Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?
BACKGROUND
Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear.


OBJECTIVE
To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI).


METHODS
We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011-2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK.


RESULTS
204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort.


CONCLUSIONS
The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective role.
Grupo de Investigación en Genética, Vacunas, Infecciones y Pediatría, Hospital Clínico Universitario and Universidade de Santiago de Compostela (USC), Galicia, Spain.|Translational Pediatrics and Infectious Diseases section, Department of Pediatrics, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Galicia, Spain.
Miriam
M
Cebey-López
Section of Paediatrics, Division of Infectious Disease, Imperial College of London, South Kensington Campus, London, United Kingdom.
Jethro
J
Herberg
Grupo de Investigación en Genética, Vacunas, Infecciones y Pediatría, Hospital Clínico Universitario and Universidade de Santiago de Compostela (USC), Galicia, Spain.|Translational Pediatrics and Infectious Diseases section, Department of Pediatrics, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Galicia, Spain.|Unidade de Xenética, Departamento de Anatomía Patolóxica e Ciencias Forenses, and Instituto de Ciencias Forenses, Grupo de Medicina Xenómica (GMX), Facultade de Medicina, Universidade de Santiago de Compostela, Galicia, Spain.
Jacobo
J
Pardo-Seco
Grupo de Investigación en Genética, Vacunas, Infecciones y Pediatría, Hospital Clínico Universitario and Universidade de Santiago de Compostela (USC), Galicia, Spain.|Translational Pediatrics and Infectious Diseases section, Department of Pediatrics, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Galicia, Spain.|Unidade de Xenética, Departamento de Anatomía Patolóxica e Ciencias Forenses, and Instituto de Ciencias Forenses, Grupo de Medicina Xenómica (GMX), Facultade de Medicina, Universidade de Santiago de Compostela, Galicia, Spain.
Alberto
A
Gómez-Carballa
Grupo de Investigación en Genética, Vacunas, Infecciones y Pediatría, Hospital Clínico Universitario and Universidade de Santiago de Compostela (USC), Galicia, Spain.|Translational Pediatrics and Infectious Diseases section, Department of Pediatrics, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Galicia, Spain.
Nazareth
N
Martinón-Torres
Grupo de Investigación en Genética, Vacunas, Infecciones y Pediatría, Hospital Clínico Universitario and Universidade de Santiago de Compostela (USC), Galicia, Spain.|Unidade de Xenética, Departamento de Anatomía Patolóxica e Ciencias Forenses, and Instituto de Ciencias Forenses, Grupo de Medicina Xenómica (GMX), Facultade de Medicina, Universidade de Santiago de Compostela, Galicia, Spain.
Antonio
A
Salas
Grupo de Investigación en Genética, Vacunas, Infecciones y Pediatría, Hospital Clínico Universitario and Universidade de Santiago de Compostela (USC), Galicia, Spain.|Translational Pediatrics and Infectious Diseases section, Department of Pediatrics, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Galicia, Spain.
José María
JM
Martinón-Sánchez
Grupo de Investigación en Genética, Vacunas, Infecciones y Pediatría, Hospital Clínico Universitario and Universidade de Santiago de Compostela (USC), Galicia, Spain.|Translational Pediatrics and Infectious Diseases section, Department of Pediatrics, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Galicia, Spain.
Antonio
A
Justicia
Grupo de Investigación en Genética, Vacunas, Infecciones y Pediatría, Hospital Clínico Universitario and Universidade de Santiago de Compostela (USC), Galicia, Spain.|Translational Pediatrics and Infectious Diseases section, Department of Pediatrics, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Galicia, Spain.
Irene
I
Rivero-Calle
Micropathology Ltd., University of Warwick Science Park, Coventry, United Kingdom.
Edward
E
Sumner
Micropathology Ltd., University of Warwick Science Park, Coventry, United Kingdom.
Colin
C
Fink
Grupo de Investigación en Genética, Vacunas, Infecciones y Pediatría, Hospital Clínico Universitario and Universidade de Santiago de Compostela (USC), Galicia, Spain.|Translational Pediatrics and Infectious Diseases section, Department of Pediatrics, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Galicia, Spain.
Federico
F
Martinón-Torres
D000208:Acute Disease; D000328:Adult; D002675:Child, Preschool; D060085:Coinfection / Q000517:prevention & control / Q000628:therapy / Q000821:virology*; D005260:Female; D006760:Hospitalization; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D022242:Pneumococcal Vaccines; D012141:Respiratory Tract Infections / Q000517:prevention & control / Q000628:therapy / Q000821:virology*
D022242:Pneumococcal Vaccines