Post-Acute COVID-19 Syndrome

Background: SARS-CoV-2 is the virus that causes COVID-19. Some people who recover from an acute COVID-19 infection may continue to have symptoms that persist for months or years. These can include neurological symptoms, such as headaches, loss of taste or smell, dizziness, or trouble walking. Pembrolizumab is a drug approved to treat certain cancers. Researchers think this drug might reduce long-term neurologic symptoms after a COVID-19 infection. Objective: To test pembrolizumab in people with ongoing neurologic symptoms of COVID-19. Eligibility: People aged 18 years or older who had COVID-19 at least 6 months ago and have ongoing neurologic symptoms. Design: Participants will have 7 clinic visits in 7 months. Participants will be screened. They will have a physical exam with blood tests. Swabs will be used to collect cells from inside the mouth and nose. They may opt to have an imaging scan. Participants will also have other tests before they are given the study drug. These include eye and skin exams; tests of their memory and thinking; and tests of involuntary body functions, such as heart rate, blood pressure, sweating, and digestion. Their grip strength and walking pace will be measured. They will wear a heart rate monitor for 24 hours. They will wear devices on a wrist and thigh to measure activity for 10 days. Participants will have a lumbar puncture (spinal tap): A thin needle will be inserted into their lower back to draw out a sample of the fluid around their spinal cord. Pembrolizumab is given through a needle inserted into a vein. Participants will receive 1 dose of the drug. Participants will have 4 follow-up visits over 6 months. Tests may be repeated during these visits.

This multicenter, observational, retrospective-prospective study aims to evaluate the prevalence and trajectory of Post-Acute Sequelae of COVID-19 (PASC) approximately 5 years after SARS-CoV-2 infection. The study will re-contact participants from an established cohort of more than 3,000 individuals with microbiologically confirmed SARS-CoV-2 infection, including both hospitalized and non-hospitalized patients, previously followed in dedicated post-COVID outpatient clinics. Participants will undergo a structured telephone interview approximately 60 ± 3 months after infection, and those meeting predefined clinical criteria will be invited to an in-person clinical assessment. The study will evaluate persistent symptoms, functional status, cognitive and nutritional status, frailty, sarcopenia, quality of life, healthcare resource utilization, and direct and indirect healthcare costs to characterize the long-term trajectory of PASC.

The primary objective of this study is to conduct a 16-week randomized controlled trial aimed at investigating the effectiveness of the Whole-Diet Approach when following a healthy US-style diet rich in anti-inflammatory properties. The study will focus on evaluating its impact on reducing symptoms related to Post-Acute Sequelae of SARS-CoV-2 Infection (PACS) in adults aged 50 years and older. The main research questions this study aims to answer are: 1. Does adhering to a healthy US-style diet, which is abundant in anti-inflammatory properties, effectively mitigate fatigue symptoms in adults with PACS? 2. Does adhering to a healthy US-style diet, which is abundant in anti-inflammatory properties, effectively mitigate declines in muscle function and physical performance in adults with PACS? At the beginning of the study, eligible participants will be randomly assigned to either the Dietary Intervention Group, where they will receive personalized dietary plans and weekly sessions, or the Attention Control Group, where they will attend general health sessions on a weekly basis as well. This research intends to shed light on the potential benefits of the Whole-Diet Approach and its role in ameliorating PACS-related symptoms among older adults. By comparing the outcomes of the two groups, we hope to gain valuable insights into the effectiveness of this dietary intervention in improving the quality of life for individuals dealing with PACS.

This study will evaluate the effects of diaphragmatic breathing exercises combined with diaphragmatic electrostimulation using KOTS currents in patients with Long COVID. Participants will be randomly assigned to one of two groups. The control group will perform diaphragmatic breathing exercises, while the intervention group will perform diaphragmatic breathing exercises combined with diaphragmatic electrostimulation using KOTS currents. The intervention will last three weeks, with two sessions per week. The study will assess respiratory function, quality of life, physical function, dyspnea, fatigue, and basal oxygen saturation.

