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The First Infant Death Associated With Human Coronavirus NL63 Infection

Konca, Capan MD; Korukluoglu, Gulay MD; Tekin, Mehmet MD; Almis, Habip MD; Bucak, İbrahim Hakan MD; Uygun, Hatice MD; Altas, Ayse Basak DVM, PhD; Bayrakdar, Fatma Bio. PhD

Author Information
The Pediatric Infectious Disease Journal: February 2017 - Volume 36 - Issue 2 - p 231-233
doi: 10.1097/INF.0000000000001390

Abstract

Lower respiratory tract infection (LRTI) is an important cause of morbidity and mortality, especially among young children. It is estimated that 25–33% of deaths observed in children younger than 5 years of age are caused by acute respiratory infections and their complications.1 In 80–90% of LRTI, the main agents are respiratory viruses.

Coronaviruses are enveloped viruses with a large plus-strand RNA genome. To date, 6 coronaviruses (HCoV-229E, HCoV-OC43, SARS-CoV, HCoV-NL63, HCoV-HKU-1 and MERS-CoV) that infect humans have been identified, 4 of which (HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU-1) circulate continuously in the human population. HCoV-NL63 was first isolated from the aspirate of a 7-month-old baby in early 2004.2 Generally, HCoV-NL63 primarily infects the upper respiratory tract, typically causing mild upper respiratory infectious symptoms such as cough, rhinorrhea and fever. But the clinical course of HCoV-NL63 infection can be more serious in some risk groups. A study reported that an elderly Canadian patient infected with HCoV-NL63 died 5 days after the onset of disease.3 Another study reported a fatal lower respiratory tract disease with HCoV-NL63 in an adult hematopoietic cell transplant recipient.4 To our knowledge, child death associated with HCoV-NL63 has not been reported. Here, we present a fatal lower respiratory tract disease associated with HCoV-NL63 in a 7-month-old baby for the first time.

CASE REPORT

A 7-month-old boy [weight: 5.4 kg (<–2 standard deviations) and height: 58 cm (<–2 standard deviations)] was admitted to another emergency department with a 2-day history of lack of appetite, dyspnea and cyanosis. He was hospitalized. Laboratory investigations revealed hypernatremia (Na: 151 mEq/L), lymphocytosis (white blood cell: 35,000/µL with 65.7% lymphocytes) and decompensated acute metabolic acidosis. Bilateral pneumonic infiltrates were detected on chest radiographs. Intravenous fluids, antibiotics, oxygen inhalation and nebulized salbutamol were started. Respiratory distress of the patient worsened within a few hours, and he developed cardiopulmonary arrest. After 15 minutes of cardiopulmonary resuscitation, he was intubated and transferred to our pediatric intensive care unit.

He was admitted to our pediatric intensive care unit 2 hours after cardiopulmonary arrest. On the physical examination, he had cheilitis, brittle hair, thin and soft nail plates and pallor. He did not breathe spontaneously, was bradycardiac (70/min), and blood pressure could not be measured. The patient was connected to the mechanical ventilator. Dopamine, dobutamine and epinephrine infusions were started for refractory hypotension in addition to repeated 0.9% NaCl boluses, and blood pressure returned to normal levels. The first chest radiograph revealed bilateral linear pneumonic infiltration (Fig., Supplemental Digital Content 1, http://links.lww.com/INF/C579). Laboratory investigations revealed hypernatremia (Na: 148 mEq/L), lymphocytosis (white blood cell: 30 K/uL with 55.6% lymphocytes), hypertransaminasemia (aspartate aminotransferase: 4202 U/L and alanine aminotransferase: 3056 U/L) and severe decompensated acute metabolic acidosis (pH: 6.8; PCO2: 28.7 mm Hg; HCO3: 5.9 mmol/L).

Bicarbonate administration by constant infusion was administered. Ampicillin-sulbactam, clarithromycin and oseltamivir were started as empiric antibacterial and antiviral coverage. After 12 hours, a significant increase was observed in the infiltrates on the chest radiograph (Fig. 1). The patient was diagnosed with acute respiratory distress syndrome. We applied lung-protective mechanical ventilator strategies to our patient for acute respiratory distress syndrome. These included gentler ventilation using lower tidal volumes, limiting the inspiratory and plateau pressures, and in that process, achieving permissible levels of hypercapnia.5

FIGURE 1
FIGURE 1:
Bilateral widespread pulmonary infiltrates on second chest radiograph.

