS-CoV-2 infection. These include anxiety, depression, and cognitive dysfunction, suggesting a lasting impact on mental health. The neuroinvasive potential of the virus, inflammatory responses, and the role of angiotensin-converting enzyme 2 (ACE2) in neuroinflammation are critical factors in neuropsychiatric COVID-19 manifestations. In addition, the review highlights the importance of monitoring biomarkers to assess Central Nervous System (CNS) involvement. Management strategies for these neuropsychiatric conditions include supportive therapy, antiepileptic drugs, antithrombotic therapy, and psychotropic drugs, emphasizing the need for a multidisciplinary approach. Understanding the long-term neuropsychiatric implications of COVID-19 is essential for developing effective treatment protocols and improving patient outcomes. [ABSTRACT FROM AUTHOR]

The S1 subunit of SARS-CoV-2 Spike is crucial for ACE2 recognition and viral entry into human cells. It has been found in the blood of COVID-19 patients and vaccinated individuals. Using BioGRID, I identified 146 significant human proteins that interact with S1. I then created an interactome model that made it easier to study functional activities. Through a reverse engineering approach, 27 specific one-to-one interactions of S1 with the human proteome were selected. S1 interacts in this manner independently from the biological context in which it operates, be it infection or vaccination. Instead, when it works together with viral proteins, they carry out multiple attacks on single human proteins, showing a different functional engagement. The functional implications and tropism of the virus for human organs/tissues were studied using Cytoscape. The nervous system, liver, blood, and lungs are among the most affected. As a single protein, S1 operates in a complex metabolic landscape which includes 2557 Biological Processes (GO), much more than the 1430 terms controlled when operating in a group. A Data Merging approach shows that the total proteins involved by S1 in the cell are over 60,000 with an average involvement per single biological process of 26.19. However, many human proteins become entangled in over 100 different biological activities each. Clustering analysis showed significant activations of many molecular mechanisms, like those related to hepatitis B infections. This suggests a potential involvement in carcinogenesis, based on a viral strategy that uses the ubiquitin system to impair the tumor suppressor and antiviral functions of TP53, as well as the role of RPS27A in protein turnover and cellular stress responses. [ABSTRACT FROM AUTHOR]

Long-term sequelae of coronavirus disease 2019 (COVID-19) infection are common and can have debilitating consequences. There is a need to understand risk factors for Long COVID-19 to give impetus to the development of targeted yet holistic clinical and public health interventions to reduce its associated healthcare and economic burden. Given the large number and variety of predictors implicated spanning health-related and sociodemographic factors, machine learning becomes a valuable tool. As such, this study aims to employ machine learning to produce an algorithm to predict Long COVID-19 risk, and thereby identify key predisposing factors. Longitudinal cohort data were sourced from the UK's "Understanding Society: COVID-19 Study" (n = 601 participants with past symptomatic COVID-19 infection confirmed by serology testing). The random forest classification algorithm demonstrated good overall performance with 97.4% sensitivity and modest specificity (65.4%). Significant risk factors included early timing of acute COVID-19 infection in the pandemic, greater number of hours worked per week, older age and financial insecurity. Loneliness and having uncommon health conditions were associated with lower risk. Sensitivity analysis suggested that COVID-19 vaccination is also associated with lower risk, and asthma with an increased risk. The results are discussed with emphasis on evaluating the value of machine learning; potential clinical utility; and some benefits and limitations of machine learning for health science researchers given its availability in commonly used statistical software. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the effects of pulmonary rehabilitation (PR) and additional progressive muscle relaxation (PMR) techniques in patients with long-term COVID-19 symptoms. Methods: We included 61 patients with long COVID-19 symptoms and randomly assigned them to two groups: PR only (group 1 with 30 subjects) and PR with PMR (group 2 with 31 subjects). The PR program consisted of gradual aerobic conditioning, strength training, and breathing exercises. Group 2 received additional 20 min daily sessions of progressive muscle relaxation techniques. Results: Following a 21-day intervention, it was observed that both groups had noteworthy improvements in lung function, exercise capacity, and sleep quality with statistical significance (p < 0.0001). Group 2 showed significant improvements in overall health (as measured by the General Health Questionnaire-12), patient health (as assessed by the Patient Health Questionnaire-9), general anxiety levels (as indicated by the Generalized Anxiety Disorders Scale-7), and sleep quality (as measured by the Pittsburgh Sleep Quality Index), with statistical significance (p < 0.0001), compared to group 1. Moreover, the statistical analysis demonstrated no significant difference in exercise capacity improvement between group 1 and group 2, as indicated by a p-value of 0.1711. Conclusions: The addition of progressive muscle relaxation to pulmonary rehabilitation significantly enhances mental health outcomes, particularly in reducing anxiety and improving sleep quality, for patients with long-term COVID-19 symptoms. These findings suggest that incorporating PMR into PR programs offers a valuable non-pharmacological approach to improving overall patient well-being during long-term COVID-19 recovery. [ABSTRACT FROM AUTHOR]

Background: Long COVID-19 is an emerging chronic illness of significant public health concern due to a myriad of neuropsychiatric sequelae, including increased suicidal ideation (SI) and behavior (SB). Methods: This review provides a concise synthesis of clinical evidence that points toward the dysfunction of astrocytes, the most abundant glial cell type in the central nervous system, as a potential shared pathology between SI/SB and COVID-19. Results: Depression, a suicide risk factor, and SI/SB were both associated with reduced frequencies of various astrocyte subsets and complex proteomic/transcriptional changes of astrocyte-related markers in a brain-region-specific manner. Astrocyte-related circulating markers were increased in depressed subjects and, to a less consistent extent, in COVID-19 patients. Furthermore, reactive astrocytosis was observed in subjects with SI/SB and those with COVID-19. Conclusions: Astrocyte dysfunctions occurred in depression, SI/SB, and COVID-19. Reactive-astrocyte-mediated loss of the blood–brain barrier (BBB) integrity and subsequent neuroinflammation—a factor previously linked to SI/SB development—might contribute to increased suicide in individuals with long COVID-19. As such, the formulation of new therapeutic strategies to restore astrocyte homeostasis, enhance BBB integrity, and mitigate neuroinflammation may reduce SI/SB-associated neuropsychiatric manifestations among long COVID-19 patients. [ABSTRACT FROM AUTHOR]

