Persons tested for SAR-CoV-2 at a military treatment facility in Hawaii.

Health inequalities based on race are well-documented, and the COVID-19 pandemic is no exception. Despite the advances in modern medicine, access to health care remains a primary determinant of health outcomes, especially for communities of color. African-Americans and other minorities are disproportionately at risk for infection with COVID-19, but this problem extends beyond access alone. This study sought to identify trends in race-based disparities in COVID-19 in the setting of universal access to care. Tripler Army Medical Center (TAMC) is a Department of Defense Military Treatment Facility (DoD-MTF) that provides full access to healthcare to active duty military members, beneficiaries, and veterans. We evaluated the characteristics of individuals diagnosed with SARS-CoV-2 infection at TAMC in a retrospective, case-controlled (1:1) study. Most patients (69%) had received a COVID-19 test within 3 days of symptom onset. Multivariable logistic regression analyses were used to identify factors associated with testing positive and to estimate adjusted odds ratios. African-American patients and patients who identified as "Other" ethnicities were two times more likely to test positive for SARS-CoV-2 relative to Caucasian patients. Other factors associated with testing positive include: younger age, male gender, previous positive test, presenting with >3 symptoms, close contact with a COVID-19 positive patient, and being a member of the US Navy. African-Americans and patients who identify as "Other" ethnicities had disproportionately higher rates of positivity of COVID-19. Although other factors contribute to increased test positivity across all patient populations, access to care does not appear to itself explain this discrepancy with COVID-19.

Background

First identified in December 2019 in Wuhan, China, SARS-COV2 quickly spread to the rest of the world [1]. COVID-19 disease has been shown to disproportionately affect communities of color, including Asian Americans and Pacific Islanders, with resultant impact on clinical outcomes attributable to limited access to care and the presence of co-morbid conditions [2-4]. Situated in the middle of the Pacific, Hawaii is of strategic importance to the Department of Defense (DOD) with over 300,000 DOD ethnically diverse beneficiaries living and working in the region, many of whom receive their medical care through Tripler Army Medical Center (TAMC). As the pandemic raged, access to health care was of concern, especially for many communities of color. Hawaii is unique in that there is a large Asian American and Pacific Islander population. Within the DOD, regardless of race/gender, medical coverage is provided through a universal health care plan (Tricare) for all service members, their families, and retirees.

The state of Hawaii and regional DOD officials implemented strict public health and infection control practices such as stay at home orders, mandatory masking, social distancing, and travel restrictions off/on the island with mandatory quarantine. TAMC implemented entry checkpoints, visitor restrictions, and liberal teleworking policies to minimize nosocomial spread. Virtual telehealth medical visits were implemented for most outpatient encounters to limit the spread of COVID-19 in the hospital. TAMC obtained and implemented numerous emergency use authorization (EUA) diagnostic platforms early on (e.g. ABI-7500, Biofire, Panther/Panther Fusion, Cepheid) for the detection of SARS-COV2 in symptomatic and asymptomatic individuals for clinical testing, Force Health Protection testing, and pre-operative/pre-admission testing. Many patients received their COVID19 testing at drive-through or field locations without an associated provider visit [4, 5].

In the early phase of the pandemic, little was known about the clinical presentation, asymptomatic infection, transmission, and real-world accuracy of EUA diagnostics. The robust testing capabilities provided a unique opportunity to evaluate these variables in a highly diverse population with reliable access to healthcare. With our study, we aimed to evaluate the epidemiology, clinical manifestation, and demographic characteristics of individuals diagnosed with SARS-COV2 infection at TAMC, assess risk factors contributing to transmission and disease progression, and assess the real-world performance of SARS-COV2 diagnostic platforms approved under Emergency Use Authorization (EUA).

