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(1) With persistent symptoms emerging as a possible global consequence of COVID-19, the need to understand, diagnose, and treat them is paramount. This systematic review aims to explore the potential of optical coherence tomography (OCT) and/or optical coherence tomography angiography (OCTA) in effectively diagnosing long COVID. (2) The database PubMed and, to reduce selection bias, the AI research assistant Elicit, were used to find relevant publications in the period between February 2021 and March 2024. Included publications on OCT and OCTA analysis of participants with acute COVID symptoms, those after recovery, and participants with long COVID symptoms were organized in a table. Studies with participants under the age of 18, case reports, and unrelated studies, such as pure slit-lamp examinations and subgroup analyses were excluded. (3) A total of 25 studies involving 1243 participants and 960 controls were reviewed, revealing several changes in the posterior eye. Long COVID participants displayed significant thinning in retinal layers in the OCT, including the macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL). Divergent findings in recovered cohorts featured mRNFL reduction, GCL increase and decrease, and GCL-IPL decrease. Long COVID OCTA results revealed reduced vessel density (VD) in the superficial capillary plexus (SCP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). In recovered patients, SCP consistently showed a reduction, and DCP exhibited a decrease in five out of six publications. The foveal avascular zone (FAZ) was enlarged in five out of nine publications in recovered participants. (4) During various stages of COVID-19, retinal changes were observed, but a comparison between long COVID and recovered cohorts was aggravated by diverse inclusion and exclusion criteria as well as small sample sizes. Changes in long COVID were seen in most OCT examinations as thinning or partial thinning of certain retinal layers, while in OCTA a consistently reduced vessel density was revealed. The results suggest retinal alterations after COVID that are variable in OCT and more reliably visible in OCTA. Further research with larger samples is important for advancing long COVID diagnosis and management. [ABSTRACT FROM AUTHOR]

Although the impact of post-acute COVID-19 syndrome (PACS) on patients and public health is undeniably significant, its etiology remains largely unclear. Much research has been conducted on the pathophysiology, shedding light on various aspects; however, due to the multitude of symptoms and clinical conditions that directly or indirectly define PACS, it is challenging to establish definitive causations. In this exploration, through systematically reviewing the latest pathophysiological findings related to the neurological symptoms of the syndrome, we aim to examine how psychosocial and neuropsychological symptoms may overlap with neurological ones, and how they may not only serve as risk factors but also contribute to the persistence of some primary symptoms of the disorder. Findings from our synthesis suggest that psychological and psychosocial factors, such as anxiety, depression, and loneliness, may interact with neurological symptoms in a self-reinforcing feedback loop. This cycle seems to be affecting both physical and psychological distress, potentially increasing the persistence and severity of PACS symptoms. By pointing out this interaction, in this review study, we attempt to offer a new perspective on the interconnected nature of psychological, psychosocial, and neurological factors, emphasizing the importance of integrated treatment approaches to disrupt this cycle and improve outcomes when possible. [ABSTRACT FROM AUTHOR]

This article explores the demand and utilization of a rural post-acute COVID syndrome clinic. Electronic health records were used to identify referrals between April 2021 and April 2022 and to describe characteristics of referred patients and referrals generated to specialty services. Of the 747 referrals received, 363 (48.6%) met the criteria for an appointment and were seen, the vast majority (89.6%) via Telehealth. Most patients resided in rural communities (63.1%) and were female (75.2%); mean age was 49, and 17% were hospitalized during their acute illness. Nearly half of patients (49%) had at least one pre-existing mental health diagnosis. Referrals to specialty care for further evaluation and/or intervention were most commonly to occupational therapy (27.3%), physical therapy (24.8%), psychiatry (19.8%), and neurology (17%). Telehealth expanded the availability of health care resources. Additional research on how to meet care needs, ameliorate symptoms, and aid recovery in rural communities is warranted. [ABSTRACT FROM AUTHOR]

According to the World Health Organization-led Delphi consensus, long COVID corresponds to the occurrence of symptoms beyond twelve weeks after the onset of acute COVID-19 illness that cannot be explained by alternate diagnosis. This cross-sectional study aimed to analyse the impacts of long COVID on general health and psychosocial well-being. For this study, the participants were interviewed either face to face or via telephone, and their responses were recorded on a questionnaire capturing information on demographics, COVID-19 status, duration of symptoms and long COVID symptoms. The psychosocial impacts of the pandemic were assessed using scales like Short Mood and feeling questionnaire (sMFQ), Warwick-Edinburgh Mental Well-being Scale (WEMWBS), Generalized Anxiety Disorder Assessment (GAD-7) and Perceived Stress Scale (PSS). Regression analysis was conducted to analyse the predictors of long COVID. A total of 300 participants were interviewed, of which 155 (52%) had COVID-19 illness. Of these 54 (35%) had persistent symptoms for a period of more than 12 weeks classified as long COVID. Muscle problems and fatigue were the most frequent (14.7%) symptoms encountered, followed by breathing problems (12.6%) and cognitive issues (12.6%). The symptoms of decrease in appetite and confusion or disorientation during the initial phase of the infection were associated with long COVID. The majority of the participants (83.3%) had moderate level of perceived stress, while moderate to severe levels of stress were observed in 17.3% of the individuals. Moreover, a high level of positive mental well-being was also observed. This study highlights the need for further research into the clinical aspects and implications of long COVID in Pakistan and emphasizes the importance of ongoing support for affected individuals. [ABSTRACT FROM AUTHOR]