Objective: To evaluate and characterize the cognitive changes in COVID-19 participants at 6-month follow-up, and to explore a possible association with clinical symptoms, emotional disturbance and disease severity. Methods: This single-center longitudinal cohort study included participants aged 20 and 60 years old to exclude cognitive impairment age-associated with confirmed COVID-19 infection. The initial evaluation occurred 10 to 30 days after hospital or ambulatory discharge, with a subsequent follow-up at 6 months. Patients who had a history of cognitive impairment, neurological conditions, or serious psychiatric disorders were not included. Information on demographics and laboratory results was gathered from medical records. Cognitive outcomes were assessed with a neuropsychological battery including attention, verbal and visual memory, language and executive function tests. Results: A total of 200 participants were included in the study, and 108 completed the follow-up visit. At the 6-month follow-up, comparing the means from baseline with those of the follow-up evaluation, significant overall improvement was observed in verbal and visual memory subtests (p = 0.001), processing speed (p = 0.001), executive function (p = 0.028; p = 0.016) and naming (p = 0.001), independently of disease severity and cognitive complaints. Anxiety and depression were significantly higher in groups with Subjective Cognitive Complaints (SCC) compared to those without (p < 0.01 for both). Conclusions: Persistent symptoms are common regardless of disease severity and are often linked to cognitive complaints. Six months after COVID-19, the most frequently reported symptoms included headache, dyspnea, fatigue, cognitive complaints, anxiety, and depression. No cognitive impairment was found to be associated with the severity of COVID-19. Overall, neuropsychological and psychopathological improvement was observed at 6 months regardless of disease severity and cognitive complaints. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to assess the prevalence of long COVID-19 and estimate the average time to its diagnosis and meta-regression for covariates. Methods: We conducted a systematic review, meta-analysis, and meta-regression from 43 studies (367,236 patients) (June 2020–August 2022). With the random-effects model, the pooled prevalence of long COVID-19 was measured. Publication bias was ascertained, and meta-regression analysis was performed on predetermined covariates. The trial was registered with PROSPERO (CRD42022328509). Results: The pooled prevalence of long COVID-19 was 42.5% (95% CI 36% to 49.3%), with 25% and 66% at four and two months, respectively. Mostly, long COVID-19 signs and symptoms occurred at three (54.3%) to six (57%) months (p < 0.0001), further increasing at 12 months (57.9%, p = 0.0148). Hypertension was significantly associated with long COVID-19 at 32% (0.322 (95% CI 0.166, 0.532) (p < 0.001) and hospital re-admission contributed to 17% (Q = 8.70, df = 1, p = 0.0032) (R2 = 0.17). All the covariates explained at least some of the variance in effect size on long COVID-19 at 53% (Q = 38.81, df = 19, p = 0.0047) (R2 analog = 0.53). Conclusion: The prevalence of long COVID-19 was 42.5% when linked with a cardiovascular disorder. Hospital re-admission majorly predicted the incidence of long COVID-19. Clinical and methodological characteristics in a specific study contributed to over 50% of long COVID-19 events, with most signs and symptoms occurring between 3 and 6 months and increasing at 12 months. [ABSTRACT FROM AUTHOR]

A rise in fungal infections has been observed worldwide among patients with extended hospital stays because of the severe infection caused by the new coronavirus pandemic. A 62-year-old female patient was admitted with a severe form of Coronavirus disease 2019 (COVID-19) and spent four weeks in the intensive care unit (ICU) requiring mechanical ventilation support before being moved to a tertiary hospital for further testing. Aspergillus fumigatus filamentous fungus, Candida spp., and positive bacteriology for multidrug-resistant Klebsiella pneumoniae and Proteus mirabilis were identified by bronchial aspirate cultures. The patient's progress was gradually encouraging while receiving oral antifungal and broad-spectrum antibiotic therapy along with respiratory physical therapy; but ultimately, thoracic surgery was necessary. Long-lasting tissue damage and severe, persistent inflammatory syndrome were the two main pathophysiological mechanisms that led to significant outcomes regarding lung lesions that were rapidly colonized by fungi and resistant flora, cardiac damage with sinus tachycardia at the slightest effort, and chronic inflammatory syndrome, which was characterized by marked asthenia, myalgias, and exercise intolerance. [ABSTRACT FROM AUTHOR]

Objective: To characterize the cognitive profile of long COVID-19 subjects and its possible association with clinical symptoms, emotional disturbance, biomarkers, and disease severity. Methods: We performed a single-center cross-sectional cohort study. Subjects between 20 and 60 years old with confirmed COVID-19 infection were included. The assessment was performed 6 months following hospital or ambulatory discharge. Excluded were those with prior neurocognitive impairment and severe neurological/neuropsychiatric disorders. Demographic and laboratory data were extracted from medical records. Results: Altogether, 108 participants were included, 64 were male (59.25%), and the mean age was 49.10 years. The patients were classified into four groups: non-hospitalized (NH, n = 10), hospitalized without Intensive Care Unit (ICU) or oxygen therapy (HOSPI, n = 21), hospitalized without ICU but with oxygen therapy (OXY, n = 56), and ICU (ICU, n = 21) patients. In total, 38 (35.18%) reported Subjective Cognitive Complaints (SCC). No differences were found considering illness severity between groups. Females had more persistent clinical symptoms and SCC than males. Persistent dyspnea and headache were associated with higher scores in anxiety and depression. Persistent fatigue, anxiety, and depression were associated with worse overall cognition. Conclusions: No cognitive impairment was found regarding the severity of post-COVID-19 infection. SCC was not associated with a worse cognitive performance, but with higher anxiety and depression. Persistent clinical symptoms were frequent independent of illness severity. Fatigue, anxiety, and depression were linked to poorer cognitive function. Tests for attention, processing speed, and executive function were the most sensitive in detecting cognitive changes in these patients. [ABSTRACT FROM AUTHOR]

Background: Beau's lines are transverse grooves in the nail plate that result from transient interruption of the growth of the proximal nail matrix after severe disease. The aim of this study is to systematically report all evidence on the association of Beau's lines with COVID-19 infection or vaccination against COVID-19. Methods: PubMed and Scopus databases were searched up to January 2024 for articles reporting Beau's lines associated with COVID-19 infection or vaccination for COVID-19. PROSPERO ID: CRD42024496830. Results: PubMed search identified 299 records while Scopus search identified 18 records. After screening the bibliography, nine studies including 35 cases were included in our systematic review. The studies were reported from different areas around the world. Included studies documented Beau's lines following COVID-19 vaccination (two studies) or after COVID-19 infection (seven studies). High variability was recorded in onset and resolution times among included cases, averaging 3 months and 6 months after COVID-19 infection, respectively. In the two studies reporting Beau's lines after vaccination, onset was at 7 days and 6 weeks and resolution occurred after 8 and 17 weeks, respectively. Conclusions: To the best of our knowledge, this is the first systematic review reporting the association of Beau's lines with COVID-19 infection and vaccination. Severe immune response can result in the formation of these nail disorders. Of importance, Beau's lines represent a potential indicator of prior severe COVID-19 infection or vaccination for COVID-19, as well as a sign of long COVID-19 syndrome. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infection is a significant health concern that needs to be addressed not only during the initial phase of infection but also after hospitalization. This is the consequence of the various pathologies associated with long COVID-19, which are still being studied and researched. Lung fibrosis is an important complication after COVID-19, found in up to 71% of patients after discharge. Our research is based on scientific articles indexed in PubMed; in the selection process, we used the following keywords: "lung fibrosis", "fibrosis mediators", "fibrosis predictors", "COVID-19", "SARS-CoV-2 infection", and "long COVID-19". In this narrative review, we aimed to discuss the current understanding of the mechanisms of initiation and progression of post-COVID-19 lung fibrosis (PC-19-LF) and the risk factors for its occurrence. The pathogenesis of pulmonary fibrosis involves various mediators such as TGF-β, legumain, osteopontin, IL-4, IL-6, IL-13, IL-17, TNF-α, Gal-1, Gal-3, PDGF, and FGFR-1. The key cellular effectors involved in COVID-19 lung fibrosis are macrophages, epithelial alveolar cells, neutrophils, and fibroblasts. The main fibrosis pathways in SARS-CoV-2 infection include hypoxemia-induced fibrosis, macrophage-induced fibrosis, and viral-fibroblast interaction-induced fibrosis. [ABSTRACT FROM AUTHOR]

Long coronavirus disease 19 (COVID-19) is an emerging multifaceted illness with the pathological hallmarks of chronic inflammation and neuropsychiatric symptoms. These pathologies have also been implicated in developing suicidal behaviors and suicidal ideation (SI). However, research addressing suicide risk in long COVID-19 is limited. In this prospective study, we aim to characterize SI development among long-COVID-19 patients and to determine the predictive power of inflammatory markers and long-COVID-19 symptoms—including those of psychiatric origin—for SI. During this prospective, longitudinal, multicenter study, healthy subjects and long-COVID-19 patients will be recruited from the University Hospital of Geneva, Switzerland, the University of Genova, the University of Rome "La Sapienza", and the University of San Francisco. Study participants will undergo a series of clinic visits over a follow-up period of 1 year for SI assessment. Baseline and SI-onset levels of inflammatory mediators in plasma samples, along with 12 long-COVID-19 features (post-exertional malaise, fatigue, brain fog, dizziness, gastrointestinal disturbance, palpitations, changes in sexual desire/capacity, loss/change of smell/taste, thirst, chronic cough, chest pain, and abnormal movements) will be collected for SI risk analysis. The proposed enrollment period is from 15 January 2024 to 15 January 2026 with targeted recruitment of 100 participants for each study group. The anticipated findings of this study are expected to provide important insights into suicide risk among long-COVID-19 patients and determine whether inflammation and psychiatric comorbidities are involved in the development of SI in these subjects. This could pave the way to more effective evidence-based suicide prevention approaches to address this emerging public health concern. [ABSTRACT FROM AUTHOR]

