Search Results (1,100)

Objective: This study aimed to evaluate physical training protocols for alleviating long COVID symptoms, especially dyspnea and fatigue, through a systematic review with meta-analysis. Method: Data were collected from EMBASE, LILACS, PubMed, Scopus, CINAHL, Web of Science, and grey literature (Google Scholar, medRxiv). Studies evaluating dyspnea and/or fatigue before and after physical rehabilitation, using validated questionnaires, were included. Studies lacking pre- and post-assessments or physical training were excluded. Two reviewers independently extracted data on intervention type, duration, frequency, intensity, and assessment methods for dyspnea and fatigue. Bias risk was evaluated using the Cochrane tool. Results: Combined methods, such as respiratory muscle training with strength and aerobic exercise, were common for long COVID symptoms. Aerobic exercise notably improved dyspnea and/or fatigue. Among 25 studies, four had a low risk of bias. Meta-analysis of two studies found no significant reduction in fatigue. Conclusion: Combined training methods, particularly aerobic exercise, alleviate dyspnea and fatigue in long COVID. More high-quality studies are needed to confirm these findings. Full article

Introduction: Long COVID syndrome is defined as persistent or new symptoms that appear after an acute SARS-CoV-2 infection and last at least three months without explanation. It is estimated that between 10% and 20% of those infected develop long COVID; however, data is not precise in Latin America. Although high immunization rates have reduced acute symptoms and the pandemic’s impact, there is a lack of evidence of its efficacy in preventing long COVID in the region. Methods: This scoping review followed PRISMA-ScR guidelines. Studies on vaccinated adults with long COVID from Central and South America and the Caribbean were included (Mexico was also considered). A comprehensive search across multiple databases was conducted. Data included study design, participant characteristics, vaccine type, and efficacy outcomes. Results are presented narratively and in tables. Results: Out of 3466 initial records, 8 studies met the inclusion criteria after rigorous selection processes. These studies encompassed populations from Brazil, Mexico, Latin America, and Bonaire, with 11,333 participants, 69.3% of whom were female. Vaccination, particularly with three or more doses, substantially reduces the risk and duration of long COVID. Variability was noted in the definitions and outcomes assessed across studies. Conclusions: This scoping review highlights that SARS-CoV-2 vaccination exhibits potential in reducing the burden of long COVID in the Americas. However, discrepancies in vaccine efficacy were observed depending on the study design, the population studied, and the vaccine regimen employed. Further robust, region-specific investigations are warranted to delineate the effects of vaccination on long COVID outcomes. Full article

The COVID-19 pandemic, caused by SARS-CoV-2, has led to a wide range of acute and chronic disease manifestations. While most infections are mild, a significant number of patients develop severe illness marked by respiratory failure, thromboinflammation, and multi-organ dysfunction. In addition, post-acute sequelae—commonly known as long-COVID—can persist for months. Recent studies have identified the emergence of diverse autoantibodies in COVID-19, including those targeting nuclear antigens, phospholipids, type I interferons, cytokines, endothelial components, and G-protein-coupled receptors. These autoantibodies are more frequently detected in patients with moderate to severe disease and have been implicated in immune dysregulation, vascular injury, and persistent symptoms. This review examines the underlying immunological mechanisms driving autoantibody production during SARS-CoV-2 infection—including molecular mimicry, epitope spreading, and bystander activation—and discusses their functional roles in acute and post-acute disease. We further explore the relevance of autoantibodies in maternal–fetal immunity and comorbid conditions such as autoimmunity and cancer, and we summarize current and emerging therapeutic strategies. A comprehensive understanding of SARS-CoV-2-induced autoantibodies may improve risk stratification, inform clinical management, and guide the development of targeted immunomodulatory therapies. Full article