The Harnessing Optimism and Perseverance in the Face of Long COVID (HOPE-LC) program, created by Drs. Eric Watson and Amelia Hicks, is a group therapy model designed to foster resilience, adjustment, and coping skills for those living with chronic Long COVID. HOPE-LC\~Español provides a culturally and linguistically adapted version for Spanish-speaking individuals in Queens, developed with input from Spanish-speaking clinicians, Long COVID experts, and people with lived experience. Partnering with H+H/Elmhurst and H+H/Queens, the project aims to recruit 25 participants and evaluate program feasibility and preliminary efficacy.

This study will compare two approaches to cognitive rehabilitation in adults with long COVID with persistent, mild to moderate, cognitive impairment. One approach will feature (A) web-based computer "games" that trains how quickly individuals process information that they receive through their senses; (B) in-lab training on everyday activities with important cognitive components, (C) procedures designed to transfer improvements in cognition from the treatment setting to everyday life, and (D) a non-invasive form of vagus nerve stimulation (VNS), i.e., trans-auricular VNS (taVNS). Component B will include work-related tasks. This approach is termed Constraint-Induced Cognitive Therapy (CICT). The other approach will feature (A) web-based computer "games" that train reaction time and eye-hand coordination; (B) in-lab training on relaxation, healthy nutrition, and healthy sleep, (C) procedures designed to promote integration of these lifestyle changes into everyday life, and (D) taVNS. This approach is termed Brain Fitness Training (BFT). A subset of participants, who qualify for and and desire vocational rehabilitation (VR), will receive VR from the Alabama Department of Rehabilitation Services (ADRS) in addition to CICT or BFT. ADRS VR will include career counseling, prescription of on-the-job accommodations, and guidance on return-to-work. Those in the CICT + VR group will also receive on-the-job coaching from a peer mentor for a month after completing training. CICT, with or without VR, will involve 30 hours of training. Ten 3-hour in-lab, face-to-face, therapist-directed sessions will be scheduled. These sessions will feature one hour of gaming; the remainder will be committed to in-lab training on the target behaviors and the procedures designed to promote transfer of therapeutic gains to daily life and improving skills essential to work; the set of the latter procedures is termed the Transfer Package. ta-VNS will administered for 10 minutes before gaming and in-lab target behavior training. To accommodate the demands of participants' other activities, training sessions will be permitted to be scheduled as tightly as every weekday over 2 weeks or as loosely as every other weekday or so over 4 weeks. If a family caregiver is available, they will receive training on how to best support participants in their therapeutic program. After training ends, four follow-up phone calls will be scheduled approximately one-week apart with participants to promote integration of the skills gained during training into everyday life. BFT, with or without VR, will involve 30 hours of training following the same schedule as for CICT. Ten 3-hour in-lab, face-to-face, therapist-directed sessions will be scheduled. These sessions will feature one hour of gaming; the remainder will be committed to in-lab training on the target behaviors (healthy sleep, nutrition and relaxation habits) and the procedures designed to promote transfer of behavior change to daily life. ta-VNS will be administered for 10 minutes before gaming and in-lab target behavior training. If a family caregiver is available, they will receive training on how to best support participants in their therapeutic program. After training ends, four follow-up phone calls will be scheduled approximately one-week apart with participants to promote integration of the skills gained during training into everyday life. Participants will be randomly assigned to the interventions. Randomization will be stratified by whether participants qualify for and desire VR from ADRS or not. If yes, participants will be randomized in equal numbers to CICT + VR or BFT + VR. If no, participants will be randomized in equal numbers to CICT or BFT. Testing will happen one month before treatment, one day before treatment, one day afterwards, and 6-months afterwards. Outcomes measured will include cognitive processing speed, cognitive function on laboratory tests, and spontaneous performance of everyday activities with important cognitive components in daily life. Another important outcome measure will be whether or not participants were able to return back to work or had significant improvements in their work activities.