Background: Rehabilitation is an effective method for improving the overall health of patients who have experienced the long-term effects of COVID-19. Methods: The double-blind, randomized prospective study assessed the effectiveness of a 6-week rehabilitation program among post-COVID-19 patients. A total of 59 patients under treatment following COVID-19 were randomly divided into two groups. Both groups completed the same six-week comprehensive exercise training program supported by a respiratory muscle trainer (Threshold IMT) during out-patient sessions. The control group performed placebo IMT. Respiratory muscle strength, chest wall expansion, spirometry, and diaphragm ultrasonography measurements were taken before and after the six weeks. Results: The applied rehabilitation program improved respiratory muscle strength in both the study and control groups (p < 0.001). There was a significant chest circumference increase in the study group (p < 0.001). Spirometric parameters improved in both groups, with the study group showing a greater improvement: 8.02% in FEV1 (p < 0.001), 13.24% in FVC EX (p < 0.001) and 9.67% in PEF (p < 0.001). Rehabilitation also increased diaphragm thickness during maximum inhalation in both groups. Conclusions: Based on the study findings, the specialized outpatient rehabilitation program developed for post-COVID-19 patients has proven to be effective and safe. [ABSTRACT FROM AUTHOR]

Background: Long COVID is a growing condition among individuals, with fatigue being one of the main symptoms experienced. Energy Management Education (EME) is a structured occupational therapy group intervention that aims to reduce the impact of fatigue in daily life. Methods: This study utilized focus groups to explore the experiences of individuals with post-COVID-related fatigue who participated in the EME program. Six participants engaged in discussions about the program immediately after its completion and again two months later. Additionally, five occupational therapists shared their experiences. Results: Former participants reported implementing strategies learned in the program to manage their condition effectively. They emphasized the importance of understanding fatigue and found the support provided by the peer group valuable. Occupational therapists highlighted the unique challenges faced by individuals with post-COVID-related fatigue compared to other populations with similar fatigue symptoms. Furthermore, insights were obtained regarding the ways individuals live and cope with post-COVID-related fatigue. Conclusion: EME participants were involved in a dynamic and complex occupational therapy process and were experiencing a slow change towards having more control over their daily routines. The study gathered valuable feedback and suggestions from participants and occupational therapists which can be used to optimize the EME program. [ABSTRACT FROM AUTHOR]

Antiviral treatment reduces the severity and mortality of SARS-CoV-2 infection; however, its effectiveness against long COVID-19 is unclear. This study aimed to evaluate the effectiveness of antiviral drugs in preventing long COVID and related hospitalizations/deaths. Scientific and medical databases were searched from 1 January 2020 to 30 June 2023. We included observational cohort studies comparing individuals receiving early antiviral therapy for COVID-19 and those receiving supportive treatment. A fixed-effects model was used to merge the effects reported in two or more studies. The risk of post-acute sequelae of COVID-19 (PASC) was combined as an odds ratio (OR). Six studies were selected, including a total of 3,352,235 participants. The occurrence of PASC was 27.5% lower in patients who received antiviral drugs during the early stages of SARS-CoV-2 infection (OR = 0.725; 95% confidence interval [CI] = 0.409–0.747) than in the supportive treatment group. Moreover, the risk of PASC-associated hospitalization and mortality was 29.7% lower in patients receiving early antiviral therapy than in the supportive treatment group (OR = 0.721; 95% CI = 0.697–0.794). Early antiviral therapy was associated with a reduced risk of PASC and related hospitalization or death. Thus, early antiviral therapy is recommended for at-risk individuals. [ABSTRACT FROM AUTHOR]

Introduction: The impact of long-COVID-19 syndrome is rather variable, since it is influenced by several residual confounders. This study aimed to investigate the prevalence of long COVID-19 in healthcare workers (HCWs) from four university hospitals in north-eastern Italy: Trieste, Padua, Verona, and Modena-Reggio Emilia. Methods: During the period June 2022–August 2022, HCWs were surveyed for past COVID-19 infections, medical history, and any acute as well as post-COVID-19 symptoms. The prevalence of long COVID-19 was estimated at 30–60 days or 61+ days since first negative swab following first and second COVID-19 episode. Furthermore, the risk of long COVID-19 was investigated by multivariable logistic regression. Results were expressed as the adjusted odds ratio (aOR) with a 95% confidence interval (95%CI). Results: 5432 HCWs returned a usable questionnaire: 2401 were infected with SARS-CoV-2 at least once, 230 were infected at least twice, and 8 were infected three times. The prevalence of long COVID-19 after a primary COVID-19 infection was 24.0% at 30–60 days versus 16.3% at 61+ days, and 10.5% against 5.5% after the second SARS-CoV-2 event. The most frequent symptoms after a first COVID-19 event were asthenia (30.3%), followed by myalgia (13.7%), cough (12.4%), dyspnea (10.2%), concentration deficit (8.1%), headache (7.3%), and anosmia (6.5%), in decreasing order of prevalence. The risk of long COVID-19 at 30–60 days was significantly higher in HCWs hospitalized for COVID-19 (aOR = 3.34; 95%CI: 1.62; 6.89), those infected with SARS-CoV-2 during the early pandemic waves—namely the Wuhan (aOR = 2.16; 95%CI: 1.14; 4.09) or Alpha (aOR= 2.05; 95%CI: 1.25; 3.38) transmission periods—and progressively increasing with viral shedding time (VST), especially 15+ days (aOR = 3.20; 95%CI: 2.07; 4.94). Further determinants of long COVID-19 at 30–60 days since primary COVID-19 event were female sex (aOR = 1.91; 95%CI: 1.30; 2.80), age >40 years, abnormal BMI, or administrative services (reference category). In contrast, HCWs vaccinated with two doses before their primary infection (aOR = 0.57; 95%CI: 0.34; 0.94), undergraduate students, or postgraduate medical trainees were less likely to experience long COVID-19 at 30–60 days. Apart from pandemic waves, the main determinants of long COVID-19 at 30–60 days were confirmed at 61+ days. Conclusions: The risk of long COVID-19 following primary infection increased with the severity of acute disease and VST, especially during the initial pandemic waves, when more virulent viral strains were circulating, and susceptibility to SARS-CoV-2 was higher since most HCWs had not been infected yet, COVID-19 vaccines were still not available, and/or vaccination coverage was still building up. The risk of long COVID-19 therefore decreased inversely with humoral immunity at the individual level. Nevertheless, the prevalence of long COVID-19 was remarkably lower after SARS-CoV-2 reinfections regardless of vaccination status, suggesting that hybrid humoral immunity did not increase protection against the syndrome compared to immunity mounted by either natural infection or vaccination separately. Since the risk of long COVID-19 is currently low with Omicron and patients who developed the syndrome following SARS-CoV-2 infection in the early pandemic waves tend to return to a state of full health with time, a cost-effective approach to screen post-COVID-19 symptoms during the Omicron time could be restricted to vulnerable individuals developing severe disease and/or with prolonged VST. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has affected the world unprecedentedly, with both positive and negative impacts. COVID-19 significantly impacted the immune system, and understanding the immunological consequences of COVID-19 is essential for developing effective treatment strategies. The purpose of this review is to comprehensively explore and provide insights into the immunological aspects of long COVID-19, a phenomenon where individuals continue to experience a range of symptoms and complications, even after the acute phase of COVID-19 infection has subsided. The immune system responds to the initial infection by producing various immune cells and molecules, including antibodies, T cells, and cytokines. However, in some patients, this immune response becomes dysregulated, leading to chronic inflammation and persistent symptoms. Long COVID-19 encompasses diverse persistent symptoms affecting multiple organ systems, including the respiratory, cardiovascular, neurological, and gastrointestinal systems. In the post-COVID-19 immunological era, long COVID-19 and its impact on immune response have become a significant concern. Post-COVID-19 immune pathology, including autoimmunity and immune-mediated disorders, has also been reported in some patients. This review provides an overview of the current understanding of long COVID-19, its relationship to immunological responses, and the impact of post-COVID-19 immune pathology on patient outcomes. Additionally, the review addresses the current and potential treatments for long COVID-19, including immunomodulatory therapies, rehabilitation programs, and mental health support, all of which aim to improve the quality of life for individuals with long COVID-19. Understanding the complex interplay between the immune system and long COVID-19 is crucial for developing targeted therapeutic strategies and providing optimal care in the post-COVID-19 era. [ABSTRACT FROM AUTHOR]

