Delayed Diagnosis of Chronic COVID Syndrome
1Resident Physician, Department of Pediatrics, University of South Florida
2Assistant Professor of Pediatrics, Department of General Pediatrics, University of South Florida
Havlicek E, Suneia U. A case of missed chronic COVID syndrome. Consultant. 2023;63(6):e2. doi:10.25270/con.2022.11.000011
Received March 30, 2022. Accepted October 25, 2022. Published online December 21, 2022.
The authors report no relevant disclosures.
Elizabeth Havlicek, DO, Tampa General Circle 5th Floor, Tampa, FL 33606 (firstname.lastname@example.org)
Introduction. For more than three years now, COVID-19 continues to appear as a variety of symptom sets in the pediatric population—from completely asymptomatic presentations to fulminant respiratory failure, and everything in between.1 Clinicians are heavily reliant on diagnosing COVID-19 through either rapid antigen testing or reverse transcription polymerase chain reaction (RT-PCR) testing due to the increasing overlap of COVID-19 symptoms to other respiratory, neurologic, and gastrointestinal pathologies.
Both laboratory-based and at-home rapid antigen testing have been shown to have reliability dependent on the brand of the test, and sensitivities for rapid antigen testing have been shown to vary anywhere from 24% to 88%.2-4,8 Some data has shown that most rapid antigen testing brands are not reliable at identifying the presence of COVID-19 in samples with low viral loads and that viral loads may not reveal a positive antigen test until 2 to 5 days after symptom onset.5 Although both nucleic acid amplification testing (NAAT) and RT-PCR has been shown to be reliable, false negative rates for these tests can remain high when utilized too early or too late during illness.6-7
The development of SARS-CoV-2 variants has raised additional concerns about the reliability of rapid antigen testing. Most antigen testing targets the nucleocapsid protein, whereas the most frequently mutated portion of the virus is the spike protein.8 Variations in spike protein have presented testing concerns with accuracy of NAAT. However, according to the FDA, this testing modality will still detect SARS-CoV-2 RNA directly, even if it fails to detect spike protein gene secondary to mutations.9
Solidifying a diagnosis of COVID-19 has proven to be challenging. Of course, our developing knowledge regarding inaccuracy of testing during certain points in the illness has helped us to improve our testing of symptomatic individuals. However, COVID-19 still has symptom presentations that are being newly discovered and analyzed, and we have not perfected our ability to recognize and diagnose based on symptomatology alone.
Data regarding chronic COVID syndrome, known as long COVID, has been published much more frequently as of this writing, however significant data still does not exist in the pediatric population. The most recent data indicates that pediatric patients may follow trends as published in adult studies, displaying persistent symptoms primarily of fatigue, poor concentration, cough, and myalgias.10 Chronic COVID syndrome has been shown to affect the adolescent population almost as significantly as the adult population,11 as we note in our case report.
Keywords: Chronic COVID-19 Syndrome, long-haul COVID-19, chronic fatigue
Case description. This was a case of a 17-year-old man who was followed by our primary care clinic at an urban, academic institution. He presented to our clinic in October of 2021 with the primary complaint of ongoing nonproductive cough and persistent fatigue.
Patient history. The patient’s symptoms had been ongoing, though improving since he contracted a flu-like illness in early August of 2021. His initial illness in August of 2021 presented with a wet cough producing green phlegm, nasal congestion, loss of appetite, weight loss of 14 lbs, sore throat, shortness of breath, myalgias, and significant fatigue that had been ongoing for roughly 8 days prior to presentation. He had fevers for 6 days. He underwent a SARS-CoV2 PCR test on day 6 of his illness at an outside facility, which was reportedly negative. He denied any night sweats, recent travel, rash, or contact within a health care facility or prison. He did not experience chills, nausea, vomiting, skin changes, diarrhea, or constipation. At baseline he is a well-developed adolescent, active basketball player, and athlete. But he admitted to poor exercise tolerance and increased fatigue, sleeping up to 14 hours per day. His medical history is significant for attention-deficit/hyperactivity disorder requiring medical management that was discontinued more than 2 years ago. He also mentioned a distant history of allergic rhinitis with no changes in recent allergen exposures or current medical management.
Physical examination. Physical examination did not reveal any lymphadenopathy, rashes, or joint swelling/tenderness. No abdominal masses or hepatosplenomegaly were noted. Genitourinary examination did not reveal any penile discharge or rashes. Mild erythema to posterior oropharynx was noted, without any exudate or subjective sore throat.
During his illness course in August 2021, it was reported that one of his most recent sexual partners tested positive for gonorrhea. He denied having unprotected intercourse. A serum gonorrhea and chlamydia test were negative at that time. He also received an influenza swab, a mononucleosis spot test, and serum HIV testing, which were all negative. A complete blood count was unremarkable. At the current visit, he reported gradual improvement in symptoms. A point of care strep antigen test was obtained given the patient’s posterior pharynx erythema noted on physical examination, which was negative. A COVID IgG antibody was ordered and returned positive.
