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BACKGROUND: Cardiac impairment has been associated with acute COVID-19 since the earliest reports of the pandemic. However, its role in post-acute sequelae of COVID-19 (PASC, or "long COVID") is undefined, and many existing observations about cardiovascular involvement in PASC are uncontrolled. OBJECTIVE: To compare the prevalence of cardiac dysfunction in patients with Long COVID, and non-infected controls from the same community, and explore their association with functional capacity. METHODS: Echocardiography was used to assess cardiac structure and function, including the measurement of global longitudinal strain (GLS), in 190 participants with Long COVID. All underwent assessment of functional impairment by subjective (Duke Activity Status Index, DASI) and objective tests (6-minute walk test, 6MWT). The 190 participants from the Long COVID group were matched with those from 979 patients who underwent the same tests in the pre-COVID-19 era, using a propensity score. RESULTS: The 190 patients with Long COVID had similar age and risk factor profiles to those of their matched controls. LV dimensions and geometry, but not diastolic parameters, were significantly altered in the Long COVID group. The Long COVID group had subclinical systolic dysfunction (GLS 18.5±2.6 vs 19.3±2.7%, p=0.005), and more Long COVID patients had abnormal (<16%) GLS (13% vs 8%, p=0.035). The association of Long COVID with abnormal GLS (OR 1.49 [1.04, 2.45]) was independent of - and had a similar or greater effect size - than age and risk factors. There was no interaction of Long COVID with the association of risk factors with GLS. As expected, the Long COVID group had significant subjective (<85% predicted METS; 72% vs 5%, p<0.001) and objective functional impairment (29% vs 24%, p=0.026), but GLS was only weakly associated with both subjective (r=0.30, p=0.005) and objective (r=0.21, p=0.05) functional impairment. The presence of Long COVID was independently associated with subjective (OR=159.7 [95% CI: 61.6-414.2]), and objective functional impairment (OR=2.8 [95% CI: 1.5-5.2]). CONCLUSIONS: Impaired GLS and LV dimensions are the echocardiographic features that are over-represented in Long COVID, and this association is similar to, and independent of other risk factors. Impaired GLS is weakly associated with functional impairment.

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Cognitive dysfunction is a commonly reported feature of Long COVID (LC). With the overlap of assessment and treatment for cognitive concerns across multiple disciplines, coupled with current guidelines supporting interdisciplinary care, the aim of this clinically focused article is to provide a review of current guidelines and research related to assessment and interventions to address LC-related cognitive concerns within clinical practice from a multidisciplinary perspective, incorporating best practices for collaboration among Clinical Neuropsychologists, Rehabilitation Psychologists, and Speech-Language Pathologists. Current guidelines for assessment and interventions for cognitive functioning are provided, with clinical suggestions for best practices offered. Additional considerations related to diversity and variable patient presentations are identified. This article provides guidance based on current research and practice standards regarding the utilization of a multidisciplinary, collaborative approach to provide comprehensive assessment and treatment for individuals with LC-related cognitive concerns.

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BACKGROUND: The long-term symptomatology of COVID-19 has yet to be comprehensively described. The aim of the study was to describe persistent COVID-19 symptoms in a cohort of hospitalized and home-isolated patients. METHODS: A retrospective cohort study was conducted on long COVID patients. Long COVID symptoms were identified, and patients were divided into hospitalized (in-patients) and home-isolated (out-patients) as well as according to the number of symptoms. Patients were examined by a multydisciplinary medical team. Blood tests, high resolution chest computed tomography (CT), physical and infectious examination were performed. Finally, in-patients were evaluated at two time-points: on hospital admission (T0) and after three months from discharge (Tpost). RESULTS: Three hundred and sixty-four COVID-19 patients were enrolled. 82% of patients reported at least one or more symptoms. The most reported symptom was fatigue. Chest CT showed alteration in 76% of patients and pulmonary function alterations were observed in 44.7% of patients. A higher risk of presenting at least one symptom was seen in patients treated with corticosteroid and a higher risk of presenting chest CT residual lesion was observed in hospitalized patients and in patients that received hydroxychloroquine treatment. Moreover, a higher risk of altered pulmonary function was observed in older patients. CONCLUSION: Long-term sequelae are present in a remarkable number of long COVID patients and pose a new challenge to the healthcare system to identify long-lasting effects and improve patients' wellbeing. Multi-disciplinary teams are crucial to develop preventive measures, and clinical management strategies.

