Search Results (174)

Background/Objectives: COVID-19 may result in persistent symptoms, some of which can be disabling, referred to as post-acute sequelae of SARS-CoV-2 (PASC, or long COVID). The growing recognition of PASC as a public health challenge underscores the need for comprehensive studies of its course, risk factors, and clinical outcomes. This multicentric study aimed to compare the prevalence, symptom spectrum, and functional impact of PASC in two patient groups: those hospitalized with COVID-19 and those managed exclusively in ambulatory care. Methods: Molecular, clinical, and demographic data were obtained from 319 patients diagnosed with COVID-19 in seven European countries. Patients were classified as PASC in accordance with the WHO definition. Results: PASC is more frequent and severe among hospitalized patients, while ambulatory patients present with milder but prolonged symptoms. Categorical age analysis suggests that older age was associated with a higher incidence of PASC, highlighting the need for multidisciplinary management and targeted support. Conclusions: Our findings highlight distinct differences in the presentation and impact of PASC across patient groups, with important implications for individualized care, multidisciplinary management, and effective healthcare planning in the post-pandemic era. Full article

Background/Objectives: The COVID-19 pandemic posed significant challenges to quality of life, particularly for individuals living with chronic physical and/or mental conditions. Psychological factors such as fear of COVID-19, psychological distress, and resilience may be associated with quality-of-life outcomes during prolonged public health crises. This study aimed to examine quality of life and its psychological correlates among individuals with chronic conditions during the later phases and aftermath of the COVID-19 pandemic crisis. Methods: A cross-sectional study was conducted among 293 adults with chronic physical and/or mental conditions attending the General Hospital of Argolida, Greece. Participants completed validated self-report measures assessing quality of life (MVQOLI), fear of COVID-19 (FCV-19S), depression, anxiety, and stress (DASS-21), and psychological resilience (CD-RISC-25). Descriptive statistics, Spearman correlation analyses, and multivariable regression models were used to examine associations and identify factors associated with quality-of-life domains. Results: Higher levels of fear of COVID-19 and depressive symptoms were significantly associated with poorer quality of life across multiple domains. Depressive symptoms showed consistent negative associations with functional, interpersonal, transcendent, and overall quality-of-life scores. In contrast, psychological resilience was positively associated with interpersonal, transcendent, and overall quality of life. Regression analyses showed that depressive symptoms were negatively associated with overall quality of life, while resilience was independently associated with better quality-of-life outcomes. Conclusions: Psychological distress, particularly depressive symptoms and fear related to COVID-19, was associated with lower quality of life among individuals with chronic conditions during the later phases and aftermath of the COVID-19 crisis. Psychological resilience was positively associated with better quality-of-life outcomes, underscoring its relevance for supporting well-being during and after public health crises. Full article

Long COVID is associated with persistent fatigue, exercise intolerance, and microcirculatory dysfunction. Altered red blood cell (RBC) rheology, including impaired deformability and increased aggregation, may contribute to these symptoms, yet the effects of exercise interventions remain unclear. This longitudinal pilot study tested whether an individualized, symptom-responsive exercise program improves RBC rheology in Long COVID. A total of 170 (110 f/60 m) participants entered a five-phase training protocol; 15 completed all phases and formed a predefined finisher subgroup. RBC aggregation and deformability, hematological parameters, and coagulation- and iron-related markers were assessed across phases; RBC morphology was additionally analyzed in finishers at baseline and completion. In the total cohort, aggregation indices decreased across training phases, accompanied by prolonged aggregation half-time, while hematological, coagulation, and iron markers remained largely unchanged. The deformability changes were not uniform in the full cohort; however, finishers showed a deformability shift after completion. Importantly, morphologically abnormal RBC decreased in finishers, and these changes correlated with deformability, suggesting that improved rheology is linked to reduced RBC abnormalities. Prospectively, larger controlled studies are needed to confirm these results and to evaluate whether exercise-induced rheological improvements translate into functional and symptomatic benefits. Full article