Background: As COVID-19 transitions to an endemic phase, long COVID symptoms remain a significant public health issue affecting both physical and mental health. A notable proportion of college students report symptoms such as fatigue, cough, and brain fog persisting for weeks or months post-infection. Objectives: This study explored the prevalence and contributing factors of long COVID symptoms among both infected and uninfected students in medicine-related departments. Methods: A cross-sectional study was conducted using online self-reported questionnaires completed by 1523 undergraduate and graduate students in medicine-related departments at a medical university. Participants who had tested positive for COVID-19 within the past three months were excluded. The survey assessed long COVID symptoms, with comparisons conducted between infected and uninfected groups. Multivariate logistic regression identified risk factors associated with long COVID symptoms. Results: Of the 1118 participants, 47.5% of those with a prior COVID-19 diagnosis reported long COVID symptoms within the past month. Significant differences between the infected and uninfected groups were observed in physical, cognitive, and psychological health. Logistic regression identified that prior COVID-19 diagnosis had an association with the presence of long COVID symptoms (odds ratio = 1.48, p = 0.024) after adjusted model analysis. Meanwhile, higher anxiety levels (odds ratio = 1.09, p < 0.001) and a BMI ≥ 24 (odds ratio = 4.50, p < 0.01) were identified as significant risk factors for post-infection syndrome among previously infected students. Sex and exercise habits also influenced symptom prevalence. Conclusions: Since late 2023, with those experiencing cumulative infections surpassing half of Taiwan’s population, long COVID symptoms have persisted as a widespread concern affecting both physical and mental health, continuing into 2025. This study underscores critical risk factors and symptom patterns among students in medicine-related departments, reinforcing the urgency of sustained surveillance and targeted interventions to facilitate comprehensive recovery. Full article

Background: Emerging evidence indicates that some individuals recovering from COVID-19 develop persistent symptoms, including fatigue, pain, cognitive difficulties, and psychological distress, commonly known as Long COVID. These symptoms often overlap with those seen in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), underscoring the need for integrative, non-pharmacological interventions. This Phase II controlled trial aimed to evaluate the feasibility and preliminary efficacy of Heart Rate Variability Biofeedback (HRV-BF) in individuals with Long COVID who meet the diagnostic criteria for CFS/ME. Specific objectives included assessing feasibility indicators (drop-out rates, side effects, participant satisfaction) and changes in fatigue, depression, anxiety, pain, and health-related quality of life. Methods: Participants were assigned alternately and consecutively to the HRV-BF intervention or Treatment-as-usual (TAU), in a predefined 1:1 sequence (quasirandom assignment). The intervention consisted of 10 HRV-BF sessions, held twice weekly over 5 weeks, with each session including a 10 min respiratory preparation and 40 min of active training. Results: The overall drop-out rate was low (5.56%), and participants reported a generally high level of satisfaction. Regarding side effects, the mean total Simulator Sickness Questionnaire score was 24.31 (SD = 35.42), decreasing to 12.82 (SD = 15.24) after excluding an outlier. A significantly greater improvement in severe fatigue was observed in the experimental group (H = 4.083, p = 0.043). When considering all outcomes collectively, a tendency toward improvement was detected in the experimental group (binomial test, p < 0.0001). Conclusions: HRV-BF appears feasible and well tolerated. Findings support the need for Phase III trials to confirm its potential in mitigating fatigue in Long COVID. Full article