(1) Background: SARS-CoV-2 infection has been a subject of extensive discussion in the medical field, particularly in relation to the risk factors and effective treatment strategies for reducing the negative health outcomes associated with the virus. However, researchers indicate that individuals in the recovery phase after COVID-19 experience a range of symptoms that significantly impact their overall well-being and quality of life. At present, there is insufficient evidence to substantiate the claim that patients in the post-acute phase of COVID-19 are at an elevated risk of developing new-onset hypertension or even metabolic syndrome. The current study aimed to assess the risk of cardiovascular diseases after COVID-19 and the optimal treatment of these conditions. (2) Methods: This research was conducted at the Cardiovascular Rehabilitation Clinic of the Iasi Clinical Rehabilitation Hospital (Romania) between the 1st of September and 31st of December 2022. From a total of 551 patients hospitalized in that period, 70 patients with multiple comorbidities were selected. This study included patients over 18 years old who were diagnosed with COVID-19 within the past 30 days. (3) Results: The included patients were mostly women (62.9%) from the urban area (61.4%). Comparing the post-COVID-19 period to the pre-COVID-19 one, it was observed that the risk of hypertension increased from 69.57% to 90% among the subjects (p = 0.005). Risk factors for the new onset of hypertension were identified as age, female gender, and an elevated body mass index. Moreover, the number of patients with dyslipidemia doubled, and a higher body mass index was noted. (4) Conclusions: Our findings suggest that patients affected by COVID-19 are at an increased risk of developing hypertension and related disorders. [ABSTRACT FROM AUTHOR]

Coronavirus disease (COVID-19) is an infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can be asymptomatic or present with multiple organ dysfunction. Many infected individuals have chronic alterations associated with neuropsychiatric, endocrine, gastrointestinal, and musculoskeletal symptoms, even several months after disease onset, developing long-COVID or post-acute COVID-19 syndrome (PACS). Microbiota dysbiosis contributes to the onset and progression of many viral diseases, including COVID-19 and post-COVID-19 manifestations, which could serve as potential diagnostic and prognostic biomarkers. This review aimed to discuss the most recent findings on gut microbiota dysbiosis and its relationship with the sequelae of PACS. Elucidating these mechanisms could help develop personalized and non-invasive clinical strategies to identify individuals at a higher risk of experiencing severe disease progression or complications associated with PACS. Moreover, the review highlights the importance of targeting the gut microbiota composition to avoid dysbiosis and to develop possible prophylactic and therapeutic measures against COVID-19 and PACS in future studies. [ABSTRACT FROM AUTHOR]

Long COVID-19 patients show systemic inflammation and persistent symptoms such as fatigue and malaise, profoundly affecting their quality of life. Since improving oxygenation can oppose inflammation at multiple tissue levels, we hypothesized that hyperbaric oxygen therapy (HBOT) could arrest inflammation progression and thus relieve symptoms of COVID-19. We evaluated oxy-inflammation biomarkers in long COVID-19 subjects treated with HBOT and monitored with non-invasive methods. Five subjects (two athletes and three patients with other comorbidities) were assigned to receive HBOT: 100% inspired O2 at 2.4 ATA in a multiplace hyperbaric chamber for 90 min (three athletes: 15 HBOT × 5 days/wk for 3 weeks; two patients affected by Idiopathic Sudden Sensorineural Hearing Loss: 30 HBOT × 5 days/wk for 6 weeks; and one patient with osteomyelitis: 30 HBOT × 5 days/wk for week for 6 weeks and, after a 30-day break, followed by a second cycle of 20 HBOT). Using saliva and/or urine samples, reactive oxygen species (ROS), antioxidant capacity, cytokines, lipids peroxidation, DNA damage, and renal status were assessed at T1_pre (basal level) and at T2_pre (basal level after treatment), and the results showed attenuated ROS production, lipid peroxidation, DNA damage, NO metabolites, and inflammation biomarker levels, especially in the athletes post-treatment. Thus, HBOT may represent an alternative non-invasive method for treating long COVID-19-induced long-lasting manifestations of oxy-inflammation. [ABSTRACT FROM AUTHOR]

Long COVID-19 is a recognized entity that affects millions of people worldwide. Its broad clinical symptoms include thrombotic events, brain fog, myocarditis, shortness of breath, fatigue, muscle pains, and others. Due to the binding of the virus with ACE-2 receptors, expressed in many organs, it can potentially affect any system; however, it most often affects the cardiovascular, central nervous, respiratory, and immune systems. Age, high body mass index, female sex, previous hospitalization, and smoking are some of its risk factors. Despite great efforts to define its pathophysiology, gaps remain to be explained. The main mechanisms described in the literature involve viral persistence, hypercoagulopathy, immune dysregulation, autoimmunity, hyperinflammation, or a combination of these. The exact mechanisms may differ from system to system, but some share the same pathways. This review aims to describe the most prevalent pathophysiological pathways explaining this syndrome. [ABSTRACT FROM AUTHOR]

The aim of this review was to identify, map, and synthesize the extent and nature of research activity on the use of telerehabilitation to support Long COVID-19 rehabilitation and examine the efficacy and safety of respiratory telerehabilitation in patients with Long COVID-19. A systematic review and meta-analysis of randomized controlled trials were performed. We included controlled trials that tested the effect of respiratory telerehabilitation interventions in patients with Long COVID-19 versus no intervention, usual care, placebo, or face-to-face intervention. The data were pooled, and a meta-analysis was completed for quality of life, dyspnea, lung function, anxiety and depression, respiratory muscle strength, functional capacity, and lower limb strength. Finally, 10 studies were included. The meta-analysis results show significant differences in favor of respiratory telerehabilitation in quality of life (p = 0.02), dyspnea (p < 0.00001), respiratory muscle strength (p < 0.001), functional capacity (p < 0.0001), and lower limb strength (p = 0.01) but not in lung function (p = 0.28) and anxiety and depression (p = 0.55). In addition, there were no statistically significant differences in adverse effects (p = 0.06) between the telerehabilitation and comparator groups. The results suggest that these interventions can improve quality of life, reduce dyspnea, and increase respiratory and lower extremity muscle strength as well as functional capacity in patients with Long COVID-19. [ABSTRACT FROM AUTHOR]

