The dominance of human coronavirus OC43 and NL63 infections in infants

Abstract

Background: It is unknown to what extent the human coronaviruses (HCoVs) OC43, HKU1, 229E and NL63 infect healthy children. Frequencies of infections are only known for hospitalized children.

Objectives: Comparing infection frequencies in children who have mild infections with frequencies in children needing hospital uptake will determine whether infection by one of the four HCoVs leads to more severe disease. In addition, the sequence of seroconversions can reveal whether infection by one HCoV protects from infection by other HCoVs.

Study design: Two distinct study groups were monitored: healthy children and children hospitalized due to respiratory infection. HCoV natural infection rates in healthy children were obtained by serology in 25 newborns (followed 0-20months). The frequencies of severe HCoVs infection was determined by real time RT-PCR among 1471 hospitalized infants (<2-years old) with acute respiratory tract disease.

Results: The majority of healthy children seroconverted for HCoV-OC43 (n=19) and HCoV-NL63 (n=17), less for HCoV-HKU1 (n=9) and HCoV-229E (n=5). Notably, HCoV-HKU1 seroconversion was absent after HCoV-OC43 infection. Also HCoV-229E infection was rarely observed after HCoV-NL63 infection (1 out of 5). In the hospital 207 (14%) out of 1471 children were HCoV positive. Again we observed most infection by HCoV-OC43 (n=85) and HCoV-NL63 (n=60), followed by HCoV-HKU1 (n=47) and HCoV-229E (n=15).

Conclusions: HCoV-NL63 and HCoV-OC43 infections occur frequently in early childhood, more often than HCoV-HKU1 or HCoV-229E infections. HCoV-OC43 and HCoV-NL63 may elicit immunity that protects from subsequent HCoV-HKU1 and HCoV-229E infection, respectively, which would explain why HCoV-OC43 and HCoV-NL63 are the most frequently infecting HCoVs. There are no indications that infection by one of the HCoVs is more pathogenic than others.

Fig. 1

Frequency of infection by the four HCoVs in children. (A) Healthy children: seroconversion for HCoV-OC43, HCoV-NL63, HCoV-HKU1, HCoV-229E during the complete follow up period. The Kaplan–Meier survival analysis was performed on the cumulative incidence of the percentage of seronegative individuals (y-axis) against time (in months; x-axis). Seroconversion to HCoV-NL63 is presented as a blue line, HCoV-OC43 as a green line, HCoV-229E as a black line and HCoV-HKU1 as a red line. (B) Hospitalized children: percentage of coronavirus HCoV-229E, HCoV-HKU1, HCoV-NL63, and HCoV-OC43 positive patients by age group as determined by viral RNA diagnostics. HCoV-NL63, HCoV-OC43, HCoV-229E and HCoV-HKU1 are presented as a blue, green, black and red bar, respectively. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of the article.)