Abstract
Background: Endemic human coronaviruses (HCoV-229E, HKU1, NL63, and OC43) are common causes of mild or asymptomatic respiratory infections in children but are considered rare causes of death.
Methods: We evaluated paediatric deaths from January 2017 to December 2022. A panel of experts determined the cause of death (CoD) by reviewing available data, including pathological and molecular findings from minimally invasive tissue sampling (lung tissues, blood, CSF, and nasopharyngeal swabs), clinical records, and verbal autopsies.
Results: Endemic HCoV were detected in the respiratory samples of 3% (n=86/3357) of enrolled decedents: 1% (n=12/2043) of neonates, 5%(n=35/681) of infants and 6% (n=39/633) of children deaths. However, HCoVs were attributed as the CoD in only two cases — both involving young infants with underlying birth defects and severe wasting, who succumbed to polymicrobial hospital-acquired infections involving HCoV-OC43, Klebsiella pneumoniae, and Acinetobacter baumannii. Amongst the remaining 84 decedents in whom an HCoV was detected, 82% (n=69/84; median Ct of 25.34; range:15.28-36.17) were deaths attributed to other infections, including 54% (n=32/69; median Ct of 23.86; range:15.28-35.2) with lower respiratory infections determined to be the CoD. The bulk of these deaths (96%,n=66/69) were attributed to other pathogens – Plasmodium falciparum (27%,n=19/69), K.pneumoniae (23%,n=16/69), Streptococcus pneumoniae (20%,n=14/69), Escherichia coli (16%,n=11/69) and Cytomegalovirus (10%,n=7/69).
Conclusion: Although endemic HCoV was identified in children who died of respiratory infections, it was rarely attributed to being in the CoD. Nevertheless, further research is warranted to explore the potential role of HCoVs in LRTI pathogenesis and their impact on facilitating more pathogenic infections.
Note:
Gates Foundation Grant Number(s): OPP1126780
Data Availability Statement: CHAMPS data are open access and datasets are available for download or request on www.champshealth.org.
Keywords: Coronavirus, child mortality, cause of death, minimally invasive tissue sampling
Declaration of Interest
SEA, KLK, and MT report receiving funding from Emory University. JAGS reports receiving funding from Emory University, the Bill & Melinda Gates Foundation, Wellcome Trust, UK Foreign Commonwealth & Development Office, European Union, and National Institute for Health Research. VB and SMad reports receiving funds from the Bill & Melinda Gates Foundation, Pfizer, Minervax, GSK, South African Medical Research Council, Merck, PATH, and Center for the AIDS Programme of Research in South Africa. All other authors declare no competing interests.
Funder Statement
CHAMPS is supported by the Bill & Melinda Gates Foundation (grant OPP1126780). The funder participated in discussions of study design and data collection. They did not participate in the conduct of the study; the management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.