Factors Associated With Persisting Olfactory Dysfunction After COVID-19.

BACKGROUND: Fortunately, the majority of COVID-19 patients recover from olfactory dysfunction (OD) within the first couple of weeks. However, from approximately 5% up to 20% continue to suffer from OD even more than 1 year after the onset. Nonetheless, factors associated with long-lasting OD are hardly known. The aim of this study was to identify favourable and disadvantageous markers of persisting OD in COVID-19 patients. METHODOLOGY: Sixty-six patients (46 female; mean age: 39.9 years) that suffer from OD longer than 6 months due to laboratory-confirmed SARS-CoV-2 infection have participated in this longitudinal study. Participants completed comprehensive psychophysical chemosensory tests (i.e., Sniffin' Sticks = TDI) and questionnaires twice at our department-on average 219 ± 80 (T-1) and 489 ± 89 (T-2) days after the onset of symptoms, respectively. Olfactory recovery rates were associated with demographic factors and questionnaires using linear regression analysis. RESULTS: Patients below 40 years of age improved better (TDI: 4.1 ± 4.3 vs. 0.7 ± 5.8; p = 0.008) and achieved statistically significant higher scores (TDI: 31.5 ± 4.0 vs. 27.3 ± 6.7; p = 0.033) regarding psychophysical chemosensory tests. Furthermore, linear regression analysis revealed that parosmia was associated with worse orthonasal smell function (T-1: ß = -0.346, p = 0.004; T-2: ß = -0.384, p = 0.001), especially concerning identification subtest (T-1: ß = -0.395, p = 0.001; T-2: ß = -0.398, p < 0.001). Moreover, increasing parosmia between T-1and T-2 led to worse orthonasal olfactory function (ß = -0.294, p = 0.016). CONCLUSIONS: Older age and parosmia seem to be unfavourable factors of persisting OD in COVID-19 patients.

Risk factors for post-coronavirus disease condition in the Alpha-, Delta-, and Omicron-dominant waves among adults in Japan: A population-based matched case-control study.

Vaccination is associated with a reduced risk of post-coronavirus disease (COVID-19) condition (PCC). Here, risk factors including vaccination for PCC in the Omicron-dominant waves among Japanese adults were investigated. This was a registry-based matched case-control study of individuals aged 18-79 years diagnosed with COVID-19 registered in a National database between March 2021 and April 2022 and matched noninfected individuals living in Yao City, Japan. A self-administered questionnaire was used to assess persistent symptoms and their risk factors. The COVID-19 vaccination status was obtained from the Vaccination Registry. PCC risk factors were analyzed using logistic regression after adjusting for potential confounding factors. Overall, 4185 infected (cases) and 3382 noninfected (controls) individuals were included in the analysis. The mean ages and proportions of women were 44.7 years and 60.2% and 45.5 years and 60.7% for cases and controls, respectively. A total of 3805 (90.9%) participants had asymptomatic or mild acute symptoms at the median (range) follow-up of 271 (185-605) days. The prevalence of PCC was 15.0% for cases while that of persistent symptoms was 4.4% for controls; among the cases, it was 27.0% in the Alpha- and Delta-dominant waves and 12.8% in the Omicron-dominant wave. Female sex, comorbidities, and hospitalization were positively associated with PCC. One or more vaccine doses of vaccination were inversely associated with PCC; the inverse association was stronger in the Alpha- and Delta-dominant waves (adjusted odds ratio [aOR]: 0.29, 95% confidence interval [CI]: 0.12-0.73) than in the Omicron-dominant wave (aOR: 0.79, 95% CI: 0.59-1.07).

Prevalence of symptoms of post-COVID-19 condition (long COVID) in children hospitalized with COVID-19: A systematic review of observational studies.

