Post-mortem study of endemic human coronaviruses (HCoV-NL63, OC43, 229E and HKU-1) in deaths of children under five in low- and middle-income countries: Findings from the Child Health and Mortality Prevention Surveillance (CHAMPS) study

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 pediatric deaths from January 2017 through 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.