Background/Objectives: In late 2019, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused a pandemic called the ‘coronavirus disease 2019’ (COVID-19). After the acute SARS-CoV-2 infection, many individuals (up to 33%) complained of unexplained symptoms involving multiple organ systems and were diagnosed as having Long COVID-19 (LC-19). Currently, LC-19 is inadequately defined, requiring the formation of consistent diagnostic parameters to provide a foundation for ongoing and future studies of epidemiology, risk factors, clinical characteristics, and therapy. LC-19 represents a significant burden on multiple levels. The reduced ability of workers to return to work or compromised work efficiency has led to consequences at national, economic, and societal levels by increasing dependence on community services. On a personal scale, the isolation and helplessness caused by the disease and its subsequent impact on the patient’s mental health and quality of life are incalculable. Methods: In this paper, we used Walker and Avants’ eight-step approach to perform a concept analysis of the term “Long COVID-19” and define its impact across these parameters. Results: Using this methodology, we provide an improved definition of LC-19 by connecting the clinical symptomology with previously under-addressed factors, such as mental, psychological, economic, and social effects. This definition of LC-19 features can help improve diagnostic procedures and help plan relevant healthcare services. Conclusions: LC-19 represents a complex and pressing public health challenge with diverse symptomology, an unpredictable timeline, and complex pathophysiology. This concept analysis serves as a tool for improving LC-19 definition, but it remains a dynamic disease with evolving diagnostic and therapeutic approaches, requiring deeper investigation and understanding of its long-term effects. Full article

Background/Objectives: Given the heterogeneous nature of long COVID, its treatment and management remain challenging. This study aimed to investigate whether poor pre-pandemic sleep quality, its deterioration during the peak of the pandemic, and circadian preference increase the risk of long COVID symptoms. Methods: An online survey was conducted between 9 October and 12 December 2022, with 384 participants who had recovered from COVID-19 at least three months prior to data collection. Participants were categorized based on the presence of at least one long COVID symptom. Logistic regression models assessed associations between sleep-related variables and long COVID symptoms. Results: Participants with long COVID symptoms reported significantly poorer sleep quality, higher perceived stress, greater somatic and cognitive pre-sleep arousal, and elevated levels of post-traumatic stress symptoms, anxiety, depression, and aggression. Fatigue (39.8%) and memory problems (37.0%) were the most common long COVID symptoms. Sleep deterioration during the pandemic peak was reported by 34.6% of respondents. Pre-pandemic poor sleep quality, its deterioration during the pandemic, and poor sleep at the time of the survey were all significantly associated with long COVID. An extreme morning chronotype consistently predicted long COVID symptoms across all models, while an extreme evening chronotype was predictive only when accounting for sleep quality changes during the pandemic. COVID-19 frequency, severity, financial impact, and somatic pre-sleep arousal were significant predictors in all models. Conclusions: Poor sleep quality before the pandemic and its worsening during the pandemic peak are associated with a higher likelihood of long COVID symptoms. These findings underscore the need to monitor sleep health during pandemics and similar global events to help identify at-risk individuals and mitigate long-term health consequences, with important clinical and societal implications. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has posed substantial health threats and triggered widespread global economic disruption. The nucleocapsid (N) protein of SARS-CoV-2 is not only a key structural protein but also instrumental in mediating the host immune response, contributing significantly to inflammation and viral pathogenesis. Due to its immunogenic properties, SARS-CoV-2 N protein also interacts with host factors associated with various pre-existing inflammatory conditions and may possibly contribute to the long-term symptoms suffered by some COVID-19 patients after recovery—known as long COVID. This review provides a comprehensive overview of recent advances in elucidating the biological functions of the N protein. In particular, it highlights the mechanisms by which the N protein contributes to host inflammatory responses and elaborates on its association with long COVID and pre-existing inflammatory disorders. Full article