Antiphospholipid antibodies (APLA) are strongly associated with thrombosis seen in patients with antiphospholipid syndrome. In COVID-19, thrombosis has been observed as one of the main comorbidities. In patients hospitalised for COVID-19, we want to check whether APLA positivity is associated with COVID-19-related thrombosis, inflammation, severity of disease, or long COVID-19. We enrolled 92 hospitalised patients with COVID-19 between March and April 2020 who were tested for 18 different APLAs (IgG and IgM) with a single line-immunoassay test. A total of 30 healthy blood donors were used to set the cut-off for each APLA positivity. Of the 92 COVID-19 inpatients, 30 (32.61%; 95% CI [23.41–43.29]) tested positive for APLA, of whom 10 (33.3%; 95% CI [17.94–52.86]) had more than one APLA positivity. Anti-phosphatidylserine IgM positivity was described in 5.4% of inpatients (n = 5) and was associated with the occurrence of COVID-19-related thrombosis (p = 0.046). Anti-cardiolipin IgM positivity was the most prevalent among the inpatients (n = 12, 13.0%) and was associated with a recorded thrombosis in their clinical history (p = 0.044); however, its positivity was not associated with the occurrence of thrombosis during their hospitalisation for COVID-19. Anti-phosphatidylinositol IgM positivity, with a prevalence of 5.4% (n = 5), was associated with higher levels of interleukin (IL)-6 (p = 0.007) and ferritin (p = 0.034). Neither of these APLA positivities was a risk factor for COVID-19 severity or a predictive marker for long COVID-19. In conclusion, almost a third of COVID-19 inpatients tested positive for at least one APLA. Anti-phosphatidylserine positivity in IgM class was associated with thrombosis, and anti-phosphatidylinositol positivity in IgM class was associated with inflammation, as noticed by elevated levels of IL-6. Thus, testing for non-criteria APLA to assess the risk of clinical complications in hospitalised COVID-19 patients might be beneficial. However, they were not related to disease severity or long COVID-19. [ABSTRACT FROM AUTHOR]

For more than two years, lingering sequalae of COVID-19 have been extensively investigated. Approximately 10% of individuals infected by COVID-19 have been found to experience long-term symptoms termed "long COVID-19". The neurological and psychiatric manifestations of long COVID-19 are of particular concern. While pathogenesis remains unclear, emerging imaging studies have begun to better elucidate certain pathological manifestation. Of specific interest is imaging with [18F]FDG PET which directly reflects cellular glycolysis often linked to metabolic and inflammatory processes. Seeking to understand the molecular basis of neurological features of long COVID-19, this review encompasses the most recent [18F]FDG PET literature in this area. [ABSTRACT FROM AUTHOR]

Although disturbance of redox homeostasis might be responsible for COVID-19 cardiac complications, this molecular mechanism has not been addressed yet. We have proposed modifying the effects of antioxidant proteins polymorphisms (superoxide dismutase 2 (SOD2), glutathione peroxidase 1 (GPX1), glutathione peroxidase 3 (GPX3) and nuclear factor erythroid 2-related factor 2, (Nrf2)) in individual susceptibility towards the development of cardiac manifestations of long COVID-19. The presence of subclinical cardiac dysfunction was assessed via echocardiography and cardiac magnetic resonance imaging in 174 convalescent COVID-19 patients. SOD2, GPX1, GPX3 and Nrf2 polymorphisms were determined via the appropriate PCR methods. No significant association of the investigated polymorphisms with the risk of arrhythmia development was found. However, the carriers of variant GPX1*T, GPX3*C or Nrf2*A alleles were more than twice less prone for dyspnea development in comparison with the carriers of the referent ones. These findings were even more potentiated in the carriers of any two variant alleles of these genes (OR = 0.273, and p = 0.016). The variant GPX alleles were significantly associated with left atrial and right ventricular echocardiographic parameters, specifically LAVI, RFAC and RV-EF (p = 0.025, p = 0.009, and p = 0.007, respectively). Based on the relation between the variant SOD2*T allele and higher levels of LV echocardiographic parameters, EDD, LVMI and GLS, as well as troponin T (p = 0.038), it can be proposed that recovered COVID-19 patients, who are the carriers of this genetic variant, might have subtle left ventricular systolic dysfunction. No significant association between the investigated polymorphisms and cardiac disfunction was observed when cardiac magnetic resonance imaging was performed. Our results on the association between antioxidant genetic variants and long COVID cardiological manifestations highlight the involvement of genetic propensity in both acute and long COVID clinical manifestations. [ABSTRACT FROM AUTHOR]

Post-COVID-19 syndrome is a complex of different symptoms, which results in a multisystemic impairment after the suffering from COVID-19 infection. The aim of the study was to reveal the clinical, laboratory, and gut disorders in patients with post-COVID-19 syndrome (n = 39) before and after taking part in the 14-day complex program of rehabilitation. A complete blood count, coagulation test, blood chemistry, biomarkers, and metabolites in serum samples, and gut dysbiosis were revealed in patients on the day of admission and after 14-day rehabilitation, in comparison with the variables of healthy volunteers (n = 48) or with reference ranges. On the day of discharge, patients noted an improvement in respiratory function, general well-being, and mood. At the same time, the levels of some metabolic (4-hydroxybenzoic, succinic, fumaric acids) and inflammatory (interleukin-6) variables, which were increased on admission, did not reach the level of healthy people during the rehabilitation program. Taxonomy disbalance was observed in patients' feces, namely, a high level of total bacterial mass, a decrease in the number of Lactobacillus spp., and an increase in pro-inflammatory microorganisms. The authors suggest that the post-COVID-19 rehabilitation program should be personalized, considering the patient's state together with not only the baseline levels of biomarkers, but also with the individual taxonomy of the gut microbiota. [ABSTRACT FROM AUTHOR]

COVID-19 may induce short- and long-term cognitive failures after recovery, but the underlying risk factors are still controversial. Here, we investigated whether (i) the odds of experiencing persistent cognitive failures differ based on the patients' disease course severity and sex at birth; and (ii) the patients' electrolytic profile in the acute stage represents a risk factor for persistent cognitive failures. We analysed data from 204 patients suffering from COVID-19 and hospitalised during the first pandemic wave. According to the 7-point WHO-OS scale, their disease course was classified as severe or mild. We investigated the presence of persistent cognitive failures collected after hospital discharge, while electrolyte profiles were collected during hospitalisation. The results showed that females who suffered from a mild course compared to a severe course of COVID-19 had a higher risk of presenting with persistent mental fatigue after recovery. Furthermore, in females who suffered from a mild course of COVID-19, persistent mental fatigue was related to electrolyte imbalance, in terms of both hypo- and hypernatremia, during hospitalisation in the acute phase. These findings have important implications for the clinical management of hospitalised COVID-19 patients. Attention should be paid to potential electrolyte imbalances, mainly in females suffering from mild COVID-19. [ABSTRACT FROM AUTHOR]

The aim of study was to investigate the transformative effect of the COVID-19 pandemic on magnetic resonance imaging (MRI) services in one tertiary cardiovascular center. The retrospective observational cohort study analyzed data of MRI studies (n = 8137) performed from 1 January 2019 to 1 June 2022. A total of 987 patients underwent contrast-enhanced cardiac MRI (CE-CMR). Referrals, clinical characteristics, diagnosis, gender, age, past COVID-19, MRI study protocols, and MRI data were analyzed. The annual absolute numbers and rates of CE-CMR procedures in our center significantly increased from 2019 to 2022 (p-value < 0.05). The increasing temporal trends were observed in hypertrophic cardiomyopathy (HCMP) and myocardial fibrosis (p-value < 0.05). The CE-CMR findings of myocarditis, acute myocardial infarction, ischemic cardiomyopathy, HCMP, postinfarction cardiosclerosis, and focal myocardial fibrosis prevailed in men compared with the corresponding values in women during the pandemic (p-value < 0.05). The frequency of myocardial fibrosis occurrence increased from ~67% in 2019 to ~84% in 2022 (p-value < 0.05). The COVID-19 pandemic increased the need for MRI and CE-CMR. Patients with a history of COVID-19 had persistent and newly occurring symptoms of myocardial damage, suggesting chronic cardiac involvement consistent with long COVID-19 requiring continuous follow-up. [ABSTRACT FROM AUTHOR]

