The burden of human coronavirus infection in children hospitalised with lower respiratory tract infection in Cape Town, South Africa

  1. Abdulmumuni S. Aliyu
  2. Adelaide N. Masu
  3. Benjamin M. Kagina
  4. Rudzani Muloiwa

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Abstract

Introduction

Human coronaviruses (HCoV) NL63, HKU, OC43 and 229E are known to cause various respiratory infections including croup, pneumonia, and bronchitis in young children. The role of these four HCoV strains in the aetiology of pneumonia is little described in South Africa.

Methods

We used data collected between September 2012 – September 2013 from children aged <13 years with lower respiratory illness at Red Cross War Memorial Children’s Hospital. Respiratory samples including a nasopharyngeal swab (NP) and induced sputum (IS) were taken and tested for the four strains of coronaviruses using FTD33 multiplex real-time PCR.

Results

A total of 460 respiratory samples were analysed. Of these, 258 (56.0%) were male and 19 (4.1%) HIV infected. The median age of the children was 8 (IQR 4-18) months.

Nasopharyngeal (NP) samples were obtained from 460 children while induced sputum (IS) was not available for six children due to sample loss prior to analysis, leaving 454 available for analysis. A total of 42 (9.1%, 95% CI 6.7-12.1%) participants tested positive for HCoV in at least one of the two specimens. PCR was able to detect a total of 35 (7.7%) cases from the 454 tested IS specimens compared to 23 (5.0%) detected out of 460 NP samples.

The commonest detected HCoVs were coronavirus OC43 with 20 (4.3%) detected from either specimen followed by coronavirus NL63 or coronavirus HKU detected in 14 (3.0%) and 10 (2.2%) of positive test samples, respectively. The least common virus detected HCoV was coronavirus 229E detected in both positive test samples of one participant.

Overall HCoVs were detected in 23 (8.9%) of boys compared to 19 (9.1%) of the girls who returned a positive test; p=0.856. The overall age distribution of children with PCR detected HCoVs was similar to that of children with a negative result with median age of 10 (IQR 5-16) months and median of 8 (IQR 4-19) months, respectively; p=0.535. Prevalence of HCoV was 11/192 (5.7%), 23/153 (15.0%) and 8/115 (7.0%) in children <6 months old, 6-18 months and over 18 months respectively; p=0.008.

Conclusion

Children aged 6 to 18 months had double the risk of other age groups.

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  1. PeerRef

    Peer review report

    Title: Burden of HCoV infection in children hospitalized with lower respiratory infection in Cape Town, South Africa

    version: 1

    Referee: Jessica Price

    institution: University of Witwatersrand

    email: Jessica.Price@wits.ac.za

    ORCID iD: 0000-0002-4020-6850

    General assessment

    This manuscript it well written, with a clear description of the methods, results and discussion of findings. I think that with minor corrections it would be ready for publication.

    Essential revisions that are required to verify the manuscript

    Methods:

    Study procedure:

    1. Please add a reference to the parent study which details the full methods of the parent study.

    2. In the third paragraph of this section the authors refer to children young than 18 months with a positive HIV Elisa as being confirmed to have HIV infection. Please double check this - I think it is supposed to be that these children were categorised as HIV- exposed with a confirmatory HIV PCR preformed to determine HIV infection.

    Results:

    1. The current phrasing of the results suggests that there were no refusals amongst those eligible to participate. Is that accurate?
    1. In table 1: HIV status “exposed by negative” – is that children under 18 months or under 6 months? If only those less than 6 months please explained where children between 6-18 months are categorised.

    Discussion:

    1. 16 patients were found to have different human coronaviruses on the IS and NP samples. Please discuss the implications of this finding. Which would you act on? Does this bring into question the validity of the two methods if they are detecting different viruses in the same patient. I would understand if one method detected additional viruses but to have completely different viruses across the two specimens on the same patient is potentially problematic.

    2. The authors note that the study group only incudes hospitalised patients and therefore cannot comment on community transmission/burden. However there have been many community-based surveillance programmes to track respiratory virus burdens and transmission patterns in SA (including work by Sharon Cohen, NICD) – it would be helpful to the readers if the authors could review some of these publications and comment on relevant similarities or differences. (most recent of these publications can be found here: https://crdm.nicd.ac.za/projects/phirst-c/)

    1. Please review and redraft this paragraph 5 in the discussion – starting “compared to RSV and other respiratory viruses…”. I could not follow what the authors are trying to say in this paragraph.

    2. Please add in a limitations/recommendations section.

    Conclusion:

    1. The final paragraph of the conclusion raises some interesting questions but does not fit as part of the conclusion. I suggest moving this to be included as part of the discussion, and more fully discussing the questions raised regarding the value of testing for disease if they do not cause severe disease, nor change treatment strategies.

    Other suggestions to improve the manuscript

    • Stylistic preferences in the introduction: avoid using “for example” when describing work referenced. Either just add the reference number, or use phrasing such as “as shown by (author name) who found …” etc.

    • Methods - Statistics: Typo in the last paragraph – please confirm if Stata 13 or stata 16, and add in the necessary stata package reference.

    Decision

    Requires revisions: The manuscript contains objective errors or fundamental flaws that must be addressed and/or major revisions are suggested.

  2. PeerRef

    Peer review report

    Title: Burden of HCoV infection in children hospitalized with lower respiratory infection in Cape Town, South Africa

    version: 1

    Referee: SOCORRO P. LUPISAN, MD MSc

    email: socorrolupisan@yahoo.com

    ORCID iD: 0000-0002-8916-4380

    General assessment

    This study reports interesting results, but the description of the methodology needs to be improved.

    Essential revisions that are required to verify the manuscript

    I provide below some comments/queries to strengthen the methodology, and to increase the clarity in the interpretation of the results.

    1. The parent study was not described in the Methods Section. The parent study was disclosed only in the Conclusion: “While this study which is a sub-study restricted itself to the burden of human coronaviruses in children, the main respiratory pathogen under review in the parent study was Bordetella pertussis which only assessed similar risk factors in the same cohort of children. “

    2. This sub study is also prospective in nature.

    3. Was the Informed Consent Form prepared for the parent study only? Did the sub study investigator get a signed Informed Consent Form for the collection and laboratory analysis of samples for this HCoV study?

    4. Study Population: In order for the study to reflect the whole season, recruitment was limited to a maximum of four qualifying participants per day. Did you do stratified and systematic sampling? Please describe your sampling procedures as you have done.

    5. In the Discussion it was written: Although the study was sufficiently powered, it had low precision and could not demonstrate statistically significant associations. How did you calculate sample size?

    Other suggestions to improve the manuscript

    I also have some clarifications which need to be addressed:

    1. Would you know the other viruses detected? If yes, include in the results as this will enrich you results.

    2. Was ceftriaxone really given prior to admission? At home, as injection?

    3. What were the clinical diagnosis of cases with HCoV and no HCoV?

    Decision

    Requires revisions: The manuscript contains objective errors or fundamental flaws that must be addressed and/or major revisions are suggested.

  3. Version published to 10.1101/2022.07.24.22277967v1 on medRxiv