Upper Respiratory Tract Co-detection of Human Endemic Coronaviruses and High-density Pneumococcus Associated With Increased Severity Among HIV-Uninfected Children Under 5 Years Old in the PERCH Study

Park, Daniel E.; Higdon, Melissa M.; Prosperi, Christine; Baggett, Henry C.; Brooks, W. Abdullah; Feikin, Daniel R.; Hammitt, Laura L.; Howie, Steve R. C.; Kotloff, Karen L.; Levine, Orin S.; Madhi, Shabir A.; Murdoch, David R.; O’Brien, Katherine L.; Scott, J. Anthony G.; Thea, Donald M.; Antonio, Martin; Awori, Juliet O.; Baillie, Vicky L.; Bunthi, Charatdao; Kwenda, Geoffrey; Mackenzie, Grant A.; Moore, David P.; Morpeth, Susan C.; Mwananyanda, Lawrence; Paveenkittiporn, Wantana; Ziaur Rahman, Mohammed; Rahman, Mustafizur; Rhodes, Julia; Sow, Samba O.; Tapia, Milagritos D.; Deloria Knoll, Maria

Severity of viral respiratory illnesses can be increased with bacterial coinfection and can vary by sex, but influence of coinfection and sex on human endemic coronavirus (CoV) species, which generally cause mild to moderate respiratory illness, is unknown. We evaluated CoV and pneumococcal co-detection by sex in childhood pneumonia. METHODS: In the 2011–2014 Pneumonia Etiology Research for Child Health study, nasopharyngeal and oropharyngeal (NP/OP) swabs and other samples were collected from 3981 children <5 years hospitalized with severe or very severe pneumonia in 7 countries. Severity by NP/OP detection status of CoV (NL63, 229E, OC43 or HKU1) and high-density (≥6.9 log(10) copies/mL) pneumococcus (HDSpn) by real-time polymerase chain reaction was assessed by sex using logistic regression adjusted for age and site. RESULTS: There were 43 (1.1%) CoV+/HDSpn+, 247 CoV+/HDSpn−, 449 CoV−/HDSpn+ and 3149 CoV−/HDSpn− cases with no significant difference in co-detection frequency by sex (range 51.2%–64.0% male, P = 0.06). More CoV+/HDSpn+ pneumonia was very severe compared with other groups for both males (13/22, 59.1% versus range 29.1%–34.7%, P = 0.04) and females (10/21, 47.6% versus 32.5%–43.5%, P = 0.009), but only male CoV+/HDSpn+ required supplemental oxygen more frequently (45.0% versus 20.6%–28.6%, P < 0.001) and had higher mortality (35.0% versus 5.3%–7.1%, P = 0.004) than other groups. For females with CoV+/HDSpn+, supplemental oxygen was 25.0% versus 24.8%–33.3% (P = 0.58) and mortality was 10.0% versus 9.2%–12.9% (P = 0.69). CONCLUSIONS: Co-detection of endemic CoV and HDSpn was rare in children hospitalized with pneumonia, but associated with higher severity and mortality in males. Findings may warrant investigation of differences in severity by sex with co-detection of HDSpn and SARS-CoV-2.