The COVID-19 sequelae have been shown to affect respiratory and cardiological functions as well as neuro-psychological functions, and, in some cases, metabolic/nutritional aspects. The Italian National Institute for Insurance against Accidents at Work (Istituto Nazionale Assicurazione Infortuni sul Lavoro, INAIL) recorded that, until December 2022, 315,055 workers were affected by COVID-19; therefore, there is a need to identify an effective approach to treat such patients. Robotic and technological devices could be integrated into the rehabilitation programme of people with long COVID conditions. A review of the literature showed that telerehabilitation may improve functional capacity, dyspnoea, performance, and quality of life in these patients, but no studies were found evaluating the effects of robot-mediated therapy or virtual reality systems. Considering the above, Fondazione Don Carlo Gnocchi and INAIL propose a multi-axial rehabilitation for workers with COVID-19 sequelae. To accomplish this goal, the two institutions merged the epidemiological information gathered by INAIL, the expertise in robotic and technological rehabilitation of Fondazione Don Carlo Gnocchi, and the literature review. Our proposal aims to facilitate a multi-axial rehabilitation approach customized to meet the unique needs of each individual, with a particular emphasis on utilizing advanced technologies to address the current and future challenges of patient care. [ABSTRACT FROM AUTHOR]

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

Long-lasting symptoms after SARS-CoV-2 infection have been described many times in the literature and are referred to as Long COVID. In this prospective, longitudinal, monocentric, observational study, we collected the health complaints of 474 patients (252 ambulatory and 222 hospitalized) at Lausanne University Hospital 1 year after COVID-19 diagnosis. Using a self-reported health survey, we explored cardiopulmonary, vascular, neurological, and psychological complaints. Our results show that age, Charlson comorbidity index, and smoking habits were associated with hospital admission. Regarding the vascular system, we found that having had thromboembolism before SARS-CoV-2 infection was significantly associated with a higher risk of recurrence of thromboembolism at 1 year. In the neurologic evaluation, the most frequent symptom was fatigue, which was observed in 87.5% of patients, followed by "feeling slowed down", headache, and smell disturbance in 71.5%, 68.5%, and 60.7% of cases, respectively. Finally, our cohort subjects scored higher overall in the STAI, CESD, Maastricht, and PSQI scores (which measure anxiety, depression, fatigue, and sleep, respectively) than the healthy population. Using cluster analysis, we identified two phenotypes of patients prone to developing Long COVID. At baseline, CCS score, prior chronic disease, stroke, and atrial fibrillation were associated with Long COVID. During COVID infection, mechanical ventilation and five neurological complaints were also associated with Long COVID. In conclusion, this study confirms the wide range of symptoms developed after COVID with the involvement of all the major systems. Early identification of risk factors associated with the development of Long COVID could improve patient follow-up; nevertheless, the low specificity of these factors remains a challenge to building a systematic approach. [ABSTRACT FROM AUTHOR]

Long-term effects of COVID-19 are becoming more apparent even as the severity of acute infection is decreasing due to vaccinations and treatment. In this scoping review, we explored the current literature for the relationship between COVID-19 infection and new-onset diabetes mellitus four weeks after acute infection. We systematically searched the peer-reviewed literature published in English between 1 January 2020 and 31 August 2022 to study the risk of new-onset diabetes mellitus post-COVID-19 infection. This scoping review yielded 11 articles based on our inclusion and exclusion criteria. Except for one, all studies suggested an increased risk of new-onset diabetes mellitus 4 weeks after acute infection. This risk appears most in the first six months after the acute COVID-19 infection and seems to increase in a graded fashion based on the severity of the initial COVID-19 infection. Our review suggests a possible association of new-onset diabetes mellitus 4 weeks after acute COVID-19 infection. Since the severity of COVID-19 infection is associated with the development of post-infectious diabetes, vaccination that reduces the severity of acute COVID-19 infection might help to reduce the risk of post-COVID-19 diabetes mellitus. More studies are needed to better understand and quantify the association of post-COVID-19 conditions with diabetes and the role of vaccination in influencing it. [ABSTRACT FROM AUTHOR]

Up to 80% of COVID-19 survivors experience prolonged symptoms known as long COVID-19. The aim of this study was to evaluate the effects of a multidisciplinary rehabilitation program in patients with long COVID-19. The rehabilitation program was composed of physical training (aerobic, resistance, and breathing exercises), education, and group psychotherapy. After 6 weeks of rehabilitation in 97 patients with long COVID-19, body composition analysis revealed a significant decrease of abdominal fatty tissue (from 2.75 kg to 2.5 kg; p = 0.0086) with concomitant increase in skeletal muscle mass (from 23.2 kg to 24.2 kg; p = 0.0104). Almost 80% of participants reported dyspnea improvement assessed with the modified Medical Research Council scale. Patients' physical capacity assessed with the 6 Minute Walking Test increased from 320 to 382.5 m (p < 0.0001), the number of repetitions in the 30 s Chair Stand Test improved from 13 to 16 (p < 0.0001), as well as physical fitness in the Short Physical Performance Battery Test from 14 to 16 (p < 0.0001). The impact of fatigue on everyday functioning was reduced in the Modified Fatigue Impact Scale from 37 to 27 (p < 0.0001). Cardiopulmonary exercise test did not show any change. The multidisciplinary rehabilitation program has improved body composition, dyspnea, fatigue and physical capacity in long COVID-19 patients. [ABSTRACT FROM AUTHOR]

(1) Introduction: The role of soluble integrins in post-COVID-19 complications is unclear, especially in long-term pulmonary lesions. The purpose of this study was to investigate the association between soluble ITGa2, ITGaM and ITGb2 integrin subunits and long COVID-19 pulmonary complications. (2) Methodology: Post-COVID-19 patients were enrolled. According to the evidence of persistent interstitial lung lesions on CT, patients were divided into a long-term pulmonary complications group (P(+)) and a control group without long-term pulmonary complications (P(−)). We randomly selected 80 patients for further investigation (40 subjects for each group). Levels of ITGa2, ITGaM and ITGb2 integrin subunits were determined by ELISA assay. (3) Results: The serum concentration of sITGaM and sITGb2 were significantly higher in the P(+) group (sITGaM 18.63 ng/mL [IQR 14.17–28.83] vs. 14.75 ng/mL [IQR 10.91–20] p = 0.01 and sITGb2 10.55 ng/mL [IQR 6.53–15.83] vs. 6.34 ng/mL [IQR 4.98-9.68] p = 0.002). We observed a statistically significant correlation between sITGaM and sITGb2 elevation in the P(+) group (R = 0.42; p = 0.01). Patients from the P(+) group had a lower (1.82 +/−0.84 G/L) lymphocyte level than the P(−)group (2.28 +/−0.79 G/L), p = 0.03. Furthermore, we observed an inverse correlation in the P(−) group between blood lymphocyte count and sITGb2 integrin subunit levels (R = −0.49 p = 0.01). (4) Conclusions: Elevated concentrations of sITGaM and sITGb2 were associated with long-term pulmonary complications in post-COVID-19 patients. Both sITGaM and sITGb2 may be promising biomarkers for predicting pulmonary complications and could be a potential target for therapeutic intervention in post-COVID-19 patients. [ABSTRACT FROM AUTHOR]