The underlying pathogenesis of neurological sequelae in post-COVID-19 patients remains unclear. Here, we used multidimensional spatial immune phenotyping and machine learning methods on brains from initial COVID-19 survivors to identify the biological correlate associated with previous SARS-CoV-2 challenge. Compared to healthy controls, individuals with post-COVID-19 revealed a high percentage of TMEM119+P2RY12+CD68+Iba1+HLA-DR+CD11c+SCAMP2+ microglia assembled in prototypical cellular nodules. In contrast to acute SARS-CoV-2 cases, the frequency of CD8+ parenchymal T cells was reduced, suggesting an immune shift toward innate immune activation that may contribute to neurological alterations in post-COVID-19 patients. [ABSTRACT FROM AUTHOR]

Reduced lymphocyte counts in peripheral blood are one of the most common observations in acute phases of viral infections. Although many studies have already examined the impact of immune (dys)regulation during SARS-CoV-2 infection, there are still uncertainties about the long-term consequences for lymphocyte homeostasis. Furthermore, as persistent cellular aberrations have been described following other viral infections, patients with "Post-COVID-19 Condition" (PCC) may present similarly. In order to investigate cellular changes in the adaptive immune system, we performed a retrospective analysis of flow cytometric data from lymphocyte subpopulations in 106 patients with confirmed SARS-CoV-2 infection who received medical care at our institution. The patients were divided into three groups according to the follow-up date; laboratory analyses of COVID-19 patients were compared with 28 unexposed healthy controls. Regarding B lymphocyte subsets, levels of IgA + CD27+, IgG + CD27+, IgM + CD27− and switched B cells were significantly reduced at the last follow-up compared to unexposed healthy controls (UHC). Of the 106 COVID-19 patients, 56 were clinically classified as featuring PCC. Significant differences between PCC and COVID-19 convalescents compared to UHC were observed in T helper cells and class-switched B cells. However, we did not detect specific or long-lasting immune cellular changes in PCC compared to the non-post-COVID-19 condition. [ABSTRACT FROM AUTHOR]

Although the impact of post-acute COVID-19 syndrome (PACS) on patients and public health is undeniably significant, its etiology remains largely unclear. Much research has been conducted on the pathophysiology, shedding light on various aspects; however, due to the multitude of symptoms and clinical conditions that directly or indirectly define PACS, it is challenging to establish definitive causations. In this exploration, through systematically reviewing the latest pathophysiological findings related to the neurological symptoms of the syndrome, we aim to examine how psychosocial and neuropsychological symptoms may overlap with neurological ones, and how they may not only serve as risk factors but also contribute to the persistence of some primary symptoms of the disorder. Findings from our synthesis suggest that psychological and psychosocial factors, such as anxiety, depression, and loneliness, may interact with neurological symptoms in a self-reinforcing feedback loop. This cycle seems to be affecting both physical and psychological distress, potentially increasing the persistence and severity of PACS symptoms. By pointing out this interaction, in this review study, we attempt to offer a new perspective on the interconnected nature of psychological, psychosocial, and neurological factors, emphasizing the importance of integrated treatment approaches to disrupt this cycle and improve outcomes when possible.

Intense investigation into the predictors and determinants of post-acute sequelae of SARS-CoV-2 infection (PASC), including 'long COVID', is underway. Recent studies provide clues to the mechanisms that might drive this condition, with the goal of identifying host or virus factors that can be intervened upon to prevent or reverse PASC.

