Several disabling symptoms potentially related to dysautonomia have been reported in "long-COVID" patients. Unfortunately, these symptoms are often nonspecific, and autonomic nervous system explorations are rarely performed in these patients. This study aimed to evaluate prospectively a cohort of long-COVID patients presenting severe disabling and non-relapsing symptoms of potential dysautonomia and to identify sensitive tests. Autonomic function was assessed by clinical examination, the Schirmer test; sudomotor evaluation, orthostatic blood pressure (BP) variation, 24-h ambulatory BP monitoring for sympathetic evaluation, and heart rate variation during orthostatism, deep breathing and Valsalva maneuvers for parasympathetic evaluation. Test results were considered abnormal if they reached the lower thresholds defined in publications and in our department. We also compared mean values for autonomic function tests between patients and age-matched controls. Sixteen patients (median age 37 years [31-43 years], 15 women) were included in this study and referred 14.5 months (median) [12.0-16.5 months] after initial infection. Nine had at least one positive SARS-CoV-2 RT-PCR or serology result. Symptoms after SARS-CoV-2 infection were severe, fluctuating and disabling with effort intolerance. Six patients (37.5%) had one or several abnormal test results, affecting the parasympathetic cardiac function in five of them (31%). Mean Valsalva score was significantly lower in patients than in controls. In this cohort of severely disabled long-COVID patients, 37.5% of them had at least one abnormal test result showing a possible contribution of dysautonomia to these nonspecific symptoms. Interestingly, mean values of the Valsalva test were significantly lower in patients than in control subjects, suggesting that normal values thresholds might not be appropriate in this population.
Subject(s)COVID-19 , Primary Dysautonomias , Humans , Female , Adult , SARS-CoV-2 , Autonomic Nervous System , Primary Dysautonomias/diagnosis , Cardiovascular Physiological Phenomena , Heart Rate/physiology
Long COVID describes an array of often debilitating symptoms in the aftermath of SARS-CoV-2 infection, with similar symptomatology affecting some people post-vaccination. With an estimated > 200 million Long COVID patients worldwide and cases still rising, the effects on quality of life and the economy are significant, thus warranting urgent attention to understand the pathophysiology. Herein we describe our perspective that Long COVID is a continuation of acute COVID-19 pathology, whereby coagulopathy is the main driver of disease and can cause or exacerbate other pathologies common in Long COVID, such as mast cell activation syndrome and dysautonomia. Considering the SARS-CoV-2 spike protein can independently induce fibrinaloid microclots, platelet activation, and endotheliitis, we predict that persistent spike protein will be a key mechanism driving the continued coagulopathy in Long COVID. We discuss several treatment targets to address the coagulopathy, and predict that (particularly early) treatment with combination anticoagulant and antiplatelet drugs will bring significant relief to many patients, supported by a case study. To help focus attention on such treatment targets, we propose Long COVID should be referred to as Spike protein Induced Thrombotic Vasculitis (SITV). These ideas require urgent testing, especially as the world tries to co-exist with COVID-19.
Subject(s)Mastocytosis , Primary Dysautonomias , Blood Coagulation Disorders , Vasculitis , COVID-19
Subject(s)COVID-19 , Primary Dysautonomias , Humans
ABSTRACT: This report highlights a new, patient-centered paradigm for managing post-COVID-19 dysautonomia symptoms during sports and exercise. The patient was a healthcare worker exposed before vaccination. She experienced postural orthostatic tachycardia plus exertional tachycardia, with postexertional fatigue, beginning a few weeks after testing positive for COVID-19. Stress test, echo, and an extensive dysautonomia evaluation were negative. Recommended nonpharmacological and pharmacological interventions were poorly tolerated. Prescription of a novel regimen of "basal-dose" ivabradine, plus very low-dose metoprolol according to an exertional "sliding scale" managed symptoms to an acceptable level for work and recreation.