Background: Although most children may experience mild to moderate symptoms and do not require hospitalization, there are little data on cardiac involvement in COVID-19. However, cardiac involvement is accurately demonstrated in children with MISC. The objective of this study was to evaluate cardiac mechanics in previously healthy children who recovered from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in a long-term follow-up by means of two-dimensional speckle-tracking echocardiography (STE). Methods: We analyzed a cohort of 157 paediatric patients, mean age 7.7 ± 4.5 years (age range 0.3–18 years), who had a laboratory-confirmed diagnosis of SARS-CoV-2 infection and were asymptomatic or mildly symptomatic for COVID-19. Patients underwent a standard transthoracic echocardiogram and STE at an average time of 148 ± 68 days after diagnosis and were divided in three follow-up groups (<180 days, 180–240 days, >240 days). Patients were compared with 107 (41 females—38%) age- and BSA-comparable healthy controls (CTRL). Results: Left ventricular (LV) global longitudinal strain (post-COVID-19: −20.5 ± 2.9%; CTRL: −21.8 ± 1.7%; p < 0.001) was significantly reduced in cases compared with CTRLs. No significant differences were seen among the three follow-up groups (p = NS). Moreover, regional longitudinal strain was significantly reduced in LV apical-wall segments of children with disease onset during the second wave of the COVID-19 pandemic compared to the first wave (second wave: −20.2 ± 2.6%; first wave: −21.2 ± 3.4%; p = 0.048). Finally, peak left atrial systolic strain was within the normal range in the post-COVID-19 group with no significant differences compared to CTRLs. Conclusions: Our study demonstrated for the first time the persistence of LV myocardial deformation abnormalities in previously healthy children with an asymptomatic or mildly symptomatic (WHO stages 0 or 1) COVID-19 course after an average follow-up of 148 ± 68 days. A more significant involvement was found in children affected during the second wave. These findings imply that subclinical LV dysfunction may also be a typical characteristic of COVID-19 infection in children and are concerning given the predictive value of LV longitudinal strain in the general population. [ABSTRACT FROM AUTHOR]

Vaccines against SARS-CoV-2 have saved millions of lives and played an important role in containing the COVID-19 pandemic. Vaccination against SARS-CoV-2 is also associated with reduced disease severity and, perhaps, with COVID-19 symptom burden. In this narrative review, we present, in a clinically relevant question-and-answer manner, the evidence regarding the association between vaccination against SARS-CoV-2 and long COVID-19. We discuss how the mechanism of action of vaccines could interplay with the pathophysiology of post-COVID-19 condition. Furthermore, we describe how specific factors, such as the number of vaccine doses and the type of SARS-CoV-2 variants, may affect post-COVID-19 condition. We also discuss the role of timing for vaccination in relation to the onset of long COVID-19 symptoms, as it seems to affect the frequency and severity of the condition. Additionally, we describe the potential modifying effect of age, as well as the association of type and level of immune response with long COVID-19. We also describe how system-specific long COVID-19 sequelae, namely neurocognitive-psychologic symptoms and cardiovascular pathology, could be altered by vaccination. Last, we address the question of whether seasonal influenza vaccination has a meaningful impact on the frequency of long COVID-19. [ABSTRACT FROM AUTHOR]

In the current global scenario, many COVID-19 survivors present a severe deterioration in physical strength, respiratory function, and quality of life due to persistent symptoms and post-acute consequences of SARS-CoV-2 infection. These alterations are known as post-COVID-19 syndrome for which there is no specific and effective treatment for their management. Currently, therapeutic exercise strategies (ThEx) are effective in many diseases by reducing the appearance of complications and side effects linked to treatment, and are consequently of great relevance. In this study, we review the effect of ThEX in reversing decreased strength, impaired respiratory function, decreased physical fitness, and decreased quality of life (QoL) caused by post-COVID-19 syndrome. A literature search was conducted through the electronic databases, Medline (PubMed), SciELO and Cochrane Library Plus for this structured narrative review for studies published from database retrieval up till 12 December 2022. A total of 433 patients with post-COVID-19 syndrome condition (60% women) were included in the nine studies which met the inclusion/exclusion criteria. Overall, post-COVID-19 syndrome patients who followed a ThEx intervention showed improvements in strength, respiratory function, physical fitness and QoL, with no exercise-derived side effects. Thus, ThEx based on strength, aerobic and respiratory training could be an adjuvant non-pharmacological tool in the modulation of post-COVID-19 syndrome. [ABSTRACT FROM AUTHOR]

Background: The identification of persistent symptoms of chronic/long COVID-19 is crucial in understanding the management of long haulers of post COVID-19. Methods: Pub Med (Medline) database was scoped for original articles based on a search strategy related to the objectives. The selected articles post-screening were analyzed for variables relating to chronic/long COVID-19. Results were analyzed using descriptive statistics. Results: A total of 33 studies were reviewed. A total of 60% of the studies were observational studies and most of them were from high income countries. Almost half of the studies were in phase 3 of post-COVID-19, i.e., symptoms lasting >24 weeks. Among the physiological and psychological symptoms studied, fatigue, dyspnea, cough, headache, memory loss, depression, brain fog and lack of concentration were found to be the most frequently reported symptoms. Excessive sleep, constipation and neuropathic pain were among the least reported symptoms. Prior hospitalization, the female gender was found to be a risk factor. Limitations were reported by all studies. Conclusions: The major physiological and psychological symptoms of long COVID-19 have been explained with risk factors and its impact on patients' lifestyles. The findings of this review hope to facilitate clinicians to draw conclusions to manage the long-term effects of post/chronic COVID-19. [ABSTRACT FROM AUTHOR]

COVID-19 made its debut as a pandemic in 2020; since then, more than 607 million cases and at least 6.5 million deaths have been reported worldwide. While the burden of disease has been described, the long-term effects or chronic sequelae are still being clarified. The aim of this study was to present an overview of the information available on the sequelae of COVID-19 in people who have suffered from the infection. A systematic review was carried out in which cohort studies, case series, and clinical case reports were included, and the PubMed, Scielo, SCOPUS, and Web of Science databases were extracted. Information was published from 2020 to 1 June 2022, and we included 26 manuscripts: 9 for pulmonary, 6 for cardiac, 2 for renal, 8 for neurological and psychiatric, and 6 for cutaneous sequelae. Studies showed that the most common sequelae were those linked to the lungs, followed by skin, cutaneous, and psychiatric alterations. Women reported a higher incidence of the sequelae, as well as those with comorbidities and more severe COVID-19 history. The COVID-19 pandemic has not only caused death and disease since its appearance, but it has also sickened millions of people around the globe who potentially suffer from serious illnesses that will continue to add to the list of health problems, and further burden healthcare systems around the world. [ABSTRACT FROM AUTHOR]

Long coronavirus disease-19 (COVID-19) is a newly discovered syndrome characterized by multiple organ manifestations that persist for weeks to months, following the recovery from acute disease. Occasionally, neurological and cardiovascular side effects mimicking long COVID-19 have been reported in recipients of COVID-19 vaccines. Hypothetically, the clinical similarity could be due to a shared pathogenic role of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike (S) protein produced by the virus or used for immunization. The S protein can bind to neuropilin (NRP)-1, which normally functions as a coreceptor for the vascular endothelial growth factor (VEGF)-A. By antagonizing the docking of VEGF-A to NRP-1, the S protein could disrupt physiological pathways involved in angiogenesis and nociception. One consequence could be the increase in unbound forms of VEGF-A that could bind to other receptors. SARS-CoV-2-infected individuals may exhibit increased plasma levels of VEGF-A during both acute illness and convalescence, which could be responsible for diffuse microvascular and neurological damage. A few studies suggest that serum VEGF-A may also be a potential biomarker for long COVID-19, whereas evidence for COVID-19 vaccines is lacking and merits further investigation. [ABSTRACT FROM AUTHOR]