The aim of this study is to assess the effect of a physical exercise program via a mobile application on functional parameters in individuals with post-COVID-19 syndrome. This is a clinical trial involving 60 individuals with post-COVID syndrome who will be randomly assigned to either a control group (physical activity guideline) or an experimental group (app-based training).

Long COVID is defined by a range of symptoms affecting multiple organs that persist for more than three months following an acute SARS-CoV-2 infection. Approximately 7% of individuals who recover from SARS-Cov-2 infection develop Long COVID. Long COVID Postural Orthostatic Tachycardia Syndrome (LCPOTS) symptoms include fatigue, exercise intolerance, orthostatic intolerance, syncope, and heightened orthostatic tachycardia. Research has found that decreased parasympathetic activity in LCPOTS increases the production of highly immunogenic neoantigens Isolevuglandins (IsoLG-adducts). IsoLG-adducts induce formation of circulating monocyte/T cell complexes(doublets) leading to the persistent and unresolved immune response that continues after the initial infection. The purpose of the this research, is to study the effects of 2-hydroxybenzylamine (2-HOBA), an Iso-LG-adduct scavenger, its effects in immune markers and compare it with Placebo

The unhide® Project is a non-interventional, longitudinal research study designed to establish a secure data repository of demographic, health, and lifestyle information from individuals with brain inflammation and related neuroinflammatory conditions. Participants in the United States aged 2 years and older will provide self-reported health data, biometrics, and symptom diaries through the MyDataHelps™ app (branded as unhide® for this study). The goal is to create comprehensive longitudinal profiles to facilitate research into disease subtypes, causes, diagnostics, and potential treatments, as well as to identify potential participants for future optional studies. "Healthy" individuals without brain inflammation are also eligible to participate. The digital health research platform used in this study was originally developed and designed by Solve M.E and was called SolveTogether. The Brain Inflammation Collaborative (BIC) expanded upon Solve M.E.'s work to include related diagnoses, pediatric participants, enhance symptom tracking, and more. BIC and Solve M.E. combined Solve Together and unhide®, to create The unhide® Solve Together Unified Platform in 2025.

The study aims to identify clinical profiles of long-COVID patients and correlate them with immunological and molecular data in order to identify prognostic biomarkers and potential therapeutic targets.

The PRECISION is a proof-of-concept, phase II randomized clinical trial aiming to evaluate the efficacy and safety of anakinra in patients with Post-Acute COVID Syndrome (PACS) of the pro-inflammatory respiratory phenotype. Improvement is measured by a composite endpoint, namely, the "Score of PACS progression reversal"

The evidence-based Concordant Care approach involves engaging in processes that: 1) validate the patient's experience, 2) develop a shared understanding of the condition, and 3) create a patient-centered, whole health-oriented action plan to manage the condition. This is consistent with published expert opinion that Concordant Care underlies patients' (and clinicians') positive experiences of care for poorly understood conditions. Despite strong evidence supporting this care approach, there are no interventions to train clinicians on practices to provide Concordant Care for Veterans with poorly understood conditions such as Long-COVID. Part 1 of the study will optimize and test if a Concordant Care training improves VA clinicians' engagement in recommended practices to provide Concordant Care (i.e., validate, shared understanding, action plan) for Veterans with Long-COVID. This study will adapt and refine Concordant Care training for Long-COVID. Part 2 of this study will determine if Concordant Care training increases clinicians' engagement in recommended practices to provide Concordant Care and will explore the effectiveness of Concordant Care on care outcomes including satisfaction, adherence to care, \& disability for Veterans with Long-COVID. Veterans treated by clinicians receiving Concordant Care training will report their clinician more frequently engaged in recommended conversations (i.e., ask about Long-COVID, validate experience with Long-COVID, create a shared understanding and action plan), and Veterans will perceive greater shared understanding of Long-COVID with their clinicians than Veterans treated by clinicians in the control arm.

