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PONE-D-21-33875COVID-19 hospitalization and mortality and hospitalization-related utilization and expenditure: Analysis of a South African private health insured population.PLOS ONE

Dear Dr. Doherty,

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: I Don't Know

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: No

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors present a study looking at the risk factors for COVID-19 hospitalization, mortality, hospital stay and cost of treatment in South Africa.

I think this is an important study which adds a lot of value, particularly as it covers a region of the world for which there has been limited information. The introduction is well written and interesting. It clearly identifies the research question and highlights the importance of this study. It is a rich dataset, which covers a long period of time, not just the beginning of the pandemic, allowing for changes in hospitalisation, mortality, hospital length and cost to be observed. However, I do have several concerns about the methodology which I have outlined below. Unfortunately, Tables 1-4 also seem to be missing from the manuscript, without which it makes it very difficult to assess the results. I have done my best without them, but would appreciate if a copy of the tables could be sent to me so that I can review the results properly. I also think there lacks interpretation and contextualisation of the results in the discussion (highlighted below).

I think if the authors could address these concerns methodological concerns, and expand the interpretation in the discussion, it is a very worthwhile paper.

1. In your population, do you know all people who have received a positive test? Or is it possible that individuals could have received a positive test from a different source, and this is not recorded in the data? This is an important point and should be made clear in the paper. If it is possible that positive tests could have been missed, then this warrants further discussion (i.e. if those individuals did not need hospitalization, this would over-estimate the estimates of hospitalisation and mortality).

2. I think there are comorbidities that are known risk factors for COVID-19 which have not been included in the study.

You state in the methods:

“Conditions were considered as comorbidity risk factors for COVID-19 based on a review of published literature: Cancer, Chronic Renal Disease, Congestive Cardiac Failure, Chronic Obstructive Pulmonary Disease, Diabetes Mellitus, HIV, Hypercholesterolaemia, Hypertension, Hypothyroidism, Ischaemic Heart Disease, Pregnancy, Tuberculosis”

There are conditions that are considered to be risk factors for COVID-19 hospitalisation and death which are not included in this list, i.e. Asthma, chronic liver disease, neurological diseases (stroke/dementia/etc), organ transplant, immunosuppressive condition (rheumatoid arthritis/lupus/etc), in addition to others. For example, see this paper: https://www.nature.com/articles/s41586-020-2521-4#Sec2

3. There are also risk factors such as smoking and obesity that have not been included presumably due to data limitations. It is mentioned in the discussion that obesity could not be included, but I think further discussion on impact of not including them and how this may have affected the results is warranted. (i.e. discussion of the smoking rates/obesity rates)

4. Table 1 - 4 seem to be missing from the manuscript. I have done my best to assess the results without them, but it would be really helpful to see these tables.

5. It is also not completely clear why vaccination could not be included within this analysis. It would be useful to have more of a discussion on the effect of vaccination on hospitalisations and length of stay, and more information on vaccine roll out in South Africa (i.e. % of people vaccinated with 1 or 2 doses during the different waves), and how this would have effected the results observed.

6. I don’t think this is included in the Tables, but I would be interested to see a summary of the different comorbidities (i.e. XX reported Diabetes, XX Cancer; rather than just 0, 1 comorbidities). Perhaps this could be a summary table of the study characteristics. I appreciate this might be a lot of different risk factors and you may have small numbers for some, so perhaps the main comorbidities rather than 0,1,2,>3. Apologies if this is already included within the table 1.

7. Adjusted odds ratios are reported, but it is not clear from the methods exactly what you have adjusted by. This is also true for the reported adusted IRR. I think this could be clarified in the methods (i.e. in the results you say that you did not adjust by medical insurance level for mortality risk as this was highly correlated with age and comorbidities, was this also the case for the hospitalization risk and length of stay/utilization?)

8. I think one of the key strengths of this study is the longer time period over which data was collected, yet this is not really touched on in the discussion. It is not clear to me why mortality and hospitalization would be lower in wave 1? I would have thought that this was before vaccination, and so mortality might have been higher? I think some further discussion would be useful to help readers contextualise these results.

Some minor points:

1. This sentence about the study size in the methods is a little confusing:

“The study population consisted of families (1.7 million) and individuals (3.5 million) belonging to 19 health insurances administered by DH, representing around a third of South Africa’s privately insured

population.”