Background: To date, no study has compared the clinical characteristics of Mycoplasma pneumoniae-associated segmental/lobar pneumonia, Mycoplasma bronchopneumonia, and COVID-19 pneumonia primarily caused by the NB.1.8.1 variant in children. Methods: We examined the epidemiologic trends of pneumonia, segmental/lobar pneumonia, and COVID-19 pneumonia at a teaching hospital from 2015 to 2025. In addition, we compared the clinical characteristics of children hospitalized with Mycoplasma segmental/lobar pneumonia, Mycoplasma bronchopneumonia, and COVID-19 pneumonia during the NB.1.8.1 variant wave in 2024–2025. Results: Between 2015 and 2024, 10,601 pneumonia cases were identified, including 525 cases of segmental/lobar pneumonia and 162 cases of COVID-19 pneumonia. An outbreak of segmental/lobar M. pneumoniae pneumonia and COVID-19 pneumonia occurred in Taiwan during 2024–2025. Starting in early 2025, monthly Mycoplasma positivity rates among children with segmental/lobar pneumonia and bronchopneumonia exceeded 60%. Mycoplasma pneumonia predominantly affected children aged 6–11 years, whereas COVID-19 pneumonia mainly occurred in those younger than 3 years of age. Fever, cough, and rhinorrhea were the most common symptoms in all groups, limiting clinical differentiation. Children with segmental/lobar Mycoplasma pneumonia were more likely to present with prolonged fever (>5 days), lymphocytopenia, a neutrophil-to-lymphocyte ratio (NLR) ≥ 3, and elevated C-reactive protein (CRP) levels, each of which was strongly associated with macrolide non-response (all p < 0.001). Conclusions: Children with segmental/lobar Mycoplasma pneumonia demonstrated more severe clinical manifestations. Segmental/lobar involvement and inflammatory markers, such as lymphocytopenia, elevated NLR, and increased CRP levels, were associated with macrolide non-response. These indicators may help guide therapeutic decision-making in pediatric M. pneumoniae pneumonia. Full article

Long COVID is a complex condition characterized by persistent symptoms following SARS-CoV-2 infection. Understanding its biochemical mechanisms is essential for effective management and treatment strategies. Objective: This study investigated biochemical alterations associated with long COVID in unvaccinated individuals presenting symptoms persisting for more than six months, highlighting the prolonged nature of the condition and its systemic and neurological manifestations. A cross-sectional study was conducted with 60 unvaccinated patients at least six months post-COVID-19 infection. Serum biomarkers, including C-reactive protein (CRP), interleukin-6 (IL-6), N-terminal pro-brain natriuretic peptide (NT-proBNP), and irisin, were analyzed. Correlations between these biomarkers and persistent symptoms were assessed using statistical regression models. Elevated CRP levels were significantly associated with persistent respiratory and musculoskeletal symptoms, suggesting ongoing inflammation. Increased IL-6 levels correlated with fatigue and musculoskeletal complaints. NT-proBNP elevations were linked to cardiovascular manifestations, including dyspnea and chest pain. A positive correlation between irisin and persistent sensory impairments, such as anosmia and dysgeusia, indicates potential neuroinflammatory mechanisms. This study highlights that persistent inflammation plays a critical role in long-term (>6 months) post-COVID manifestations. Monitoring biomarkers such as CRP, IL-6, NT-proBNP, and irisin may enhance understanding and management of prolonged post-COVID conditions. Full article

Background: Cardiac arrhythmias are a frequent complication of acute SARS-CoV-2 infection. However, their long-term prevalence and clinical determinants among patients with post-COVID-19 syndrome, especially those previously hospitalized, remain poorly defined. Objectives: To assess the prevalence and types of arrhythmias in long COVID patients following hospitalization and to identify associated clinical risk factors. Methods: In this cross-sectional study, 53 patients previously hospitalized with confirmed COVID-19 were evaluated ≥3 months post-infection. All participants underwent a standardized clinical assessment, 12-lead electrocardiography, and 24 h Holter monitoring. Logistic and Cox regression analyses were performed to identify predictors of arrhythmia. Results: Arrhythmias were identified in 41.5% (n = 22) of patients. Atrial fibrillation (32%) was the most frequent arrhythmia, followed by sinus bradycardia (27%) and sinus tachycardia (18%). Age (OR 1.06, 95% CI 1.01–1.10, p = 0.01) and length of hospital stay (OR 1.1, 95% CI 1.01–1.2, p = 0.04) were independently associated with arrhythmia. Biguanide (metformin) therapy was inversely associated with the occurrence of arrhythmia (Exp(B) = 0.017, p = 0.008). Dyspnea (82.4%) and palpitations (41.5%) were the most commonly reported symptoms. Conclusions: Arrhythmias are common in patients with long COVID following severe disease. Advanced age and prolonged hospitalization are significant risk factors, while biguanide use may offer a protective effect. These findings underscore the need for targeted cardiac surveillance in this population. Full article