Blood, urine and respiratory tract samples taken at admission and were sent to our hospital microbiology laboratory for examination. Because extensive virologic examination cannot be performed in our laboratory, we also sent respiratory tract samples to the Virology Reference Central Laboratory, Public Health Agency of Turkey. Nasopharyngeal and throat swabs were sent to the laboratory in virus transport medium (Virocult, Medical Wire & Equipment, Corsham, UK); bronchoalveolar lavage and transtracheal aspirate samples were sent in a sterile cap. In the virology laboratory, RNA extraction were performed using Qiagen EZ1Virus Mini Kit v2.0 (Qiagen, Hilden, Germany) according to manufacturer’s instructions. Then multiplex real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test performed with Fast Track Diagnostics/Respiratory Pathogens 21 (Fast-track Diagnostics, Luxemburg) kit that detects respiratory pathogens. HCoV-NL63 was detected in all samples that were sent to Virology Reference Central Laboratory.

Despite supportive treatment, the patient had a second cardiac arrest in the 26th hour of hospitalization. Cardiopulmonary resuscitation was performed for 30 minutes, but was unsuccessful.

DISCUSSION

The human coronavirus NL63 was discovered in 2004 by Dutch virologists.2 HCoV-NL63 mostly causes mild upper respiratory infectious symptoms. However, it can lead to severe LRTIs. We present a fatal LRTI associated with HCoV-NL63 in a 7-month-old malnourished infant.

Because most nutrients in the diet are essential for maintaining the function of immune cells, malnutrition is the main cause of immunodeficiency worldwide. Several studies have reported that in malnourished patients, common immune defects include an imbalance in the ratio of CD4/CD8+ T cells, low expression levels of CD69 on lymphocytes, biased T helper cell responses and reduced antibody responses.6,7 We believe that malnutrition altered the patient’s immune response and led to severe disease. The thymus was not present in radiographs. We could not perform basic immune work-up including lymphocyte subsets and serum immunoglobulin value because of insufficient time and poor clinical condition.

RT-PCR, enzyme-linked immunosorbent assays and real-time PCR are diagnostic tests for respiratory tract viruses.8–10 We performed the real-time RT-PCR assays for detecting respiratory tract viruses, and HCoV-NL63 detected in all samples.

Our patient initially presented with upper respiratory prodrome, which progressed to pneumonia and respiratory failure. Initial blood tests and radiologic evaluation were compatible with a acute respiratory virus illness. Based on clinical features and the detection of HCoV-NL63 in respiratory tract samples taken on admission and the absence of any bacterial or fungal agents, the respiratory disease in our patient was considered HCoV-NL63-associated LRTI. In conclusion, HCoV-NL63 may be fatal in children with immunodeficiency conditions such as malnutrition.

ACKNOWLEDGMENTS

We gratefully acknowledge Dr. Mehmet Turgut, Head of Department of Pediatrics, for all contributions.

REFERENCES

1. World Health Organization. Programme for the Control of Acute Respiratory Infections: Fifth Programme Report 1990–1991. 1992.Geneva: World Health Organization.
2. van der Hoek L, Pyrc K, Jebbink MF, et al. Identification of a new human coronavirus. Nat Med. 2004;10:368–373.
3. Bastien N, Anderson K, Hart L, et al. Human coronavirus NL63 infection in Canada. J Infect Dis. 2005;191:503–506.
4. Oosterhof L, Christensen CB, Sengeløv H. Fatal lower respiratory tract disease with human corona virus NL63 in an adult haematopoietic cell transplant recipient. Bone Marrow Transplant. 2010;45:1115–1116.
5. Jahagirdar A, Prayag S. Low tidal volume ventilation in acute respiratory distress syndrome. Indian J Crit Care Med. 2005;9:189–194.
6. Nájera O, González C, Toledo G, et al. CD45RA and CD45RO isoforms in infected malnourished and infected well-nourished children. Clin Exp Immunol. 2001;126:461–465.
7. Rodríguez L, González C, Flores L, et al. Assessment by flow cytometry of cytokine production in malnourished children. Clin Diagn Lab Immunol. 2005;12:502–507.
8. Liolios L, Jenney A, Spelman D, et al. Comparison of a multiplex reverse transcription-PCR-enzyme hybridization assay with conventional viral culture and immunofluorescence techniques for the detection of seven viral respiratory pathogens. J Clin Microbiol. 2001;39:2779–2783.
9. Dijkman R, Jebbink MF, El Idrissi NB, et al. Human coronavirus NL63 and 229E seroconversion in children. J Clin Microbiol. 2008;46:2368–2373.
10. Gaunt ER, Hardie A, Claas EC, et al. Epidemiology and clinical presentations of the four human coronaviruses 229E, HKU1, NL63, and OC43 detected over 3 years using a novel multiplex real-time PCR method. J Clin Microbiol. 2010;48:2940–2947.
Keywords:

death; fatal; human corona virus NL63; infant; lower respiratory tract infections

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