Abstract Background Long COVID is a debilitating chronic condition that has affected over 100 million people globally. It is characterized by a diverse array of symptoms, including fatigue, cognitive dysfunction and respiratory problems. Studies have so far largely failed to identify genetic associations, the mechanisms behind the disease, or any common pathophysiology with other conditions such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) that present with similar symptoms. Methods We used a combinatorial analysis approach to identify combinations of genetic variants significantly associated with the development of long COVID and to examine the biological mechanisms underpinning its various symptoms. We compared two subpopulations of long COVID patients from Sano Genetics’ Long COVID GOLD study cohort, focusing on patients with severe or fatigue dominant phenotypes. We evaluated the genetic signatures previously identified in an ME/CFS population against this long COVID population to understand similarities with other fatigue disorders that may be triggered by a prior viral infection. Finally, we also compared the output of this long COVID analysis against known genetic associations in other chronic diseases, including a range of metabolic and neurological disorders, to understand the overlap of pathophysiological mechanisms. Results Combinatorial analysis identified 73 genes that were highly associated with at least one of the long COVID populations included in this analysis. Of these, 9 genes have prior associations with acute COVID-19, and 14 were differentially expressed in a transcriptomic analysis of long COVID patients. A pathway enrichment analysis revealed that the biological pathways most significantly associated with the 73 long COVID genes were mainly aligned with neurological and cardiometabolic diseases. Expanded genotype analysis suggests that specific SNX9 genotypes are a significant contributor to the risk of or protection against severe long COVID infection, but that the gene-disease relationship is context dependent and mediated by interactions with KLF15 and RYR3. Comparison of the genes uniquely associated with the Severe and Fatigue Dominant long COVID patients revealed significant differences between the pathways enriched in each subgroup. The genes unique to Severe long COVID patients were associated with immune pathways such as myeloid differentiation and macrophage foam cells. Genes unique to the Fatigue Dominant subgroup were enriched in metabolic pathways such as MAPK/JNK signaling. We also identified overlap in the genes associated with Fatigue Dominant long COVID and ME/CFS, including several involved in circadian rhythm regulation and insulin regulation. Overall, 39 SNPs associated in this study with long COVID can be linked to 9 genes identified in a recent combinatorial analysis of ME/CFS patient from UK Biobank. Among the 73 genes associated with long COVID, 42 are potentially tractable for novel drug discovery approaches, with 13 of these already targeted by drugs in clinical development pipelines. From this analysis for example, we identified TLR4 antagonists as repurposing candidates with potential to protect against long term cognitive impairment pathology caused by SARS-CoV-2. We are currently evaluating the repurposing potential of these drug targets for use in treating long COVID and/or ME/CFS. Conclusion This study demonstrates the power of combinatorial analytics for stratifying heterogeneous populations in complex diseases that do not have simple monogenic etiologies. These results build upon the genetic findings from combinatorial analyses of severe acute COVID-19 patients and an ME/CFS population and we expect that access to additional independent, larger patient datasets will further improve the disease insights and validate potential treatment options in long COVID.

IntroductionLong COVID patients experience a decrease in their quality of life due to the symptomatology produced by the disease. It is also important to understand how long COVID affects both men and women. The objective of this study is to examine the impact of long COVID symptomatology on the quality of life of Spanish adults from a gender perspective.MethodsAn observational and cross-sectional study was carried out. Participants were able to complete an online questionnaire using an online platform. A sample of 206 people participated in the study.ResultsThe 80.6% of the sample were women with a mean age of 46.51 (±8.28) and the 19.4% were men with a mean age of 48.03 (±9.50). The medium score in the PAC19-QoL test was 141.47 (±24.96) and segmented by gender, 141.65 (±23.95) for women and 140.82 (±28.66) for men. The most common symptoms in women were muscle and joint pain (94.6%), fatigue (94.0%), discomfort (92.2%), difficulty concentrating (91.0%), and memory loss (88.6%). For men the symptoms included muscle and joint pain (97.5%) and fatigue (97.5%) both occupying first position, discomfort (92.0%), difficulty concentrating (90.0%), mood disturbances (90.0%), and memory loss (87.5%). The chi-square test showed statistical significance (p

Background We investigated the effect of Post–Acute COVID Syndrome or "long-COVID" on kidney function among patients followed in post-COVID recovery clinics (PCRC) in British Columbia, Canada. Methods Long-COVID patients referred to PCRC between July 2020 to April 2022, aged ≥18 years who had an estimated glomerular filtration rate (eGFR) value recorded at 3 months from the coronavirus disease 2019 (COVID-19) diagnosis (index) date were included. Those requiring renal replacement therapy prior to index date were excluded. Primary outcome was change in eGFR and urine albumin–creatinine ratio (UACR) after COVID-19 infection. The proportion of patients in each of the six eGFR categories (<30, 30–44, 45–59, 60–89, 90–120 and >120 mL/min/1.73 m2) and three UACR categories (<3, 3–30 and >30 mg/mmol) in all of the study time points were calculated. Linear mixed model was used to investigate change in eGFR over time. Results The study sample included 2212 long-COVID patients. Median age was 56 years, 51% were male. Half (∼47%–50%) of the study sample had normal eGFR (≥90 mL/min/1.73 m2) from COVID-19 diagnosis to 12 months post-COVID and <5% of patients had an eGFR <30 mL/min/1.73 m2. There was an estimated 2.96 mL/min/1.73 m2 decrease in eGFR within 1 year after COVID-19 infection that was equivalent to 3.39% reduction from the baseline. Decline in eGFR was highest in patients hospitalized for COVID-19 (6.72%) followed by diabetic patients (6.15%). More than 40% of patients were at risk of CKD. Conclusions People with long-COVID experienced a substantial decline in eGFR within 1 year from the infection date. The prevalence of proteinuria appeared to be high. Close monitoring of kidney function is prudent among patients with persistent COVID-19 symptoms. [ABSTRACT FROM AUTHOR]