Subject(s)COVID-19 , Postural Orthostatic Tachycardia Syndrome , Primary Dysautonomias , Female , Humans , Post-Acute COVID-19 Syndrome , Primary Dysautonomias/diagnosis , Tachycardia , Patient-Centered Care , Postural Orthostatic Tachycardia Syndrome/diagnosis , Postural Orthostatic Tachycardia Syndrome/therapy
Subject(s)COVID-19 , Postural Orthostatic Tachycardia Syndrome , Primary Dysautonomias , Humans , Posture , Tachycardia
Background: Significant clinical similarities have been observed between the recently described Long-Haul COVID-19 (LHC) syndrome, Postural Orthostatic Tachycardia Syndrome (POTS) and Inappropriate Sinus Tachycardia (IST). Shared symptoms include light-headedness, palpitations, tremulousness, generalized weakness, blurred vision, chest pain, dyspnea, brain-fog, and fatigue. Ivabradine is a selective sinoatrial node blocker FDA-approved for management of tachycardia associated with stable angina and heart failure not fully managed by beta blockers. In our study we aim to identify risk factors underlying LHC, as well as the effectiveness of ivabradine in controlling heart rate dysregulations and POTS/IST related symptoms. Methods/Design: A detailed prospective phenotypic evaluation combined with multi-omic analysis of 200 LHC volunteers will be conducted to identify risk factors for autonomic dysfunction. A comparator group of 50 volunteers with documented COVID-19 but without LHC will be enrolled to better understand the risk factors for LHC and autonomic dysfunction. Those in the cohort who meet diagnostic criteria for POTS or IST will be included in a nested prospective, randomized, placebo-controlled trial to assess the impact of ivabradine on symptoms and heart rate, assessed non-invasively based on physiologic response and ambulatory electrocardiogram. Additionally, studies on catecholamine production, mast cell and basophil degranulation, inflammatory biomarkers, and indicators of metabolic dysfunction will be measured to potentially provide molecular classification and mechanistic insights. Discussion: Optimal therapies for dysautonomia, particularly associated with LHC, have yet to be defined. In the present study, ivabradine, one of numerous proposed interventions, will be systematically evaluated for therapeutic potential in LHC-associated POTS and IST. Additionally, this study will further refine the characteristics of the LHC-associated POTS/IST phenotype, genotype and transcriptional profile, including immunologic and multi-omic analysis of persistent immune activation and dysregulation. The study will also explore and identify potential endotheliopathy and abnormalities of the clotting cascade.
Subject(s)Chest Pain , Tachycardia , Postural Orthostatic Tachycardia Syndrome , Dyspnea , Primary Dysautonomias , Fatigue , Chronobiology Disorders , Heart Failure , Angina Pectoris , Metabolic Diseases , Vision Disorders , Tachycardia, Sinus , COVID-19
Background: A significant percentage of COVID-19 patients experience post-COVID-19 symptoms and signs. Post-COVID-19 syndrome affects physical and mental health of patients in several ways. Aim: To investigate the impact of post-COVID-19 syndrome and related dysautonomia on patients life and work productivity. Methods: We conducted a cross-sectional study in Greece using an online questionnaire. Study population included 108 workers over 18 years old that have been diagnosed with post-COVID-19 syndrome. Patients were recruited from the Long COVID Greece patients society. We measured demographic and clinical characteristics of patients, resilience, and social support. Results: Among patients, 68.5% stated that post-COVID-19 syndrome affected their daily life to a great extent, 25% to a moderate level, and 6.5% to a small extent. Moreover, 56.5% stated that post-COVID-19 syndrome affected their work productivity to a great extent, 27.8% to a moderate level, and 15.7% to a small extent. Multivariable analysis identified that females and patients with post-COVID-19 dysautonomia had more problems in their daily life. Moreover, increased duration of COVID-19 symptoms was associated with increased daily problems. Increased resilience was related with fewer problems in daily life. Also, we found that patients with post-COVID-19 dysautonomia had less work productivity. Moreover, increased duration of COVID-19 symptoms was associated with more problems in work. Resilience was related with increased work productivity. Conclusions: Post-COVID-19 syndrome and related dysautonomia affect significantly patients daily and work life. Also, resilience is an important preventive factor improving patients life. Policy makers should develop and implement educational programs to improve patients life. Healthcare professionals should be aware of the post-COVID-19 syndrome and its consequences in order to understand post-COVID-19 patients and their problems.