Increasing numbers of patients who recover from COVID-19 report lasting symptoms, such as fatigue, muscle weakness, dementia, and insomnia, known collectively as post-acute COVID syndrome or long COVID. These lasting symptoms have been examined in different studies and found to influence multiple organs, sometimes resulting in life-threating conditions. In this review, these symptoms are discussed in connection to the COVID-19 and long-COVID-19 immune changes, highlighting oral and psychiatric health, as this work focuses on the gut microbiota's link to long-COVID-19 manifestations in the liver, heart, kidney, brain, and spleen. A model of this is presented to show the biological and clinical implications of gut microbiota in SARS-CoV-2 infection and how they could possibly affect the therapeutic aspects of the disease. Probiotics can support the body's systems in fighting viral infections. This review focuses on current knowledge about the use of probiotics as adjuvant therapies for COVID-19 patients that might help to prevent long-COVID-19 complications. [ABSTRACT FROM AUTHOR]

A calibrated mathematical model of antiviral immune response to SARS-CoV-2 infection is developed. The model considers the innate and antigen-specific responses to SARS-CoV-2 infection. Recently published data sets from human challenge studies with SARS-CoV-2 were used for parameter evaluation. The calibration of the mathematical model of SARS-CoV-2 infection is based on combining the parameter guesses from our earlier study of influenza A virus infection, some recent quantitative models of SARS-CoV-2 infection and clinical data-based parameter estimation of a subset of the model parameters. Hence, the calibrated mathematical model represents a theoretical exploration type of study, i.e., 'in silico patient' with mild-to-moderate severity phenotype, rather than a completely validated quantitative model of COVID-19 with respect to all its state-space variables. Understanding the regulation of multiple intertwined reaction components of the immune system is necessary for linking the kinetics of immune responses with the clinical phenotypes of COVID-19. Consideration of multiple immune reaction components in a single calibrated mathematical model allowed us to address some fundamental issues related to the pathogenesis of COVID-19, i.e., the sensitivity of the peak viral load to the parameters characterizing the antiviral specific response components, the kinetic coordination of the individual innate and adaptive immune responses, and the factors favoring a prolonged viral persistence. The model provides a tool for predicting the infectivity of patients, i.e., the amount of virus which is transmitted via droplets from the person infected with SARS-CoV-2, depending on the time of infection. The thresholds for variations of the innate and adaptive response parameters which lead to a prolonged persistence of SARS-CoV-2 due to the loss of a kinetic response synchrony/coordination between them were identified. [ABSTRACT FROM AUTHOR]

Introduction: Although the understanding of several aspects of long COVID-19 syndrome is increasing, there is limited literature regarding the treatment of these signs and symptoms. The aim of our systematic review was to understand which therapies have proved effective against the symptoms of long COVID-19. Methods: A systematic search for randomized controlled or clinical trials in several databases was conducted through 15 May 2022. Specific inclusion criteria included: (1) intervention studies, either randomized controlled (RCTs) or clinical trials; (2) diagnosis of long COVID-19, according to the World Health Organization criteria; (3) presence of long COVID-19 for at least 12 weeks after SARS-CoV-2 infection. Results: We initially found 1638 articles to screen. After removing 1602 works based on their title/abstract, we considered 35 full texts, and among them, two intervention studies were finally included. The first RCT focused on the greater improvement of treatment combining olfactory rehabilitation with oral supplementation with Palmitoylethanolamide and Luteolin in patients with olfactory dysfunction after COVID-19. The second study evaluated the positive impact of aromatherapy vs. standard care in adult females affected by fatigue. Conclusion: Our systematic review found only two intervention studies focused on patients affected by long COVID-19. More intervention studies are needed to investigate potentially positive interventions for long COVID-19 symptoms. [ABSTRACT FROM AUTHOR]

Signaling by Keap1/Nrf2/p62 (accumulation of p62 and inhibition of Keap1 mediates Nrf2 activation) has an important role in reducing cell senescence accelerated by excessive cellular oxidative stress due to COVID-19 infection [[75], [78]]. These amino acid residues have been reported to be crucial in the interface structure of Keap1-Nrf2; thus, the results indicate that a high binding affinity with Keap1 might directly inhibit Keap1-Nrf2 protein-protein interaction as Nrf2 activators. It has been reported that Keap1 is an important unit of the Keap1-Nrf2 system, functions to protect against oxidative damage to cells under oxidative stress, and in Nrf2 the activity of Nrf2 [[75]]. The post-COVID or COVID period can be classified into two stages, namely, post-acute COVID and chronic COVID, as shown in Figure 2. Keywords: long COVID-19; Keap1; Nrf2; natural antioxidant EN long COVID-19 Keap1 Nrf2 natural antioxidant N.PAG N.PAG 25 08/29/22 20220801 NES 220801 1. [Extracted from the article]

Few data are available regarding the incidence and the evolution of neuropsychiatric manifestations in children with a history of COVID-19. We herein report five consequent cases of pediatric patients with psychiatric and neurological symptoms of long COVID-19. All patients, mainly males, reported asymptomatic-to-mild COVID-19 and underwent home self-isolation. Abnormal movements, anxiety, and emotional dysregulation were the most recurrent symptoms observed from a few weeks to months after the resolution of the acute infection. A later onset was observed in younger patients. Blood tests and brain imaging resulted in negative results in all subjects; pharmacological and cognitive behavioral therapy was set. A multifactorial etiology could be hypothesized in these cases, as a result of a complex interplay between systemic and brain inflammation and environmental stress in vulnerable individuals. Longer follow-up is required to observe the evolution of neuropsychiatric manifestation in the present cohort and other young patients with previous SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) has quickly become a global pandemic. Reports from different parts of the world indicate that a significant proportion of people who have recovered from COVID-19 are suffering from various health problems collectively referred to as "long COVID-19". Common symptoms include fatigue, shortness of breath, cough, joint pain, chest pain, muscle aches, headaches, and so on. Vitamin D is an immunomodulatory hormone with proven efficacy against various upper respiratory tract infections. Vitamin D can inhibit hyperinflammatory reactions and accelerate the healing process in the affected areas, especially in lung tissue. Moreover, vitamin D deficiency has been associated with the severity and mortality of COVID-19 cases, with a high prevalence of hypovitaminosis D found in patients with COVID-19 and acute respiratory failure. Thus, there are promising reasons to promote research into the effects of vitamin D supplementation in COVID-19 patients. However, no studies to date have found that vitamin D affects post-COVID-19 symptoms or biomarkers. Based on this scenario, this review aims to provide an up-to-date overview of the potential role of vitamin D in long COVID-19 and of the current literature on this topic. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is a threat to patients not only because of its acute course, but also because of various complications occurring in the following period, that is, more than 28 days after the onset of acute infection. The present study identified a total of 121 patients hospitalized 29 or more days after the first positive result of a PCR test for SARS-CoV-2, of whom 98 patients were included in the study. Patients were divided into two groups by the time interval between the positive COVID-19 test result and hospitalization date. The time intervals were week 5–11 in an ongoing-COVID group (57.1% of patients) and 12 or more weeks in a post-COVID-group (42.9%). The most frequent reason for hospitalization was respiratory tract infection (58.2%). Pneumonia accounted for 77.2% of these cases. Other reasons for hospitalization were interstitial lung disease (22.4%), pulmonary embolism (8.2%), and sarcoidosis (6.1%). The study group was further divided according to the causes of hospitalization into subgroups with infections and other causes. In the group with infectious diseases, there was a shorter time period between PCR positivity and hospitalization and there were significantly more frequent non-respiratory complications. In the entire sample, the in-hospital mortality was 5.1%. [ABSTRACT FROM AUTHOR]