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BACKGROUND: Persistent post-COVID conditions (PCCs) have become inevitable challenges for individuals who have survived COVID. The National Research Plan on Long COVID-19 underscores the priority of addressing post-COVID conditions (PCCs) within specific subgroups of the United States (US) population. This study aimed to investigate the prevalence and factors associated with PCCs among stroke survivors in the US. METHOD: In this retrospective cross-sectional study, we utilized the Behavioral Risk Factor Surveillance System (BRFSS) 2022 dataset. First, we identified respondents with a positive history of both COVID-19 and stroke. Subsequently, we categorized these respondents based on whether they experienced PCCs and conducted a comparative analysis of their characteristics. Additionally, our study included a comparison of our findings with those among individuals who have survived myocardial infarction (MI) and cancer. RESULTS: A total of 3999 stroke, 5406 MI, and 10551 cancer survivors were included. The estimated prevalence of PCCs among stroke survivors was 30.6%, compared to 22.4%, 29.2%, and 24.6% among non-stroke (p<0.001), MI, and cancer survivors, respectively. Fatigue, dyspnea, and taste/smell loss were the most common primary symptoms. In multivariate regression analysis, female sex (adjusted odds ratio (aOR):1.62, 95%CI:[1.17-2.24]), stroke-belt residence (aOR:1.67, 95%CI: [1.13-2.46]), pulmonary disease (aOR:2.12, 95%CI:[1.53-2.92]), and depression (aOR:1.55, 95%CI: [1.1-2.2]) were independent factors associated with higher odds of PCCs among stroke survivors. Additionally, age above 64 years was associated with lower odds of PCCs (aOR:0.6, 95%CI: [0.41-0.86]). CONCLUSION: Our study highlights a considerable prevalence of PCCs among stroke survivors, particularly among younger women and individuals with other chronic conditions.

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Patients undergoing maintenance hemodialysis (MHD) are a high-risk group susceptible to SARS-CoV-2 infection and long-COVID syndrome appearance. However, there is limited and unclear evidence for long COVID in MHD patients. We collected the general information, symptoms, signs and laboratory indices of 366 MHD patients infected with COVID-19 and conducted 12 months follow-up with a series of questionnaires. As a result, 285 MHD patients had long COVID, with the most common symptoms were fatigue (84.69%) and muscle weakness (72.45%). Mobility problem (p < 0.001), anxiety/depression (p = 0.002) and breathlessness (p < 0.001) were more prevalent in long COVID patients than in non-long COVID patients. Persistent long COVID people were more likely to report all domains problems of the EQ-5D-5L. Age, female, inadequate dialysis (Kt/V < 1.2), coagulation abnormalities (d-dimer > 1 mg/L) and more comorbidities were risk factors for the development of long COVID. In addition to these factors, elevated inflammatory markers (CRP > 10 mg/L) represent an extra risk factor for the persistence of long COVID symptoms in MHD patients. And more than 80% of long COVID symptoms would resolve after 1 year in MHD patients, of which the sixth month after COVID-19 infection is a critical turning point. In conclusion, more than 68% of MHD patients have long COVID, which has a poor impact on their health status and quality of life. These risk factors for the development and persistence of long COVID deserve the attention of clinicians.

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Hypermobility spectrum disorders (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS) are the most common joint hypermobility conditions encountered by physicians, with hypermobile and classical EDS accounting for >90% of all cases. Hypermobility has been detected in up to 30-57% of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia, postural orthostatic tachycardia syndrome (POTS), and long COVID (LC) compared to the general population. Extrapulmonary symptoms, including musculoskeletal pain, dysautonomia disorders, cognitive disorders, and fatigue, are seen in both LC and HSD. Additionally, ME/CFS has overlapping symptoms with those seen in HSD. Mast cell activation and degranulation occurring in both LC and ME/CFS may result in hyperinflammation and damage to connective tissue in these patients, thereby inducing hypermobility. Persistent inflammation may result in the development or worsening of HSD. Hence, screening for hypermobility and other related conditions including fibromyalgia, POTS, ME/CFS, chronic pain conditions, joint pain, and myalgia is essential for individuals experiencing LC. Pharmacological treatments should be symptom-focused and geared to a patient's presentation. Paced exercise, massage, yoga, and meditation may also provide benefits.