Subject(s)COVID-19 , Primary Dysautonomias
Background: Post-COVID-19 syndrome affects a significant number of SARS-CoV-2 infected individuals even asymptomatic cases causing several neurological and neuropsychiatric symptoms and signs. Materials and Methods: An online cross-sectional study with a convenience sample was conducted in Greece from November 2022 to January 2023. We measured demographic and clinical characteristics of patients, post-COVID-19 dysautonomia, quality of life with the EQ-5D-3L, and anxiety and depressive symptoms with the Patient Health Questionnaire-4. Results: Study population included 122 patients with post-COVID-19 syndrome. One out of four patients (27.8%) manifested post-COVID-19 dysautonomia, while mean duration of COVID-19 symptoms was 11.6 months. Anxiety and depressive symptoms were worse after the post-COVID-19 syndrome (p<0.001 in both cases). A statistically significant reduction in quality of life was observed among patients after the post-COVID-19 syndrome (p<0.001 for both EQ-5D-3L index value and EQ-5D-3L VAS). Post-COVID-19 dysautonomia increased depression symptoms after the post-COVID-19 syndrome (p=0.02). We found a negative relationship between duration of COVID-19 symptoms and quality of life (p<0.001). Moreover, our results showed that depressive symptoms were more often among females after the post-COVID-19 syndrome (p=0.01). Also, quality of life was lower among females than males (p=0.004 for EQ-5D-3L index value, and p=0.007 for EQ-5D-3L VAS). Conclusions: Our results suggest that post-COVID-19 syndrome causes a tremendous impact on patients quality of life and mental health. In addition, we found that the groups most psychologically affected were patients with post-COVID-19 dysautonomia, females, and patients with longer duration of symptoms. Policy makers should attach priority to vulnerable groups in future psychiatric planning. Policy measures should focus on mental health of post-COVID-19 patients who seem to be particularly vulnerable.
Subject(s)Anxiety Disorders , Primary Dysautonomias , Mental Disorders , Severe Acute Respiratory Syndrome , Depressive Disorder , COVID-19
Covid-19 may be associated with various neurological disorders, including dysautonomia, a dysfunction of the autonomic nervous system (ANS). In Covid-19, hypoxia, immunoinflammatory abnormality, and deregulation of the renin-angiotensin system (RAS) may increase sympathetic discharge with dysautonomia development. Direct SARS-CoV-2 cytopathic effects and associated inflammatory reaction may lead to neuroinflammation, affecting different parts of the central nervous system (CNS), including the autonomic center in the hypothalamus, causing dysautonomia. High circulating AngII, hypoxia, oxidative stress, high pro-inflammatory cytokines, and emotional stress can also provoke autonomic deregulation and high sympathetic outflow with the development of the sympathetic storm. During SARS-CoV-2 infection with neuro-invasion, GABA-ergic neurons and nicotinic acetylcholine receptor (nAChR) are inhibited in the hypothalamic pre-sympathetic neurons leading to sympathetic storm and dysautonomia. Different therapeutic modalities are applied to treat SARS-CoV-2 infection, like antiviral and anti-inflammatory drugs. Ivermectin (IVM) is a robust repurposed drug widely used to prevent and manage mild-moderate Covid-19. IVM activates both GABA-ergic neurons and nAChRs to mitigate SARS-CoV-2 infection- induced dysautonomia. Therefore, in this brief report, we try to identify the potential role of IVM in managing Covid-19-induced dysautonomia.