It is confusing as to whether it is individuals + families, or total individuals, and of these, there are 2.7 families. Maybe it could be re-phrased to make it slightly clearer (if this is the correct meaning):

“The study population consisted of 3.5 million, which included 1.7 million families belonging...”

Also, what is meant by families? Household members sharing the same health insurance policy?

2. In supplementary table 1 – there is a ** after “Rest of the insured population” but no ** underneath the table.

Reviewer #2: COVID-19 hospitalization and mortality and hospitalization-related utilization and expenditure: Analysis of a South African private health insured population.

This paper looking at data from 188000 members of a health insurance in South Africa. The cross sectional study looked at the rates of hospitalisation and death of these insured people.

The value of the study would be to see if the risks, hospitalisation and mortality differed between the public and private sectors in SA.

In the background only relying on systematic reviews is limiting when it comes to studying Africa. Other papers exist and reports etc . for example:

Jassat, W., Cohen, C., Tempia, S., Masha, M., Goldstein, S., Kufa, T., Murangandi, P., Savulescu, D., Walaza, S., Bam, J. L., Davies, M. A., Prozesky, H. W., Naude, J., Mnguni, A. T., Lawrence, C. A., Mathema, H. T., Zamparini, J., Black, J., Mehta, R., Parker, A., … DATCOV author group (2021). Risk factors for COVID-19-related in-hospital mortality in a high HIV and tuberculosis prevalence setting in South Africa: a cohort study. The lancet. HIV, 8(9), e554–e567. https://doi.org/10.1016/S2352-3018(21)00151-X

Mendelsohn AS, De Sá A, Morden E, Botha B, Boulle A, Paleker M, Davies MA. COVID-19 wave 4 in Western Cape Province, South Africa: Fewer hospitalisations, but new challenges for a depleted workforce. S Afr Med J. 2022 Feb 1;112(2):13496. PMID: 35139985.

Van der Westhuizen JN, Hussey N, Zietsman M, et al. Low mortality of people living with diabetes mellitus diagnosed with COVID-19 and managed at a field hospital in Western Cape Province, South Africa. South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde 2021; 111(10): 961-7.

Phaswana-Mafuya N, Shisana O, Jassat W, et al. Understanding the differential impacts of COVID-19 among hospitalised patients in South Africa for equitable response. South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde 2021; 111(11): 1084-91.

The other issue missing in the background is that there was (during waves) hospital overcrowding (with private hospitals and /or public hospitals turning people away. – which would impact on mortality)

Costs are also relative and perhaps the Health Market Inquiry should be mentioned which describes over servicing in the private sector.

A spelling mistake on page 12 – Comorbidities

Methods: I am not able to comment on the statistical analysis and suggest that a statistician is consulted.

Results

It would be useful to compare the study population’s demographics to the general population.

Discussion

The hospitalisation and mortality rates vary according to the phase of the epidemic and the improvement in treatment.

It isn’t clear if diabetes with hypertension and heart disease has higher morbidity and mortality or whether it is diabetes with either one?

In paragraph 1 on page 16 – the HIV rates differ, is the number of H positive people too small? 4.7% seems still quite a number to me.– is there an assumption that those with HIV are more compliant? Is there evidence for this.

Page 16 paragraph 2 the other differences between public and private sector relate to testing and diagnosis.

Provincial differences needs more discussion – there are similar hospital groups in different provinces – are their systems different. Were there differences in private hospital access to oxygen, ICU specialists/ expertise, and overcrowding in different provinces?

The average length of stay appears to be longer in the national surveillance system, any ideas on this? It is unclear what exactly is included in the costing.

You should compare the costs to those found in Edoka et al.

Edoka I, Fraser H, Jamieson L, Meyer-Rath G, Mdewa W. Inpatient Care Costs of COVID-19 in South Africa’s Public Healthcare System. Int J Health Policy Manag 2021.)

Which policies will be affected by these results – are they substantially different to those in the public sector and the literature?

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Reviewer #1: No

Reviewer #2: No

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COVID-19 hospitalization and mortality and hospitalization-related utilization and expenditure: Analysis of a South African private health insured population.

PONE-D-21-33875R1

Dear Dr. Doherty,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Raymond Nienchen Kuo, Ph.D

Academic Editor

PLOS ONE

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

Reviewer #2: I acknowledge and am happy with the changes the authors have made. The paper is ready for publication.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No