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INTRODUCTION: Following an infection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), many individuals fully recover. On the other hand, a few have symptoms that last for weeks, months, or even years after their initial diagnosis. Symptoms of COVID-19 persisting for four weeks and more are termed long COVID. AIM: To assess the long-term cardiovascular morbidity by battery of cardiac autonomic function tests as well as the persistence of inflammation in COVID-recovered patients three months after initial infection.  Methodology: 150 patients were selected who had recovered from COVID-19 at least three months prior to the study. After obtaining informed written consent, a throat swab was tested for COVID-19, and those with negative reverse transcription polymerase chain reaction (RT-PCR) results were subjected to autonomic function testing. Serum interleukin-6 and C-reactive protein levels were determined by enzyme-linked immunosorbent assay (ELISA) test. RESULTS: Out of 150 subjects 36 were found to have autonomic dysfunction graded according to Ewing's criteria. Individuals with autonomic dysfunction also had significantly increased inflammatory biomarker levels. There was also significant correlation between inflammatory markers and autonomic function test and heart rate variability parameters. CONCLUSION: Even years after the COVID-19 pandemic was declared, new symptom patterns and syndromes such as 'long COVID' are appearing. A better understanding of the pathophysiological mechanisms of post-COVID manifestations that affect the autonomic nervous system, as well as customized therapeutic care, should help reduce COVID-19 sequelae, particularly if we act early in the disease.

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Background: Concerns have been raised about cardiac inflammation in patients with long COVID-19, particularly those with myocardial injury during the acute phase of the disease. This study was conducted to examine myopericardial involvement, detected by cardiac magnetic resonance (CMR) imaging in patients hospitalized for COVID-19. Methods: Adult patients hospitalized with COVID-19 who presented myocardial injury or increased D-dimers were enrolled in this prospective study. All patients were invited to undergo CMR imaging examination after discharge. During follow-up, patients with nonischemic myocardial or pericardial involvement detected on the first CMR imaging examination underwent second examinations. CMR imaging findings were compared with those of a control group of healthy patients with no comorbidity. Results: Of 180 included patients, 53 underwent CMR imaging examination. The mean age was 58.4 ± 18.3 years, and 73.6 % were male. Myocardial and pericardial LGE was reported in 43.4 % and 35.8 % of patients, respectively. Nonischemic myocardial or pericardial involvement was reported in 26 (49.1 %) patients. The prevalence of pericardial LGE was associated inversely with the interval between hospital discharge and CMR. COVID-19 survivors had higher end-systolic volume indices (ESVis) and lower left-ventricular ejection fractions than did healthy controls. Seventeen patients underwent follow-up CMR imaging; the end-diastolic volume index, ESVi, and prevalence of pericardial LGE, but not that of nonischemic LGE, were reduced. Conclusion: Among COVID-19 survivors with myocardial injury during the acute phase of the disease, the incidences of nonischemic myocardial and pericardial LGE and CMR imaging-detected signs of cardiac remodeling, partially reversed during follow-up, were high.

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Long COVID is a complex pathophysiological condition. However, accumulating data suggests that COVID-19 is a systemic microvascular endothelial dysfunction with different clinical manifestations. In this study, a microvascular function was assessed in long COVID patients (n = 33) and healthy controls (n = 30) using flow-mediated skin fluorescence technique (FMSF), based on measurements of nicotinamide adenine dinucleotide fluorescence intensity during brachial artery occlusion (ischemic response, IR) and immediately after occlusion (hyperemic response, HR). Microcirculatory function readings were taken twice, 3 months apart. In addition, we quantified biochemical markers such as the serum L-arginine derivatives and hypoxia-inducible factor 1α (HIF1α) to assess their relation with microvascular parameters evaluated in vivo. In patients with long COVID, serum HIF1α was significantly correlated to IRindex (r = -0.375, p < 0.05). Similarly, there was a significant inverse correlation of serum asymmetric dimethyl-L-arginine levels to both HRmax (r = -0.343, p < 0.05) and HRindex (r = -0.335, p < 0.05). The IR parameters were found lower or negative in long COVID patients and recovered in three-month follow-up. Hypoxia sensitivity value was significantly higher in long COVID patients examined after three months of treatment based on the combination of ACE-inhibitors and beta-adrenolytic compared to baseline condition (85.2 ± 73.8 vs. 39.9 ± 51.7 respectively, p = 0.009). This study provides evidence that FMSF is a sensitive, non-invasive technique to track changes in microvascular function that was impaired in long COVID and recovered after 3 months, especially in patients receiving a cardioprotective therapy.