Treatment and management. Thyroid profile was also considered due to fatigue symptoms, though was not obtained secondary to COVID IgG results and improvement of symptoms. The patient was not vaccinated against SARS-CoV-2 so the antibody positivity was attributed to a probable recent COVID infection. Patient and family were counseled on the importance of supportive care while gradually recovering from his suspected chronic COVID symptoms.
Patient outcome. The family received reassurance through diagnosis and education that this illness can be managed with supportive care, and they can likely expect continued improvement. It was recommended the patient be seen in 3 to 6 months for repeat evaluation, though the patient was lost to follow-up.
Discussion. Given this patient’s symptom timeline of 7 to 8 weeks at time of presentation, it is unknown whether he would have tested positive for IgG antibodies at his initial presentation in late August 2021, after having symptoms for 8 days. Of course, the positive SARS-CoV-2 IgG does not allow us to confirm with 100% certainty a diagnosis of COVID-19 and it does not eliminate the chance that he could have previously been infected prior to his presentation in August.
Since this patient’s initial presentation, the scientific community has continued to gather even more knowledge of risk factors, symptom presentation, therapies, and management of chronic COVID syndrome. In a single review published in December of 2021, the prevalence of chronic COVID syndrome varied from 4% to 66% across 10 previous internationally published articles.12, 15 As of this writing, researchers have identified chronic COVID syndrome as one of two major complications of SARS-CoV-2 infection in children, the other being multisystem inflammatory syndrome in children (MIS-C). Although chronic COVID syndrome carries a much lower morbidity and mortality than MIS-C, it is estimated to be more prevalent in the pediatric population. Still, significant data on the outcomes of chronic COVID syndrome have yet to be published. MIS-C exists on a very severe end of a post-infectious pro-inflammatory spectrum, and though chronic COVID syndrome may not present as severely, it has been hypothesized that it is this same post-infectious multi-organ system inflammation and metabolic alteration that may lead to the symptoms as described below.12,17
Several studies have described the adverse effects associated with COVID-19 infection or chronic COVID syndrome in pediatric patients. Symptoms of chronic COVID syndrome have been shown to impact nearly every organ system, though the most described symptoms are largely neuropsychiatric in nature: prolonged fatigue, impaired concentration, and sleep disturbances.12,13Persistent headache, abdominal pain, gastrointestinal disturbances, myalgias, cough, chest tightness, alterations in smell, and fluctuations in weight have also all been described in pediatric patients with chronic COVID syndrome.12-14 Thus far, the literature seems to have a wide timeline of persistence of symptoms, ranging anywhere from 4 weeks to 8 months after presence of initial infection with SARS-CoV-2.12-16,19
Though gastrointestinal changes are not the most prevalent symptoms of chronic COVID syndrome, one study found that the persistence of viral shedding in the gastrointestinal tract may play a part in prolonged course and symptom duration of patients with sub-acute and long COVID-19.18
Other studies have shown that patients who were admitted to the intensive care unit, children with pre-existing allergic conditions, and individuals of older age were more likely to experience symptoms of long COVID.11,17 Our patient’s history of allergic rhinitis in addition to his age at time of infection may both be contributors to his experienced fatigue severity. It is worth noting that the difficulty in diagnosing long COVID is due largely to its ability to act on multiple organ systems, present in a variety of ways, and at a varying timeline in illness course.19
While some symptoms of chronic COVID syndrome may be difficult to manage for many providers, there are interventions that may prove beneficial to minimize symptom burden and shorten the course of illness in many pediatric patients. Children with underlying respiratory conditions or pulmonary symptoms of chronic COVID syndrome may benefit from thorough pulmonary assessments, with the possibility of benefit from bronchodilators, inhaled steroids, or both. General rehabilitation in the adult and pediatric populations has been mentioned as likely beneficial for recovery of chronic COVID syndrome, largely for physical symptoms of fatigue and deconditioning. In addition, neuropsychologic support through counseling and cognitive therapy has been reviewed as a possible benefit to well-being and mental health.12,17
In short, review of the presenting symptoms and severity of each individual patient is important to assess follow-up and appropriate management. There is a possibility for subspecialist involvement if the general pediatrician feels the patient may warrant more specific therapies. The American Academy of Pediatrics has endorsed follow-up for patients experiencing residual symptoms of initial SARS-CoV-2 infection at the discretion of the pediatrician, though some authors have published their recommendations for follow up at 3-month intervals after SARS-CoV-2 infection to assess for residual symptoms and possible interventions.12,20
- Gavriatopoulou M, Korompoki E, Fotiou D, et al. Organ-specific manifestations of COVID-19 infection. Clin Exp Med. 2020;20(4):493-506. doi:10.1007/s10238-020-00648-x.
- Dinnes J, Deeks JJ, Berhane S, et al. Rapid, point-of-care antigen and molecular-based tests for diagnosis of SARS-CoV-2 infection. Cochrane Database Syst Rev. 2021;3(3):CD013705. doi:10.1002/14651858.CD013705.pub2.