This systematic review aimed to investigate the prevalence of symptoms of post-COVID-19 condition (long COVID), in children hospitalized with COVID-19. We searched PUBMED and EMBASE on 15 March, 2023, using search strategy: "long COVID" OR "post-COVID-19" OR "postacute COVID-19" OR "long-term COVID" OR "COVID-19 sequelae" OR "persistent COVID-19" OR "chronic COVID-19". We included observational studies (case-control, cross-sectional, cohort, or case series) that investigated symptoms of post-COVID-19 condition (long COVID) in children (<18 years) admitted with COVID-19. We used the WHO case definition of post-COVID-19 condition. Long COVID was defined as persistence of otherwise unexplained symptoms for at least three months after SARS-CoV-2 infection. We used the command "metaprop" to perform random-effects meta-analysis. Eleven studies involving 2279 patients were included. In the period between ≥3 months and <12 months after acute COVID-19, the most frequent symptom was exercise intolerance with a pooled prevalence of 29% (95% CI: 7%-57%, I2 = 95%), followed by nonspecific respiratory symptoms (12%, 95% CI: 0%-48%, I2 = 0%), psychological disorders (10%, 95% CI: 1%-25%, I2 = 97%), and nonspecific gastrointestinal symptoms (10%, 95% CI: 0%-37%, I2 = 99%). In the period ≥12 months after the initial infection, the pooled prevalence of post COVID symptoms was lower, with 6% (95% CI: 2%-10%, I2 = 83%) for exercise intolerance and 3% (95% CI: 0%-8%, I2 = 89%) for fatigue. In conclusion, symptoms of post-COVID condition (long COVID) in hospitalized children affect multiple organ systems, with higher prevalence in the period up to 12 months after the acute phase of COVID-19.

Global Challenges After a Global Challenge: Lessons Learned from the COVID-19 Pandemic.

Coronavirus disease 2019 (COVID-19) has affected not only individual lives but also the world and global systems, both natural and human-made. Besides millions of deaths and environmental challenges, the rapid spread of the infection and its very high socioeconomic impact have affected healthcare, economic status and wealth, and mental health across the globe. To better appreciate the pandemic's influence, multidisciplinary and interdisciplinary approaches are needed. In this chapter, world-leading scientists from different backgrounds share collectively their views about the pandemic's footprint and discuss challenges that face the international community.

Addressing Long COVID Sequelae and Neurocovid: Neuropsychological Scenarios and Neuroimaging Findings.

In the face of increasing reports of CNS involvement in COVID-19 cases, it is likely that the current epidemic may be accompanied by a significant increase in the prevalence of neurological sequelae, cognitive dysfunction, and long-term behavioural alterations affecting quality of life and autonomy in daily life. This is consequential to the neuroinvasion and multi-organ dysfunction, but also to the psychological distress and socioeconomic changes that occur. Long COVID and neurocovid are now an established concept worldwide. However, the clinical features of these two entities are still debated. The chapter provides information about the nosographic framing, associated pathophysiological mechanisms, alterations in the central and peripheral nervous systems, and the associated neurocognitive profile, indications about predictor and clinical evaluation according to a patient-centred multidimensional immuno-behavioural approach.

Association of COVID-19 Vaccination With Risk of Medically Attended Postacute Sequelae of COVID-19 During the Ancestral, Alpha, Delta, and Omicron Variant Eras.

Background: Uncertainty exists regarding the effectiveness of COVID-19 vaccine to prevent postacute sequelae of COVID-19 (PASC) following a breakthrough infection. While most studies based on symptom surveys found an association between preinfection vaccination status and PASC symptoms, studies of medically attended PASC are less common and have reported conflicting findings. Methods: In this retrospective cohort of patients with an initial SARS-CoV-2 infection who were continually empaneled for primary care in a large US health system, the electronic health record was queried for preinfection vaccination status, demographics, comorbidity index, and diagnosed conditions. Multivariable logistic regression was used to model the outcome of a medically attended PASC diagnosis within 6 months of SARS-CoV-2 infection. Likelihood ratio tests were used to assess the interaction between vaccination status and prevalent variant at the time of infection and between vaccination status and hospitalization for SARS-CoV-2 infection. Results: During the observation period, 6.9% of patients experienced medically attended and diagnosed PASC. A diagnosis of PASC was associated with older age, female sex, hospitalization for the initial infection, and an increased severity-weighted comorbidity index and was inversely associated with infection during the Omicron period. No difference in the development of diagnosed PASC was observed between unvaccinated patients and those vaccinated with either 2 doses of an mRNA vaccine or >2 doses. Conclusions: We found no association between vaccination status at the time of infection and development of medically diagnosed PASC. Vaccine remains an important measure to prevent SARS-CoV-2 infection and severity. Further research is needed to identify effective measures to prevent and treat PASC.

Long COVID is not the same for everyone: a hierarchical cluster analysis of Long COVID symptoms 9 and 12 months after SARS-CoV-2 test.

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.

Effectiveness of an online multimodal rehabilitation program in long COVID patients: a randomized clinical trial.

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.

Deciphering the role of FOXP4 in long COVID: exploring genetic associations, evolutionary conservation, and drug identification through bioinformatics analysis.

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.