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BACKGROUND: Identifying symptom clusters in Long COVID is necessary for developing effective therapies for this diverse condition and improving the quality of life of those affected by this heterogeneous condition. In this study, we aimed to identify and compare symptom clusters at 9 and 12 months after a SARS-CoV-2 positive test and describe each cluster regarding factors at infection. METHODS: This is a cross-sectional study with individuals randomly selected from the Portuguese National System of Epidemiological Surveillance (SINAVE) database. Individuals who had a positive RT-PCR SARS-CoV-2 test in August 2022 were contacted to participate in a telephonic interview approximately 9 and 12 months after the test. A hierarchical clustering analysis was performed, using Euclidean distance and Ward's linkage. Clustering was performed in the 35 symptoms reported 9 and 12 months after the SARS-CoV-2 positive test and characterised considering age, sex, pre-existing health conditions and symptoms at time of SARS-CoV-2 infection. RESULTS: 552 individuals were included at 9 months and 458 at 12 months. The median age was 52 years (IQR: 40-64 years) and 59% were female. Hypertension and high cholesterol were the most frequently reported pre-existing health conditions. Memory loss, fatigue or weakness and joint pain were the most frequent symptoms reported 9 and 12 months after the positive test. Four clusters were identified at both times: no or minor symptoms; multi-symptoms; joint pain; and neurocognitive-related symptoms. Clusters remained similar in both times, but, within the neurocognitive cluster, memory loss and concentration issues increased in frequency at 12 months. Multi-symptoms cluster had older people, more females and more pre-existing health conditions at 9 months. However, at 12 months, older people and those with more pre-existing health conditions were in joint pain cluster. CONCLUSIONS: Our results suggest that Long COVID is not the same for everyone. In our study, clusters remained similar at 9 and 12 months, except for a slight variation in the frequency of symptoms that composed each cluster. Understanding Long COVID clusters might help identify treatments for this condition. However, further validation of the observed clusters and analysis of its risk factors is needed.

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Background: Children can develop Long Covid, however long term outcomes and their predictors are poorly described in these patients. The primary aim is to describe characteristics and predictors of Long Covid in children assessed in-clinics up to 36 months post-SARS-CoV-2 infection, as well as investigate the role of vaccines in preventing Long Covid, risk of reinfections and development of autoimmune diseases. Methods: Children aged 0-18 years old with confirmed SARS-CoV-2 infection were invited for a prospective follow-up assessment at a peadiatric post-covid clinic in Rome, Italy, at serial intervals (3-, 6-, 12-, 18-, 24- and 36-months post-infection onset, between 01/02/2020 and 28/02/2024). Long Covid was defined as persistence of otherwise unexplained symptoms for at least three months after initial infection. Findings: 1319 patients were initially included, 1296 reached the 3 months follow-up or more. Of the patients who underwent multiple follow-ups, 23.2% (301), 169 (13.2%), 89 (7.9%), 67 (6.1%), 47 (7.1%) were diagnosed with Long Covid at 3-6-12-18-24 months, respectively For the primary outcome of Long Covid at three months, age >12 years (P < 0.001, OR 11.33, 95% CI 4.2; 15.15), comorbidities (P = 0.008, OR 1.83, 95% CI 1.06; 2.44), being infected with original variants (P < 0.001, OR 4.77, 95% CI 2.46; 14.47), female sex (P < 0.001, OR 1.62, 95% CI 1.02; 1.89) were statistically significant risk factors. Age >12 years (P = 0.002, OR 9.37, 95% CI 1.58; 8.64), and infection with original (P = 0.012, OR 3.52, 95% CI 1.32; 8.64) and alfa (P < 0.001, OR 4.09, 95% CI 2.01; 8.3) SARS-CoV-2 variants remained statistically significant risk factors for Long Covid duration for at least 18 months. Vaccination was associated with a lower risk of long covid at 3, 6 and 12 months for older children and a lower risk of reinfections. Being infected with the original SARS-CoV-2 variant was associated with a higher risk of new-onset autoimmune diseases ((P = 0.035, 95% CI 1.12; 2.4). One patient was diagnosed with Long Covid after a re-infection. Interpretation: This is the longest follow-up study of children with SARS-CoV-2 infection, showing a significant and long-lasting burden of Long Covid in the pediatric population. Our findings highlight the urgent need of investing in pediatric Long Covid in order to find effective diagnostic and therapeutic approaches, as well can inform preventive strategies in case of future pandemics. Funding: This study has been funde by Pfizer non-competitive grant, granted to DB (#65925795).

