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Rhabdomyolysis and Acute Kidney Injury as Leading COVID-19 Presentation in an Adolescent

Tram, Nathalie MD*; Chiodini, Benedetta MD, PhD*; Montesinos, Isabel MD, PhD; Vicinanza, Alfredo MD; Beretta-Piccoli, Xavier MD; Gubbelmans, Natacha MD§; Demey, Milena MD§; Genis, Nathalie MD§; Tilmanne, Anne MD, PhD; Smeesters, Pierre R. MD¶,‖,**,††; Ismaili, Khalid MD, PhD*

Author Information
The Pediatric Infectious Disease Journal: October 2020 - Volume 39 - Issue 10 - p e314-e315
doi: 10.1097/INF.0000000000002853
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Abstract

The ongoing COVID-19 pandemic has reached most countries in the world. This infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a member of the Coronaviridae family, is highly contagious with significant human-to-human transmission. Infected patients show different manifestations from asymptomatic cases to severe acute respiratory distress syndrome with a high mortality rate, mainly in elder adults with comorbidities.1,2 Pediatric cases account for around 1%–5% of infected patients.3 Clinical symptoms in young patients seem to be less severe with mostly flu-like symptoms.3,4 While myalgia is a well-known symptom of COVID-19 disease, rhabdomyolysis is exceptional5,6 and has, to our best knowledge, not yet been described in the pediatric population.

CASE REPORT

A 15-year-old boy with uneventful medical history was admitted to the pediatric intensive care unit of our tertiary hospital with severe rhabdomyolysis and renal failure. He had been in lockdown since the 13th of March and had no contact with known ill people. The clinical history started on the 23th of March when he developed an intense proximal muscle pain without history of trauma or physical exercise. On day 3, he went to the emergency room, his physical examination was normal, and the laboratory analyses were unremarkable (Table 1). He was discharged with supportive care (paracetamol). At home, he presented abdominal pain over 2 days, associated with vomiting and mild diarrhea. On day 6, he developed tea-colored urines, polyuria, polydipsia, and general fatigue. He did never exhibit fever or respiratory symptoms. No alcohol or drug consumption was reported. On day 10, he was admitted to pediatric intensive care unit. Vital parameters were within normal ranges (SpO2: 98%, respiratory rate: 19/min, heart rate: 110/min, t°: 35.8°C, blood pressure: 120/69 mm Hg). Laboratory analyses showed severe renal failure, mild hypocalcemia, mild hepatic cytolysis, C-reactive protein elevation, and severe rhabdomyolysis (Table 1). At admission, SARS-CoV-2 rapid antigenic test (COVID-19 Ag Respi-Strip®; Coris BioConcept, Gembloux, Belgium) on nasopharyngeal specimen resulted positive, and extended polymerase chain reaction panel for respiratory diseases (FilmArray® Respiratory Panel 2 plus; BioMérieux, Craponne, France), testing adenovirus, endemic coronavirus (OC43, NL63, HKU1, 229E), influenza A (H1, H1-pdm2009, H3), influenza B, human metapneumovirus, parainfluenza 1–4, rhino/enterovirus, respiratory syncytial virus, Chlamydophila pneumoniae and Mycoplasma pneumoniae to, resulted negative. The possibility of other concomitant viral infections such as cytomegalovirus, Epstein-Barr virus, herpes simplex virus, human immunodeficiency virus, varicella zoster, and hantavirus was unlikely due to negative single point serology. Chest radiogram and cardiac ultrasound were normal. No amphetamine, cocaine, benzodiazepines, or opiates were found in urine testing. There were no reasons to suspect a connective tissue disease or metabolic inherited disorder. During hospitalization, the patient showed a favorable clinical evolution and received only supportive care (sodium bicarbonate and aggressive hydration). Muscle pain disappeared with a steady decrease of serum creatinine kinase and a rapid recovery of renal function. He was discharged 9 days after entry. When last seen on day 29, his clinical condition and serum creatinine level returned to normal. A specific SARS-CoV-2 serology has been performed on day 10 and day 29 with 2 different test kits: Liaison® SARS-CoV-2 IgG; DiaSorin, Saluggia, Italy and Novalisa® SARS-CoV-2 [COVID-19] IgG, IgM, IgA; NovaTec Immundiagnostica GmbH, Dietzenbach, Germany. On day 10, SARS-CoV-2 serology was negative for all class immunoglobulins, while on day 29, SARS-CoV-2 IgG titers were positive for both tests (Table 1).

