A Practice-Based Approach to Emergency Department Evaluation and Management of Patients With Postacute Sequelae after COVID-19 Infection: Long COVID

Table of Contents

 

About This Issue

Though long COVID is a diagnosis of exclusion, patients who present to the ED with common symptoms may actually harbor a life-threatening condition unrelated to their COVID infection, or they may be suffering an exacerbation of a comorbidity. For emergency clinicians, the difficulty is in knowing how to provide effective, compassionate care without ordering unnecessary testing. In this issue, you will learn:

The definitions of COVID infection and the risk factors for progression to long COVID

The potential etiologies and mechanisms of the diverse symptoms that long COVID may produce

What to look for in patients with persistent pulmonary and cardiovascular complaints that may signal a life-threatening event

The highest-value laboratory and imaging studies, what you might expect to find, and when further testing is needed

The symptoms pediatric patients are most prone to

How to involve multidisciplinary collaboration in caring for long COVID patients: ED to outpatient follow-up

1. About This Issue
2. Abstract
3. Case Presentations
4. Introduction
5. Critical Appraisal of the Literature
6. Etiology and Pathophysiology
   1. Acute COVID Infection
   2. Long COVID Manifestations
   3. Long COVID Pathophysiology
      1. Postural Orthostatic Tachycardia Syndrome
      2. Persistent Fatigue
      3. Musculoskeletal and Dermatologic Disorders
      4. Pulmonary Pathology
      5. Cardiovascular and Coagulation Disorders
7. Prehospital Care
8. Differential Diagnosis, Emergency Department Evaluation, and Diagnostic Studies: Long COVID as a Phenotype and Diagnosis of Exclusion
   1. Initial Evaluation
   2. Laboratory Testing
      1. Ordering Further Testing
   3. Imaging Studies
   4. Cardiac Evaluation
   5. Neurologic Evaluation
   6. Psychiatric Evaluation
9. Treatment
   1. Pulmonary Symptoms
   2. Persistent Cough
   3. Fatigue
   4. Neurological Sequelae
   5. Depression and Mood Disorders
10. Special Populations
    1. Pediatric Patients
11. Disposition
12. Cutting-Edge Research
13. 5 Things That Will Change Your Practice
14. Risk Management Pitfalls for Emergency Department Patients With Long COVID
15. Summary
16. Time- and Cost-Effective Strategies
17. Case Conclusions
18. Tables and Figures
19. References

Abstract

Afflicting millions of people across the world, “long COVID” is a new disease entity that can present with a diverse array of symptoms of variable severity, affecting nearly every organ system. The presumptive diagnosis of long COVID is largely clinical, and should be made only after other serious etiologies have been excluded. Workup is driven by the patient‘s presenting acute symptoms, comorbidities, and physical examination findings. This issue reviews the research and current evidence on the etiology of COVID-19 infection and long COVID and presents a practice-based approach to the management of patients presenting with its postacute sequelae.

Case Presentations

A 35-year-old woman presents to the ED complaining of palpitations and retrosternal chest pain that is mostly relieved by sitting forward…

• The patient, who works as a paralegal and has been healthy all her life (although she smokes a half-pack of cigarettes daily), reports that her symptoms occasionally prompt anxiety so severe that she has self-treated with recreational marijuana. The palpitations have recurred frequently over the past 3 months, but she dates their initial incidence to a PCR-confirmed diagnosis of COVID-19 about 2 weeks before that.
• Her temperature is 37.8°C; heart rate,122 beats/min; blood pressure, 124/84 mm Hg; and respiratory rate, 24 breaths/min, with shallow breathing. Her ECG shows pronounced sinus arrhythmia.
• The patient reports that her initial COVID infection was treated conservatively as an outpatient but caused 2 weeks’ absence from work. Since then, her more-constant symptoms have been dyspnea with even minimal activity such as climbing 1 flight of stairs. She also complains of cough that is sometimes productive of yellowish sputum, with both tussive chest pain and back pain. The palpitations are worse than usual today and make her feel like she is “having a heart attack, or an aneurysm, or something bad.” This is her first ED visit for these symptoms, but she has visited her primary care provider’s office several times and been encouraged to hydrate and take acetaminophen.
• You consider whether there is anything that can be done to pinpoint a treatable cause of her symptoms—always following a “consider the worst case first” (here, perhaps pulmonary embolism), while also assuaging her anxiety...