Background: While COVID-19 vaccination significantly reduces acute disease severity, its impact on the incidence of long COVID remains debated, with some observational studies paradoxically suggesting higher symptom rates among vaccinated individuals. This study aimed to resolve this controversy by distinguishing between the protective effects of prior immunity and the confounding influence of reverse causality. Methods: We conducted a retrospective cohort study of 627 adults hospitalised for COVID-19 in London. Participants were stratified into two analytical cohorts based on vaccination timing: a “prevention cohort” (vaccinated ≥14 days pre-infection) and a “post-acute cohort” (vaccinated post-infection). Multivariable Bayesian logistic regression was employed to estimate Adjusted Odds Ratios (aOR) for long COVID, controlling for age, gender, BMI, comorbidities, and acute length of hospital stay (LoS). Results: In the prevention cohort, prior vaccination demonstrated a non-significant protective trend against long COVID (aOR 0.81; 95% CI 0.45–1.42; p = 0.45), with no significant difference observed between homologous and heterologous regimens. The post-acute cohort exhibited a strong, significant positive association (aOR 3.41; 95% CI 2.23–5.52; p < 0.001), indicating substantial indication bias, with symptomatic individuals more likely to seek vaccination. The strongest independent predictors of long COVID were comorbidities (aOR 2.78) and prolonged acute hospitalisation (≥4 days; aOR 1.82). Conclusions: Vaccination administered prior to infection demonstrates a protective trend against long COVID, whereas the strong association observed with post-infection vaccination reflects indication bias, with symptomatic survivors being more likely to seek immunisation. Clinical strategies to mitigate post-acute sequelae should prioritise reducing acute disease severity and managing comorbidities, which were identified as the dominant independent predictors of risk in hospitalised patients. Full article

Background: Although the main target of SARS-CoV-2 is the respiratory system, in some patients, it may affect multiple organ systems, leading to multi-organ failure. Acute kidney injury (AKI) remains one of the most frequent and clinically significant complications of severe COVID-19, with clinical importance extending beyond the acute phase due to its association with long-term renal outcomes and persistent morbidity. The incidence of AKI is particularly high among patients admitted to the intensive care unit (ICU), where its development has been consistently associated with prolonged hospitalization and increased mortality. The primary aim of this study was to determine the incidence of COVID-19-associated AKI, identify factors related to its development and severity, and evaluate mortality as a clinical outcome. Methods: Data from 238 COVID-19 patients monitored in the Intensive Care Unit of Ankara University Ibni Sina Hospital (ISH-ICU) between 1 January 2021 and 1 January 2022 were retrospectively reviewed. Patients were divided into two groups according to the presence of AKI. Those with AKI were staged according to KDIGO criteria (stages 1–2–3). Demographic characteristics, comorbidities, disease severity scores, laboratory parameters, and mortality outcomes were analyzed and compared between groups. Results: AKI was identified in 54.6% of patients. Of the patients with AKI, 32 (13.4%) had stage 1, 25 (10.5%) had stage 2, and 73 (30.7%) had stage 3 AKI. Thirteen patients (5.5%) had already developed AKI at ICU admission. AKI developed at a median of 11 days after symptom onset and 3 days after ICU admission. Advanced age, hypertension, cardiovascular disease, and chronic kidney disease were more frequent in patients with AKI (p < 0.001). Higher Charlson Comorbidity Index (CCI) and Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) scores were observed in patients with stage 3 AKI. Lymphopenia and elevated levels of D-dimer, ferritin, IL-6, CRP, and procalcitonin were significantly higher in patients with stage 3 AKI than in patients with other AKI stages and the non-AKI group. Mortality rates were higher in patients with AKI and increased with advancing AKI stage (p < 0.001). ICU length of stay was significantly longer in the AKI group (p < 0.001). Conclusions: AKI is a common complication among critically ill patients with COVID-19 and is associated with prolonged ICU stay and higher mortality rates, particularly in advanced stages. Early identification of clinical and laboratory factors associated with AKI may support timely risk stratification and targeted management in this high-risk population. Full article