Methods

Before the study began, it was determined to be exempt from IRB review by the Deputy Institutional Officer. This study is a review retrospective, case-controlled (1:1) study. A case was defined as having a positive test via one of the polymerase chain reaction (PCR) testing platforms, while a control was defined as having a negative test via the same platform. We conducted a review of the electronic medical records of patients seen at TAMC between 1 March 2020 to 15 September 2020 to identify variables such as age, gender, BMI, clinical symptoms, travel history, exposure risk, time to testing, and indication for testing. All data were fully anonymized before researcher accessed them to ensure patient’s confidentiality. Cycle Threshold (Ct) values were obtained from our CAP-certified clinical lab; these values were not released to clinicians and were not used to guide clinical decisions. Multivariable logistic regression analyses were used to identify factors associated with testing positive and to estimate adjusted odds ratios.

Results

We found that most (69%) patients received a COVID-19 test within 3 days of symptom onset (Fig 1). Patients who tested negative were twice as likely to have zero symptoms as those who tested positive (56% v. 26%, p<0.001), and patients who tested positive were almost twice as likely to present with ≥ 3 symptoms (Fig 2) than those who tested negative (46% v. 24%, p<0.001). Symptomatic patients with close contact to COVID-19 positive patients were 4 times more likely to test positive than those with symptoms but no close contacts (OR = 3.76) (Figs 3 and 4). As expected, lower rates of positivity were seen in asymptomatic individuals tested for screening purposes. Interestingly, nearly half these individuals tested for screening were positive on these highly sensitive tests.

Fig 1

Days between onset of symptoms and specimen collection date.

Fig 2

Number of symptoms with Covid positive and negative test.

Fig 3

Reason for testing.

Fig 4

Adjusted ORs for positivity based on case-control sample.

African-American patients were two times more likely to test positive for SARS-COV2 relative to Caucasians patients; however, no difference in positivity was seen in Asian-American/Pacific Islanders relative to Caucasians patients (Fig 4). Cough, myalgia, fever, and anosmia were most associated with COVID-19 infection. In our test pool, active duty military made up 63% of all patients tested. Among with an identified race, Caucasians represented 62% of all tests, 17% African-American, 9% Asian American/Pacific Islanders, and 11% other. The percentage tested is representative of the Tricare beneficiary enrollment demographic at TAMC. We found that US Navy personnel were most likely to test positive (OR 1.42) and US Marines were least likely to test positive (OR 0.47) relative to US Army personnel.

Civilian personnel comprised the highest positivity rate relative to US Army personnel (OR 4.32 Fig 5). Among active duty personnel, male gender and African-Americans/other race had higher positivity rates. We also found that patients with higher BMI were less likely to test positive than those with lower BMI (Figs 4 and 6).

Fig 5

Adjusted ORs for positivity based on all active duty service member test case-control sample.

Fig 6

Unadjusted BMI ORs for positivity based on case-control sample.

May-June 2020 saw the lowest positivity rates since March 2020 with a subsequent rise Aug/Sep 2020 timeframe, correlating to tightening and loosening of COVID-19 restrictions. Lower cycle threshold values were seen soon after symptom onset with a slow decline over two weeks (Fig 7).

Fig 7

Mean CT and % CT <24 by days between symptom onset and specimen.

Discussion

Access to healthcare for rapid and accurate diagnosis of COVID-19 infection is one of the cornerstones of infection control and prevention. Cases that are identified rapidly can be appropriately instructed to quarantine to prevent the spread of disease. This facility has a unique benefit of a diverse population of US military, their beneficiaries, and retirees who have universal access to healthcare. We recognize that access to care remains a primary determinant of health outcomes, and this is particularly true for communities of color. We were able to compare rates of COVID-19 positivity in a diverse population with universal access to healthcare, identifying that African-Americans were two times more likely to test positive than their Caucasian counterparts despite no differences in access to care. Further study is warranted to determine the underlying mechanisms at play behind this racial disparity in COVID-19 rates.

Our study also confirmed data previously published that patients who tested negative were twice as likely to be asymptomatic [6, 7]. In addition, we found that patients with close contact with a COVID-19 positive individual were more likely to test positive. This finding is not surprising given what we know about viral transmission.