A 25-year-old male healthcare worker presents to the ED complaining of several days of subjective fever, generalized fatigue and myalgias, sore throat, headache, and anosmia…

• The patient’s vital signs are normal, as are his cardiovascular and pulmonary examinations. There is a localized 4-cm-wide scaly, pink, macular eruption on his back that is notably pruritic. With his eyes covered, he cannot differentiate the odors of coffee, iodine solution, and water.
• The patient reports that similar symptoms have waxed and waned over the preceding 6 to 8 weeks, but the anosmia had been consistent since he was diagnosed with COVID-19 about 3 months ago. Upon further questioning, he reports 3 episodes over the past several weeks of mucoid, nonbloody diarrhea, which resolved with over-the-counter medications; relatively persistent nausea and poor appetite (though he reported no weight loss); easy fatigability; and recurrent episodes of “hives” that he had never experienced before and with which he had identified no potential precipitant.
• Other than being obese (body mass index, 32.1 kg/m²) and having a history of childhood asthma, he considers himself to be healthy. He presents today because he feels believes that these symptoms are related to his prior COVID infection, and he is concerned he may still be “carrying” the virus and putting both coworkers and patients at risk.
• You consider what the etiology of his rash might be, how ill he is, and how to discuss contagion risk with him at this point in his clinical course...

A 45-year-old woman presents to the ED complaining of 2 days of persistent diaphoresis and lightheadedness, with bilateral upper extremity “pins-and-needles” shooting pain…

• The patient reports that she had a confirmed COVID-19 diagnosis 8 weeks ago. Her acute COVID symptoms were mild headache and dizziness as well as typical upper respiratory infection symptoms. She was treated with nirmatrelvir/ritonavir (Paxlovid™) but had rebound symptoms after the treatment course. Her symptoms eventually subsided 2 weeks after stopping the medication.
• On physical examination, the patient has a normal temperature of 36.6°C; heart rate, 104 beats/min; blood pressure, 112/62 mm Hg; respiratory rate, 22 breaths/min; and oxygen saturation, 92% on room air. She is diaphoretic, but has an otherwise unremarkable physical examination, and a normal neurological examination.
• On further history, she reports that her upper extremity neurological symptoms occur several times a day. They are associated with activity and exertion, and are usually relieved by rest. She has seen several neurologists and had been put on a trial of pregabalin, without relief. This visit to the ED was prompted by the associated diaphoresis and lightheadedness that had not occurred in the past.
• At this point, what other diagnostic testing should be done for this patient, or should she be reassured and discharged?

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Risk Management Pitfalls for Emergency Department Patients With Long COVID

4. “His chest pain was really nonspecific, started only as his acute COVID symptoms resolved, and he’s only 39 years old. I didn’t feel like a full cardiac workup was indicated.” Myocarditis does occur in some patients with acute and post-COVID diagnoses, and it can be a significant cause of morbidity. Chest symptoms should be evaluated, even outside the usual risk groups in the setting of long COVID. Long COVID is not known to be associated specifically with acute coronary syndromes, but patients who have pre-existing coronary artery disease may be predisposed to acute ischemic events resulting from the physiologic stress of the acute or long-term symptomatology. As with patients who have no COVID considerations, chest pain and related potential anginal equivalents should always be taken seriously in the ED.