Background and Aims: The majority of individuals with COVID-19 developed acute symptoms. Post-COVID-19 syndrome refers to the signs and symptoms of COVID-19 that persist for more than 12 weeks. The present study was conducted to estimate the prevalence and risk factors for post-COVID-19 syndrome in the Omani population. Methods: This is a cross-sectional study that was conducted at the University Hospital Center (UHC). All patients diagnosed with COVID-19 (through polymerase chain reaction PCR testing) between March 2020 and March 2022 were included. Eligible participants were interviewed through a phone call, informed about the study procedure, and invited to participate in the study. Results: The study enrolled 265 COVID-19 patients, of whom 156 (59.2%) were females and 204 (77.3%) had been vaccinated. The overall prevalence of post-COVID-19 syndrome was 48.5%. The most common symptom was fatigue (71, 26.9%), followed by joint pain (44, 16.7%). The other symptoms included loss of taste/smell (34, 12.9%), cough (32, 12.1%), palpitation (25, 9.5%), and hair loss (27, 10.2%). Unvaccinated patients showed a higher incidence of fatigue (p = 0.03) and loss of smell/taste (p = 0.01) on univariate analysis. Females were at high risk for the development of various symptoms, including fatigue, muscular pain, breathing difficulty, cough, chest pain, palpitation, headache, and hair loss. Multivariate analysis showed that female gender is a significant independent predictor (odds ratio: 3.1; p = 0.00) for the development of post-COVID-19 syndrome. Conclusions: The prevalence of post-COVID-19 syndrome among the Omani population was high, highlighting the need for targeted interventions to manage long-term symptoms in vulnerable groups. Full article

(1) Background: Physical activity (PA) plays a crucial role in preserving and enhancing mental health, particularly in the aftermath of major health crises such as the COVID-19 pandemic. However, the specific levels and domains of physical activity that have the greatest impact on alleviating symptoms of anxiety, depression, and stress in the post-COVID-19 period remain unclear. The aim of this study was to examine the influence of different levels and domains of PA on mental health parameters, specifically symptoms of anxiety, depression, and stress, in individuals who had recovered from COVID-19. (2) Methods: The study included initial measurements (2–4 weeks post-recovery) and final measurements (14–16 weeks post-recovery). The sample comprised 288 participants aged 20 to 60 years (M = 47.06; SD = 12.41), with 95 men and 193 women. PA was assessed using the long version of the IPAQ questionnaire, while mental health was evaluated using the long version of the DASS scale. (3) Results: Stepwise regression analysis revealed that low- (p = 0.010) and moderate-intensity (p = 0.022) PA was significantly associated with reductions in anxiety symptoms as well as lower stress levels (low PA: p = 0.014; moderate PA: p = 0.042). Total PA (p < 0.001) and vigorous-intensity PA (p = 0.008) emerged as significant predictors of reduced depression levels. Among the domains of PA, home-based activities had a statistically significant impact on all three mental health components: anxiety (p = 0.005), depression (p = 0.002), and stress (p = 0.041). Transport-related PA was significantly associated with anxiety (p = 0.011) and stress (p = 0.022), but not with depression. (4) Conclusions: The results suggest that a combined model incorporating different levels and domains of PA may represent an effective approach to improving mental health in individuals recovering from COVID-19. Further longitudinal studies are needed to establish more precise causal relationships. Full article

Objectives: COVID-19, caused by the SARS-CoV-2 virus, has infected over 777 million individuals and led to approximately 7 million deaths worldwide. Despite significant efforts to develop effective therapies, treatment remains largely supportive, especially for severe complications like acute respiratory distress syndrome (ARDS). Numerous compounds from diverse pharmacological classes are currently undergoing preclinical and clinical evaluation, targeting both the virus and the host immune response. Methods: Despite the large number of articles published and after a preliminary attempt was published, we discarded the option of a systematic review. Instead, we have done a description of therapies with these results and a tentative mechanism of action. Results: Preliminary studies and early-phase clinical trials have demonstrated the potential of Mesenchymal Stem Cells (MSCs) in mitigating severe lung damage in COVID-19 patients. Previous research has shown MSCs to be effective in treating various pulmonary conditions, including acute lung injury, idiopathic pulmonary fibrosis, ARDS, asthma, chronic obstructive pulmonary disease, and lung cancer. Their ability to reduce inflammation and promote tissue repair supports their potential role in managing COVID-19-related complications. This review demonstrates the utility of MSCs in the acute phase of COVID-19 and postulates the etiopathogenic role of mitochondria in Long-COVID. Even more, their combination with other therapies is also analyzed. Conclusions: While the therapeutic application of MSCs in COVID-19 is still in early stages, emerging evidence suggests promising outcomes. As research advances, MSCs may become an integral part of treatment strategies for severe COVID-19, particularly in addressing immune-related lung injury and promoting recovery. However, a full pathogenic mechanism may explain or unify the complexity of signs and symptoms of Long COVID and Post-Acute Sequelae (PASC). Full article