This is a monocentric, randomized pilot study conducted at the Max Planck Institute of Psychiatry, Munich. The study investigates the effects of two different intermittent theta-burst stimulation (iTBS) schedules on biological and clinical outcomes in patients with depression and comorbid Post-COVID-19 condition (PCC). Participants will be randomized into two arms, both receiving a total of 30 active iTBS sessions applied to the left dorsolateral prefrontal cortex (DLPFC) at 90% resting motor threshold using a PowerMAG 100 ppTMS stimulator: * Standard Arm: One iTBS session per day, five days per week, over six weeks. * Intensified Arm: Six iTBS sessions per day, approximately one-hour apart, over five consecutive days. The primary outcomes are changes in immunological blood markers (C-reactive protein \[CRP\], tumor necrosis factor \[TNF\], interleukin-1β \[IL-1β\], interleukin-6 \[IL-6\]) and depressive symptomatology measured by Beck Depression Inventory-II (BDI-II) and Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes include fatigue (Fatigue Severity Scale \[FSS\], Fatigue Scale for Motor and Cognitive Functions \[FSMC\], Post-Exertional Malaise questionnaire \[PEM\]), sleep quality (Pittsburgh Sleep Quality Index \[PSQI\]), daytime sleepiness (Epworth Sleepiness Scale \[ESS\]), functioning (Sheehan Disability Scale \[SDS\]), anxiety (Beck Anxiety Inventory \[BAI\]) and an exploratory adverse effect screening. Follow-up assessments will be performed three days after treatment completion and again at three months post-intervention to evaluate both short- and medium-term effects. Biospecimen collection will include approximately 141 ml of peripheral blood per participant across three time points (baseline, post-treatment, +3 days). Samples will be analyzed for inflammatory markers and securely stored in the institutional biobank of the Max Planck Institute of Psychiatry in accordance with data protection and ethical guidelines. Safety and tolerability will be continuously monitored, including documentation of adverse events. The results of this pilot study are expected to provide preliminary evidence on whether accelerated iTBS protocols may exert differential effects on neuroinflammatory processes and depressive symptomatology in patients with Post-COVID-19 condition, thereby informing larger controlled clinical trials.

Investigation of the correlation of CT-morphological changes of the lung compared to regional ventilation distribution on electrical impedance tomography in patients with post-acute-Covid-19 symptoms.

This research is being done to study a mindfulness intervention among people who have symptoms of Post-Acute Sequelae of SARS-CoV-2 infection (PASC), also known as Long COVID. Mindfulness is defined as paying attention to the present moment with non-judgment and acceptance. Here the investigators are studying whether a mindfulness intervention can help reduce stress, reduce Long COVID symptoms, and improve quality of life among people living with Long COVID. The mindfulness intervention is a series of recorded mindfulness sessions, which were created by the study team. People who decide to take part will be randomly assigned to receive the study mindfulness intervention immediately after joining the study or to receive the study mindfulness intervention 8 weeks after joining the study. All participants will continue their usual medical care. Participants will complete online surveys to measure symptoms over time. The study will last 6 months.

This is an open label, multicentre, phase II clinical trial that aims to assess the efficacy and safety of oral Apabetalone with background dapagliflozin for up to 12 weeks in T2DM patients with a history of probable or confirmed SARS-CoV-2 infection, with symptoms within 3 months from the onset of COVID-19 that last for at least 2 months and cannot be explained by an alternative diagnosis.

This is a national retrospective cohort study with internet-based recruitment which intends to enroll 1,694 adult patients with COVID-19 diagnosis during the SARS-CoV-2 omicron wave in Brazil. Participants with confirmed symptomatic COVID-19 after january 2022 will be evaluated in order to assess incidence, potential risk factors and impact of post COVID-19 condition according to the WHO definition on health-related quality of life and other relevant patient-centered outcomes.

