Effect of natural products use prior to infection with COVID-19 on disease severity and hospitalization: A self-reported cross-sectional survey study

{ 'indexed': {'date-parts': [[2022, 7, 6]], 'date-time': '2022-07-06T12:11:33Z', 'timestamp': 1657109493504}, 'reference-count': 63, 'publisher': 'F1000 Research Ltd', 'license': [ { 'start': { 'date-parts': [[2022, 6, 10]], 'date-time': '2022-06-10T00:00:00Z', 'timestamp': 1654819200000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'http://creativecommons.org/licenses/by/4.0/'}], 'funder': [ { 'DOI': '10.13039/501100019004', 'name': 'Deanship of Research, Jordan University of Science and Technology', 'doi-asserted-by': 'publisher', 'award': ['Grantnumber20210173']}], 'content-domain': {'domain': ['f1000research.com'], 'crossmark-restriction': False}, 'abstract': '<ns3:p><ns3:bold>Background:</ns3:bold> Managing coronavirus disease 2019 (COVID-19) using ' 'available resources is essential to reduce the health burden of disease. The severity of ' 'COVID-19 is affected by nutritional status. In this study the effect of natural product use ' 'prior to infection with COVID-19 on disease severity and hospitalization was ' 'explored.</ns3:p><ns3:p> <ns3:bold>Methods:</ns3:bold> This was a cross-sectional study. ' 'Between March and July 2021, a self-administered survey was conducted in Jordan. Individuals ' 'who recovered from COVID-19 and were ≥18 years old were the study population. Study measures ' 'included the use of natural products, COVID-19 severity, and hospitalization status. A ' 'multivariate regression model was used for statistical analysis.</ns3:p><ns3:p> ' '<ns3:bold>Results:</ns3:bold><ns3:italic> </ns3:italic>The mean age (mean ± SD) of the study ' 'sample (n=2,148) was 40.25 ± 15.58 years old. Multivariate logistic regression showed that ' 'the regular intake of carnation (OR [0.56], CI [0.37–0.85]), onion (OR [0.69], CI ' '[0.52–0.92]), lemon (OR [0.68], CI [0.51–0.90]), and citrus fruits (OR [0.66], CI ' '[0.50–0.89]) before infection were associated with a substantial reduction in COVID-19 ' 'severity (P&lt;0.01). Also, the consumption of carnation (OR [0.55], CI [0.34–0.88]), lemon ' '(OR [0.57], CI [0.42–0.78]), and citrus fruits (OR [0.61], CI [0.44–0.84]) were associated ' 'with a significant decrease in the frequency of COVID-19-induced hospitalization ' '(P&lt;0.01).</ns3:p><ns3:p> <ns3:bold>Conclusions:</ns3:bold> Regular consumption of ' 'carnation, lemon, and citrus fruits before infection was associated with better outcomes for ' 'COVID-19. Studies on other populations are required to confirm these findings.</ns3:p>', 'DOI': '10.12688/f1000research.121933.1', 'type': 'journal-article', 'created': {'date-parts': [[2022, 6, 10]], 'date-time': '2022-06-10T15:25:27Z', 'timestamp': 1654874727000}, 'page': '639', 'update-policy': 'http://dx.doi.org/10.12688/f1000research.crossmark-policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Effect of natural products use prior to infection with COVID-19 on disease severity and ' 'hospitalization: A self-reported cross-sectional survey study', 'prefix': '10.12688', 'volume': '11', 'author': [ { 'ORCID': 'http://orcid.org/0000-0002-0545-3311', 'authenticated-orcid': False, 'given': 'Refat M.', 'family': 'Nimer', 'sequence': 'first', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-3006-3104', 'authenticated-orcid': False, 'given': 'Omar F.', 'family': 'Khabour', 'sequence': 'additional', 'affiliation': []}, {'given': 'Samer F.', 'family': 'Swedan', 'sequence': 'additional', 'affiliation': []}, {'given': 'Hassan M.', 'family': 'Kofahi', 'sequence': 'additional', 'affiliation': []}], 'member': '2560', 'published-online': {'date-parts': [[2022, 6, 10]]}, 'reference': [ { 'key': 'ref1', 'doi-asserted-by': 'publisher', 'first-page': '265-269', 'DOI': '10.1038/s41586-020-2008-3', 'article-title': 'A new coronavirus associated with human respiratory disease in China.', 'volume': '579', 'author': 'F Wu', 'year': '2020', 'journal-title': 'Nature.'}, { 'key': 'ref2', 'doi-asserted-by': 'publisher', 'first-page': '1678-1685', 'DOI': '10.7150/ijbs.45053', 'article-title': 'SARS-CoV-2: an emerging coronavirus that causes a global threat.', 'volume': '16', 'author': 'J Zheng', 'year': '2020', 'journal-title': 'Int. 