“What remains in diseases after the crisis is apt to produce relapses.”
“What people need to know is the pandemic’s toll is likely much higher than we are imagining. It’s an area that merits urgent attention. There will be people living with the impact of COVID long after the pandemic is over.”
- Craig Spencer, M.D., Director of Global Health in Emergency Medicine, New York—Presbyterian/Columbia University Irving Medical Center
Why revisit the long-term complications of COVID-19 only seven months after my last Germ Gems post on this topic? (“Post-COVID Fatigue: The New Chronic Fatigue Syndrome?” August 5, 2020 Germ Gems.) The main reason is the enormity of its impact has come into much sharper focus. It is now known that the long-term complications of COVID-19 not only affect the lives of those afflicted, but also the healthcare system, the economy, and society in general. Even if one conservatively assumes that only 10% of COVID-19 survivors suffer with post-COVID-19 fatigue, that means that more than 9 million people globally are afflicted with this debilitating disorder.
A second reason for revisiting this topic is that, although there are still more questions than answers, we already know a lot more about the long-term complications of COVID-19 than we did seven months ago. In this Germ Gems post, I provide an update on research on this complication of COVID-19.
And the good news is…Since my August 5th post, a number of research programs have been launched to study the long-term complications of COVID-19. And their results are now beginning to be published. Most notably are:
· The Center for Post-COVID Care at Mount Sinai Hospital in New York City (featured in a January, 2021 New York Times article: “What If You Never Get Better From Covid-19”);
· An interdisciplinary research program at Jin Yin-tan Hospital in Wuhan, China (where the COVID-19 pandemic emerged in December 2019) recently provided results of a study of hospitalized patients in The Lancet on January 2021: “6-month consequences of COVID-19 in patients discharged from hospital: a cohort study”;
· The University of Washington’s “COVID-19 Resource Center” published data on outpatients in the Journal of American Medical Association in February, 2021: “Sequelae in Adults at 6 Months After COVID-19 Infection”; and
· University College London’s “COVID Symptom Study” report on both hospitalized and outpatients in the March, 2021 issue of Nature Medicine: “Attributes and predictors of long COVID.”
Hopefully, in the not too distant future, we should all have a better understanding of this disorder.
What’s in a name? You might think that naming an illness is much ado about nothing. But it is not. Naming an illness is actually critical so that researchers are sure they’re studying the same entity. So, what is the best (agreed upon name) for the long-term complications of COVID-19?
In my earlier post, I called this illness “post-COVID-19 fatigue.” A number of other names have been proposed, such as, “long COVID,” “long hauler syndrome,” “post-acute Covid syndrome,” and most recently, “PASC,” an acronym standing for post-acute sequelae of SARS-CoV-2 infection suggested by National Institute of Allergy and Infectious Diseases director, Dr. Anthony Fauci. (In my research career, I studied another disabling illness called chronic fatigue syndrome [CFS] that was renamed “Systemic Exercise Intolerance Disease” by the National Academy of Medicine—a name that never caught on. Based on my past experience with CFS, I am skeptical the name “PASC” will stick.) It may be awhile before the international research community finally settles on a name for this disorder. For now, I think “long COVID” is most apt.
Epidemiology of long COVID. By definition, all patients with long COVID have a laboratory-confirmed diagnosis of acute SARS-CoV-2 infection and continue to suffer with symptoms attributed to COVID-19 for a prolonged time period. This definition gives doctors and researchers a starting point in helping determine which patients may have long COVID. It is, however, imprecise and begs two questions that are as yet unresolved: What are the symptoms? How long is prolonged?
Dozens of symptoms have been recorded in long COVID patients. “Fatigue” is, however, the most common. It is followed by “neurocognitive abnormalities” (difficulties with memory and concentrating, often referred to as “brain fog”), sleep difficulties, headache, dyspnea (shortness of breath), and anosmia (loss of the sense of smell). The degree of disability varies from patient to patient. But many patients with long COVID are unable to work or attend school, and some can barely get out of bed or walk up a flight of stairs.
Researchers are not in agreement as to how long the symptoms must last to qualify as “prolonged.” Some research groups say prolonged means continuing for “at least 4 weeks,” others suggest a duration of “at least 6 months” to meet the long COVID-19 criterion.
