Clues from other coronaviruses?

NL63 was only isolated in 2004. What's interesting about this piece is it raises a few topics to observe with the current Wuhan virus as it unfolds:

1) The CDC just came out with new observations of the current flu season in the United States. Some suggestion that the season may be affecting younger patients more than normal (less dead because younger patients infected but more hospitalizations).

2) To date Wuhan is going after older, sicker patients. However, this piece below (focused only on children so the generalizations are sketchy at best) are interesting. If older patients and/or the Wuhan virus creates some of the co-infection respiratory interactions seen with NL63 then the prospect of "superinfections" is truly worrisome.

3) Coinfection, especially in the United States as we're still at the height of an ill-matched flu season, gives me pause (especially as I've seen many reports among family/friends that current hospitals are already "bursting at the seams" with flu patients). Perhaps some of these considerations explain the extraordinary steps China is taking at present. Time will tell.


Human Coronavirus NL63
Burtram C Fielding

DISCLOSURESFuture Microbiol. 2011;6(2):153-159.

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Abstract and Introduction
Abstract
Respiratory tract infection is a leading cause of morbidity and mortality worldwide, especially among young children. Human coronaviruses (HCoVs) have only recently been shown to cause both lower and upper respiratory tract infections. To date, five coronaviruses (HCoV-229E, HCoV-OC43, SARS-CoV, HCoV-NL63 and HCoV HKU-1) that infect humans have been identified, four of which (HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU-1) circulate continuously in the human population. Human coronavirus NL63 (HCoV-NL63) was first isolated from the aspirate from a 7-month-old baby in early 2004. Infection with HCoV-NL63 has since been shown to be a common worldwide occurrence and has been associated with many clinical symptoms and diagnoses, including severe lower respiratory tract infection, croup and bronchiolitis. HCoV-NL63 causes disease in children, the elderly and the immunocompromised, and has been detected in 1.0–9.3% of respiratory tract infections in children. In this article, the current knowledge of human coronavirus HCoV-NL63, with special reference to the clinical features, prevalence and seasonal incidence, and coinfection with other respiratory viruses, will be discussed.

Introduction
Acute respiratory tract infections (ARTIs) are among the most common causes of disease in humans.[1] The majority of ARTIs are caused by viruses with rhinovirus, respiratory syncytial virus, influenza virus, enterovirus, human metapneumovirus and parainfluenza virus considered the major pathogens.[1–3] Those most at risk of severe complications from these viral infections include young children, the elderly or persons with compromised cardiac, pulmonary or immune systems.[2,4] The high burden of disease caused by respiratory viruses in young children has led to the development of diagnostic tests and vaccines for the treatment of these infections.[5]

Until recently, it was commonly accepted that the known human coronaviruses (HCoVs), with the exception of severe acute respiratory syndrome Cov (SARS-CoV), mainly cause mild upper respiratory tract infections (URTIs).[6] For this reason, the circulation of HCoVs was not monitored and no attempt to develop vaccines or drugs against these viruses was made.[7] CoVs are ssRNA viruses that infect humans and animals. In animals, CoVs cause a wide spectrum of diseases, including respiratory, enteric, hepatic and neurological diseases, with symptoms ranging from mild to severe.[8,9] HCoVs causing URTIs were first isolated from patients in the 1960s,[8] with HCoV-229E and HCoV-OC43 the best characterized. Then, following the outbreak of SARS in China in 2003, three additional human coronaviruses were identified – SARS-CoV,[10–12] HCoV-NL63[13,14] and HCoV-HKU1.[15] Of the five known HCoVs, four (HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1) are circulating continuously in the human population.

This article aims to summarize the current knowledge of HCoV-NL63 with reference to the clinical features, prevalence and seasonal incidence, and coinfection with other respiratory viruses. Finally, perspectives for future developments in the field are discussed.

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Coinfections with Other Respiratory Viruses
Coinfections of HCoV-NL63 and other respiratory viruses, including other HCoVs, influenza A virus, respiratory syncytial virus, parainfluenza virus and human metapneumovirus (hMPV), are common.[19,23,27,30,31,43,44,72,73] Interestingly, coinfected patients are more likely to be hospitalized, indicating the severity of this kind of superinfection.[74] In a study from Germany, respiratory syncytial virus A and HCoV-NL63 was the most common coinfection identified in children less than 3 years of age. This is probably due to the high incidence of respiratory syncytial virus A in winter and the overlap in the seasonality of the viruses.[30] Co-infection in hospitalized children with HCoV-NL63 and bocavirus is reported.[75] The viral load of HCoV-NL63 is lower in coinfected patients than in patients infected with HCoV-NL63 only.[5,30] The clinical significance of these coinfections are not clear, but various plausible explanations for the lower HCoV-NL63 viral load have previously been discussed: HCoV-NL63 causes the initial infection that weakens the immune system enough for a second viral infection to gain a foothold. By the time this second infection shows symptoms, the HCoV-NL63 infection might have already been brought under control by the host immune system; HCoV-NL63 and the other virus may be in competition for the same cellular receptor or target cell in the respiratory organs; the activation of the innate immune response triggered by the second respiratory virus may cause inhibition of HCoV-NL63; or prolonged persistence of HCoV-NL63 at low levels of expression.[30,74] Even though these reports may reflect biological complexity or interaction, it is important to keep in mind that virtually all the published studies comprise solely of cohorts of children hospitalized for ARTI and thus are extremely biased.

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Future Perspective
New data concerning HCoV-NL63 and other HCoVs indicate that HCoVs may be more clinically important in children and the immunocompromised than previously thought. Since vaccines are not currently available for these respiratory viruses, it is necessary to monitor epidemic patterns and investigate the spread of respiratory infections to efficiently identify, control and prevent epidemics. More comprehensive population-based studies are required to determine the involvement of HCoV-NL63 in other body systems. Also, the development of technologies to accurately identify HCoV-NL63 infections will shed light on the true incidence of this virus in the human population.

Finally, a detailed manipulation of the HCoV-NL63 genome to understand the role of the HCoV-NL63 viral genes in pathogenesis and replication, and for the subsequent development of HCoV-NL63 as a vaccine vector, is needed. This, however, is hampered by the poor growth of the virus in cell culture, as well as the lack of an appropriate animal model. The recent development of the first full-length infectious clone of HCoV-NL63 allows for the systematic experimental study – genes can be modified and/or deleted from the genome – of the functions of the various corresponding HCoV-NL63 proteins, which will lead to a better understanding of the role of the viral genes in infectivity and pathogenicity. This manipulation of the virus genome, in turn, provides a reverse genetics platform that can lead to the development of HCoV-NL63-based vector vaccines.[76]

https://www.medscape.com/viewarticle/738623_6