Post-Coronavirus Disease (COVID-19) condition, known as "post-COVID syndrome," is associated with a range of complications persisting even after recovery. Among these complications, cognitive dysfunction, including memory impairment, has been relatively common observed, impacting executive function and quality of life. To date, no approved treatment exists for this specific complication. Therefore, the present clinical trial aimed to investigate the impact of Donepezil Hydrochloride on post-COVID memory impairment. A randomized, controlled trial (Approval ID: IRCT20210816052203N1) was conducted, enrolling 25 patients with post-COVID memory impairment. Participants with a history of hospitalization were randomly assigned to either the drug group (n = 10) or the control group (n = 15). Memory indices were assessed at baseline, one month, and three months later using the Wechsler Memory Scale-Revised test. SPSS software and appropriate statistical tests were employed for data analysis. The statistical analysis revealed no significant difference in WMS-R subtest and index scores between the drug and control groups at the 4-week and 12-week follow-up periods. However, within the drug group, there was a notable increase in the visual reproduction I and verbal paired associates II subtests during the specified time intervals. While donepezil 5 mg did not exhibit a significant overall increase in memory scales compared to the control group over time, our findings suggest that this medication may exert a positive effect on specific memory subtests. Further research and exploration are warranted to better understand the potential benefits of donepezil in managing post-COVID-related memory impairment. The study was approved by the Research Ethics Committee of Aja University of Medical Sciences (Approval ID: IR.AJAUMS.REC.1400.125) and registered in the Iranian Registry of Clinical Trials (IRCT) (Approval ID: IRCT20210816052203N1). [ABSTRACT FROM AUTHOR]

Summary: Background: COVID-19 survivors may experience a wide range of chronic cognitive symptoms for months or years as part of post-COVID-19 conditions (PCC). To date, there is no definitive objective cognitive marker for PCC. We hypothesised that a key common deficit in people with PCC might be generalised cognitive slowing. Methods: To examine cognitive slowing, patients with PCC completed two short web-based cognitive tasks, Simple Reaction Time (SRT) and Number Vigilance Test (NVT). 270 patients diagnosed with PCC at two different clinics in UK and Germany were compared to two control groups: individuals who contracted COVID-19 before but did not experience PCC after recovery (No-PCC group) and uninfected individuals (No-COVID group). All patients with PCC completed the study between May 18, 2021 and July 4, 2023 in Jena University Hospital, Jena, Germany and Long COVID clinic, Oxford, UK. Findings: We identified pronounced cognitive slowing in patients with PCC, which distinguished them from age-matched healthy individuals who previously had symptomatic COVID-19 but did not manifest PCC. Cognitive slowing was evident even on a 30-s task measuring simple reaction time (SRT), with patients with PCC responding to stimuli ∼3 standard deviations slower than healthy controls. 53.5% of patients with PCC's response speed was slower than 2 standard deviations from the control mean, indicating a high prevalence of cognitive slowing in PCC. This finding was replicated across two clinic samples in Germany and the UK. Comorbidities such as fatigue, depression, anxiety, sleep disturbance, and post-traumatic stress disorder did not account for the extent of cognitive slowing in patients with PCC. Furthermore, cognitive slowing on the SRT was highly correlated with the poor performance of patients with PCC on the NVT measure of sustained attention. Interpretation: Together, these results robustly demonstrate pronounced cognitive slowing in people with PCC, which distinguishes them from age-matched healthy individuals who previously had symptomatic COVID-19 but did not manifest PCC. This might be an important factor contributing to some of the cognitive impairments reported in patients with PCC. Funding: Wellcome Trust (206330/Z/17/Z), NIHR Oxford Health Biomedical Research Centre, the Thüringer Aufbaubank (2021 FGI 0060), German Forschungsgemeinschaft (DFG, FI 1424/2-1) and the Horizon 2020 Framework Programme of the European Union (ITN SmartAge, H2020-MSCA-ITN-2019-859890).

Background: Long COVID is a debilitating chronic condition that has affected over 100 million people globally. It is characterized by a diverse array of symptoms, including fatigue, cognitive dysfunction and respiratory problems. Studies have so far largely failed to identify genetic associations, the mechanisms behind the disease, or any common pathophysiology with other conditions such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) that present with similar symptoms. Methods: We used a combinatorial analysis approach to identify combinations of genetic variants significantly associated with the development of long COVID and to examine the biological mechanisms underpinning its various symptoms. We compared two subpopulations of long COVID patients from Sano Genetics' Long COVID GOLD study cohort, focusing on patients with severe or fatigue dominant phenotypes. We evaluated the genetic signatures previously identified in an ME/CFS population against this long COVID population to understand similarities with other fatigue disorders that may be triggered by a prior viral infection. Finally, we also compared the output of this long COVID analysis against known genetic associations in other chronic diseases, including a range of metabolic and neurological disorders, to understand the overlap of pathophysiological mechanisms. Results: Combinatorial analysis identified 73 genes that were highly associated with at least one of the long COVID populations included in this analysis. Of these, 9 genes have prior associations with acute COVID-19, and 14 were differentially expressed in a transcriptomic analysis of long COVID patients. A pathway enrichment analysis revealed that the biological pathways most significantly associated with the 73 long COVID genes were mainly aligned with neurological and cardiometabolic diseases. Expanded genotype analysis suggests that specific SNX9 genotypes are a significant contributor to the risk of or protection against severe long COVID infection, but that the gene-disease relationship is context dependent and mediated by interactions with KLF15 and RYR3. Comparison of the genes uniquely associated with the Severe and Fatigue Dominant long COVID patients revealed significant differences between the pathways enriched in each subgroup. The genes unique to Severe long COVID patients were associated with immune pathways such as myeloid differentiation and macrophage foam cells. Genes unique to the Fatigue Dominant subgroup were enriched in metabolic pathways such as MAPK/JNK signaling. We also identified overlap in the genes associated with Fatigue Dominant long COVID and ME/CFS, including several involved in circadian rhythm regulation and insulin regulation. Overall, 39 SNPs associated in this study with long COVID can be linked to 9 genes identified in a recent combinatorial analysis of ME/CFS patient from UK Biobank. Among the 73 genes associated with long COVID, 42 are potentially tractable for novel drug discovery approaches, with 13 of these already targeted by drugs in clinical development pipelines. From this analysis for example, we identified TLR4 antagonists as repurposing candidates with potential to protect against long term cognitive impairment pathology caused by SARS-CoV-2. We are currently evaluating the repurposing potential of these drug targets for use in treating long COVID and/or ME/CFS. Conclusion: This study demonstrates the power of combinatorial analytics for stratifying heterogeneous populations in complex diseases that do not have simple monogenic etiologies. These results build upon the genetic findings from combinatorial analyses of severe acute COVID-19 patients and an ME/CFS population and we expect that access to additional independent, larger patient datasets will further improve the disease insights and validate potential treatment options in long COVID. [ABSTRACT FROM AUTHOR]