6. “He has had these chest symptoms for months since he had COVID, and his chest radiograph was unremarkable. The scanner was backed up with traumas, so I decided to have his primary care provider order the chest CT.” The most common abnormalities on chest CT in patients diagnosed with long COVID are ground-glass opacities, which are not related to specific, treatable pathology, and pulmonary fibrosis, which may present with acute flares. With or without a history of COVID, pulmonary embolism is always a differential consideration with nonspecific breathlessness. While CT scans in patients presumed to have long COVID are infrequently indicated in the ED, be sure to take the entire situation into consideration, including the reliability of follow-up for further workup as an outpatient.

9. “Her orthostasis persisted but hadn’t been worsening, so I just told her to push fluids.” A special subset of cardiovascular symptomatology that is not uncommon in patients with long COVID is POTS, which is thought to most likely be due to virus- or autoimmune-mediated dysfunction of the intrathoracic and brainstem chemoreceptors and mechanoreceptors. This can be debilitating for patients and can result in fall-related injury. When POTS is suspected, clinicians should take a patient history, conduct a physical examination, including orthostatic vital signs at regular intervals after standing up (with recording of associated symptoms), and order 12-lead electrocardiography. POTS symptoms typically respond to a combination of diet, salt/fluid intake management, and other treatments. This can be initiated in the ED and followed-up as an outpatient.

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Tables and Figures

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Key References

Following are the most informative references cited in this paper, as determined by the authors.

17. * U.S. Centers for Disease Control and Prevention. Long COVID or post-COVID conditions. 2022. Accessed December 10, 2023. (CDC website)

24. * Deer RR, Rock MA, Vasilevsky N, et al. Characterizing long COVID: deep phenotype of a complex condition. EBioMedicine. 2021;74:103722. (Review) DOI: 10.1016/j.ebiom.2021.103722

25. * Greenhalgh T, Knight M, A’Court C, et al. Management of post-acute COVID-19 in primary care. BMJ. 2020;370:m3026. (Review) DOI: 10.1136/bmj.m3026

26. * Mahase E. COVID-19: what do we know about “long COVID”? BMJ. 2020;370:m2815. (Review) DOI: 10.1136/bmj.m2815

41. * Mizrahi B, Sudry T, Flaks-Manov N, et al. Long COVID outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study. BMJ. 2023;380:e072529. (Retrospective nationwide cohort study) DOI: 10.1136/bmj-2022-072529

45. * Korompoki E, Gavriatopoulou M, Hicklen RS, et al. Epidemiology and organ specific sequelae of post-acute COVID-19: a narrative review. J Infect. 2021;83(1):1-16. (Review) DOI: 10.1016/j.jinf.2021.05.004

54. * Silva Andrade B, Siqueira S, de Assis Soares WR, et al. Long-COVID and post-COVID health complications: an up-to-date review on clinical conditions and their possible molecular mechanisms. Viruses. 2021;13(4):700. (Review) DOI: 10.3390/v13040700

56. * Disser NP, De Micheli AJ, Schonk MM, et al. Musculoskeletal consequences of COVID-19. J Bone Joint Surg Am. 2020;102(14):1197-1204. (Review) DOI: 10.2106/JBJS.20.00847

82. * Estiri H, Strasser ZH, Brat GA, et al. Evolving phenotypes of non-hospitalized patients that indicate long COVID. BMC Med. 2021;19(1):249. (Retrospective elecronic health record analysis; >96,000 patients) DOI: 10.1101/2021.04.25.21255923

103. *Sanchez-Ramirez DC, Normand K, Zhaoyun Y, et al. Long-term impact of COVID-19: a systematic review of the literature and meta-analysis. Biomedicines. 2021;9(8):900. (Review; 24 articles, 5323 adult patients) DOI: 10.3390/biomedicines9080900

143. National Institutes of Health. “NIH launches long COVID clinical trials through RECOVER Initiative, opening enrollment.” U.S. Department of Health and Human Services; 2023. Accessed December 10, 2023. (News release)

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Keywords: postacute sequelae after long COVID; PASC; COVID; SARS-CoV-2; cytokine storm; POTS; fatigue; cough