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Background: Experts estimate that in up to 10% of the infected, SARS-CoV-2 would cause persistent symptoms, activity limitations and reduced quality of life. Referred to as long COVID, these conditions might, in the future, specifically impact German-speaking countries due to their higher rates of unvaccinated people compared to other Western countries. Accurate measurement of symptom burden and its consequences is needed to manage conditions such as long COVID, and several tools have been developed to do so. However, no patient-reported instrument existed in the German language at the time of writing. Objective: This study, therefore, aimed to develop a German version of the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS). Methods: We conducted a translation and qualitative evaluation, including cultural adaptation, of the C19-YRS and assessed its face validity. After creating a preliminary version, 26 individuals (14 women [53%]) participated in cognitive interviews (January 2022 to March 2022). Using cognitive debriefing interviews, we ensured the content's comprehensibility. The matrix-framework method guided the qualitative data analysis. Results: Compared to the original English version, adaptations were necessary, resulting in changes to the introductory text, while the items for recording persistent symptoms were hardly changed. Conclusion: The German version of the C19-YRS is expected to support standardized long COVID care.

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Long COVID (LC) refers to a condition characterized by a variety of lingering symptoms that persist for more than 4 to 12 weeks following the initial acute SARS-CoV-2 infection. Recent research has suggested that the FOXP4 gene could potentially be a significant factor contributing to LC. Owing to that, this study investigates FOXP4's role in LC by analyzing public datasets to understand its evolution and expression in diverse human populations and searching for drugs to reduce LC symptoms. Population genetic analysis of FOXP4 across human populations unmasks distinct genetic diversity patterns and positive selection signatures, suggesting potential population-specific susceptibilities to conditions like LC. Further, we also observed that FOXP4 experiences high expression during LC. To identify potential inhibitors, drug screening analysis identifies synthetic drugs like Glisoxepide, and natural compounds Kapurimycin A3 produced from Streptomyces sp, and Cucurbitacin B from Begonia nantoensis as promising candidates. Overall, our research contributes to understanding how FOXP4 may serve as a therapeutic target for mitigating the impact of LC.

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BACKGROUND: During the COVID-19 pandemic sex-related differences concerning the spectrum of cardiovascular complications have been observed in the acute infection, and during recovery. This study aims to emphasize sex-related disparities regarding left ventricular systolic function (LVSF), right ventricular function (RVF), diastolic dysfunction (DD), and pericardial pathologies during the post-COVID-19 syndrome. METHODS: 274 patients with post-acute COVID-19 syndrome, 127 men and 147 women, aged under 55, were evaluated within 90 days after the acute illness and followed at 3 and 6 months. RESULTS: Based on detailed transthoracic echocardiography (TTE), we identified significantly more frequently (p˂0.001) altered LVSF in men, while in women impaired RVF, and DD were significantly more common (p˂0.001). Pericardial impairment did not seem to be influenced by gender. The TTE parameters characterizing these patterns were correlated with the severity of the initial infection and the time elapsed since and alleviated in time. The multivariate regression analysis confirmed these sex-related associations and their impact on patients' functional status. CONCLUSIONS: Male patients had a higher tendency to develop altered LVSF, while female subjects had more frequently impaired RVF and DD. These abnormalities alleviated in time and exerted a significant influence on patients' functional status.