Subject(s)COVID-19 , Primary Dysautonomias , Humans , Animals , Bees , SARS-CoV-2 , Ivermectin , Hypoxia , gamma-Aminobutyric Acid
Subject(s)COVID-19 , Primary Dysautonomias , Humans , Consensus , SARS-CoV-2 , Disease Progression , Post-Acute COVID-19 Syndrome
IntroductionLong covid (LC), also known as Post-COVID-19 syndrome, refers to symptoms persisting 12 weeks after COVID-19 infection. It affects up to 1 in 7 people contracting the illness and causes a wide range of symptoms, including fatigue, breathlessness, palpitations, dizziness, pain and brain fog. Many of these symptoms can be linked to dysautonomia or dysregulation of the autonomic nervous system after SARS-CoV2 infection. This study aims to test the feasibility and estimate the efficacy, of the Heart Rate Variability Biofeedback (HRV-B) technique via a standardised slow diaphragmatic breathing programme in individuals with LC. Methods and Analysis30 adult LC patients with symptoms of palpitations or dizziness and an abnormal NASA Lean Test (NLT) will be selected from a specialist Long COVID rehabilitation service. They will undergo a 4-week HRV-B intervention using a Polar chest strap device linked to the Elite HRV phone application while undertaking the breathing exercise technique for two 10-min periods every day for at least 5 days a week. Quantitative data will be gathered during the study period using: HRV data from the chest strap and wrist-worn Fitbit, the modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm), composite autonomic symptom score (COMPASS 31), World Health Organisation Disability Assessment Schedule (WHODAS 2.0) and EQ-5D-5L health related quality of life measures. Qualitative feedback on user experience and feasibility of using the technology in a home setting will also be gathered. Standard statistical tests for correlation and significant difference will be used to analyse the quantitate data. Ethics and DisseminationThe study has received ethical approval from Health Research Authority (HRA) Leicester South Research Ethics Committee (21/EM/0271). Dissemination plans include academic and lay publications. Study RegistrationClinicaltrials.gov No: NCT05228665 Strengths and limitations of the studyO_LITo our knowledge, this is the first study of HRVB in long covid and will provide new information regarding the feasibility of the technology-based intervention in this condition. C_LIO_LIThe estimation of efficacy will determine the scope and sample size for a larger controlled trial in the condition that currently has no definitive treatments C_LIO_LIThe study will provide preliminary evidence on the correlation between long covid symptoms and dysautonomia. C_LIO_LIThe limitation of this study is the small sample size of 30 participants which might not give an accurate estimate of efficacy. C_LIO_LIHRV-B is a technology-based intervention, therefore its take-up could be limited in those with a lack of experience in using digital technology in daily life, particularly those from less privileged backgrounds. C_LI
Subject(s)Primary Dysautonomias , Fatigue , Severe Acute Respiratory Syndrome , Pain , Dizziness , COVID-19
Long-COVID-19 refers to the signs and symptoms that continue or develop after the "acute COVID-19" phase. These patients have an increased risk of multiorgan dysfunction, readmission, and mortality. In Long-COVID-19 patients, it is possible to detect a persistent increase in D-Dimer, NT-ProBNP, and autonomic nervous system dysfunction. To verify the dysautonomia hypothesis in Long-COVID-19 patients, we studied heart rate variability using 12-lead 24-h ECG monitoring in 30 Long-COVID-19 patients and 20 No-COVID patients. Power spectral analysis of heart rate variability was lower in Long-COVID-19 patients both for total power (7.46 ± 0.5 vs. 8.08 ± 0.6; p < 0.0001; Cohens-d = 1.12) and for the VLF (6.84 ± 0.8 vs. 7.66 ± 0.6; p < 0.0001; Cohens-d = 1.16) and HF (4.65 ± 0.9 vs. 5.33 ± 0.9; p = 0.015; Cohens-d = 0.76) components. The LF/HF ratio was significantly higher in Long-COVID-19 patients (1.46 ± 0.27 vs. 1.23 ± 0.13; p = 0.001; Cohens-d = 1.09). On multivariable analysis, Long-COVID-19 is significantly correlated with D-dimer (standardized ß-coefficient = 0.259), NT-ProBNP (standardized ß-coefficient = 0.281), HF component of spectral analysis (standardized ß-coefficient = 0.696), and LF/HF ratio (standardized ß-coefficient = 0.820). Dysautonomia may explain the persistent symptoms in Long COVID-19 patients. The persistence of a procoagulative state and an elevated myocardial strain could explain vagal impairment in these patients. In Long-COVID-19 patients, impaired vagal activity, persistent increases of NT-ProBNP, and a prothrombotic state require careful monitoring and appropriate intervention.
