The isolation of the coronavirus (CoV) identified as the cause of severe acute respiratory syndrome and the detection of 2 new human CoVs (HCoV-NL63 and HCoV-HKU1) have led to studies of the epidemiology and clinical and socioeconomic effects of infections caused by all HCoVs, including those known since the late 1960s (HCoV-229E and HCoV-OC43). HCoV infections can be associated with respiratory and extrarespiratory manifestations, including central nervous system involvement. Furthermore, unlike other RNA viruses, HCoVs can easily mutate and recombine when different strains infect the same cells and give rise to a novel virus with unpredictable host ranges and pathogenicity. Thus, circulating HCoVs should be closely monitored to detect the spread of particularly virulent strains in the community at an early stage and to facilitate the development of adequate preventive and therapeutic measures
Assessment of the importance of known HCoVs in Children Superficial analysis of all of the available data concerning the effects of HCoVs in children suggests that the assessment of the importance of HCoVs made before SARS-CoV was identified can still be considered valid. In general, all of these viruses (including SARS-CoV) have been confirmed as mainly respiratory viruses with limited clinical relevance in children. They cause mainly URTIs, are not frequently isolated in hospitalized children, and, because they are rarely transmitted to other household members, have a marginal socioeconomic effects on families. Even SARS-CoV infection, which had a dramatic effect on adults, was mainly associated with relatively mild disease in almost all patients <12 years of age. Moreover, most children with a diagnosis of severe respiratory syndrome in whom a HCoV was isolated were co-infected by other respiratory viruses. These finding suggest that the severity of the respiratory disease at least in some of these cases was attributable to the second virus.
Because only premature infants, neonates with a low birthweight, and children with an underlying severe chronic disease are at risk of experiencing a severe respiratory problem associated with HCoV infection, we could conclude that no further studies of the role of HCoVs in children are needed because what is already known is enough to make such investigations superfluous. Furthermore, on the basis of the data regarding the natural outcome of respiratory infections, developing vaccines or specific drugs appear to be unnecessary.
However, different conclusions can be drawn when the global spectrum of the diseases caused by these viruses in animals and humans is considered. It is now well known that an enormous reservoir of CoVs exists among animals, particularly horseshoe bats, and that CoV isolates recovered from animals in China have up to 99.8% nucleotide identity with SARS-CoV. Because CoVs can easily mutate, this means that (as in 2003) sustained exposure to the infected animals can lead to a SARS-like CoV strain that is newly adapted to infect humans and capable of causing the reappearance of SARS. Moreover, it has been shown experimentally and in nature that all CoVs undergo a high rate of genetic mutations and can recombine when 2 different strains infect the same cells. This finding means that it is theoretically possible that future situations similar to those involving SARS-CoV may involve CoVs that currently infect only some animals, thus leading to novel viruses with unpredictable host ranges and pathogenicity.
Phylogenetic analyses of the genes spanning the HCoV-HUK1 genome suggest that this virus may be the result of a recombination event between related but distinct HCoVs and that SARS-CoV may have originated from a unique recombination. In this regard, the behavior of CoVs could be quite similar to that of influenza viruses, for which genetic changes and recombinations of avian or swine strains are required to allow them to cross the species barrier and replicate in humans to cause a pandemic. Consequently, as is usually the case with influenza, a systematic evaluation of the characteristics of CoVs should be planned. Patients with severe respiratory syndrome seem to be the best target for this kind of evaluation and, in this population, studies of children (in whom the incidence of infection is higher) may also have application to adults because the findings may lead to a reduction in the risk for the spread of particularly virulent HCoV strains.
In addition to the risk for a pandemic related to the reappearance of SARS or other new CoVs, the data regarding the possible relationship between HCoV infection and CNS diseases also suggest the need for a systematic evaluation of the circulation of CoVs. If >1 HCoVs are demonstrated to play a real role in causing some of the CNS diseases with which they have been associated, substantial changes would be required in our diagnostic, prophylactic, and therapeutic approaches to many neurologic illnesses in children.
Conclusions HCoV infections can be associated with respiratory and extrarespiratory manifestations, including central nervous system involvement. The clinical and genetic characteristics of circulating HCoVs in the pediatric population should be monitored to detect the spread of particularly virulent HCoV strains in the community at an early stage and, if required, to facilitate the development of adequate preventive and therapeutic measures.
Reference & Source information: https://www.ncbi.nlm.nih.gov/
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