As the population of patients recovering from COVID-19 grows, post COVID-19 challenges are recognizing by ongoing evidences at once. Long COVID is defined as a syndrome with a range of persistent symptoms that remain long after (beyond 12 weeks) the acute SARS-CoV-2 infection. Studies have shown that long COVID can cause multi-organ damages with a wide spectrum of manifestations. Many systems, but not limited to, including respiratory, cardiovascular, nervous, gastrointestinal, and musculoskeletal systems, are involved in long COVID. Fatigue and dyspnea are the most common symptoms of long COVID. Long COVID-19 may be driven by tissue damage caused by virus-specific pathophysiologic changes or secondary to pathological long-lasting inflammatory response because of viral persistence, immune dysregulation, and autoimmune reactions. Some risk factors like sex and age, more than five early symptoms, and specific biomarkers have been revealed as a probable long COVID predicator discussed in this review. It seems that vaccination is the only way for prevention of long COVID and it can also help patients who had already long COVID. Managing long COVID survivors recommended being in a multidisciplinary approach, and a framework for identifying those at high risk for post-acute COVID-19 must be proposed. Possible therapeutic options and useful investigation tools for follow-up are suggested in this review. In sum, as evidence and researches are regularly updated, we provide the current understanding of the epidemiology, clinical manifestation, suspected pathophysiology, associated risk factors, and treatment options of long COVID in this review. [ABSTRACT FROM AUTHOR]

Background: Characterizing the post-COVID health conditions is helpful to direct patients to appropriate healthcare. Aims: To describe the presence of symptoms in COVID-19 patients within 6 months after diagnosis and to investigate the associated factors in terms of reporting symptoms. Methods: Data of DEU-COVIMER (a telephone interview-based COVID-19 follow-up center established in a tertiary care hospital) was analyzed for SARS-CoV-2 RNA positive participants aged ≥ 18 years from November 1st, 2020, to May 31st, 2021. Symptom frequencies were stratified by demographic and clinical characteristics at one, three, and 6 months after diagnosis. With the patients who had symptoms at baseline, generalized estimating equations were applied to identify the factors associated with reporting of symptoms. Results: A total of 5610 patients agreed to participate in the study. Symptom frequency was 37.2%, 21.8%, and 18.2% for the first, third, and sixth months. Tiredness/fatigue, muscle or body aches, and dyspnea/difficulty breathing were the most common symptoms in all time frames. In multivariate analysis, older age, female gender (odds ratio OR 1.74, 95% confidence interval 1.57–1.93), bad economic status (OR 1.37, 1.14–1.65), current smoking (OR 1.15, 1.02–1.29), being fully vaccinated before COVID-19 (OR 0.53, 0.40–0.72), having more health conditions (≥ 3 conditions, OR 1.78, 1.33–2.37), having more symptoms (> 5 symptoms, OR 2.47, 2.19–2.78), and hospitalization (intensive care unit, OR 2.18, 1.51–3.14) were associated with reporting of symptoms. Conclusions: This study identifies risk factors for patients who experience post-COVID-19 symptoms. Healthcare providers should appropriately allocate resources prioritizing the patients who would benefit from post-COVID rehabilitation. [ABSTRACT FROM AUTHOR]