Subject(s)COVID-19 , Primary Dysautonomias , COVID-19/complications , Electrocardiography , Heart Rate/physiology , Humans , Post-Acute COVID-19 Syndrome
Subject(s)Autonomic Nervous System Diseases , COVID-19 , Primary Dysautonomias , Autonomic Nervous System Diseases/etiology , COVID-19/complications , Heart Rate/physiology , Humans , Sympathetic Nervous System/physiology , Ultrasonography, Doppler, Transcranial , Vagus Nerve , Post-Acute COVID-19 Syndrome
BACKGROUND: The association between autonomic dysfunction and long-COVID syndrome is established. However, the prevalence and patterns of symptoms of dysautonomia in long-COVID syndrome in a large population are lacking. OBJECTIVE: To evaluate the prevalence and patterns of symptoms of dysautonomia in patients with long-COVID syndrome. METHODS: We administered the Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaire to a sample of post-COVID-19 patients who were referred to post-COVID clinic in Assiut University Hospitals, Egypt for symptoms concerning for long-COVID syndrome. Participants were asked to complete the COMPASS-31 questionnaire referring to the period of more than 4 weeks after acute COVID-19. RESULTS: We included 320 patients (35.92 ± 11.92 years, 73% females). The median COMPASS-31 score was 26.29 (0-76.73). The most affected domains of dysautonomia were gastrointestinal, secretomotor, and orthostatic intolerance with 91.6%, 76.4%, and 73.6%, respectively. There was a positive correlation between COMPASS-31 score and long-COVID duration (p < 0.001) and a positive correlation between orthostatic intolerance domain score and post-COVID duration (p < 0.001). There was a positive correlation between orthostatic intolerance domain score and age of participants (p = 0.004). Two hundred forty-seven patients (76.7%) had a high score of COMPASS-31 >16.4. Patients with COMPASS-31 >16.4 had a longer duration of long-COVID syndrome than those with score <16.4 (46.2 vs. 26.8 weeks, p < 0.001). CONCLUSIONS: Symptoms of dysautonomia are common in long-COVID syndrome. The most common COMPASS-31 affected domains of dysautonomia are gastrointestinal, secretomotor, and orthostatic intolerance. There is a positive correlation between orthostatic intolerance domain score and patients' age.
Subject(s)COVID-19 , Orthostatic Intolerance , Primary Dysautonomias , COVID-19/complications , COVID-19/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Prevalence , Primary Dysautonomias/epidemiology , Primary Dysautonomias/etiology , Syndrome , Post-Acute COVID-19 Syndrome
BACKGROUND: The emergence of dysautonomia as a consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; or COVID-19) is becoming more prevalent. We have seen evidence in several post-COVID patients and in the literature of varying degrees of autonomic dysfunction. Symptoms, among others, include inappropriate tachycardia, sweating, anxiety, insomnia and blood pressure variability from the effects of excessive catecholamine, as well as cognitive impairment, fatigue, headaches and orthostatic intolerance from decreased brain perfusion. CASE PRESENTATION: We present a case of severe dysautonomia in a previously healthy 27-year-old runner. About five weeks after her initial mild COVID-19 infection, the patient began to develop weakness, which progressed into severe post-exertional fatigue, slowed cognition, headaches, blurred vision and generalized body aches. She also endorsed palpitations, especially when getting up from a seated or lying position as well as with mild exertion. She became reliant on her husband for help with her activities of daily living. Exam was significant for orthostasis; laboratory workup unremarkable. Over the following months, the patient's symptoms have improved slowly with fluid and sodium intake, compression stockings and participating in a graduated exercise program. CONCLUSIONS: Dysautonomia as a consequence of infection with COVID-19 is becoming increasingly discussed, especially as more patients recover from COVID-19. This is a case of a non-hospitalized patient with a mild initial presentation and significant, debilitating dysautonomia symptoms. More research on its pathophysiology, especially in relation to a precedent viral insult, as well as its treatment, is needed.
Subject(s)COVID-19 , Primary Dysautonomias , Activities of Daily Living , Adult , COVID-19/complications , Exercise , Female , Humans , Primary Dysautonomias/diagnosis , Primary Dysautonomias/etiology , SARS-CoV-2
Subject(s)COVID-19 , Primary Dysautonomias , Small Fiber Neuropathy , COVID-19/complications , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Primary Dysautonomias/etiology , SARS-CoV-2 , Small Fiber Neuropathy/etiology , Syndrome , Vaccination/adverse effects , Post-Acute COVID-19 Syndrome
The clinical characteristics of Guillain-Barré syndrome (GBS) after coronavirus disease 2019 (COVID-19) remain unclear due to the small number of cases. We herein report a case of a Japanese patient with post-COVID-19 GBS who presented with facial and limb muscle weakness, sensory deficits, and autonomic dysfunction. Nerve conduction studies revealed demyelination. Head magnetic resonance imaging showed contrast enhancement in the bilateral facial nerves. Systemic management, including intubation, intravenous immunoglobulin therapy, and rehabilitation, improved the patient's condition. This was the first Japanese case of acute inflammatory demyelinating polyneuropathy after COVID-19 and was characterized by autonomic dysfunction and facial nerve enhancement.
