Respiratory Viruses in Babies: Important Insights From Down Under

For those of us interested in respiratory viruses, there is a lot to like about the study by Sarna et al that appears in this issue of The Journal of Infectious Diseases [1]. The study analyzes data from a birth cohort established as part of the Observational Research in Childhood Infectious Diseases (ORChID) Project, based in Brisbane, Australia [2]. Impressive study attributes include large size, community base, enrollment from birth, scheduled frequent longitudinal sampling with or without illness, high percentage of specimen acquisition rate, even enrollment of subjects throughout the year to account for virus seasonality, and testing of samples with an extensive panel of real-time polymerase chain reaction (PCR) assays. Participating babies had anterior nasal and “dirty nappy” swabs obtained at birth and weekly thereafter by parents trained by research staff. Parents also kept daily symptom diaries listing predefined symptoms. The present manuscript reports only on the respiratory swabs. This massive undertaking yielded analyzable data on 9594 samples from 152 participants, corresponding to 163 098 individual virus-specific PCR queries! This intensive prospective study of respiratory viruses in infants finds that human rhinovirus (HRV) is by far the most frequent virus detected in the infant respiratory tract. This single-stranded, positive-sense RNA virus is increasingly recognized as an important human pathogen, with a strong relationship to childhood asthma [3]. Significantly, Sarna et al found that HRV was detected in an impressive 20.0% of all samples tested, accounting for 77.3% of all virus-positive swabs. By 2 years of age, 98% of participating infants had experienced HRV-C, 94% HRV-A, and 56% HRV-B. Although impressive, this large proportional load of HRV should not be surprising, as it has also been shown in previous community-based studies using molecular tests, including an earlier study by these authors [4] and several others [5– 8]. Similarly, laboratories using multiplex respiratory virus panels that include sensitive rhinovirus detection capability usually find rhinovirus/enterovirus to be the most common positive result. The US Food and Drug Administration (FDA)–cleared multiplex respiratory panels do not distinguish between rhinoviruses and enteroviruses, but apart from outbreak situations, such as occurred in 2014 with enterovirus D-68 [9], most of the positive results from rhinovirus/enterovirus assays reflect HRV infection. It has become clear that in relation to respiratory viruses, HRV is the elephant in the room. In comparison to the universal occurrence of HRV, infections with other respiratory viruses were less frequent. RSV and parainfluenza viruses were each detected in 58% of subjects, influenza A in 8%, influenza B in 3%, human metapneumovirus in 21%, human coronaviruses in 72%, adenovirus in 51%, human polyomaviruses in 77%, and human bocavirus in 75%. The 58% occurrence of RSV is surprisingly low, as common understanding is that almost all infants experience RSV within the first 2 years of life [10]. Possible explanations for the discrepancy include inadequate sample collection (samples were collected by parents), seasonal variation in the occurrence of RSV, and complete reliance on molecular assays. In some studies, serology has indicated some infections are not detected by PCR [11]. The authors point out the difference between their estimate and that of the Houston family study [12], which is a basis for the concept of universal RSV infection early in life and which relied heavily on serology [12]. However, they also cite a number of more recent studies that support their finding of less than universal infection. These results suggest that we may need to fine-tune our understanding of the frequency of RSV infection early in life. The focus of the Sarna et al study was first respiratory virus infections, and the frequency of first HRV infections in young infants is noteworthy. Of the 152 infants followed, 81% experienced a first infection with HRV by 6 months of age, compared to 8.5% for RSV, and 0.7%–9.4% for the other respiratory viruses. Influenza A and B infections were infrequent, with only 0.8% and E D I T O R I A L C O M M E N T A R Y