Prevalence and risk factors of long COVID among maintenance hemodialysis patients post SARS-CoV-2 infection: A one-year follow-up study in China.

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.

Long COVID and hypermobility spectrum disorders have shared pathophysiology.

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.

Neurological long-COVID: Associations among fatigue, dysautonomia, depression, and subjective memory complaints.

INTRODUCTION: Long-COVID is a multisystem disease characterized by a varied presentation of symptoms. According to most recent research, the most common symptom of long-COVID is fatigue, which up to this date lacks a universally accepted definition. This study aimed to investigate neurocognitive and physical manifestations of neurological long-COVID, particularly fatigue and its relation with autonomic disfunction, cognitive impairment (known as, brain fog), and depressive symptoms. Furthermore, the study provided insights into predictors of fatigue in long-COVID. METHODS: The included patients (n=141) were referred to the neuro-long-COVID ambulatory service of Trieste from 30 September 2021-02 March 2022. Patients were given self-reporting questionnaires to screen for fatigue, autonomic dysfunction, cognitive impairment and depressive symptoms. The questionnaires adopted for these conditions to be assessed were Fatigue Severity Scale (FSS), COMPASS-31, Prospective-Retrospective Memory Questionnaire (PRMQ), and Beck Depression Inventory (BDI). Participants were divided into two groups, fatigued and non-fatigued patients, based on FSS scoring (scores > 4.67 indicate fatigued patients). The questionnaire scores of the two groups were then compared. RESULTS: Fatigued patients had significantly higher scores in COMPASS (p<0.001, Cohen's d=1.077), BDI (p<0.001, Cohen's d=0.862), and PRMQ ( p<0.001, Cohen's d=1.159). Furthermore, the multivariate regression analysis showed that predictors of fatigue in long-COVID were symptomatological burden in acute infection (OR=1.38, 95 % CI 1.020-1.887, p=0.037) and in long-COVID (OR=1.78, 95 % CI 1.133-2.2824, p=0.013), COMPASS-31>16 (OR=3.44, 95 % CI 1240-9.560, p=0.018) and BDI>15 (OR=5.1, 95 % CI 1.715-15.164, p=0.003). CONCLUSION: This study showed associations between fatigue, dysautonomia and depression, as well as with symptom burden in acute and long-COVID.

Chest CT Airway and Vascular Measurements in Females with COPD or Long-COVID.

Chest CT provides a way to quantify pulmonary airway and vascular tree measurements. In patients with COPD, CT airway measurement differences in females are concomitant with worse quality-of-life and other outcomes. CT total airway count (TAC), airway lumen area (LA), and wall thickness (WT) also differ in females with long-COVID. Our objective was to evaluate CT airway and pulmonary vascular and quality-of-life measurements in females with COPD as compared to ex-smokers and patients with long-COVID. Chest CT was acquired 3-months post-COVID-19 infection in females with long-COVID for comparison with the same inspiratory CT in female ex-smokers and COPD patients. TAC, LA, WT, and pulmonary vascular measurements were quantified. Linear regression models were adjusted for confounders including age, height, body-mass-index, lung volume, pack-years and asthma diagnosis. Twenty-one females (53 ± 14 years) with long-COVID, 17 female ex-smokers (69 ± 9 years) and 13 female COPD (67 ± 6 years) patients were evaluated. In the absence of differences in quality-of-life scores, females with long-COVID reported significantly different LA (p = 0.006) compared to ex-smokers but not COPD (p = 0.7); WT% was also different compared to COPD (p = 0.009) but not ex-smokers (p = 0.5). In addition, there was significantly greater pulmonary small vessel volume (BV5) in long-COVID as compared to female ex-smokers (p = 0.045) and COPD (p = 0.003) patients and different large (BV10) vessel volume as compared to COPD (p = 0.03). In females with long-COVID and highly abnormal quality-of-life scores, there was CT evidence of airway remodelling, similar to ex-smokers and patients with COPD, but there was no evidence of pulmonary vascular remodelling.Clinical Trial Registration: www.clinicaltrials.gov NCT05014516 and NCT02279329.

Autonomic Imbalance and Elevated Inflammatory Cytokines in Long COVID: A Cross-Sectional Study.

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.

Advance in the mechanism and clinical research of myalgia in long COVID.