Introduction: At the pandemic's beginning, significant concern has risen about the prevalence of myocardial involvement after SARS‐CoV‐2 infection. We assessed the cardiovascular burden of SARS‐CoV‐2 in a large cohort of athletes and identified factors that might affect the disease course. We included 633 athletes in our study on whom we performed extensive cardiology examinations after recovering from SARS‐CoV‐2 infection. More than half of the athletes (n = 322) returned for a follow‐up examination median of 107 days after the commencement of their infection. Results: Troponin T positivity was as low as 1.4% of the athletes, where the subsequently performed examinations did not show definitive, ongoing myocardial injury. Altogether, 31% of the athletes' rapid training rebuild was hindered by persistent or reoccurring symptoms. Female athletes reported a higher prevalence of return to play (RTP) symptoms than their male counterparts (34% vs. 19%, p = 0.005). The development of long COVID symptoms was independently predicted by increasing age and acute symptoms' severity in a multiple regression model (AUC 0.75, CI 0.685–0.801). Athletes presenting with either or both cough and ferritin levels higher than >150 μg/L had a 4.1x (CI 1.78–9.6, p = 0.001) higher odds ratio of developing persistent symptoms. Conclusion: While SARS‐CoV‐2 rarely affects the myocardium in athletes, about one in three of them experience symptoms beyond the acute phase. Identifying those athletes with a predisposition to developing long‐standing symptoms may aid clinicians and trainers in finding the optimal return‐to‐play timing and training load rebuild pace. [ABSTRACT FROM AUTHOR]

COVID-19 is an infectious disease that can have a multi-system involvement, most notably, the respiratory tract. After acute infection, a considerable proportion of patients suffer from persistent symptoms and signs, defined as long COVID-19. Depending on the affected systems and organs, patients can experience various clinic pictures. Rehabilitation approaches serve a crucial role in providing functional recovery and improving quality of life for COVID-19 survivors. As a result of the wideness of the clinical spectrum of the long COVID-19, rehabilitation practices differ according to the affected systems. Therefore, the formation of multidisciplinary rehabilitation teams is an inevitable necessity. The establishment of specific centers for long COVID-19 rehabilitation will be beneficial. If it is not possible, existing rehabilitation centers should be strengthened for this purpose. Since the pulmonary system and respiratory tract are the most affected structures, one of the main issues to be considered in long COVID-19 cases is cardiopulmonary rehabilitation. Patients experience musculoskeletal disorders such as atrophy, sarcopenia, poor physical performance and contracture due to long-term hospitalization, intensive care treatment, quarantine practices and immobilization. Rehabilitation practices also focus on these disorders. All rehabilitation practices in long COVID-19 patients should start with low intensity, and parameters such as intensity and frequency should be increased as the patient's tolerance improves. In high-risk cases, parameters including oxygen saturation, blood pressure, and heart rhythm should be monitored. Health-care authorities should prioritize the rehabilitation of the long COVID-19 syndrome and invest in this area. Authorities, physicians and patients should collaborate to facilitate long COVID-19 rehabilitation and to establish a self-contained system.

Objective Studies suggest a large number of patients have persistent symptoms following COVID-19 infection—a condition termed "long COVID." Although children and parents often report cognitive difficulties after COVID, very few if any studies have been published including neuropsychological testing. Methods A retrospective chart review was completed for the first 18 patients referred for a neuropsychological evaluation from a multidisciplinary pediatric post-COVID clinic. The neuropsychological screening battery assessed verbal fluency and category switching, attention, working memory, processing speed, and verbal learning and memory. Patients' caregivers also completed standardized questionnaires regarding day-to-day mood and behavior. Results At intake, the most common neurologic symptoms reported by caregivers were attention problems (83.3%), fatigue/lethargy (77.7%), sleep disturbance (77.7%), dizziness/vertigo (72.2%), and headaches (72.2%). On rating scales, most caregivers endorsed concerns for depressed mood and anxiety (14/15 and 12/15). A large proportion of patients had difficulties with attention (9/18) and depressed mood/anxiety (13/18) before COVID. On cognitive testing, the majority of the patients performed within or above broad average range (≥16th percentile) across most domains. However, a little over half of the patients performed below average on auditory attention measures. Conclusions Within our clinically referred sample, children who reported lingering cognitive symptoms after COVID-19 often had a preexisting history of attention and/or mood and anxiety concerns. Many of these patients performed below average in attention testing, but it remains to be seen whether this was due to direct effects of COVID, physical symptoms, and/or preexisting difficulties with attention or mood/anxiety. [ABSTRACT FROM AUTHOR]

Post-acute COVID-19 syndrome (PACS) is characterized by the persistence of one or more symptoms after the acute phase, leading to physical disabilities. This study aims to investigate whether the functional capacity and respiratory function 120 days post-COVID-19 differed according to the level of respiratory support needed during hospitalization in acute COVID-19 in the pre-vaccine rollout period. We followed up with 118 COVID-19 hospitalized patients in the acute phase until 120 days post-acute disease, with patients split into a Non-Invasive Oxygen Therapy Group (OTG, n = 72), Invasive Mechanical Ventilation Group (IMV, n = 12), and Room Air Group (RAG, n = 34), assessing the body composition, respiratory muscle strength, pulmonary function, functional capacity, and muscle strength at the follow-up visit. In total, 54 individuals (45.8%) were female, with a median age of 48 years old (IQR: 41-58). We found that the group with IMV was older ( p < 0.001), had more admissions to the ICU ( p < 0.001), and had longer hospital stays ( p < 0.001). There were no statistically significant differences between groups (OTG, IMV, and RAG) for the spirometry function ( p = 0.31), DASI score ( p = 0.77), manovacuometry (MIP p = 0.74; MEP p = 0.23), 6MWT ( p = 0.43), and handgrip ( p = 0.19) outcomes. At D120, the IMV group had an important loss of body muscle mass (BMM) and a higher BMM than RAG ( p = 0.02). Reduction in MIP ( p = 0.01) and MEP ( p = 0.02) in the IMV group and OTG group when compared to the RAG was also observed. Functional outcomes at 120 days from COVID-19 hospitalization were not found to be associated with the levels of oxygen supplementation during acute disease in this group of participants.

