Patients with Long COVID may share symptoms and receive similar treatment, but the disease remains an enigma.
For more than a decade after the 1918 influenza pandemic, “a mysterious Parkinson-like syndrome with sleep disturbance, hypomimia, and a high mortality rate developed in thousands of people across the globe,” write the authors of a recent editorial in the Annals of Internal Medicine. In 1920 the U.S. Surgeon General declared that the syndrome, popularly termed “encephalitis lethargica,” was caused by influenza. However, opinions varied, and even today, questions remain regarding its cause, transmission and treatment.
And here we are, a hundred years later, short on answers to another ill-defined post-pandemic illness, which some call “Long COVID.”
An enigma
It wasn’t until October 2021 that the World Health Organization published a clinical case definition: “Post COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually three months from the onset of COVID-19 with symptoms that last for at least two months and cannot be explained by an alternative diagnosis.” Common symptoms include fatigue, shortness of breath, cognitive dysfunction, and other symptoms that affect everyday functioning.
Complicating matters, some presentations of Long COVID resemble those of other post-viral syndromes, such as chronic fatigue syndrome, dysautonomia (e.g., postural orthostatic tachycardia syndrome [POTS]), or mast cell activation syndrome (MCAS). The CDC reports that some of these conditions have been reported in patients who recovered from severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), two other life-threatening illnesses resulting from coronavirus infections.
Given the difficulty defining Long COVID, it’s not surprising that statistics about its incidence vary widely. The World Health Organization, for example, believes that approximately 10% to 20% of COVID-19 patients experience lingering symptoms for weeks to months following acute SARS-CoV-2 infection.
The authors in the Annals editorial note that studies of SARS-CoV-2 infections indicate that up to 61% of patients have experienced symptoms that persist for months, occurring in hospitalized and nonhospitalized adults, adolescents and children. “However, the absence of well-defined control groups or reliance on serologic testing or self-reporting will limit improving our current understanding,” they write. “Even if only 10% of patients experience persistent symptoms after COVID-19, the number afflicted will easily be tens of millions.”
Meanwhile, a report in the Journal of the American College of Cardiology estimates that 33% to 98% of patients who have recovered from initial COVID-19 illness experience long-term manifestation of PASC, or post-acute sequelae of COVID-19 – a more formal name for Long COVID. The most-often reported symptoms are fatigue (28.3%-98%), headache (91.2%), dyspnea (13.5%-88%), cough (10%-13%), chest pain (5%-42.7%), anxiety/depression (14.6%-23%), and olfactory/gustatory deficits (13.1%-67.5%). Less frequent symptoms include palpitations/tachycardia (11.2%), concentration or memory deficits (23%), tinnitus or earache (3.6%), and sensory neuropathy (2.0%). Most symptoms are more frequently reported by women and older individuals.
Hard to believe
“Long COVID is a brewing public health crisis, yet there is no consistent system for how to manage people affected in the UK,” writes Professor Brendan Delaney from Imperial College London. “[W]hen patients go to their GP they often find themselves being bounced back and forth with different referrals and no clear answers.” Some providers fail to take complaints from their patients seriously. It’s a pattern set with other postinfectious disorders, such as mononucleosis and Lyme disease.
“Frustration frequently arises in these often marginalized patients with symptoms that some clinicians dismiss as only nonphysiologic or related to mental health,” according to Delaney. “On another angle, some alternative practitioners offer false hope with antibiotic treatments, using Lyme disease as a stand-in for chronic, medically unexplained symptoms without a basis in demonstrable infection. Moreover, desperate patients seek information through social media and take non-evidence-based treatments for chronic Lyme disease, partly due to modern mainstream medicine’s lack of effective approaches.”
CDC suggests that healthcare professionals choose a conservative diagnostic approach in the first four to 12 weeks following SARS-CoV-2 infection. Laboratory and imaging studies can often be normal or nondiagnostic in patients experiencing post-COVID conditions, and symptoms may improve or resolve during the first few months after acute infection in some patients.
“However, workup and testing should not be delayed when there are signs and symptoms of urgent and potentially life-threatening clinical conditions (e.g., pulmonary embolism, myocardial infarction, pericarditis with effusion, stroke, renal failure). Symptoms that persist beyond three months should prompt further evaluation.