Lastly, our study was able to compare COVID-19 positivity rates in patients with obesity. Obesity was defined as BMI >30. Much like COVID-19, obesity is a global disease. Previous studies have found that obese patients are at higher risk of mortality from COVID-19 [8]. In this study, we found that patients with obesity had lower COVID-19 positivity rates. Further research is needed in order to understand these results.

Conclusion

Clinical symptoms of fever, cough, myalgia, and anosmia were most associated with COVID-19 infection in our patient population; this is consistent with the literature. Overall positivity rate of all person tested was 3.2%. African-Americans had disproportionately higher rates of positivity even in the setting of universal access to medical care. Obesity was not associated with higher positivity rate. However, there was a slightly lesser chance of having a positive test with a BMI of > 35. Routine screening in asymptomatic individuals, as expected, had lower positivity rates, suggesting infrequent asymptomatic infection/transmission. We did not identify any nosocomial transmission in our hospital in staff or patients. This is likely a result of the strict enforcement of infection control policies and enhanced testing. Universal access to care and robust diagnostic capabilities at TAMC contributed to the short interval between development of symptoms and COVID-19 testing and contributed to low infection rates in DOD beneficiaries. The use of telehealth visits, implementation of COVID-19 restrictions, and stay-at -home mandates limited provider visits so minimal clinical information was available in the medical records to help us refine our analysis of certain variables such as BMI and risk factors for infection.

Characteristics of COVID positive and COVID negative patients.

(XLSX)

Click here for additional data file.

Symptoms prevalence data.

(XLSX)

Click here for additional data file.

OR BMI.

(XLSX)

Click here for additional data file.

BMI.

(XLSX)

Click here for additional data file.

26 Nov 2021

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Sanjay Kumar Singh Patel, Ph.D.

Academic Editor

PLOS ONE

Journal Requirements:

1. When submitting your revision, we need you to address these additional requirements.

Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Please ensure that you refer to Figure 7 in your text as, if accepted, production will need this reference to link the reader to the figure.

3. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.

[Note: HTML markup is below. Please do not edit.]

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: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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: Yes

Reviewer #2: Yes

**********

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

**********

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: In the current research article entitled " Persons Tested for Sar-CoV-2 at a Military Treatment Facility in Hawaii", by Barranco-Trabiet al., studied to identify trends in race-based disparities in COVID-19 in the setting of universal access to care. They evaluated the characteristics of individuals diagnosed with SARS-CoV-2 infection at TAMC in a retrospective, case-controlled (1:1) study by using Multivariable logistic regression analyses. Authors concluded that the African-American patients and patients who identified as “Other “ethnicities were two times more likely to test positive for SARS-CoV-2 relative to Caucasian patients. This article addresses a research topic of great interest, which is under intense investigation in the past years and the manuscript is generally well-written. However, this reviewer has certain suggestions that would help produce a more comprehensive overview of the topic:

Suggestions: -

1, Figures quality may be improved with high resolution images (minor).

2, The English of manuscript can be refined (minor).

3, It is required to provide an additional illustrative figure as to highlight the summary or prospect of this study.

4, More discussion needed to explain the findings.

5, Authors should cite some research to strengthen their hypothesis.

Reviewer #2: IIn this paper entitled "Persons tested for SAR-CoA-2 at a military treatment facility in Hawaii", the authors investigate a trend in race-based disparities in COVID-19 in individuals diagnosed with SARS-COV-2 infection in a retrospective, case-controlled study. The results are exciting and easy to understand. Many studies have found similar results in different settings. The manuscript is acceptable for publication. However, there is notable problem with the manuscript.

Comments:

1) The bar graphs in the manuscript (figure1,2,& 3) are regular Microsoft excel graphs. They should be changed for publication.

2) Discussion is completely missing from the manuscript. Please discuss our results.

3) Figure legends are also missing from the manuscript.

4) Proper reference is not provided in the manuscript.