Background: The hyperventilation provocation test (HPTest) is a diagnostic tool for idiopathic hyperventilation syndrome (HVS), encountered in some long-COVID patients. However, interpretation of the HPTest remains unclear regarding the relevant PETCO2 values to focus on and whether subjective symptoms should be considered. This study aimed to re-evaluate objective HPTest results for diagnosing HVS by determining accurate PETCO2 kinetics in two groups of patients previously screened via the Nijmegen questionnaire (NQ). Methods: The kinetics of PETCO2 during the HPTest were mathematically modeled and compared between 37 HVS patients (NQ ≥23/64) and 37 healthy controls (NQ <23/64) matched for gender, age, and body dimensions. AUC values with sensitivity and specificity were calculated, and analysis was monitored in a validation cohort of 152 routine HPTests. Results: A threshold value of a less than 12.8 mmHg increment of PETCO2 at the 5th minute of the recovery phase of the HPTest diagnosed HVS patients with excellent sensitivity (0.92) and specificity (0.84). These results were confirmed in the validation cohort, highlighting the presence of 24% false positives/negatives when diagnosing on the basis of complaints in the NQ. Conclusions: For HVS diagnosis, we suggest considering the HPTest, which can more reliably reflect the mechanisms of CO2 homeostasis and the response of the respiratory center to a stimulus, regardless of the subjective onset of symptoms. [ABSTRACT FROM AUTHOR]

Purpose: Apart from the global disease burden of acute COVID-19 disease, the health complications arising after recovery have been recognized as a long-COVID or post-COVID-19 syndrome. Evidences of long-COVID symptoms involving various organ systems are rapidly growing in literature. The objective was to perform a rapid review and evidence mapping of systemic complications and symptoms of long-COVID and underlying pathophysiological mechanisms. Methods: Publications reporting clinical trials, observational cohort studies, case–control studies, case-series, meta-analysis, and systematic reviews, focusing on the squeal of the disease, consequences of COVID-19 treatment/hospitalization, long-COVID, chronic COVID syndrome, and post acute COVID-19 were reviewed in detail for the narrative synthesis of frequency, duration, risk factors, and pathophysiology. Results: The review highlights that pulmonary, neuro-psychological, and cardiovascular complications are major findings in most epidemiological studies. However, dysfunctional gastrointestinal, endocrine, and metabolic health are recent findings for which underlying pathophysiological mechanisms are poorly understood. Analysis of the clinical trial landscape suggests that more than 50% of the industry-sponsored trials are focused on pulmonary symptoms. In contrast to the epidemiological trends and academic trials, cardiovascular complications are not a focus of industry-sponsored trials, suggestive of the gaps in the research efforts. Conclusion: The gap in epidemiological trends and academic trials, particularly concerning cardiovascular complications not being a focus of industry-sponsored trials is suggestive of the gaps in research efforts and longer follow-up durations would help identify other long-COVID-related health issues such as reproductive health and fertility. [ABSTRACT FROM AUTHOR]

We studied the short- and long-term effects of imatinib in hospitalized COVID-19 patients. Participants were randomized to receive standard of care (SoC) or SoC with imatinib. Imatinib dosage was 400 mg daily until discharge (max 14 days). Primary outcomes were mortality at 30 days and 1 year. Secondary outcomes included recovery, quality of life and long COVID symptoms at 1 year. We also performed a systematic review and meta-analysis of randomized trials studying imatinib for 30-day mortality in hospitalized COVID-19 patients. We randomized 156 patients (73 in SoC and 83 in imatinib). Among patients on imatinib, 7.2% had died at 30 days and 13.3% at 1 year, and in SoC, 4.1% and 8.2% (adjusted HR 1.35, 95% CI 0.47–3.90). At 1 year, self-reported recovery occurred in 79.0% in imatinib and in 88.5% in SoC (RR 0.91, 0.78–1.06). We found no convincing difference in quality of life or symptoms. Fatigue (24%) and sleep issues (20%) frequently bothered patients at one year. In the meta-analysis, imatinib was associated with a mortality risk ratio of 0.73 (0.32–1.63; low certainty evidence). The evidence raises doubts regarding benefit of imatinib in reducing mortality, improving recovery and preventing long COVID symptoms in hospitalized COVID-19 patients. • We found no short or long-term benefit from imatinib in hospitalized COVID-19. • Pooled evidence raises doubts regarding benefit of imatinib in reducing mortality. • Fatigue and sleeping problems common at 1 year after hospitalized COVID-19. [ABSTRACT FROM AUTHOR]