Background: Long COVID remains a challenging and heterogeneous condition, with mechanisms that are still incompletely understood. Emerging evidence suggests that patients with allergic disease may experience more persistent post-COVID symptoms, possibly due to immune dysregulation and epithelial barrier fragility. Methods: We carried out an observational, single-center study at the Allergy and Clinical Immunology Unit of Policlinico Universitario A. Gemelli IRCCS (Rome, Italy). Seventeen adults with confirmed allergic disease and long COVID were evaluated between July and December 2024. Biomarkers reflecting allergic inflammation and barrier integrity, blood eosinophil count, total immunoglobulin E (IgE), eosinophil cationic protein (ECP), and serum free light chains (FLCs), were measured and analyzed for interrelationships and symptom correlations. Results: Participants (10 men, 7 women; mean age 43.7 years) showed variable biomarker profiles, consistent with the heterogeneity of allergic inflammation. Mean eosinophil count was 179 ± 72 cells/µL, total IgE 165.4 ± 140.6 kU/L, ECP 64.2 ± 48.5 ng/mL, and the kappa/lambda FLC ratio 1.20 ± 0.69. Notably, elevated kappa FLC levels (>19.4 mg/L) were significantly associated with high ECP (>20 ng/mL) (χ² = 10.6, p = 0.001) and increased IgE (>200 kU/L) (χ² = 6.0, p = 0.015). Individuals with higher ECP and FLCs more often reported respiratory and systemic symptoms, especially fatigue, dyspnea, and cognitive fog, that persisted beyond six months. Conclusions: These findings suggest that biomarkers of allergic inflammation and barrier dysfunction, particularly ECP and FLCs, may contribute to the persistence of long-COVID symptoms in allergic patients. The observed links between humoral activation, eosinophilic activity, and prolonged symptom burden support a model of sustained inflammation and delayed epithelial recovery. Larger, longitudinal studies including non-allergic controls are warranted to confirm these associations and to explore whether restoring barrier integrity could shorten recovery trajectories in this vulnerable population. Full article

Objectives: Obesity has been suggested as a possible risk factor for the post-COVID-19 condition, but most studies rely only on body mass index (BMI), which does not reflect body fat distribution. Waist-to-height ratio (WHtR) is a simple anthropometric indicator of central obesity and a practical proxy for body fat distribution, yet it has not been studied in relation to the post-COVID-19 condition. This study aimed to examine whether obesity, measured by BMI and WHtR, is associated with the post-COVID-19 condition. Methods: A total of 500 male military conscripts (aged 18 years) underwent anthropometric measurements (height, weight, and waist circumference). Participants with prior COVID-19 were asked whether they had persistent or new symptoms after infection. BMI categories followed WHO definitions, and WHtR ≥ 0.50 was used to define central obesity. Results: Of the 376 participants who had previously experienced COVID-19, 82 (21%) experienced the post-COVID-19 condition. Obesity (BMI ≥ 30) was more common among those with the post-COVID-19 condition than those without (15% vs. 5%). BMI-defined obesity was associated with higher odds of the post-COVID-19 condition (OR 2.80, 95%CI 1.25–6.24). Central obesity was also more frequent in the post-COVID-19 condition (26% vs. 14%) and was linked to increased odds as well (OR 2.18, 95% CI 1.20–3.97). Conclusions: Both BMI-defined obesity and central obesity were associated with the post-COVID-19 condition. While WHtR does not directly quantify body fat distribution, it represents a simple and feasible anthropometric indicator. Therefore, it may be an additional useful tool for identifying individuals at higher risk of prolonged symptoms after COVID-19 infection. Full article