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BACKGROUND: The pathophysiological mechanisms underlying the post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) are not well understood. Our study aimed to investigate various aspects of theses mechanisms, including viral persistence, immunological responses, and laboratory parameters in patients with and without PASC. METHODS: We prospectively enrolled adults aged ≥ 18 years diagnosed with coronavirus disease 2019 (COVID-19) between August 2022 and July 2023. Blood samples were collected at three time-points: within one month of diagnosis (acute phase) and at 1 month, and 3 months post-diagnosis. Following a recent well-designed definition of PASC, PASC patients were defined as those with a questionnaire-based PASC score ≥ 12 persisting for at least 4 weeks after the initial COVID-19 diagnosis. RESULTS: Of 57 eligible COVID-19 patients, 29 (51%) had PASC, and 28 (49%) did not. The PASC group had significantly higher nucleocapsid protein (NP) antigenemia 3 months after COVID-19 diagnosis (P = 0.022). Furthermore, several cytokines, including IL-2, IL-17A, VEGF, RANTES, sCD40L, IP-10, I-TAC, and granzyme A, were markedly elevated in the PASC group 1 and/or 3 month(s) after COVID-19 diagnosis. In contrast, the median values of several serological markers, including thyroid markers, autoimmune indicators, and stress-related hormones, were within the normal range. CONCLUSION: Levels of NP antigen and of various cytokines involved in immune responses become significantly elevated over time after COVID-19 diagnosis in PASC patients compared to non-PASC patients. This suggests that PASC is associated with prolonged immune dysregulation resulting from heightened antigenic stimulation.

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Background: As the world population recovers from the COVID-19 infection, a series of acute sequelae emerge including new incident diabetes. However, the association between COVID-19 infection and new incident diabetes is not fully understood. We purpose to determine the risk of new incident diabetes after COVID-19 infection. Methods: PubMed, Embase, and Cochrane Library were used as databases to search for cohort studies published from database inception to February 4, 2024. Two reviewers independently conducted the study screening, data extraction, and risk of bias assessment. A random-effects model was adopted to pool the hazard ratio (HR) with corresponding 95% confidence intervals (CI). Subgroup analysis was conducted to explore the potential influencing factors. Results: A total of 20 cohort studies with over 60 million individuals were included. The pooling analysis illustrates the association between COVID-19 infection and an increased risk of new incident diabetes (HR = 1.46; 95% CI: 1.38-1.55). In subgroup analysis, the risk of type 1 diabetes was HR=1.44 (95% CI: 1.13-1.82), and type 2 diabetes was HR=1.47 (95% CI: 1.36-1.59). A slightly higher risk of diabetes was found in males (HR=1.37; 95% CI: 1.30-1.45) than in females (HR=1.29; 95% CI: 1.22-1.365). The risk of incident diabetes is associated with hospitalization: non-hospitalized patients have an HR of 1.16 (95% CI: 1.07-1.26), normal hospitalized patients have an HR of 2.15 (95% CI: 1.33-3.49), and patients receiving intensive care have the highest HR of 2.88 (95% CI: 1.73-4.79). Conclusions: COVID-19 infection is associated with an elevated risk of new incident diabetes. Patients ever infected with COVID-19 should be recognized as a high-risk population with diabetes. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42024522050.