Despite intense investigation, the pathogenesis of COVID-19 and the newly defined long COVID-19 syndrome are not fully understood. Increasing evidence has been provided of metabolic alterations characterizing this group of disorders, with particular relevance of an activated tryptophan/kynurenine pathway as described in this review. Recent histological studies have documented that, in COVID-19 patients, indoleamine 2,3-dioxygenase (IDO) enzymes are differentially expressed in the pulmonary blood vessels, i.e., IDO1 prevails in early/mild pneumonia and in lung tissues from patients suffering from long COVID-19, whereas IDO2 is predominant in severe/fatal cases. We hypothesize that IDO1 is necessary for a correct control of the vascular tone of pulmonary vessels, and its deficiency in COVID-19 might be related to the syndrome's evolution toward vascular dysfunction. The complexity of this scenario is discussed in light of possible therapeutic manipulations of the tryptophan/kynurenine pathway in COVID-19 and post-acute COVID-19 syndromes. [ABSTRACT FROM AUTHOR]

• Prevalence of symptoms high 10 months after acute COVID-19 disease. • Lung function and exercise capacity close to normal after 10 months. • No correlation between symptoms and somatic functional impairments. • Correlation between scores for depression/HrQoL and major symptoms. For a better understanding of the factors underlying the Post-Acute COVID Syndrome, we studied the relationship between symptoms and functional alterations in COVID-19 patients 10 months after hospitalization. One-hundred-one patients hospitalized between March 1st and June 30th 2020 participated in a follow-up visit for an assessment of clinical history, comorbidities, lung function, physical capacity and symptoms, including the SGRQ for health-related quality of life, PHQ-9-D for depression, and SOMS-2 J for somatoform disorders. Data were analyzed by univariate comparisons and multiple logistic regression analyses. Median age was 60 years, 42% were female, 76% had at least one comorbidity, the median length of the hospital stay was 8 days, 19% had been on the ICU. The most prevalent symptoms included shortness of breath (49%), fatigue (49%) and cognitive impairment (39%). Signs of major depression (PHQ-9- D ≥ 10) occurred in 28%/2% (p < 0.05) of patients with/without self-reported cognitive impairment, with median total SGRQ score being 25.4/5.3 (p < 0.05). There were associations between shortness of breath and BMI, SGRQ and hemoglobin levels; between fatigue, SGRQ and PHQ-9-D; and between cognitive impairment and PHQ-9-D (p < 0.05 each) but not with lung function or physical capacity. Characteristics of the acute disease were not related to symptoms. The findings demonstrate that 10 months after discharge from a hospital stay due to COVID-19, the percentages of patients with symptoms were high. Symptoms showed a consistent pattern but could not be attributed to altered lung function or physical capacity. Our results suggest a role for alternative etiologies including psychosocial factors. [ABSTRACT FROM AUTHOR]

Despite intense investigation, the pathogenesis of COVID-19 and the newly defined long COVID-19 syndrome are not fully understood. Increasing evidence has been provided of metabolic alterations characterizing this group of disorders, with particular relevance of an activated tryptophan/kynurenine pathway as described in this review. Recent histological studies have documented that, in COVID-19 patients, indoleamine 2,3-dioxygenase (IDO) enzymes are differentially expressed in the pulmonary blood vessels, i.e., IDO1 prevails in early/mild pneumonia and in lung tissues from patients suffering from long COVID-19, whereas IDO2 is predominant in severe/fatal cases. We hypothesize that IDO1 is necessary for a correct control of the vascular tone of pulmonary vessels, and its deficiency in COVID-19 might be related to the syndrome’s evolution toward vascular dysfunction. The complexity of this scenario is discussed in light of possible therapeutic manipulations of the tryptophan/kynurenine pathway in COVID-19 and post-acute COVID-19 syndromes.

Introduction Acute COVID-19 patients can suffer from chronic symptoms known as post-acute sequelae of SARS-CoV-2 infection (PASC). Point-of-care ultrasound (POCUS) is established in acute COVID, but its utility in PASC is unclear. We sought to determine the incidence of cardiac and pulmonary abnormalities with POCUS in patients with PASC in a COVID-19 recovery clinic. Methods This prospective cohort study included adults (>18 years old) presenting with cardiopulmonary symptoms to the COVID-19 recovery clinic. A lung ultrasound and standard bedside echocardiogram were performed by ultrasound-trained physicians. Images were interpreted in real time by the performing sonographer and independently by a blinded ultrasound faculty member. Discrepancies in interpretation were addressed by consensus review. A modified Soldati score was calculated by the sum of the scores in each of the 12 lung zones, with each zone score ranging from 0 to 3 (maximum score of 36). The score was then compared to clinical outcomes and outpatient testing.  Results Between April and July 2021, 41 patients received POCUS examinations, with 24 of those included in the study. In all, 15 out of 24 (62.5%) had a normal lung ultrasound. Of the nine subjects with lung abnormalities, the median modified Soldati score was 2. Three patients had trivial pericardial effusions, and all had normal left and right ventricular size and function. Conclusion The majority (62.5%) of patients presenting to the PASC clinic had a normal pulmonary ultrasound, and the vast majority (87.5%) had normal cardiac ultrasounds. These findings suggest that cardiopulmonary symptoms in PASC may be from etiologies not well evaluated by POCUS., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Dearing et al.)