“Overall, it is important for healthcare professionals to listen to and validate patients’ experiences, recognizing that diagnostic testing results may be within normal ranges even for patients whose symptoms and conditions negatively impact their quality of life, functioning (e.g., with activities of daily living), and ability to return to school or work.”
According to the CDC, holistic support for the patient throughout their illness course can be beneficial. Many post-COVID conditions can be improved through already established symptom management approaches (e.g., breathing exercises to improve symptoms of dyspnea). A comprehensive rehabilitation plan may be helpful for some patients and might include physical and occupational therapy, speech and language therapy, vocational therapy, as well as neurologic rehabilitation for cognitive symptoms.
Gradual return to exercise as tolerated could be helpful for most patients. Optimizing management of underlying medical conditions might include lifestyle counseling such as nutrition, sleep and stress reduction.
Long COVID clinics
Some health systems have created clinics specifically for people with Long COVID.
Norton Children’s in Louisville, Kentucky, for example, launched its Long COVID clinic in October 2020. “As infectious disease doctors, we’re always looking for up-to-date information about evolving diseases, as most infectious diseases do evolve,” infectious disease specialist Daniel Blatt, M.D., told Repertoire. “Long COVID was an emerging syndrome for a new disease. There wasn’t a lot of information out there, and we wanted to set up an all-encompassing clinic for people experiencing it. It isn’t only a resource for families and pediatricians, but also an exercise in learning about the disease and gathering data so we can help clinics all over the country.
“We provide a medical home for these patients, with the time and expertise in infectious disease to not only track their progress, but make sure we deal with compounding developments if necessary,” he says. The clinic has a sophisticated data-gathering system, which allows clinicians to track even subtle changes over time, and if necessary, refer the child to a specialist. “That’s the medical perspective. From the patient point of view, we offer a lot of reassurance and time, and someone to just listen to them. Most kids get better.”
WMCHealth in Valhalla, New York, launched its Post-COVID-19 Recovery Program in October 2020. The major symptoms with which patients present include fatigue, mental “fogginess” and shortness of breath, according to Carol Karmen, M.D. and Garry Rogg, M.D., internal medicine specialists with
Westchester Medical Center and the clinical leaders of the program. “These symptoms can be moderate to severe and very persistent. We have patients presenting now who have been sick since the start of the pandemic in the spring of 2020.
Given Westchester Medical Center’s wide variety of clinical specialties, “we are having success treating many of the symptoms,” they say. That said, “the neurocognitive effects of COVID-19, namely mental ‘fogginess’ and fatigue, are the most difficult problems to treat.”
Common diagnostic tests may turn up normal, “but after caring for so many patients with these symptoms, sometimes over many, many months, we are certain these symptoms are real. Program patients have shared stories telling how other physicians dismissed them. Because of this, they are so grateful WMCHealth established this program at Westchester Medical Center.”
The University of Texas Medical Branch in Galveston launched its Post-COVID Recovery Clinic in July 2020, says Tammy McCrumb, RN, clinic manager. “Our original mission was to support post-hospitalized patients, some of whom were going home oxygen-dependent and with limited physical mobility and overall status. Gradually, we shifted to treating more patients who had not been hospitalized. Now we have a combination of both.”
The hospital has a robust pulmonary rehabilitation program and is a COPD Center of Excellence, says McCrumb. “We treat [Long COVID] patients with chronic shortness of breath similarly as we do patients with COPD.” Most undergo pulmonary function testing and a comprehensive assessment of mobility, nutrition, sleep and mental health. Oxygen-dependent patients with complex medical histories receive one-on-one rehabilitation, while others receive group therapy and exercises to perform at home. Patients reporting dizziness or palpitations are often treated with an initial Holter monitor and are referred to cardiology for further evaluation if necessary.
“Early on, we referred many patients to neuropsychology, because we didn’t understand brain fog,” says McCrumb. “Now we evaluate all our patients using the Pittsburgh Sleep Quality Index, and we’re finding that some have undiagnosed sleep apnea and probably had it prior to COVID.”
Patients with Long COVID may share symptoms and receive similar treatment, but the disease remains an enigma. “Some of our elderly patients who were very sick recover amazingly well after a couple of sessions of pulmonary rehab,” says McCrumb. “On the other hand, some younger patients – even those who weren’t hospitalized – may struggle for months to recover. Everyone recovers differently.”