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BACKGROUND: Following the initial acute phase of COVID-19, health care resource use has escalated among individuals with SARS-CoV-2 infection. OBJECTIVE: This study aimed to compare new diagnoses of long COVID and the demand for health services in the general population after the Omicron wave with those observed during the pre-Omicron waves, using similar assessment protocols for both periods and to analyze the influence of vaccination. METHODS: This matched retrospective case-control study included patients of both sexes diagnosed with acute SARS-CoV-2 infection using reverse transcription polymerase chain reaction or antigen tests in the hospital microbiology laboratory during the pandemic period regardless of whether the patients were hospitalized. We included patients of all ages from 2 health care departments that cover 604,000 subjects. The population was stratified into 2 groups, youths (<18 years) and adults (≥18 years). Patients were followed-up for 6 months after SARS-CoV-2 infection. Previous vaccination, new diagnoses, and the use of health care resources were recorded. Patients were compared with controls selected using a prospective score matched for age, sex, and the Charlson index. RESULTS: A total of 41,577 patients with a history of prior COVID-19 infection were included, alongside an equivalent number of controls. This cohort encompassed 33,249 (80%) adults aged ≥18 years and 8328 (20%) youths aged <18 years. Our analysis identified 40 new diagnoses during the observation period. The incidence rate per 100 patients over a 6-month period was 27.2 for vaccinated and 25.1 for unvaccinated adults (P=.09), while among youths, the corresponding rates were 25.7 for vaccinated and 36.7 for unvaccinated individuals (P<.001). Overall, the incidence of new diagnoses was notably higher in patients compared to matched controls. Additionally, vaccinated patients exhibited a reduced incidence of new diagnoses, particularly among women (P<.001) and younger patients (P<.001) irrespective of the number of vaccine doses administered and the duration since the last dose. Furthermore, an increase in the use of health care resources was observed in both adult and youth groups, albeit with lower figures noted in vaccinated individuals. In the comparative analysis between the pre-Omicron and Omicron waves, the incidence of new diagnoses was higher in the former; however, distinct patterns of diagnosis were evident. Specifically, depressed mood (P=.03), anosmia (P=.003), hair loss (P<.001), dyspnea (<0.001), chest pain (P=.04), dysmenorrhea (P<.001), myalgia (P=.011), weakness (P<.001), and tachycardia (P=.015) were more common in the pre-Omicron period. Similarly, health care resource use, encompassing primary care, specialist, and emergency services, was more pronounced in the pre-Omicron wave. CONCLUSIONS: The rise in new diagnoses following SARS-CoV-2 infection warrants attention due to its potential implications for health systems, which may necessitate the allocation of supplementary resources. The absence of vaccination protection presents a challenge to the health care system.

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BACKGROUND: More than four years after the start of the COVID-19 pandemic, understanding of SARS-CoV-2 burden and post-acute sequela of COVID (PASC), or long COVID, continues to evolve. However, prevalence estimates are disparate and uncertain. Leveraging survey responses from a large serosurveillance study, we assess prevalence estimates using five different long COVID definitions among California residents. METHODS: The California Department of Public Health (CDPH) conducted a cross-sectional survey that included questions about acute COVID-19 infection and recovery. A random selection of California households was invited to participate in a survey that included demographic information, clinical symptoms, and COVID-19 vaccination history. We assessed prevalence and predictors of long COVID among those previously testing positive for SARS-CoV-2 across different definitions using logistic regression. FINDINGS: A total of 2883 participants were included in this analysis; the majority identified as female (62.5 %), and the median age was 39 years (interquartile range: 17-55 years). We found a significant difference in long COVID prevalence across definitions with the highest prevalence observed when participants were asked about incomplete recovery (20.9 %, 95 % confidence interval [CI]: 19.4-22.5) and the lowest prevalence was associated with severe long COVID affecting an estimated 4.9 % (95 % CI 4.1-5.7) of the participant population. Individuals that completed the primary vaccination series had significantly lower prevalence of long COVID compared to those that did not receive COVID vaccination. INTERPRETATION: There were significant differences in the estimated prevalence of long COVID across different definitions. People who experience a severe initial COVID-19 infection should be considered at a higher probability for developing long COVID. FUNDING: Centers for Disease Control and Prevention - Epidemiology and Laboratory Capacity.

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BACKGROUND: Digital interventions are expected to facilitate the treatment of patients suffering from Long COVID. This trial assesses the effectiveness of a multimodal rehabilitation program -comprising both online and synchronous components- in managing the characteristic symptoms of Long COVID and, consequently, in improving quality of life. It also aims to identify which changes in measured variables from baseline (T0) to post-intervention (T1) predict an improvement in quality of life. METHODS: A blind randomized controlled trial was conducted with two parallel groups: (1) the control group, which received usual treatment from the primary care physician and (2) the intervention group, which received usual treatment in addition to an online multimodal rehabilitation program. The data were collected at two time points: prior to the start of the intervention and three months after it. The main outcome variable was quality of life, encompassing both mental health and physical health-related quality of life. Sociodemographic and clinical variables were collected as secondary variables. RESULTS: A total of 134 participants (age 48.97 ± 7.64; 84.33% female) were included and randomized into the control group (67 participants) and the intervention group (67 participants). Comparative analyses conducted before and after the intervention showed a significant improvement in the mental health-related quality of life of the participants who received the intervention, with a mean increase of 1.98 points (p < 0.05). Linear regression analyses revealed that both received the intervention (b = 3.193; p < 0.05) and an increased self-efficacy (b = 0.298; p < 0.05) were predictors of greater improvement in mental health-related quality of life.