Subject(s)COVID-19 , Guillain-Barre Syndrome , Primary Dysautonomias , Facial Nerve , Guillain-Barre Syndrome/complications , Guillain-Barre Syndrome/diagnosis , Humans , Primary Dysautonomias/etiology , SARS-CoV-2
BACKGROUND: Individuals who contract coronavirus disease 2019 (COVID-19) can suffer with persistent and debilitating symptoms long after the initial acute illness. Heart rate (HR) profiles determined during cardiopulmonary exercise testing (CPET) and delivered as part of a post-COVID recovery service may provide insight into the presence and impact of dysautonomia on functional ability. OBJECTIVE: Using an active, working-age, post-COVID-19 population, the purpose of this study was to (1) determine and characterize any association between subjective symptoms and dysautonomia; and (2) identify objective exercise capacity differences between patients classified "with" and those "without" dysautonomia. METHODS: Patients referred to a post-COVID-19 service underwent comprehensive clinical assessment, including self-reported symptoms, CPET, and secondary care investigations when indicated. Resting HR >75 bpm, HR increase with exercise <89 bpm, and HR recovery <25 bpm 1 minute after exercise were used to define dysautonomia. Anonymized data were analyzed and associations with symptoms, and CPET outcomes were determined. RESULTS: Fifty-one of the 205 patients (25%) reviewed as part of this service evaluation had dysautonomia. There were no associations between symptoms or perceived functional limitation and dysautonomia (P >.05). Patients with dysautonomia demonstrated objective functional limitations with significantly reduced work rate (219 ± 37 W vs 253 ± 52 W; P <.001) and peak oxygen consumption (VÌo2: 30.6 ± 5.5 mL/kg/min vs 35.8 ± 7.6 mL/kg/min; P <.001); and a steeper (less efficient) VÌe/VÌco2 slope (29.9 ± 4.9 vs 27.7 ± 4.7; P = .005). CONCLUSION: Dysautonomia is associated with objective functional limitations but is not associated with subjective symptoms or limitation.
Subject(s)COVID-19 , Heart Failure , Primary Dysautonomias , COVID-19/complications , COVID-19/diagnosis , Exercise , Exercise Test , Humans , Oxygen Consumption/physiology , Primary Dysautonomias/diagnosis , Primary Dysautonomias/etiology
The SARS-CoV-2 pandemic has resulted in a secondary pandemic of individuals suffering from pernicious symptoms termed “Long COVID” or PASC. In spite of significant societal impact, the condition remains mysterious and effective treatment remains elusive. Individuals experience debilitating symptoms including fatigue, “brain fog,” loss or altered smell and/or taste, anxiety and depression. Most of these symptoms are included in the “sickness behavior response” initiated from the brainstem when levels of circulating pro-inflammatory cytokines are high. Ordinarily a feedback loop prevents excessive production of these cytokines, however the SARS-CoV-2 virus has demonstrated the ability to induce the sympathetic nervous system (SNS), likely due to imbalance between ACE1 and ACE2 activity. Persistent sympathetic drive causes increased cytokine release, which interferes with the feedback loop that ends “sickness behaviors.” The stellate ganglion is a paravertebral collection of sympathetic nerves located in the cervical region that provides a convenient entry point to reduce activity of the SNS using local anesthetic blockade. The stellate ganglion block (SGB) has a well-established safety and efficacy profile for a variety of conditions involving the SNS. In this case report series, we treated three consecutive “Long COVID” patients with SGB. All three patients reported significant and durable improvement in symptoms including fatigue, “brain fog,” and smell and taste derangements. Our findings provide evidence implicating dysautonomia as the main etiology of Long COVID/PASC symptoms and suggest that SGB is an effective intervention for this condition with the potential to change the course of the second COVID pandemic, “Long COVID”/PASC.