Background: Persistent low-grade inflammation has been proposed as part of the biological mechanisms underlying post-COVID condition (PCC), which can result in laboratory tests abnormalities. However, the accuracy of routine laboratory tests for the diagnosis and follow-up of PCC is still under discussion. Methods: Patients with SARS-CoV-2 infection enrolled in the prospective, multinational ORCHESTRA cohort study, which included both European and non-European countries, were followed up for 18 months after acute infection. Blood test results were collected at acute infection and at 6, 12, and 18 months. A multivariable analysis was performed to estimate the relationship between the alterations of biochemical markers and the presence of four distinct PCC phenotypes, identified previously through a principal component analysis—respiratory (RESc), chronic pain (CPc), chronic fatigue (CFc), and neurosensorial (NSc)—during follow-up. Furthermore, this study investigated the correlation between biochemical parameters measured during the acute phase and the subsequent development of PCC. Finally, the relationship between the severity of the acute infection and biochemical abnormalities observed during follow-up was assessed. Results: The cohort included 4587 patients, 58% male, with a mean age of 58.7 (±15.5) years. A robust multivariable analysis demonstrated that, compared to controls, patients with PCC, and in particular those in the RESc cluster, presented higher mean C-reactive protein (CRP) levels at the 12- and 18-month follow-up (p-value = 0.01). In each follow-up, CRP values in patients with PCC and RESc were above 3 mg/L, corresponding to those observed in low-grade inflammation (3–10 mg/L). The severity of COVID-19 acute infection was associated with increased levels of CRP, ferritin and LDH during follow-up (p < 0.001). Biochemistry abnormalities detected during the early stages of acute COVID-19 did not correlate with an increased risk of developing PCC and its phenotypes. Conclusions: In patients with the RESc PCC phenotype, identified through a principal component analysis, blood test abnormalities consistent with prolonged and sustained low-grade inflammation can be detected up to 18 months after acute infection, supporting its role in the pathogenesis of PCC. Based on these results, trials on anti-inflammatory drugs, together with symptom-tailored interventions for patients with RESc, should be planned to prove their effectiveness in managing PCC and improving patient outcomes. Full article

This review article attempts to provide a unifying hypothesis to explain the myriad of symptoms and predispositions underlying the development of PASC (Postacute Sequelae of COVID), often referred to as Long COVID. The hypothesis described here proposes that Long COVID is best understood as a disorder of persistent immune dysregulation, with chronic macrophage activation representing the fundamental underlying pathophysiology. Unlike transient post-viral syndromes, Long COVID involves a sustained innate immune response, particularly within monocyte-derived macrophages, driven by persistent spike protein (peripherally in MAIT cells and centrally in Microglial cells), epigenetic imprinting, and gut-related viral reservoirs. These macrophages are not merely activated temporarily but also become epigenetically “trained” into a prolonged inflammatory state, as demonstrated by enduring histone acetylation markers such as H3K27acDNA Reprogramming. It is proposed that recognizing macrophage activation as the central axis of Long COVID pathology offers a framework for personalized risk assessment, targeted intervention, and therapeutic recalibration. Full article

Background: The link between clinical recovery and immune restoration after severe COVID-19 remains poorly defined. Although most survivors experience symptomatic improvement, persistent symptoms have been hypothesized to reflect ongoing immune dysregulation. Methods: This prospective cohort study followed 93 unvaccinated adults with RT-PCR-confirmed moderate-to-critical COVID-19 at 3, 6, and 12 months post-discharge. Clinical assessments used structured interviews to evaluate the persistent symptoms. Peripheral blood analyses were used to measure lymphocyte subsets, immunoglobulins, and complement components. Results: Clinical recovery was substantial; fatigue prevalence declined from 70.9% to 24.7% and dyspnea prevalence from 81.7% to 25.8% by 12 months (p < 0.001 for both). However, immune recovery exhibited divergent patterns. Activated T cells (CD3⁺HLA-DR⁺) decreased significantly (from 20% to 13%; p < 0.001), complement C3c levels paradoxically increased from 1.23 to 1.35 g/L (p < 0.001), and serum IgA increased by 32% (p = 0.003). NK cells remained stable overall but were persistently reduced in a subset (~25%) of patients, particularly among those with fatigue and dyspnea. Critical illness was associated with slower T-cell resolution, prolonged IgM elevation, and increased complement activity. Conclusions: One year after hospitalization, most patients achieved substantial clinical improvement, but immune reconstitution lagged behind. These findings highlight the dissociation between clinical and immunological recovery and suggest that persistent immune dysregulation may be associated with long COVID manifestations. Incorporating immune monitoring into post-COVID care may help identify patients at risk of prolonged sequelae and guide targeted therapeutic strategies. Full article