The physician practice
Physicians in solo or small-group practices should refer patients with dyspnea or fatigue to a regional pulmonary rehabilitation program, if one is available, advises McCrumb. Lacking such a program, however, they can point to online resources for breathing exercises for the home. “Above all, encourage your patients to increase their activity level. Encourage them to take two laps around the neighborhood instead of one. The more they increase their endurance, the quicker their recovery tends to be, even if it is little by little each day.”
Says Dr. Blatt, “If the private practitioner can tap into a local health system with infectious disease or multidisciplinary support, I would recommend doing that. We have the time to help these patients, and we’re available. Not every infectious disease practice focuses on Long COVID, but a primary care physician can always refer to the proper specialist based on the patient’s presentation.”
The independent practitioner can reassure patients that almost universally, patients with Long COVID get better, he says. “But in order to keep those patients safe during the process and to decrease the duration of the disease, refer for a specialist intervention when necessary.”
Drs. Karmen and Rogg at the WMCHealth’s Post-COVID-19 Recovery Program encourage physicians to keep in mind that the symptoms patients with Long COVID are complaining of are, in fact, real. “So many of our patients were told by a medical professional they have psychosomatic illness, PTSD, depression, or that they’re just ‘tired’ from the pandemic in general. After seeing close to 400 patients since we started this program, we are sure these symptoms are real, and we are doing everything we can do to help.”
Knowledge of post-COVID conditions is likely to change rapidly with ongoing research, says the CDC. Healthcare professionals and patients should continue to check for updates on evolving guidance for
post-COVID conditions.
Sidebar 1:
Smell retraining therapy
Smell retraining therapy (SRT) is a treatment for loss of smell, also referred to as hyposmia or anosmia. It is believed to work as a combination of the unique ability for smell nerves to regrow while encouraging improved brain connectivity.
Most studies on SRT have been done on patients with post-viral smell loss (i.e., following a cold or upper respiratory infection). Research findings on SRT for COVID-19-related smell loss are not yet available.
The process of SRT involves the repeated presentation of different smells through the nose to stimulate the olfactory system and establish memory of that smell. It is best to start with at least four different scents, especially smells you remember. The most recommended fragrances are rose (floral), lemon (fruity), cloves (spicy), and eucalyptus (resinous). Many people use essential oils, which can be purchased online or from local health food, aromatherapy or craft stores.
Take sniffs of each scent for 10 to 20 seconds at least once or twice a day. While sniffing, it is important to be focused on the task. Try to concentrate on your memory of that smell. After each scent, take a few breaths and then move on to the next fragrance. It is recommended that you do this for at least 12 weeks, but you can do it longer, alternating the scents if you like.
Source: American Academy of Otolaryngology–Head and Neck Surgery
Sidebar 2:
Long COVID and the lab
Before ordering laboratory testing for post-COVID conditions, the healthcare professional should be clear about the goals of testing, advises the Centers for Disease Control and Prevention. Laboratory testing should be guided by the patient history, physical examination and clinical findings.
A basic panel of laboratory tests should be considered for patients with ongoing symptoms (including testing for non-COVID conditions that may be contributing to illness). Expanded testing should be considered if symptoms persist for 12 weeks or longer.
Basic diagnostic lab testing
- Blood count, electrolytes, and renal function.
- Complete blood count with possible iron studies to follow, basic metabolic panel, urinalysis.
- Liver function.
- Liver function tests or complete metabolic panel.
- Inflammatory markers.
- C-reactive protein, erythrocyte sedimentation rate, ferritin.
- Thyroid function.
- TSH and free T4.
- Vitamin deficiencies.
More specialized testing
Specialized diagnostic tests for Long COVID should be ordered in the context of suggestive findings on history and physical examination. They include testing for:
- Rheumatological conditions.
- Antinuclear antibody, rheumatoid factor, anti-cyclic citrullinated peptide, anti-cardiolipin, and creatine phosphokinase.
- Coagulation disorders.
- D-dimer, fibrinogen.
- Myocardial injury.
- Troponin.
- Differentiate symptoms of cardiac versus pulmonary origin.
- B-type natriuretic peptide.
Source: U.S. Centers for Disease Control and Prevention