Appendix B: Suggestions for Future Research Focused on the Cellular and Molecular Basis of Long‐COVID Syndrome

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You should consult with a specialist where appropriate. Further, readers should be aware that websites listed in this work may have changed or disappeared between when this work was written and when it is read. Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages. Cover Title Page Copyright Page Contents Introduction Reference Section 1 Long-COVID Disease Chapter 1 Long-COVID Disease or Long-COVID Syndrome? Defining Long COVID Long-COVID Disease or Syndrome? Long COVID in Hospitalized Patients Long COVID in Non-hospitalized Patients Comparing Hospitalized and Non-hospitalized Patients Long COVID in Children Long-term Outcomes Summary References Chapter 2 Lung, Heart Disease, and Other Organ Damage Lung Disease Persistent Dyspnea, Not Always Correlated with Pulmonary Damage The Heart Is There Unanticipated Long-term Cardiac Damage? Other Organ Disease Summary References Chapter 3 COVID-19 Direct Effects on the Central Nervous System Introduction There are Multiple Ways for Infections to Disturb the Nervous System Overview Loss of Senses of Smell and Taste Hypoxic Brain Damage and the Post-ICU Syndrome Guillian-Barre Syndrome and Other Neuropathies – Effects of COVID-19 on Peripheral Nerves Other Neurological Disorders Due to Acute COVID-19 Summary References Section 2 Long-COVID Syndrome and Unexplained Symptoms Chapter 4 Unexplained Symptoms: Medicine’s Blind Spot Overview Fatigue Chronic Fatigue in the General Population Chronic Fatigue in Long-COVID Syndrome Cognitive Disturbances Cognitive Disturbances in the General Population Cognitive Disturbances in Long-COVID Syndrome Dyspnea In the General Population Unexplained Dyspnea in Long COVID Chronic Pain Chronic Pain in the General Population Chronic Pain in Long-COVID Syndrome Headaches Headaches in the General Population Headaches in Long-COVID Syndrome Sleep Disturbances Sleep Disturbances in the General Population Sleep Disturbances in Long-COVID Syndrome Mood Disturbances In the General Population Mood Disturbances in Long COVID Summary References Chapter 5 Historical Perspectives, Including Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Fibromyalgia Chronic Fatigue Syndrome, Myalgic Encephalomyelitis (CFS/ME) Fibromyalgia Syndrome CFS/ME, Fibromyalgia in Long-COVID Post-treatment Lyme-disease Syndrome (PTLDS) Similar Patient Characteristics Shared Illness Mechanisms Lessons Learned from CFS/ME, Fibromyalgia, PTLDS Syndrome, Disease, and Diagnostic Labels Infection and Causation Patient-Physician Information and Misinformation Mind or Body? Summary References Section 3 Mechanisms and Pathways Chapter 6 Brain Homeostasis Run Amok Brain Homeostasis in Health and Disease Our Physical Brain Regulates Our Thoughts Brain Circuits and Networks Neuroplasticity Brain Dysfunction Detecting Structural and Functional Brain Changes Changes in the Autonomic Nervous System, Neurohormones, and the Stress Response Summary References Chapter 7 Neuroimmune Dysfunction Is Long COVID an Autoimmune Disease? Evidence that Long-COVID Syndrome is a Neuroimmune Disorder Cytokines and the Brain Autoantibodies in Long-COVID Syndrome Can Vaccines also Cause Autoimmune Reactions? Immune Tests for Long COVID Neuroimmune Studies in CFS/ME, Fibromyalgia, and Depression Is a Unifying Theory of How Long-COVID Syndrome Develops Possible? Summary References Section 4 Evaluation and Management Chapter 8 Patient Evaluation and Research Need: Widely Accepted Long-COVID Term and Case Definition Need: Uniform Symptom and Outcome Measures Initial Evaluation, Primary Care Role Long-COVID Clinics Research General Clinical Research Basic Research Summary References Chapter 9 Patient Management and Rethinking Healthcare Amid Long COVID Management General Issues Pulmonary and Physical Rehabilitation Exercise Evaluate and Treat Autonomic Dysfunctions and Postural Orthostatic Tachycardia Syndrome Psychological Rehabilitation Medications and Other Therapies SARS-CoV-2 Vaccine Health Coverage, Disability Rethinking Healthcare Amid Long COVID Dealing with Medical Uncertainty Patient Advocacy Integrated, Patient-centric Care A Biopsychosocial Illness Model References Chapter 10 The Way Forward: For Patients, Healthcare Providers, and Research For Patients Do I have Long COVID? Where Do I Go for a Diagnosis? Assessing Illness Severity General Principles You Should Know Who Do You Listen To? Avoiding Misinformation and Disinformation Disability and Disability Insurance Biopsychological Perspectives to Remember For Healthcare Providers Making the Diagnosis Specialty Care Research, Patients, and the Public Basic Scientific Issues Bringing Long-COVID Patients and Researchers Together Treatment Trials A New Chronic Illness Strategy Summary References Appendix A Long-COVID Clinics in the US and Europe Appendix B Suggestions for Future Research Focused on the Cellular and Molecular Basis of Long-COVID Syndrome Hypothesis 1: Brain-restricted Autoimmunity causes Long-COVID Syndrome Background Evidence in Long- COVID How Else Might SARS-CoV-2 Infection Influence the Immune Response Leading to Long COVID? Hypotheses 2: SARS-CoV-2 Infection Alters the Microbiome, which in turn Initiates Long-COVID Syndrome What is the Microbiome and How does it Affect Immunity and the Brain? The Microbiome in COVID-19 Patients and in Individuals with Long-COVID Syndrome Hypothesis 3: Long-COVID Syndrome is Related to Persistent SARS-CoV-2 Virus or Virus Fragments Sequestered in Brain Cells Background References Index EULA Unravelling Long COVID An authoritative medical reference on the various ways in which Long-COVID presents and an in-depth discussion of its mechanisms and potential therapeutic options. Unravelling Long COVID aims to provide a better awareness and understanding of the persistent health problems that can arise following SARS-CoV-2 infection. Variously described as Long-COVID, Long-Haulers'Syndrome, and Post-Acute Sequelae of SARS-CoV-2, this newly-designated disorder is estimated to have affected somewhere between 50 to 250 million people. It is in fact considered by many as the next global public health disaster. With such a broad and important topic, the authors of Unravelling Long COVID have focused