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, mortality rates of coronavirus disease 2019 (COVID-19) have significantly decreased. However, a variable proportion of patients exhibit persistent prolonged symptoms of COVID-19 infection (long COVID). This virus primarily attacks respiratory system, but numerous individuals complain persistent skeletal muscle pain or worsening pre-existing muscle pain post COVID-19, which severely affects the quality of life and recovery. Currently, there is limited research on the skeletal muscle pain in long COVID. In this brief review, we review potential pathological mechanisms of skeletal muscle pain in long COVID, and summarize the various auxiliary examinations and treatments for skeletal muscle pain in long COVID. We consider abnormal activation of inflammatory response, myopathy, and neurological damages as pivotal pathological mechanisms of skeletal muscle pain in long COVID. A comprehensive examination is significantly important in order to work out effective treatment plans and relieve skeletal muscle pain. So far, rehabilitation interventions for myalgia in long COVID contain but are not limited to drug, nutraceutical therapy, gut microbiome-targeted therapy, interventional therapy and strength training. Our study provides a potential mechanism reference for clinical researches, highlighting the importance of comprehensive approach and management of skeletal muscle pain in long COVID. The relief of skeletal muscle pain will accelerate rehabilitation process, improve activities of daily living and enhance the quality of life, promoting individuals return to society with profound significance.

A Mixed Methods Analysis of Long COVID Symptoms in Black Americans: Examining Physical and Mental Health Outcomes.

BACKGROUND: While several reports confirm that long COVID is associated with poorer health, few studies explore how long COVID directly impacts the lives of Black Americans who experienced higher mortality rates early in the pandemic. Even fewer studies utilize both quantitative and qualitative methods to identify pertinent long COVID symptoms. The current study, therefore, sought to identify points of overlap and divergence when comparing qualitative vs. quantitative descriptions of long COVID experiences among Black adults in the United States. METHODS: We analyzed cross-sectional surveys collected from the AmeriSpeak panel through the National Opinion Research Center (NORC) at the University of Chicago. This panel includes a probability-based sample of adults across the United States. Respondents completed online surveys between April and June 2022. We compared outcomes among participants who reported experiencing post-acute sequelae of COVID-19 (i.e., long COVID) to those who reported experiencing SARS-CoV-2 without long COVID. RESULTS: Nearly all qualitative responses focused on matters of physical health like prolonged coughing, cardiovascular concerns, troubled breathing, fatigue, headaches, memory loss, and bodily pains. Quantitative results, however, showed that Black adults living with long COVID reported significantly more anxiety, depressive symptoms, and hopelessness. Persons with long COVID were also significantly more likely to report experiencing psychosis, suicidal ideation, suicide plans, and suicide attempts within the last year. CONCLUSIONS: Black adults with long COVID experienced worse outcomes across all mental health measures. Despite the COVID-19 Public Health Emergency expiration in May 2023, urgent efforts are still required to not only treat both the physical and mental health needs of persons living with long COVID, but to effectively prevent the spread and transmission of COVID-19.

Follow-up assessment of the microvascular function in patients with long COVID.

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.

Characteristics and predictors of Long Covid in children: a 3-year prospective cohort study.

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).

Translation and cultural adaptation of the COVID-19 Yorkshire Rehabilitation Scale into German.

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.

Increased luminal area of large conducting airways in patients with COVID-19 and post-acute sequelae of COVID-19: A retrospective case-control study.

Coronavirus disease 2019 (COVID-19) is associated with enlarged luminal areas of large conducting airways. In 10-30% of patients with acute COVID-19 infection, symptoms persist for more than 4 weeks (referred to as post-acute sequelae of COVID 19, or PASC), and it is unknown if airway changes are associated with this persistence. Thus, we aim to investigate if luminal area of large conducting airways is different between PASC and COVID-19 patients, and healthy controls. In this retrospective case-control study 75 patients with PASC (48 females) were age-, height-, and sex-matched to 75 individuals with COVID-19 and 75 healthy controls. Using three-dimensional digital reconstruction from computed tomography imaging, we measured luminal areas of seven conducting airways, including trachea, right and left main bronchi, bronchus intermediate, right and left upper lobe, and left lower lobe bronchi. Kruskal-Wallis H test was used to compare measurements between the three groups, as appropriate. Airway luminal areas between COVID-19 and PASC groups were not different (p>0.66). There were no group differences in airway luminal area (PASC vs. control) for trachea and right main bronchus. However, in the remaining five airways, airway luminal areas were 12% to 39% larger among PASC patients compared to controls (all, p<0.05). Patients diagnosed with COVID-19 and PASC have greater airway luminal area in most large conducting airways compared to healthy controls. No differences in luminal area between patients with COVID-19 and PASC suggest persistence of changes or insufficient time for reversal of changes.