- Khandker SS, Nik Hashim NHH, Deris ZZ, Shueb RH, Islam MA. Diagnostic accuracy of rapid antigen test kits for detecting SARS-CoV-2: a systematic review and meta-analysis of 17,171 suspected COVID-19 patients. J Clin Med. 2021;10(16):3493. doi:10.3390/jcm10163493.
- Brümmer LE, Katzenschlager S, Gaeddert M, et al. Accuracy of novel antigen rapid diagnostics for SARS-CoV-2: A living systematic review and meta-analysis [published correction appears in PLoS Med. 2021 Oct 13;18(10):e1003825]. PLoS Med. 2021;18(8):e1003735. doi:10.1371/journal.pmed.1003735.
- Yamayoshi S, Sakai-Tagawa Y, Koga M, et al. Comparison of rapid antigen tests for COVID-19. Viruses. 2020;12(12):1420. doi:10.3390/v12121420.
- Ciotti M, Maurici M, Pieri M, Andreoni M, Bernardini S. Performance of a rapid antigen test in the diagnosis of SARS-CoV-2 infection. J Med Virol. 2021;93(5):2988-2991. doi:10.1002/jmv.26830.
- Kucirka LM, Lauer SA, Laeyendecker O, Boon D, Lessler J. Variation in false-negative rate of reverse transcriptase polymerase chain reaction-based sars-cov-2 tests by time since exposure. Ann Intern Med. 2020;173(4):262-267. doi:10.7326/M20-1495.
- Korenkov M, Poopalasingam N, Madler M, et al. Evaluation of a rapid antigen test to detect SARS-CoV-2 infection and identify potentially infectious individuals. J Clin Microbiol. 2021;59(9):e0089621. doi:10.1128/JCM.00896-21.
- US Food and Drug Administration. Genetic variants of SARS-CoV-2 may lead to false negative results with molecular tests for detection of SARS-CoV-2 – Letter to clinical laboratory staff and health care providers. Available at: https://www.fda.gov/medical-devices/letters-heath-care-providers/genetic-variants-sars-cov-2-may-lead-false-negative-results-molecular-tests-detection-sars-cov-2. Accessed on May 13, 2022.
- Buonsenso D, Munblit D, De Rose C, et al. Preliminary evidence on long COVID in children. Acta Paediatr. 2021;110(7):2208-2211. doi:10.1111/apa.15870.
- Asadi-Pooya AA, Nemati H, Shahisavandi M, et al. Long COVID in children and adolescents [published correction appears in World J Pediatr. 2022 Jul 3:]. World J Pediatr. 2021;17(5):495-499. doi:10.1007/s12519-021-00457-6.
- Fainardi V, Meoli A, Chiopris G, et al. Long COVID in children and adolescents. Life (Basel). 2022;12(2):285. doi:10.3390/life12020285.
- Radtke T, Ulyte A, Puhan MA, Kriemler S. Long-term symptoms after SARS-CoV-2 infection in children and adolescents. JAMA. 2021;326(9):869-871. doi:10.1001/jama.2021.11880.
- Raveendran AV, Jayadevan R, Sashidharan S. Long COVID: An overview [published correction appears in Diabetes Metab Syndr. 2022 May;16(5):102504] [published correction appears in Diabetes Metab Syndr. 2022 Nov 7:102660]. Diabetes Metab Syndr. 2021;15(3):869-875. doi:10.1016/j.dsx.2021.04.007.
- Zimmermann P, Pittet LF, Curtis N. How common is long COVID in children and adolescents? Pediatr Infect Dis J. 2021;40(12):e482-e487. doi:10.1097/INF.0000000000003328.
- Sisó-Almirall A, Brito-Zerón P, Conangla Ferrín L, et al. Long covid-19: proposed primary care clinical guidelines for diagnosis and disease management. Int J Environ Res Public Health. 2021;18(8):4350. doi:10.3390/ijerph18084350.
- Osmanov IM, Spiridonova E, Bobkova P, et al. Risk factors for post-COVID-19 condition in previously hospitalised children using the ISARIC Global follow-up protocol: a prospective cohort study. Eur Respir J. 2022;59(2):2101341. doi:10.1183/13993003.01341-2021.
- Yong SJ. Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments. Infect Dis (Lond). 2021;53(10):737-754. doi: 10.1080/23744235.2021.1924397.
- Baig AM. Deleterious outcomes in long-hauler covid-19: the effects of sars-cov-2 on the cns in chronic COVID syndrome. ACS Chem Neurosci. 2020;11(24):4017-4020. doi:10.1021/acschemneuro.0c00725.
- American Academy of Pediatrics. Post-COVID-19 conditions in children and adolescents. Published December, 2021. Accessed November 15, 2022. https://www.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/clinical-guidance/post-covid-19-conditions-in-children-and-adolescents/.