Long-COVID (LC) is characterized by diverse and persistent symptoms, potentially mirroring different molecular pathways. Recent data might offer that one of them is mediated by functional autoantibodies (fAAb) targeting G protein-coupled receptors (GPCR). Thus, the aim of this study was to investigate the clinical phenotype of patients with LC in relation to their GPCR-fAAb seropositivity. The present study recruited 194 patients with LC and profiled them based on self-reported symptoms. GPCR-fAAb seropositivity was identified by using a cardiomyocyte bioassay, testing the presence and functionality of the AAbs. Logistic regression, clustering, and decision tree analyses were applied to examine associations between GPCR-fAAb profiles and self-reported symptoms considering age and gender. The most prevalent GPCR-fAAbs in patients with LC were fAAB targeting the β2 adrenergic receptor (β2-fAAb, 92.8%), the muscarinergic M2 receptor (M2-fAAb, 87.1%), the Angiotensin II type 1 receptor (AT1-fAAb, 85.6%), and angiotensin (1–7) Mas receptor (MAS-fAAb, 85.6%). β2-fAAb showed a significant relation with dizziness, lack of concentration, and POTS, while Endothelin Type A receptor functional autoantibody (ET-A-fAAb) was significantly related to deterioration of pre-existing neurological disorders. Statistical analysis indicated a strong positive correlation between M2- and β2-fAAb; as in addition, an association of β2-fAAb and gender was observed to one of the major clinical symptoms (fatigue/PEM), a critical impact of GPCR-fAAb on LC-pathogenesis can be assumed. Summing up, the present data show that specific GPCR-fAAb are associated with distinct clinical phenotypes. Especially, the combination of M2- and β2-fAAb seemed to be essential for the LC-phenotype with a combination of fatigue/PEM and lack of concentration as major clinical symptoms. Full article

Background: This study investigates the potential mechanisms behind changes in cardiac structure and function in long COVID patients. Methods: This study involved 176 consecutive outpatients in follow-up care (average age 55.9 years; 58.5% male) who experienced symptoms for over 12 weeks (average 6.2 ± 2.7 months), following coronavirus infection (COVID-19). Results: The patients with long COVID and cardiovascular manifestations were significantly more hospitalized (88.5% vs. 75.9%) and had longer hospital stays. Significant echocardiography changes were observed in the left ventricular ejection fraction (LVEF) (59.6 ± 5.4% vs. 62.5 ± 3.8%); longitudinal strain (LS) in the sub-endocardium and intra-myocardium layers (−20.9 vs. −22.0% and −18.6 vs. −19.5%); circumferential strain (CS) in the sub-epicardium layers (−9.6 vs. −10.5%); and CS post-systolic shortening (CS PSS) (0.138 vs. 0.088 s). Additionally, pathological cardiac magnetic resonance (CMR) findings were seen in 58.2% of the group of patients with long COVID and cardiovascular manifestation; 43.3% exhibited positive late gadolinium enhancement (LGE), 21.0% had elevated native T1 mapping, and 22.4% had elevated native T2 mapping. Conclusions: Most patients with long COVID showed structural and functional changes in their cardiovascular systems, primarily caused by prolonged inflammation. Using multimodality imaging is important for uncovering the mechanisms to predict chronic myocarditis, early-stage heart failure, and pre-ischemic states, which can lead to serious complications. Recognizing the specific cardiovascular phenotypes associated with long COVID is essential in order to provide timely and appropriate treatment. Full article

