Human rhinoviruses (HRV) are a major cause of common cold in adults and children.1 Usually HRV infections run a mild course, but it has recently been shown that HRV can be associated with severe lower respiratory tract infection in children.2 There are no published data available on HRV infections in preterm infants. We retrospectively analyzed the data of all neonates with confirmed HRV infection admitted to our neonatal intensive care unit (NICU) from 2003 until 2008.
MATERIALS AND METHODS
We included all infants with a confirmed diagnosis of HRV infection and admitted from 2003, when the HRV real-time polymerase chain reaction (PCR) was introduced in our hospital, until 2008. We analyzed the clinical, virologic, radiologic and laboratory data of these infants. The diagnosis of HRV infection was made on the basis of a positive real-time PCR for HRV in a nasopharyngeal aspirate. Samples of all infants were also tested by real-time PCR for the following viral and bacterial pathogens: respiratory syncytial virus (RSV), human metapneumovirus, parainfluenzaviruses 1 to 4, influenzaviruses A and B, human coronaviruses (HCoV: 229E, OC43, and NL-63), adenoviruses, Mycoplasma pneumoniae, Chlamydia pneumoniae, and since 2006 bocavirus. All PCRs were real-time assays based on TaqMan probes. The target for the HRV PCR was the 5′ noncoding region of the genome. The amount of virus in each sample was recorded semi-quantitatively based on the cycle threshold (Ct) value of the sample in the PCR. The Ct value indicates the number of cycles needed in PCR before a sample becomes positive, and is therefore directly related to the amount of viral genome in the sample. Thus, a low Ct value corresponds to a high viral load, and a high Ct value to a low viral load. HRV was recorded as the dominating virus in a sample when the Ct value was at least 4 cycles lower than the Ct value for any other virus. Ct values above 45 were considered to be negative. Molecular typing of HRV was not performed.
During the study period viral infection was suspected in 62 infants admitted to our NICU. Depending on the clinical presentation (sepsis, meningitis, or pneumonia) we looked for viral agents of infection in different clinical samples. In patients with pneumonia we performed a PCR on respiratory viruses in nasopharyngeal aspirate as described in the methods section. In 8 of 62 infants, we could not identify any virus. In 22 (41%) of 54 infants with a proven viral infection, we identified 24 respiratory viruses. The most frequently detected viruses were HRV (n = 11) and RSV (n = 8). The remaining respiratory viruses were HCoV (n = 2), influenza virus (n = 1), adenovirus (n = 1), and parainfluenza virus (n = 1). In 1 infant, 3 different respiratory viruses (HRV, RSV, and HCoV) were found.
The characteristics of 11 infants with HRV infection are shown in Table 1. Nine of 11 infants (82%) were born prematurely with a median gestational age of 30 weeks (range: 26–32 weeks). The other 2 infants were born at term (39 and 41 weeks, respectively). One underwent surgical correction because of a diaphragmatic hernia, whereas the other was admitted from home at 5 days of age. The median age at onset of symptoms was 49 days (range: 5–94 days). In 7 of 11 infants HRV infection was acquired during their hospital stay.
The main presenting symptoms were respiratory distress (9/11), apnea (7/11), rhinorrhea (6/11), and hypothermia (5/11). All infants required respiratory support for a median of 6 days (range: 3–11 days), in 9 infants mechanical ventilation was necessary. The C-reactive protein was slightly elevated at onset of symptoms with a median value of 15 mg/L, and the white blood cell count was consistently normal. The Ct value of HRV was low in all infants with a median of 21 (range: 18.4–28.8) at onset of symptoms, indicating the presence of high viral loads of HRV in the respiratory tract. In 2 infants (patient 9 and 11), the Ct value increased from 24.6 to 29.4 and from 18.4 to 35.6, respectively, in samples taken 7 days later. Chest radiographs revealed perihilar streakiness (10/11), atelectasis (9/11), focal consolidation (6/11), and hyperinflation (6/11). Most infants had 2 or more of the above mentioned radiologic findings. One patient (patient 4) had a coinfection with 2 other viral pathogens, HCoV and RSV, but the viral loads of RSV (Ct: 35.1) and HCoV (Ct: 31.2) were considerably lower than that of HRV (Ct: 26.5). We did not find any nosocomial spread of HRV among our infants. Our patients were not clustered in time, but represented separate events. All infants recovered from the episode of HRV infection, but 4 patients (1 term and 3 preterm) subsequently developed recurrent lower respiratory tract infections.
Our study shows that HRV can cause severe pulmonary disease among infants admitted to a NICU. HRV is generally known as the causative agent of the common cold. The association of HRV with asthma exacerbations, wheezing, and lower respiratory tract infections has been well recognized.2–4 Recently, HRV also appeared to be an important reason for hospitalization in young children.5–7 However, HRV can also be detected in asymptomatic children.8 It is suggested that the identification of HRV in asymptomatic infants represents low-level infection without clinical symptoms, or is a first sign of developing illness.5 Data on HRV infections in very young infants are limited. In our previous retrospective analysis (1992–2003) of viral infections in our NICU, we found that HRV contributed to 2% of all proven viral infections among admitted infants.9 This percentage recently increased to 20% (unpublished data), which can be explained by the introduction of real-time PCR for the identification of viruses in infants with severe respiratory disease.
The clinical presentation of HRV infection in infants described in our study did not differ from that of RSV infection.10,11 All infants developed rhinorrhea, respiratory distress, apnea, and hypothermia, and required respiratory support for 3 to 11 days. It was not possible to differentiate between RSV and HRV infection based on radiologic findings. The presence of atelectasis which changed position daily and the huge production of sputum were common findings. We recorded relatively low Ct values corresponding to relatively high viral loads in the respiratory samples of our patients. In one infant (patient 4), who was infected with 3 different respiratory viruses, HSV was considered the major causative agent because of its lowest Ct value. In 2 infants the Ct value performed again after 7 days was increased significantly, which was associated with clinical recovery. All infants recovered, but 4 developed recurrent respiratory tract infections which could not be explained solely by prematurity. In conclusion, HRV can cause severe pulmonary disease in preterm infants, requiring respiratory support.
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