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Long COVID Management
Emerging Insights Into Long COVID Management: Embracing the Unknowns

Released: February 13, 2023

Expiration: February 12, 2024

Roger Paredes
Roger Paredes, MD, PhD
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Key Takeaways
  • Definitions of long COVID are imprecise, diagnostic and prognostic biomarkers are lacking, and its presentation is often confused with other conditions .
  • Patients with long COVID should be involved in the design of their individual care plans and therapeutic clinical trials.

Using conservative estimates, between 5% and 10% of COVID-19 cases (comprising at least 30 to 60 million people worldwide) may have developed long COVID. This is a novel, long-lasting, poorly understood, heterogeneous, and highly disabling post-viral syndrome.

Persisting circulation of increasingly transmissible SARS-CoV-2 variants forecasts that long COVID cases will continue to mount in coming years. This poses huge challenges to healthcare systems, has important implications for countries’ economies, impacts workforce organization, and threatens with sociopolitical unrest.

Defining Long COVID

Achieving a unified and robust definition of long COVID is essential to devise pathogenesis, diagnostics, and therapeutic clinical trials to optimize care for and provide relief to patients. It is also key to inform policymakers on how to best structure medical care and allocate resources for supporting patients with long COVID and their societies.

Using a Delphi consensus approach, the World Health Organization (WHO) defined post–COVID-19 condition as a syndrome occurring “in individuals with a history of probable or confirmed SARS CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms and that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include fatigue, shortness of breath, cognitive dysfunction but also others, and generally have an impact on everyday functioning. Symptoms may be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms may also fluctuate or relapse over time.”

Development of a clinical definition is a huge step forward, but it is still imprecise. On their own, most long COVID symptoms are nonspecific and have a small ability to discriminate long COVID from other conditions.

The WHO Delphi consensus was unable to quantify a minimum number of symptoms required to fulfil the long COVID definition. My experience caring for patients with long COVID, however, suggests symptoms tend to present in clusters. In our clinic, virtually all patients with post-COVID conditions present with fatigue and dyspnea; 30% have headache, arthralgia, and/or neurocognitive concerns; and approximately 20% report chest pain with tachycardia. Additionally, dysphagia, dysphonia, palpitations, shortness of breath, and intestinal motility symptoms often appear together, suggesting vagus cranial nerve dysfunction.

Although such “low-hanging fruit” symptom patterns require proper validation in large, curated clinical cohorts, there is emerging evidence of organicity in all of them. Brain fog translates in alterations in neuropsychological assessments and brain magnetic resonance imaging (MRI). Patients with new onset anginal chest pain often show small vessel subendocardial ischemia with normal coronary arteries in adenosine-stress myocardial MRIs. Palpitations often develop in patients with sinus dysfunction syndrome in electrophysiological studies. Patients in the vagus nerve dysfunction cluster often have diminished maximum inspiratory and expiratory pressures in functional lung evaluations, diaphragm asymmetries, and slower esophageal-gastric-intestinal transit in imaging techniques. 

The Many Unknowns

Post-viral syndromes have been described before, yet long COVID bears the largest patient burden ever seen in any of them and has specific particularities. Long COVID should not be confused with post-intensive care syndrome (PICS), even though some symptoms like weakness, brain dysfunction, and mental health challenges overlap.

Whereas PICS is made up of health problems that remain after critical illness, the vast majority of long COVID patients had mild—or even asymptomatic—acute COVID-19 and did not require hospitalization, suggesting each syndrome has a different pathogenesis.

Patients with long COVID are not simply depressed or fabricating their mental and/or physical concerns. In psychiatric evaluations, most patients with long COVID do not fulfil anxiety or depression criteria when they first present. However, patients may later develop anxiety and/or depression, particularly when they realize the persistence and lack of improvement of their disability. Long COVID is also different from fibromyalgia in many aspects; confusing these syndromes is not helpful for patients with either of them.

The main limitation in long COVID management today is the lack of objective, clinically validated diagnostic and prognostic biomarkers. Whereas an increasing understanding of long COVID pathogenesis is emerging from animal studies, the lack of a clear phenotypic definition or stratification in humans has led to biomarker studies often mixing patients with long COVID and PICS, patients with long COVID and acute or early post-acute COVID-19, and patients from different long COVID clusters with presumably different pathogenesis.

Long COVID Management Today

While we wait for these complexities to be disentangled, there are several ways we can greatly help our patients with long COVID.

First, we must believe patients and be empathetic. Be sincere with them and acknowledge the current limitations in long COVID knowledge and lack of specific therapeutics.

Second, we must work together with them to overcome their limitations caused by long COVID. Patients need to be involved in the design and implementation of clinical trials and patient care plans. It is also critical to offer them patient-centered, multidisciplinary care. Ideally, patient care should be organized around monographic, multidisciplinary long COVID units, and should include infectious disease, rheumatology, cardiology, pneumology, psychiatry, and occupational care and rehabilitation healthcare professionals. Hospitalists and primary care providers must work together to ensure seamless transitions of care. Primary care should be the mainstay of long COVID management, but efficient circuits with tertiary care are also essential to provide complementary diagnostic techniques such as MRIs, functional respiratory tests, and other means to rule out other conditions.

Finally, any therapeutic intervention for long COVID should be tested in a randomized clinical trial. It is essential to produce good quality evidence to determine what works and what does not for patients with such a complex syndrome.

Your Thoughts?

What is your biggest challenge in diagnosing patients with long COVID? What management or treatment strategies have you used successfully for patients with long COVID? Join the discussion by posting a comment below.