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

10 Jan 2022

Dear Editors,

Thank you for inviting us to submit a revised draft of our manuscript entitled, " Persons tested for SAR-CoV-2 at a military treatment facility in Hawaii" to PLOS ONE. We also appreciate the time and effort you and each of the reviewers have dedicated to providing insightful feedback on ways to strengthen our paper. Thus, it is with great pleasure that we resubmit our article for further consideration. We have incorporated changes that reflect the detailed suggestions you have graciously provided. We also hope that our edits and the responses we provide below satisfactorily address all the issues and concerns you and the reviewers have noted.

To facilitate your review of our revisions, the following is a point-by-point response to the questions and comments delivered in your letter dated Dec 9th, 2021.

EDITOR SUGGESTIONS:

1. Please ensure that your manuscript meets PLOS ONE's style requirements

• RESPONSE: The editing changes were made based on PLOS ONE’s style requirements.

2. Please ensure that you refer to Figure 7 in your text as, if accepted, production will need this reference to link the reader to the figure.

• RESPONSE: Thank you for bring this up. Figure 7 has been added to the text.

REVIEWER 1 COMMENTS:

4. Figures quality may be improved with high resolution images (minor).

• RESPONSE: We increased the image quality of our graphs.

5. The English of manuscript can be refined (minor).

• RESPONSE: We review the manuscript and refined the English. Grammar changes has been made. Thank you for your feedback.

6. It is required to provide an additional illustrative figure as to highlight the summary or prospect of this study.

• RESPONSE: Thank you for this suggestion; however, we already provide 7 graphs with our results.

7. More discussion needed to explain the findings.

• RESPONSE: We included a discussion section.

8. Authors should cite some research to strengthen their hypothesis

• Response: Thank you for your suggestion, this has been addressed. We included several studies to support our findings.

REVIEWER 2 COMMENTS:

9. The bar graphs in the manuscript (figure1,2,& 3) are regular Microsoft excel graphs. They should be changed for publication.

• RESPONSE: All figures are Microsoft excel graphs. We are open to suggestions to programs that are free. Meanwhile, we increase the quality of our image to better represents our graphs.

10. Discussion is completely missing from the manuscript. Please discuss our results

• RESPONSE: Discussion section was added.

11. Figure legends are also missing from the manuscript.

• RESPONSE: Legends were added

12. Proper reference is not provided in the manuscript.

• RESPONSE: Reference were added to the manuscript

Again, thank you for giving us the opportunity to strengthen our manuscript with your valuable comments and queries. We have worked hard to incorporate your feedback and hope that these revisions persuade you to accept our submission.

Please address all correspondence concerning this manuscript to me at Javier.j.barranco@gmail.com

Thank you for your consideration of this manuscript.

Javier Barranco-Trabi, MD

Tripler Army Medical Center

Internal Medicine

Submitted filename: Cover letter.docx

Click here for additional data file.

20 Jan 2022

PERSONS TESTED FOR SAR-CoV-2 AT A MILITARY TREATMENT FACILITY IN HAWAII

PONE-D-21-35130R1

Dear Dr. Barranco-Trabi,

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.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Sanjay Kumar Singh Patel, 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

Reviewer #1: This article entitled "PERSONS TESTED FOR SAR-CoV-2 AT A MILITARY TREATMENT FACILITY IN HAWAII" has improved.

Reviewer #2: In this paper entitled "Persons tested for SAR-CoV-2 at a military treatment facility in Hawaii." the authors aimed to identify trends in race-based disparities in COVID-19 in the setting of universal access to care. There is huge improvement in the manuscript from the past version. In addition, the author has addressed all the comments in the manuscript. The manuscript looks much better now for publication. There is no technical limitation that can be held responsible for the rejection of the manuscript. I congratulate the authors for the work.

27 Jan 2022

PONE-D-21-35130R1

Persons tested for SAR-CoV-2 at a military treatment facility in Hawaii

Dear Dr. Barranco-Trabi:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Sanjay Kumar Singh Patel

Academic Editor

PLOS ONE