Background/Objective: The SARS-CoV-2 pandemic, emerging in late 2019, led to a global health crisis, with many patients developing prolonged symptoms after infection known as sequelae of COVID-19. This condition is theorized to be driven by systemic inflammation and immune dysregulation and presents with diverse symptoms from cardiovascular, pulmonary, and neurological systems. This study investigates the prevalence, risk factors, and long-term impacts of sequelae of COVID-19. Method: Using Denmark’s healthcare databases, this population-based cohort study included 1,034,093 individuals over 40 years who tested positive for COVID-19 between 1 March 2020 and 28 February 2022. Participants were divided into two age groups: 40–59 years and 60 years or older. Part A examined the risk of sequelae of COVID-19 diagnoses (ICD-10 code B94.8A) based on the Charlson Comorbidity Index (CCI). Part B assessed two-year outcomes for patients diagnosed with sequelae of COVID-19. Results: Results showed a 0.55% prevalence of sequelae of COVID-19 in both age groups. Higher CCI scores correlated with an increased risk of sequelae of COVID-19. During the two-year follow-up, patients with sequelae of COVID-19 faced significantly elevated risks of thromboembolic events, chronic lung diseases, and infections. Adjusted hazard ratios were notably high: 14.50 (7.54–27.86) and 12.50 (6.95–22.49) for thromboembolic events in adults and older adults, respectively; 33.81 (13.30–85.96) and 9.83 (6.09–15.87) for chronic lung disease; and 8.40 (4.49–15.70) and 15.44 (10.47–22.78) for infections. Conclusions: While the overall prevalence of sequelae of COVID-19 was low among individuals over 40, those with higher comorbidity burdens were at greater risk of severe sequelae and subsequent health complications. These findings underscore the need for clinical monitoring, especially for patients with pre-existing comorbidities, to mitigate long-term health risks associated with COVID-19 sequelae. Full article

Background/Objectives: Machine learning is an extremely important issue, considering the potential to prevent the onset of long-term complications from coronavirus disease or to ensure timely detection and effective treatment. The aim of our study was to develop an algorithm and mathematical model to predict the risk of developing long COVID in children who have had acute SARS-CoV-2 viral infection, taking into account a wide range of demographic, clinical, and laboratory parameters. Methods: We conducted a cross-sectional study involving 305 pediatric patients aged from 1 month to 18 years who had recovered from acute SARS-CoV-2 infection. To perform a detailed analysis of the factors influencing the development of long-term consequences of coronavirus disease in children, two models were created. The first model included basic demographic and clinical characteristics of the acute SARS-CoV-2 infection, as well as serum levels of vitamin D and zinc for all patients from both groups. The second model, in addition to the aforementioned parameters, also incorporated laboratory test results and included only hospitalized patients. Results: Among 265 children, 138 patients (52.0%) developed long COVID, and the remaining 127 (48.0%) fully recovered. We included 36 risk factors of developing long COVID in children (DLCC) in model 1, including non-hospitalized patients, and 58 predictors in model 2, excluding them. These included demographic characteristics of the children, major comorbid conditions, main symptoms and course of acute SARS-CoV-2 infection, and main parameters of complete blood count and coagulation profile. In the first model, which accounted for non-hospitalized patients, multivariate regression analysis identified obesity, a history of allergic disorders, and serum vitamin D deficiency as significant predictors of long COVID development. In the second model, limited to hospitalized patients, significant risk factors for long-term sequelae of acute SARS-CoV-2 infection included fever and the presence of ≥3 symptoms during the acute phase, a history of allergic conditions, thrombocytosis, neutrophilia, and altered prothrombin time, as determined by multivariate regression analysis. To assess the acceptability of the model as a whole, an ANOVA analysis was performed. Based on this method, it can be concluded that the model for predicting the risk of developing long COVID in children is highly acceptable, since the significance level is p < 0.001, and the model itself will perform better than a simple prediction using average values. Conclusions: The results of multivariate regression analysis demonstrated that the presence of a burdened comorbid background—specifically obesity and allergic pathology—fever during the acute phase of the disease or the presence of three or more symptoms, as well as laboratory abnormalities including thrombocytosis, neutrophilia, alterations in prothrombin time (either shortened or prolonged), and reduced serum vitamin D levels, are predictors of long COVID development among pediatric patients. Full article