Long- or post-COVID-19 syndrome, which is also designated by WHO as Post COVID-19 Condition (PCC), is characterized by the persistent symptoms that remain after recovery from SARS-CoV-2 infection. A worldwide consortium of Long COVID-19 Host Genetics Initiative (Long COVID-19 HGI) identified an SNP rs9367106 (G>C; chr6:41,515,652, GRCh38, p = 1.76 × 10⁻¹⁰, OR = 1.63, 95% CI: 1.40–1.89) that is associated with PCC. Unraveling the functional significance of this SNP is of prime importance to understanding the development of the PCC phenotypes and their therapy. Here, in Silico, I explored how the risk allele of this SNP alters the functional mechanisms and molecular pathways leading to the development of PCC phenotypes. Bioinformatic methods include physical interactions using HI-C and Chia-PET analysis, Transcription Factors (TFs) binding ability, RNA structure modeling, epigenetic, and pathway analysis. This SNP resides within two long RNA genes, LINC01276 and FOXP4-AS1, and is located at ~31 kb upstream of a transcription factor FOXP4. This DNA region, including this SNP, physically interacts with FOXP4-AS1 and FOXP4, implying that this regulatory SNP could alter the normal cellular function of FOXP4-AS1 and FOXP4. Furthermore, rs9367106 is in eQTL with the FOXP4 gene in lung tissue. rs9367106 carrying DNA sequences act as distant enhancers and bind with several transcription factors (TFs) including YY1, PPAR-α, IK-1, GR-α, and AP2αA. The G>C transition extensively modifies the RNA structure that may affect the TF bindings and enhancer functions to alter the interactions and functions of these RNA molecules. This SNP also includes an ALU/SINE sequence and alteration of which by the G>C transition may prevent IFIH1/MDA5 activation, leading to suppression of host innate immune responses. LINC01276 targets the MED20 gene that expresses mostly in brain tissues, associated with sleep disorders and basal ganglia abnormalities similar to some of the symptoms of PCC phenotypes. Taken together, G>C transition of rs9367601 may likely alter the function of all three genes to explain the molecular basis of developing the long-term symptomatic abnormalities in the lungs and brain observed after COVID-19 recovery. Full article

Background: Since the pathophysiology of long COVID is not yet fully understood, there are no specific methods for its treatment; however, its individual symptoms can currently be treated. Long COVID is characterized by symptoms that persist at least 2 to 3 months after contracting COVID-19, although it is difficult to predict how long such symptoms may persist. Methods: In the present study, 774 patients who first visited our outpatient clinic during the Omicron period from February 2022 to October 2024 were divided into two groups: the early recovery (ER) group (370 cases; 47.8%), who recovered in less than 180 days (median 33 days), and the persistent-symptom (PS) group (404 cases; 52.2%), who had symptoms that persisted for more than 180 days (median 437 days). The differences in clinical characteristics between these two groups were evaluated. Results: Although the median age of the two groups did not significantly differ (40 and 42 in ER and PS groups, respectively), the ratio of female patients was significantly higher in the PS group than the ER group (59.4% vs. 47.3%). There were no significant differences between the two groups in terms of the period after infection, habits, BMI, severity of COVID-19, and vaccination history. Notably, at the first visit, female patients in the PS group had a significantly higher rate of complaints of fatigue, insomnia, memory disturbance, and paresthesia, while male patients in the PS group showed significantly higher rates of fatigue and headache complaints. Patients with more than three symptoms at the first visit were predominant in the PS groups in both genders. Notably, one to two symptoms were predominant in the male ER group, while two to three symptoms were mostly reported in the female PS group. Moreover, the patients in the PS group had significantly higher scores for physical and mental fatigue and for depressive symptoms. Conclusions: Collectively, these results suggest that long-lasting long COVID is related to the number of symptoms and presents gender-dependent differences. Full article