Fatal Community-acquired Pneumonia in Children Caused by Re-emergent Human Adenovirus 7d Associated with Higher Severity of Illness and Fatality Rate

Abstract

Human adenoviruses (HAdVs) are highly contagious pathogens causing acute respiratory disease (ARD), such as community-acquired pneumonia. HAdV-7d, a re-emergent genomic variant, has been recently reported in Asia and the United States after a several-decade absence. However, whether HAdV-7d is associated with higher severity than other types is currently unclear. In this study, the clinical and epidemiological investigation showed that fever, cough, and sore throat were the three most common respiratory symptoms of HAdV infections. HAdV-7 caused longer duration of fever, higher morbidity of tachypnea/dyspnea, pleural effusion, diarrhea, hepatosplenomegaly, consciousness alteration, as well as higher rates of pneumonia, mechanical ventilation and higher fatality rate (28.6%) than other types, particularly HAdV-3 and HAdV-2. The genomes of seven HAdV-7d isolates from mild, severe, and fatal cases were sequenced and highly similar with each other. Surprisingly, two isolates (2011, 2012) had 100% identical genomes with an earlier strain from a fatal ARD outbreak in China (2009), which elucidates the virus origin and confirms the unexpected HAdV genomic conservation and stability. Phylogenetic analysis indicated that L1 52/55-kDa DNA packaging protein may be associated with the higher severity of illness and fatality rate of HAdV-7. Clinicians need to be aware of HAdVs in children with ARD.

Distribution of the atypical pathogens of community-acquired pneumonia to disease severity

“…Their findings were consistent to ours. Wang et al (15) reported that HRV was associated with severe adult CAP in Chinese; Yu et al (16) reported that human adenovirus 7 type caused higher fatality rate (28.6%) of Chinese child acute respiratory infectious disease than other types. However, their conclusions were almost drew from univariate analyses, and some confounding factors, such as underlying disease, should be excluded.…”

An outbreak of acute respiratory disease caused by a virus associated RNA II gene mutation strain of human adenovirus 7 in China, 2015

“…Considering the role of L1 52/55K protein in promoting the formation of infectious virions, the up-regulation of L1 52/55K might explain the rapid growth of the Wuhan strain and this outbreak. In addition, a previous report suggested that the L1 52/ 55K gene, which recombined from HAdV-B16, was a reason for the virulence of HAdV-7 strains predominated in China [32]. The WH strain identified in this outbreak shared 100% identity with this reported L1 52/55K gene.…”

Infective factors and PCT/CRP levels in 112 emergency cases of respiratory tract infection

“…2,23 However, among the 112 cases in our study, only 4 were diagnosed with viral pneumonia, probably because of a general assumption of bacterial pneumonia. Many previous studies have seriously underestimated the incidence of pneumonia caused by viral infections, especially by new respiratory viruses, which can cause severe pneumonia with a high fatality rate [24][25][26] . Taking the 2003 SARS outbreak as an example, the Asian Development Bank estimated that this epidemic cost Hong Kong ~$6 billion.…”