A Quick Reference Guide to Common Conditions Associated with Long Covid

Coronavirus disease 2019, also known as COVID-19, is a systemic viral infection caused by the SARS-CoV-2 virus, initially identified in December 2019. Individuals with a COVID-19 infection may be asymptomatic. However, the majority will experience a range of signs and symptoms such as fever, cough, body aches, rashes, and loss of the sense of smell that resolves spontaneously within two weeks. However, in some individuals, signs and symptoms of COVID-19 may persist beyond the acute phase; this is called Long COVID, or post-COVID conditions (PCC), and involves long-term effects that can be physical, cognitive, or psychological. The exact cause of Long COVID isn’t fully understood but is likely related to multiple pathophysiologic interactions between the virus and the body’s immune system.

Let’s take a closer look at some of the common signs and symptoms related to Long COVID.

Fatigue

One of the most common symptoms of long COVD is a type of fatigue that tends to worsen following exertion, so it’s also sometimes called post-exertional malaise (PEM). PEM is often described as overwhelming, severe, and affecting one’s quality of life, including the ability to complete activities of daily living (ADLs). It typically occurs following any physical, emotional, cognitive, or social activity, worsens 12 to 72 hours following the activity, and can worsen other medical conditions or Long COVID symptoms.

PEM is diagnosed based on a thorough history and review of symptoms. Treatment can involve a combination of nonpharmacologic and pharmacologic interventions. Nonpharmacologic interventions are typically first-line and can take the approach following the three Ps: planning, pacing, and prioritizing. Planning involves identifying tasks done on a daily and weekly basis, then developing a schedule for how to complete those tasks by considering energy levels and level of difficulty for each task. Next, pacing involves completing tasks in shorter increments by spreading them throughout the day, planning rest time, or adjusting the tasks to require less energy. Finally, prioritizing involves identifying the order of our tasks to determine which should be handled first and those which are less important, and focusing on those that must be done, like eating, showering, or dressing.

Other nonpharmacologic interventions can include establishing a healthy sleep routine, using relaxation techniques, keeping an activity diary, eating a balanced diet, and engaging in regular physical activity as possible.

Individuals who don’t respond to these initial interventions may try exercise-based therapy or rehabilitation, which uses various exercises to help them regain, maintain, or strengthen their flexibility, endurance, and balance. These types of interventions may be beneficial for PEM as well as other symptoms associated with Long COVID.

While we need more research on pharmacologic interventions for PEM, early evidence has shown some promising medications may help, including methylphenidate, a stimulant; duloxetine, a serotonin-norepinephrine reuptake inhibitor (SNRI), and brexpiprazole, a serotonin-dopamine activity modulator. Other medications that may be beneficial include modafinil, a non-amphetamine stimulant, and amantadine, a dopamine agonist. There is also promise that low-dose naltrexone, an opioid antagonist, may be helpful in individuals who have not responded to other pharmacologic interventions.

Headache

Next, headaches are a common symptom of Long COVID. COVID-19 headaches are most commonly classified as new, daily, persistent headaches, though some individuals may present with intermittent headaches. They are typically moderate to severe in intensity with variable location (e.g., frontal, periocular, temporal).

Long COVID diagnosis is made using a thorough history and review of symptoms. Treatment of these headaches can include nonpharmacologic and pharmacologic interventions. Nonpharmacologic interventions include lifestyle modifications, like healthy sleep habits and physical exercise, physical therapy, and cognitive behavior therapy (CBT). Pharmacologic interventions begin with analgesics, like acetaminophen; non-steroidal anti-inflammatories (NSAIDs), like ibuprofen; and triptans, like sumatriptan. Some individuals may require prophylactic medications meant to prevent headache onset, which can include tricyclic antidepressants (TCAs), like amitriptyline, and antiseizure medications, like valproate.

Changes to Sense of Smell

Next, changes to the patient’s sense of smell are a common symptom of COVID-19 infection and arguably the most specific to the SARS-CoV-2 virus. In some individuals, sense of smell changes can persist past the acute phase and be a symptom of Long COVID, lasting months to years. However, for most individuals, symptoms resolve gradually within 12 months. Changes experienced may involve parosmia or a distorted sense of smell, like when a normally pleasant odor now smells bad; anosmia, or a complete loss of smell; or hyposmia, a partial loss of smell.

Diagnosis of parosmia, anosmia, and hyposmia relies on a history and review of symptoms. The Sniffin’ Sticks Parosmia Test (SSParoT), which uses smelling sticks with both pleasant and unpleasant odors to qualitatively assess changes to the sense of smell, may also be used to aid in diagnosis. The healthcare professional may also assess whether the changes to the sense of smell have affected an individual’s appetite and nutritional status by evaluating their weight and laboratory tests (e.g., albumin, ferritin).

Treatment for changes to sense of smell caused by COVID-19 may not always be necessary, as most cases spontaneously resolve. However, for those requiring treatment, interventions are currently limited but can include nonpharmacologic and pharmacologic interventions.

Nonpharmacologic interventions can include smell training, which involves exposure to different odors daily to gradually improve their sense of smell. On the other hand, pharmacologic interventions can include antiepileptic medications, such as valproate acid and gabapentin. Studies also show promise in stellate ganglion blocks to improve or restore sense of smell. Further research into pharmacologic options for parosmia, anosmia, and hyposmia are ongoing.

Dysautonomia

Lastly, dysautonomia, also called autonomic dysfunction or secondary dysautonomia when it is due to Long COVID, can be one of the most debilitating symptoms. Dysautonomia is a group of disorders that occur when the autonomic nervous system, responsible for involuntary processes in the body, is dysfunctional.

Signs and symptoms include palpitations, dizziness, low blood pressure, and syncope, and can occur suddenly and unexpectedly. Classically, dysautonomia can present with orthostatic hypotension, which is low blood pressure that occurs after changing position and is often associated with dizziness, shortness of breath, near-syncope, or syncope.

Diagnosis is made using a thorough history, physical examination, laboratory tests, and bedside tests (e.g., orthostatic vital signs, tilt table) to aid in diagnosis. Treatment for dysautonomia focuses on symptom management and improving quality of life. Treatments can include interventions to maintain blood pressure, like using compression socks, changing position slowly, increasing salt and water intake, and avoiding warm and humid environments. For some individuals, pharmacologic management may be indicated and can include midodrine or droxidopa, both adrenergic agonists; fludrocortisone, a corticosteroid; or infusions of intravenous (IV) fluids, among others.

Explore Additional Common Conditions

About the Author

Kelsey LaFayette, DNP, ARNP, FNP-C, Nursing Content Manager at Osmosis from Elsevier, obtained a Bachelor of Arts in Nursing degree from Luther College in 2011. As an RN, she has a clinical background in medical and pulmonary inpatient units, urgent care, and critical care, and obtained her Doctor of Nursing Practice degree at the University of Illinois at Chicago in 2022. Throughout her career, Kelsey has had many opportunities to function in an education role by being a charge nurse, preceptor to new RNs and nursing students, as well as a Clinical Team Lead in charge of creating orientation programs and policies. Through these opportunities, Kelsey realized her ideal career path should focus on the education of nurses, nursing students, patients, families, and anyone else with a desire to learn. Kelsey serves as a manager on the Nursing Content team and has been able to work on various projects that fulfill her love of perpetual learning.

Reviewer

Lisa Miklush, PhD, RN, CNS, Senior Content Editor

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