primarily on two major problems in the current understanding of Long-COVID: 1.) the failure to distinguish patients with organ damage—here called Long-COVID Disease – and those with unexplained, persistent symptoms—what is termed Long-COVID syndrome, and 2.) the failure of current medical approaches to comprehend and treat those persistent unexplained symptoms. Unravelling Long COVID is: One of the first books focused specifically on defining and understanding Long-COVID with the goal of establishing optimal management A unique reference to distinguish patients with organ damage caused by Long-COVID disease from those with unexplained, persistent symptoms that manifest as Long-COVID syndrome An in-depth exploration of neuroimmune pathways to help clarify the previously unexplained symptoms of Long-COVID Unravelling Long COVID isan essential reference for anyone interested in Long-COVID and the impact that this condition has had on the population. It will be a useful resource for both patients suffering from the Long-Covid syndrome, their physicians and for the growing number of Long-COVID clinics that have been established across the US, the UK, and other countries.This book is paired with a long-COVID blog, updated regularly by the authors, so the reader will be kept up to date with new clinical and research findings, in real time. To visit this site, follow this link: unravellinglongcovid.com – providing the latest information on long-COVID An authoritative medical reference on the various ways in which Long-COVID presents and an in-depth discussion of its mechanisms and therapeutic options. Unravelling Long-COVID aims to provide a better awareness and understanding of the persistent health problems that can arise following SARS-CoV-2 infection. Variously described as Long-COVID, Long-Haulers’ Syndrome, and Post-Acute Sequelae of SARS-CoV-2, this newly-designated disorder is estimated to have affected somewhere between 50 to 250 million people. It is in fact considered by many as the next global public health disaster. With such a broad and important topic, the authors of Unravelling Long-COVID have focused primarily on two major problems in the current understanding of Long-COVID: 1.) the failure to distinguish patients with organ damage—here called Long-COVID Disease – and those with unexplained, persistent symptoms—what is termed Long-COVID syndrome, 2.) and the failure of current medical approaches to comprehend and treat those persistent unexplained symptoms Unravelling Long-COVID is: One of the first books focused specifically on defining and understanding Long-COVID with the goal of establishing optimal management A unique reference to distinguish patients with organ damage caused by Long-COVID disease from those with unexplained, persistent symptoms that manifest as Long-COVID syndrome An in-depth exploration of neuroimmune pathways to help clarify the previously unexplained symptoms of Long-COVID Unravelling Long-COVID isan essential reference for anyone interested in Long-COVID and the impact that this condition has had on the population. It will be a useful resource for the growing number of Long-COVID clinics that have been established across the US, the UK, and other countries. This book will be paired with a long-COVID website, updated regularly by the authors, so the reader will be kept up to date with new clinical and research findings. Unravelling Long COVID An authoritative medical reference on the various ways in which Long-COVID presents and an in-depth discussion of its mechanisms and potential therapeutic options. Unravelling Long COVID aims to provide a better awareness and understanding of the persistent health problems that can arise following SARS-CoV-2 infection. Variously described as Long-COVID, Long-Haulers’ Syndrome, and Post-Acute Sequelae of SARS-CoV-2, this newly-designated disorder is estimated to have affected somewhere between 50 to 250 million people. It is in fact considered by many as the next global public health disaster. With such a broad and important topic, the authors of Unravelling Long COVID have focused primarily on two major problems in the current understanding of Long-COVID: 1.) the failure to distinguish patients with organ damage—here called Long-COVID Disease – and those with unexplained, persistent symptoms—what is termed Long-COVID syndrome, and 2.) the failure of current medical approaches to comprehend and treat those persistent unexplained symptoms. Unravelling Long COVID is: One of the first books focused specifically on defining and understanding Long-COVID with the goal of establishing optimal management A unique reference to distinguish patients with organ damage caused by Long-COVID disease from those with unexplained, persistent symptoms that manifest as Long-COVID syndrome An in-depth exploration of neuroimmune pathways to help clarify the previously unexplained symptoms of Long-COVID Unravelling Long COVID is an essential reference for anyone interested in Long-COVID and the impact that this condition has had on the population. It will be a useful resource for both patients suffering from the Long-Covid syndrome, their physicians and for the growing number of Long-COVID clinics that have been established across the US, the UK, and other countries. "An authoritative medical reference on the various ways in which Long-COVID presents and an in-depth discussion of its mechanisms and therapeutic options. Unravelling Long-COVID aims to provide a better awareness and understanding of the persistent health problems that can arise following SARS-CoV-2 infection. Variously described as Long-COVID, Long-Haulers' Syndrome, and Post-Acute Sequelae of SARS-CoV-2, this newly designated disorder is estimated to have affected somewhere between 50 to 250 million people. It is in fact considered by many as the next global public health disaster. With such a broad and important topic, the authors of Unravelling Long-COVID have focused primarily on two major problems in the current understanding of Long-COVID: 1. the failure to distinguish patients with organ damage--here called Long-COVID Disease -- and those with unexplained, persistent symptoms--what is termed Long-COVID syndrome, 2.and the failure of current medical approaches to comprehend and treat those persistent unexplained symptoms"-- Provided by publisher