Unravelling Long COVID

Description:

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.

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Introduction

As the COVID-19 pandemic stretched on, it became abundantly clear that many patients had persistent symptoms long after all signs of the initial infection vanished. These lingering symptoms persist for months in 30% to 80% of patients who were hospitalized with COVID-19 infection and 10% to 30% who were not hospitalized. They appear in people across a wide spectrum of COVID-19 sufferers, including those with mild illness or even asymptomatic infections. These longlasting symptoms are present in adults and children, and current estimates suggest that at least 25 million Americans, and ten times that worldwide, have been or will be affected. Many experts believe that the persistent symptoms following acute COVID-19 will become the next major, global public health disaster.

Understanding these persistent symptoms has been wrought with confusion. Researchers and clinicians have not even agreed upon a name, with long COVID or long-haulers’ syndrome often used and post-acute sequelae of SARS-Cov-2 (PASC) recommended by most medical societies. There is not a uniform definition, and the proposed diagnostic criteria focus on the duration of symptoms rather than the nature of the symptoms. At the present time, patients, healthcare professionals, and scientists find themselves looking for answers about the nature of long COVID.

We believe that there are two main issues that have interfered with understanding long COVID. The first involves a failure to distinguish patients with an obvious source for their persistent symptoms from the many patients whose symptoms cannot be easily explained. The term long COVID was coined by patients to describe a constellation of persistent symptoms that were not being adequately acknowledged nor explained. Patients saw multiple physicians and were undergoing numerous tests, without answers.

We have made such a distinction, outlined initially in Section 1, by grouping patients with organ damage after COVID-19, what we term long-­COVID­disease, apart from those whose persistent symptoms are unexplained, what we call long-­COVID­syndrome. This grouping answers a diagnostic dilemma, described by Alwan in the July 2021 Science, “One important issue is whether ‘Long Covid’, as a label, will include organ pathology diagnosed weeks or months after COVID-19, or whether these cases move out into an alternative diagnostic category, leaving only those with ‘unexplained’ symptoms as having Long Covid” [1].

In the book’s first section, we detail the persistent symptoms and clinical course of patients with organ damage, suggesting that their disease pathways and outcomes are similar to those of patients after any severe illness. The perplexing issue is how to better understand the lingering symptoms following COVID-19 infection that are not explained by organ damage. These persistent symptoms have been called “medicine’s blind spot.” Such common, persistent symptoms have been a source of confusion and controversy for centuries. In Section 2, we compare such persistent symptoms to those in the general population and then in medical conditions most often compared to long COVID, including chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and fibromyalgia.

In Section 3, we explore the mechanisms underlying long-COVID syndrome. This requires an appreciation of brain homeostasis in health and disease and how alterations in central nervous system pathways can explain these symptoms. We suggest that, rather than a traditional autoimmune disease, long-COVID syndrome fits best within a neuroimmunologic framework.

In the final section of the book, we discuss current and future patient evaluation, including innovative research in long COVID. Finally, we discuss ongoing treatment programs, including dedicated long-COVID clinics throughout the world and guidelines for primary care awareness and optimal management. We examine the important role of patient advocacy and the potential impact of consumer-directed research. We suggest new approaches to balance physician and patient perspectives.

One of us, DG, was already researching long COVID, while writing his book Covid’s Impact on Heath and Health Care Workers. DG, Emeritus Professor of Medicine at Tufts University School of Medicine, is a rheumatologist and an international expert in many of the illnesses often compared to long COVID, including CFS/ME and fibromyalgia. He has evaluated and treated more than twentythousand patients with these conditions and has experienced the frustrations of his profession’s unsuccessful attempts to understand the causes of these very disabling conditions that inflict suffering on so many people. His interests in long COVID were stimulated by the common symptoms affecting long-COVID patients to those he has dealt with in patients for four decades.

Simultaneously and independently, his long-time friend and medical colleague, MD, Emeritus Professor of Neurology and Former Director of the Mahoney Institute of Neurological Sciences at the Perelman School of Medicine, University of Pennsylvania, is a neurologist physician-scientist with a life-long research interest in the intricate workings of the brain under normal conditions and in a variety of disease states. MD is particularly interested in researching and understanding the persistent or new brain-related symptoms that occur in people recovering from COVID-19. Despite living on opposite sides of the United States from one another, Portland, Oregon and Philadelphia, Pennsylvania, the two specialists decided to write this book together, meshing their complementary clinical and research interests.

The authors’ backgrounds in medicine are ideally suited to help people understand this vexing and mysterious disorder. DG has spent much of his career dealing with chronic illnesses that cannot be easily pigeonholed as physical or psychologic and are best appreciated from a biopsychological illness model. MD has focused his research on brain disease from a biomedical disease model. We believe that long COVID can be best understood by integrating biomedical and biopsychological illness models.

Table of contents :

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