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Letters to the Editor

Severe Foodborne Bacterial Infections Mimicking Multisystem Inflammatory Syndrome in Children Associated With COVID-19

Toledano, Javier MD; Saavedra-Lozano, Jesús MD, PhD; Navarro-Gómez, María Luisa MD, PhD; Santiago-García, Begoña MD, PhD; Aguilera-Alonso, David MD

Author Information
The Pediatric Infectious Disease Journal: May 2021 - Volume 40 - Issue 5 - p e210-e211
doi: 10.1097/INF.0000000000003093
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To the Editors:

We read with interest the article by Campbell et al1 entitled “Non-SARS-CoV-2 infections among patients evaluated for multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C).” As underlined by the authors, the features of multisystem inflammatory syndrome (MIS-C) included in case definitions overlap with many infectious diseases.

The authors describe 39 children evaluated with suspected MIS-C, 11 of whom had nonsevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections. We also diagnosed 4 cases of foodborne bacterial infection, mimicking MIS-C attended in a tertiary hospital between September 2, 2020, and November 18, 2020. They were previously healthy males between 4 and 15 years old presenting with clinical and laboratory signs compatible with MIS-C (Table 1). All cases had fever and abdominal pain, 2 cases had vomiting and 1 associated diarrhea. None reported respiratory symptoms or skin lesions. All children presented with tachycardia, and 3 developed shock, requiring intravenous fluids. Additionally, 1 child required vasoactive support with intensive care unit admission.

TABLE 1. - Characteristics of Children With Foodborne Bacterial Infections Mimicking Multisystem Inflammatory Syndrome Associated With COVID-19 (MIS-C)
Case 1 2 3 4
 Age (yr)/gender 4/male 15/male 12/male 8/male
Clinical findings
 Fever (duration*) Yes (6 d) Yes (7 hr) Yes (8 hr) Yes (1 d)
 Abdominal pain Yes Yes Yes Yes
 Vomiting Yes Yes No No
 Diarrhea Yes No No No
 Tachycardia Yes Yes Yes Yes
 Hypotension No Yes Yes Yes
 Rash No No No No
Laboratory findings
 CRP (mg/dL) 9 (11.2) 4 5.4 (10.2) 7.6 (11.8)
 Procalcitonin (mcg/L) 8.5 (8.5) 1.9 0.6 (1.3) 0.6 (0.6)
 Leukocytes (cells/mm3) 4300 (6100) 16,600 16,600 (17,200) 12,000 (12,000)
 Neutrophils (cells/mm3) 3200 (3250) 14,700 14,900 (16,300) 10,200 (10,200)
 Lymphocytes(cells/mm3) 900 (900) 700 600 (500) 1300 (1300)
 Platelets (cells/mm3) 145,000 (340,000) 217,000 213,000 (273,000) 261,000 (261,000)
 APTT (s) 30.4 (30.4) NP 29.2 (29.3) 36.4 (36.4)
 Prothrombin time (s) 13.3 (13.3) NP 19.9 14.8 (15.5)
d-dimer (ng/mL) 5618 NP 477 (497) 391
 Ferritin (mcg/L) 2561 89 NP 154
 Troponins (ng/L) 2.1 <1.6 <1.6 <1.6
 NT-pro-BNP (ng/L) 82 110 475 69
 IL-6 (pg/mL) NP 138 732.2 15.6
Microbiology
 Blood culture Salmonella Typhi No isolation No isolation No isolation
 Stools culture Salmonella Typhi Campylobacter jejuni Campylobacter coli C. jejuni
 SARS-CoV-2 PCR Negative Negative Negative Negative
 SARS-CoV-2 IgG Negative Negative Negative Positive
 COVID-19 contact No No No Yes
Imaging
 Echocardiogram Normal NP Normal Normal
 Abdominal ultrasound Nonspecific diffuse gallbladder wall thickening Right hemicolitis with terminal ileitis and mesenteric adenitis Right ileocolitis and mesenteric adenitis NP
Treatment
 Fluid resuscitation No Yes Yes Yes
 PICU admission No No Yes No
 Inotropes No No Yes (norepinephrine) No
 Respiratory support No No Yes (standard nasal cannulas) No
 Antibiotic Ceftriaxone Ceftriaxone Ceftriaxone Cefotaxime
 Methylprednisolone Yes (2 mg/kg/d) No Yes (2 mg/kg/d) No
 Immunoglobulin Yes (2 g/kg) No Yes (2 g/kg) No
 Acetylsalicylic acid No No No No
*Duration before consultation.
†Laboratory values represent the value at emergency department and maximum value during admission (inside parenthesis), except for lymphocytes, whose values represent the value at emergency department and the minimum value during admission. Some values were tested only once during admission.
APTT indicates activated partial thromboplastin time; COVID-19, coronavirus disease 2019; CRP, C-reactive protein; IL, interleukin; NP, not performed; NT-Pro-BNP, N-terminal prohormone of brain natriuretic peptide; PCR, polymerase chain reaction; PICU, pediatric intensive care unit.
Normal laboratory values: APTT (27–38 seconds), prothrombin time (10.5–13.5 seconds), d-dimer (0–250 ng/mL), ferritin (22–274 mcg/L), troponins (<34.2 ng/L), NT-pro-BNP (0–300 ng/L) and IL-6 (<4.3 pg/mL).