The goal of this observational study with a cross-sectional design is to investigate what signs, symptoms and assessment which can describe and explain dysfunctional breathing in patients with post COVID-19 condition. The main question aims to answer which measurements can identify and asses dysfunctional breathing in patients with post COVID-19 condition? Participants for this study will be recruited from the ReCov cohort will be evaluated with diffrent measurments and questionnaires.

The objective of the study is to compare the acute cardiorespiratory and perceptual responses to a physical exercise session in those infected by Covid-19 with and without persistent symptoms.

The goal of this clinical trial is to evaluate the effectiveness and safety of mesenchymal stem cell therapy in long-COVID patients. The main questions it aims to answer include: * whether umbilical cord mesenchymal stem cell therapy does benefit long-COVID patients * whether umbilical cord mesenchymal stem cell therapy is safe for long-COVID patients. Participants' demographics, chief complaints, and vital signs will be collected and recorded. Basic physical examinations, bloodwork routine, biochemical indexes, oxygen saturation (SpO2) levels, 6-minute walk tests, high-resolution computed tomography (HRCT) scan (if necessary) results will be conducted. Participants will receive either an intravenous infusion of mesenchymal stem cells, or a placebo for one time. Participants' symptoms will be assessed on Day 28 of the trial. If there is no significant effect, an additional infusion will be given on Days 35-42, and the symptoms will be reassessed 28 days after that. Continuous nebulized inhalation of UCMSC-derived exosomes will be administered for 5 days twice daily to treatment group, with no treatment given to the control group. Researchers will compare data and information collected from the treatment and control groups to evaluate the safety and efficacy of UCMSC-derived exosomes for the treatment of chronic cough after COVID-19 infection.

Sleep quality and duration are critical to cognitive, emotional and physical well-being, and poor sleep quality has been associated with an increased risk of cognitive, psychological and cardiometabolic disorders. Several important physiological activities occur during sleep including a reduction in heart rate and blood pressure. In addition, sleep exerts important modulatory effects on hormone release. Previous studies have shown that lack of sleep can generate exaggerated cortisol responses or psychological and physiological stressors. Cortisol has widespread effects throughout the body and brain, affecting mood, arousal, energy, metabolic processes, and immune and inflammatory system functioning. Therefore, disruptions in cortisol secretion during the night can influence a wide variety of processes in our body that may contribute to the perception of poorer sleep quality. In addition, the salivary enzyme α-amylase is considered a biomarker of cognitive, psychosocial, emotional or physical stress. It is important to note that the autonomic nervous system (ANS) regulates several physiological processes, including heart rate, blood pressure, respiration, and digestion. The ANS consists primarily of the sympathetic system and the parasympathetic system. Increased parasympathetic activity is considered to promote health, whereas a dominant or overactive sympathetic branch is considered to be detrimental to health. A recent study found that both sleep quality and quantity of sleep were associated with resting ANS functioning. They found that poorer sleep quality was associated with greater sympathetic dominance. Research on the sympathetic and parasympathetic branches of the ANS has shown that autonomic imbalances are precursors to disease formation and other health-related risks. Coronavirus disease 2019 (COVID-19), has in many cases involved the presence of long-lasting symptoms several weeks or months after surviving acute infection with the virus, leading to a new disease called long COVID-19 or post-COVID-19 syndrome (PCS). A recent study showed that sleep quality influences the relationship between symptoms associated with sensitization and mood disorders with health-related quality of life in people suffering from long COVID. Non-invasive neuromodulation directed to ANS may be an option to treat the sleep disorders observed in patients with long COVID. OBJETIVES: Therefore, the primary objective of this study is to evaluate the efficacy of a treatment protocol on the ANS by means of non-invasive neuromodulation in aspects related to sleep in long COVID patients compared to placebo. As secondary objectives, we propose to evaluate the efficacy of a treatment protocol on the ANS by non-invasive neuromodulation in aspects related to ANS functioning, psychological variables, fatigue, pain perception and quality of life in patients with long COVID.