Discovery of a subgenotype of human coronavirus NL63 associated with severe lower respiratory tract infection in China, 2018

Abstract

Human coronavirus NL63 (HCoV-NL63) is primarily associated with common cold in children, elderly and immunocompromised individuals. Outbreaks caused by HCoV-NL63 are rare. Here we report a cluster of HCoV-NL63 cases with severe lower respiratory tract infection that arose in Guangzhou, China, in 2018. Twenty-three hospitalized children were confirmed to be HCoV-NL63 positive, and most of whom were hospitalized with severe pneumonia or acute bronchitis. Whole genomes of HCoV-NL63 were obtained using next-generation sequencing. Phylogenetic and single amino acid polymorphism analyses showed that this outbreak was associated with two subgenotypes (C3 and B) of HCoV-NL63. Half of patients were identified to be related to a new subgenotype C3. One unique amino acid mutation at I507 L in spike protein receptor binding domain (RBD) was detected, which segregated this subgenotype C3 from other known subgenotypes. Pseudotyped virus bearing the I507 L mutation in RBD showed enhanced entry into host cells as compared to the prototype virus. This study proved that HCoV-NL63 was undergoing continuous mutation and has the potential to cause severe lower respiratory disease in humans. Article summary lineThis study reports an outbreak of severe lower respiratory illness caused by two subgenotypes (C3 and B) of human coronavirus NL63 (HCoV-NL63). The new subgenotype C3 with enhanced viral entry into host cells accounts for half of patients, which alerted that HCoV-NL63 which consist of multiple subgenotypes, is undergoing continuous mutation, and has the potential to cause large-scale severe infections in humans.

Zoonotic origins of human coronaviruses

“…Similar to HCoV-NL63, HCoV-229E and HCoV-OC43, HCoV-HKU1 was found worldwide, causing mild respiratory diseases [37]. All these four communityacquired HCoVs have been well adapted to humans and are generally less likely to mutate to cause highly pathogenic diseases, though accidents did occur for unknown reasons as in the rare case of a more virulent subtype of HCoV-NL63, which has recently been reported to cause severe lower respiratory tract infection in China [38]. Generally, when these HCoVs acquire the abilities to transmit efficiently and to maintain themselves continuously within humans, they also become less virulent or pathogenic.…”

Endemic Non–SARS-CoV-2 Human Coronaviruses in a Community-Based Australian Birth Cohort

“…The latter is especially relevant as endemic HCoVs continue to evolve with the potential to cause outbreaks and severe LRIs. 41,42 Although hospital-based studies report most children with HCoV had LRIs, such as bronchiolitis, pneumonia and croup, [12][13][14] community-based cohort studies are more likely to describe symptoms of an URI. 14,21,22 However, illnesses vary between cohort studies as different criteria were used for collecting respiratory samples.…”

A tug-of-war between severe acute respiratory syndrome coronavirus 2 and host antiviral defence: lessons from other pathogenic viruses

“…Only in rare cases, they might be accidentally mutated to cause more severe lower respiratory tract disease. For example, a subtype of NL63 was recently found to be associated with severe lower respiratory tract infection in China [17].…”