All had increased acute phase reactants and lymphopenia, and 3 had elevated d-dimer, with only 1 patient having a significant ferritin increase. All children had normal cardiac enzymes, electrocardiogram, echocardiogram and chest radiograph. Two patients had inflammatory findings on abdominal ultrasound, showing ileocolitis and mesenteric lymphadenopathy, whereas 1 child had gallbladder wall thickening.

Upon suspicion of MIS-C, all children were hospitalized following national MIS-C guidelines.2 All received empirical antibiotics, and 2 started treatment with methylprednisolone and intravenous immunoglobulin for MIS-C. All 4 children tested negative for SARS-CoV-2 by polymerase chain reaction, and only 1 had SARS-CoV-2-positive IgG antibodies. After a broad diagnostic workup, gastrointestinal bacterial infection was diagnosed in all patients, and MIS-C was excluded. Salmonella typhi was isolated in blood culture in 1 case (autochthonous acquisition) and Campylobacter spp isolated in stool cultures in the remaining 3 cases (Campylobacter jejuni in 2 and Campylobacter coli in 1). All children had resolution of symptoms and improvement of inflammatory markers.

Compared with our report, no patient in Campbell’s study was diagnosed with a gastrointestinal bacterial infection, which may be related to different local epidemiologies. Another case series of 6 children received intravenous immunoglobulin as therapy for MIS-C despite not fulfilling MIS-C case definition and subsequently being diagnosed with murine typhus during an outbreak.3

Since gastrointestinal symptoms are common in MIS-C, differential diagnosis with other gastrointestinal conditions may be difficult, including acute appendicitis or gastrointestinal infections.4 Two of our cases had inflammatory signs on the abdominal ultrasound, including ileitis, which has been broadly described in MIS-C.5

Our case series show that foodborne bacterial infections should be ruled out when evaluating possible MIS-C, especially if gastrointestinal symptoms are predominant. Foodborne infections can also present with severe manifestations, including hemodynamic instability, which can resemble MIS-C. Despite the increasing concern about severe inflammatory conditions associated with SARS-CoV-2, we should continue assessing other infectious conditions within the differential diagnosis, obtaining appropriate samples and initiating timely empirical antibiotic treatment. Given the broad differential diagnosis of MIS-C, clinically stable patients with low suspicion of the disease could be admitted to the hospital under close monitorization before deciding to initiate immunomodulatory treatment.

ACKNOWLEDGMENT

The authors thank Cindy McCoig for kindly reviewing the article.

REFERENCES

1. Campbell JI, Roberts JE, Dubois M, et al.Non-SARS-CoV-2 infections among patients evaluated for MIS-C associated with COVID-19. Pediatr Infect Dis J.2021; 40:e90–e93
2. García-Salido A, Antón J, Martínez-Pajares JD, et al.Spanish consensus document on diagnosis, stabilisation and treatment of pediatric multisystem inflammatory syndrome related to SARS-CoV-2 (SIM-PedS) [published online ahead of print October 31, 2020]. An Pediatr (Barc). doi: 10.1016/j.anpedi.2020.09.005
3. Alamarat Z, Pérez N, Wootton S, et al.Murine typhus outbreak presenting as multisystem inflammatory syndrome in children during SARS-CoV-2 pandemic. Pediatr Infect Dis J.2020; 39:e447–e449
4. Lishman J, Kohler C, de Vos C, et al.Acute appendicitis in multisystem inflammatory syndrome in children with COVID-19. Pediatr Infect Dis J.2020; 39:e472–e473
5. Tullie L, Ford K, Bisharat M, et al.Gastrointestinal features in children with COVID-19: an observation of varied presentation in eight children. Lancet Child Adolesc Health.2020; 4:e19–e20
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