TABLE 1. - Laboratory Features
Laboratory Values March 26, 2020 (Day 3) April 2, 2020 (Day 10) April 5, 2020 (Day 13) April 9, 2020 (Day 17) April 11, 2020 (Day 19) April 21, 2020 (Day 29) Normal Range
Urea (mg/dL) 28 290 239 89 68 24 15–43
Creatinine (mg/dL) 1.01 8.91 5.98 2.13 1.63 0.87 0.7–1.2
Calcium (mmol/L) 2.18 2.08 2.29 2.47 2.48 2.47 2.10–2.55
ASAT (UI/L) 319 201 62 22 20 22 <32
ALAT (UI/L) 42 118 78 35 22 35 <18
CRP (mg/L) 28.6 60.9 23.5 36.1 39.9 1.6 <5
Creatine-kinase (UI/L) ND 21,876 2000 428 409 165 39–308
Myoglobin (µg/L) ND 855 150 80 ND ND <72
Liaison® SARS-CoV-2 IgG (UA/mL) 0 17 <12
Novalisa® SARS-CoV-2
 IgG 8.5 30 <9 (ratio)
 IgA 2.3 7.4 <9 (ratio)
 IgM 1.7 2.3 <9 (ratio)
ALAT, alanine transaminase; ASAT, aspartate transaminase; CRP, C-reactive protein; ND, not done; SARS-CoV-2, severe acute respiratory syndrome coronavirus.

DISCUSSION

Rhabdomyolysis, a potential life-threatening condition, results from important skeletal muscle injury leading to the release of massive amount of creatine-kinase and myoglobin.7,8 Myoglobin is harmful for the kidneys and leads to renal failure by direct tubular toxicity.7,8 Several factors can lead to rhabdomyolysis, mainly muscle traumatism or sustained exertion, toxics such as drugs, alcohol, or medications, metabolic and infectious diseases.7,8 In the pediatric population, most cases are secondary to viral myositis (mainly influenza A and B, cytomegalovirus, Epstein-Barr virus) or inherited metabolic disorders.7,8 In our patient, a viral cause has been suspected due to the acute onset myalgia and gastrointestinal symptoms. In children, COVID-19 infection can be asymptomatic or typically shows fever and mild respiratory symptoms (sore throat, cough, or shortness of breath).3,4 However, new warnings have arisen concerning possible SARS-CoV-2–associated severe systemic inflammatory disease in pediatric population.9 Although our patient did not show the classical symptoms of this disease, we promptly tested for COVID-19 with the rapid antigen and serologic tests.

The positive result of the SARS-CoV-2 rapid antigenic test in addition to the significant rise in serum IgG levels 1 month after the disease onset, suggest that SARS-CoV-2 may well have been responsible of the rhabdomyolysis, in particular as testing for other viruses was negative.

Two cases of COVID-19–associated rhabdomyolysis have been so far described in adult patients.5,6 Unlike our case, both adults presented severe respiratory symptoms and fever. The mechanism of the muscle cell damage remains unknown but similar to other viruses, direct viral, or toxin-induced injury could be involved.10

Our patient was affected by rhabdomyolysis, an unusual COVID-19 clinical manifestation, without fever or respiratory symptoms. This case illustrates that COVID-19–associated rhabdomyolysis should be suspected in all age patients with acute onset myalgia.

REFERENCES

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3. Ludvigsson JF. Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults. Acta Paediatr. 2020;109:1088–1095.
4. Parri N, Lenge M, Buonsenso D; Coronavirus Infection in Pediatric Emergency Departments (CONFIDENCE) Research Group. Children with Covid-19 in Pediatric Emergency Departments in Italy. N Engl J Med. 2020;383:187–190.
5. Suwanwongse K, Shabarek N. Rhabdomyolysis as a presentation of 2019 novel coronavirus disease. Cureus. 2020;12:e7561.
6. Jin M, Tong Q. Rhabdomyolysis as potential late complication associated with COVID-19. Emerg Infect Dis. 2020;26:1618–1620.
7. Mannix R, Tan ML, Wright R, et al. Acute pediatric rhabdomyolysis: causes and rates of renal failure. Pediatrics. 2006;118:2119–2125.
8. Elsayed EF, Reilly RF. Rhabdomyolysis: a review, with emphasis on the pediatric population. Pediatr Nephrol. 2010;25:7–18.
9. Riphagen S, Gomez X, Gonzalez-Martinez C, et al. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020;395:1607–1608.
10. Fadila MF, Wool KJ. Rhabdomyolysis secondary to influenza a infection: a case report and review of the literature. N Am J Med Sci. 2015;7:122–124.
Keywords:

COVID-19; SARS-CoV-2; rhabdomyolysis; pediatrics; acute kidney injury

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