Another important question that hasn’t yet been answered is how many patients develop long COVID? Estimates vary from 10% to 80%. Most studies, however, suggest that about one-third of COVID-19 patients develop long COVID. Patients with severe COVID-19 appear to be at greatest risk of developing this illness. But in some studies, the onset of long COVID developed in patients who were asymptomatic at the time of their SARS-CoV-2 infection. Consistently, women appear to be at greater risk of long COVID than men. And while most of the literature to date has focused on adults, an increasing number of reports deal with children suffering with this disorder.
Proposed mechanisms underlying long COVID. Fatigue is a prominent symptom in many medical conditions, including chronic heart, lung, liver, or kidney disease, autoimmune diseases, a variety of endocrine disorders, cancers and CFS. It is estimated that every year 1.5 million Americans see their physicians due to feeling fatigued; it is one of the most common reasons patients seek medical help. Yet there is absolutely nothing known about the pathophysiology of the symptom fatigue. Because many patients with severe COVID-19 experience heart, lung, or kidney disease during the acute phase of their SARS-CoV-2 infection, this may complicate assessment of patients with long COVID.
Many of the features of long COVID are reminiscent of CFS, a syndrome that was first described for researchers in the Annals of Internal Medicine in 1988. Many infectious diseases, including infectious mononucleosis, brucellosis, and Q fever, were recognized historically to trigger a CFS-like illness. But as hard as research groups around the world tried to discover the cause and mechanism underlying CFS, the disease remains idiopathic, that is, its cause is unknown. (As I have suggested before, the word more accurately means it is “idiotic” on the part of physicians and “pathetic” for patients).
Many of the same hypotheses that were tested in research on CFS have resurfaced in the thinking about long COVID. For example, some think it’s an immunological disorder (cytokine-mediated), or an autoimmune disease, or a form of dysautonomia, or a chronic neurological condition. Some researchers, however, have opined that attempts to compare long COVID to other conditions is a disservice to thousands of people, and could result in missed pathology to the detriment of patients. I agree. Simply put, it is essential that researchers keep open and fresh minds when searching for the cause of this illness.
Treatment and prognosis. Several potential therapies of long COVID have been mentioned in the literature, including administration of the COVID-19 vaccine (under investigation at Imperial College London). The hypothesis behind this treatment is that the virus SARS-CoV-2, or bits of the virus, are lurking in the body of patients with long COVID and that stimulation of their immune system eradicates this nidus of chronic infection.
Another treatment that looks promising is under study at Mt. Sinai Hospital in New York City. Researchers there were struck by the abnormal breathing pattern of long COVID patients. They introduced a science-based breathwork program, designed by a company called Stasis, to try to restore normal breathing patterns in the sickest patients. The Stasis program is deceptively simple and strikingly low-tech. It involves inhaling and exhaling through your nose in prescribed counts in the morning and at night.
No treatments have yet been subjected to randomized clinical trials. So it is too early to endorse any particular treatment. The same can be said about providing a prognosis of long COVID. At this time in research of the illness, it is simply too early to tell how many patients recover on their own, despite being ill for 6 or more months.
Encouraging future prospects. Initially, many physicians and people in general dismissed CFS as being a real illness. As a result, many CFS patients were not taken seriously and suffered needlessly. As Linda Hillenbrand, American Author of “Seabiscuit” and “Unbroken”, who is a CFS patient wrote: "Most people, when they hear the disease name, it’s all they know about. It sounds so mild. When I was first sick, I was dismissed. I was ridiculed and told I was lazy. It was a joke."
In contrast to CFS, long COVID is being taken seriously from the very beginning. On March 4, 2021, under the leadership of its director, Francis Collins, the National Institutes of Health announced an investment of $1 billion to investigate long COVID. On March 12, 2021, CNN reported that the investment of Ron Davis, a professor of biochemistry and genetics at Stanford University whose son suffers from CFS, could “help unravel the mystery of Covid-19 long haulers.” Professor Davis has raised considerable funding for research on his son’s disease, the hallmark of which is disabling fatigue, that hopefully will yield insights that are also relevant to other conditions in which fatigue is a prominent symptom, like long COVID.
For those suffering with long COVID, it should be reassuring to know that such illustrious research institutions and researchers are pulling for them. And as an infectious diseases physician who did research on CFS and cared for many patients considered at the time to have an invalidated illness, I personally find this extremely encouraging.