The Emerging Role of Rhinoviruses in Lower Respiratory Tract Infections in Children – Clinical and Molecular Epidemiological Study From Croatia, 2017–2019

Abstract

Rhinoviruses (RVs) are increasingly implicated not only in mild upper respiratory tract infections, but also in more severe lower respiratory tract infections; however, little is known about species diversity and viral epidemiology of RVs among the infected children. Therefore, we investigated the rhinovirus (RV) infection prevalence over a 2-year period, compared it with prevalence patterns of other common respiratory viruses, and explored clinical and molecular epidemiology of RV infections among 590 children hospitalized with acute respiratory infection in north-western and central parts of Croatia. For respiratory virus detection, nasopharyngeal and pharyngeal flocked swabs were taken from each patient and subsequently analyzed with multiplex RT-PCR. To determine the RV species in a subset of positive children, 5′UTR in RV-positive samples has been sequenced. Nucleotide sequences of referent RV strains were retrieved by searching the database with Basic Local Alignment Tool, and used to construct alignments and phylogenetic trees using MAFFT multiple sequence alignment tool and the maximum likelihood method, respectively. In our study population RV was the most frequently detected virus, diagnosed in 197 patients (33.4%), of which 60.4% was detected as a monoinfection. Median age of RV-infected children was 2.25 years, and more than half of children infected with RV (55.8%) presented with lower respiratory tract infections. Most RV cases were detected from September to December, and all three species co-circulated during the analyzed period (2017–2019). Sequence analysis based on 5′UTR region yielded 69 distinct strains; the most prevalent was RV-C (47.4%) followed by RV-A (44.7%) and RV-B (7.9%). Most of RV-A sequences formed a distinct phylogenetic group; only strains RI/HR409-18 (along with a reference strain MF978777) clustered with RV-C strains. Strains belonging to the group C were the most diverse (41.6% identity among strains), while group B was the most conserved (71.5% identity among strains). Despite such differences in strain groups (hitherto undescribed in Croatia), clinical presentation of infected children was rather similar. Our results are consistent with newer studies that investigated the etiology of acute respiratory infections, especially those focused on children with lower respiratory tract infections, where RVs should always be considered as potentially serious pathogens.

Seasonal Coronaviruses and Other Neglected Respiratory Viruses: A Global Perspective and a Local Snapshot

“…A recent prospective study conducted in 11 European countries has shown that in adults presenting to primary care with LRTI, the most common viral pathogens detected were human rhinoviruses (20.1%) (45). Another recent study conducted on hospitalized children with ARI in Croatia also revealed rhinovirus as the most frequently detected virus, diagnosed in 33.4% patients; 60.4% as monoinfection, and 39.6 % as co-infection with other respiratory viruses (46). More than half of children infected with rhinovirus (55.8%) presented with LRTI (46).…”

“…The complexity of these observations is emphasized by the finding that the relationship between species and disease severity also depends in some extent on age, i.e., it is frequently noted that RV-C tends to cause more severe disease in children (56) and HRV-A in adults (54). Most studies are however in agreement that RV-B tends to occur sporadically and often in asymptomatic patients (46,54,57).…”

“…Since the discovery of rhinovirus, many longitudinal studies have shown that rhinoviruses can be detected throughout the year (62), with the awareness that in countries with temperate climate they occur more frequently in autumn and spring (63). Recent studies from Croatia have also shown this pattern of rhinovirus prevalence with peak of rhinovirus prevalence detected during autumn and spring, while influenza viruses, respiratory syncytial virus, and metapneumovirus predominate in the winter (46,64). However, some studies indicate that severe rhinovirus infection are more common in the winter (65), possibly due to a weaker induction of interferon at low temperatures, resulting in less efficient antiviral defence response of infected cells (66).…”

Neuropsychiatric Symptoms of COVID-19 Explained by SARS-CoV-2 Proteins’ Mimicry of Human Protein Interactions

“…It was demonstrated that retroviruses leading to neural involvement like HIV and HTLV-1 can cause tight junction disintegration ( Miller et al, 2012 ). Similarly, the Zika virus has been shown to alter BBB structure especially the tight junctions ( Ljubin-Sternak et al, 2019 ). Additionally, the virus has an important interaction with ACE-2 receptors located on both endothelium as well as brain vascular pericytes.…”

A Core Genome Multilocus Sequence Typing Scheme for Streptococcus mutans

“…Maximum likelihood phylogenetic trees were generated based on 594 cgMLST core genes and 8 MLST housekeeping genes in all 80 samples via TreeBeST under Hasegawa-Kishino-Yano (HKY) and general time-reversible (GTR) models (49)(50)(51). The reliability of the branching orders was evaluated via 1,000 bootstrap replicates (52). The Phylogenetic trees were annotated using Interactive Tree Of Life (iTOL) v5 (https://itol.embl.de/) (53).…”