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[Dataset].', 'author': 'R Nimer', 'year': '2022', 'DOI': '10.6084/m9.figshare.19758820.v2'}], 'container-title': 'F1000Research', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://f1000research.com/articles/11-639/v1/xml', 'content-type': 'application/xml', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://f1000research.com/articles/11-639/v1/pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://f1000research.com/articles/11-639/v1/iparadigms', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2022, 7, 6]], 'date-time': '2022-07-06T11:50:21Z', 'timestamp': 1657108221000}, 'score': 1, 'resource': {'primary': {'URL': 'https://f1000research.com/articles/11-639/v1'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2022, 6, 10]]}, 'references-count': 63, 'URL': 'http://dx.doi.org/10.12688/f1000research.121933.1', 'relation': { 'has-review': [ { 'id-type': 'doi', 'id': '10.5256/f1000research.133852.r140507', 'asserted-by': 'subject'}, { 'id-type': 'doi', 'id': '10.5256/f1000research.133852.r140506', 'asserted-by': 'subject'}]}, 'ISSN': ['2046-1402'], 'subject': [ 'General Pharmacology, Toxicology and Pharmaceutics', 'General Immunology and Microbiology', 'General Biochemistry, Genetics and Molecular Biology', 'General Medicine'], 'container-title-short': 'F1000Res', 'published': {'date-parts': [[2022, 6, 10]]}, 'assertion': [ { 'value': 'Approved with reservations, Approved with reservations', 'URL': 'https://f1000research.com/articles/11-639/v1#article-reports', 'order': 0, 'name': 'referee-status', 'label': 'Referee status', 'group': {'name': 'current-referee-status', 'label': 'Current Referee Status'}}, { 'value': '10.5256/f1000research.133852.r140507, Fatin Y. Atrooz, Department of ' 'Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of ' 'Houston, Houston, TX, USA, 22 Jun 2022, version 1, 2 approved with reservations', 'URL': 'https://f1000research.com/articles/11-639/v1#referee-response-140507', 'order': 0, 'name': 'referee-response-140507', 'label': 'Referee Report', 'group': {'name': 'article-reports', 'label': 'Article Reports'}}, { 'value': '<b>Refat Nimer</b>; \n' '<i>Posted: 02 Jul 2022</i>; We would like to thank the reviewers for careful ' 'and thorough reading of this manuscript and for the thoughtful comments and ' 'constructive suggestions, which helped to improve the quality of this ' 'manuscript. Please find attached a point-by-point response to reviewers’ ' 'concerns. We hope that you find our responses satisfactory and that the ' 'manuscript is now acceptable for publication. \n' '<u>Reviewer #1 (Comments to the Author):</u>&nbsp; - Recruitment method is not ' 'clear, how the investigators reached out to the potential participants is not ' 'stated. The study suggests that only people who were previously infected with ' 'COVID-19 were included in the study. This assumption should be discussed in the ' 'inclusion criteria. \n' '<b>Authors’ response:</b> The recruitment method has now been illustrated in ' 'the revised manuscript. In the cover page for the questionnaire, we outlined ' 'the criteria for participation in the study, which includes infection with ' 'COVID-19 and recovery from illness. The research assistance emphasized that ' "participants' infection should have been confirmed by polymerase chain reaction " '(PCR). Participants were approached in public places such as bus stations, ' 'parks, religious places, universities and restaurants. - Calculation of the ' 'study sample assumed that the total population is the number of COVID-19 ' 'infected people as reported by the end of July 2021. Does this report include ' 'only adults or total confirmed cases? As the survey targeted only adults, the ' 'authors should identify precisely the study population as a reference for ' 'sample size calculation. \n' "<b>Authors' response:</b> The sample size for our study was calculated using " 'Raosoft Online Sample Size Calculator (Raosoft Inc., Seattle, WA, USA). 770,712 ' 'is the total confirmed cases reported by the end of July 2021, and the ' 'recommended sample size was 1067. However, this calculation is to check whether ' 'the sample size in our study is sufficient and representative. The number of ' 'cases under 18 years of age during the time of sample collection (before the ' 'emergence of the Omicron variant) was expected to be small compared to the ' 'adult cases (no data available). Therefore, if patients under 18 years are ' 'subtracted from the total cases, this would lead to a negligible change in the ' 'sample size. Nonetheless, the study sample size was larger than required (n= ' '2,148) even if child cases are considered. This point is now clarified in the ' 'Method section. - Why is lemon considered a separate category from citrus? I ' 'suggest including all citrus fruit, including lemon as one category. \n' '<b>Authors’ response:&nbsp; </b>Thank you for your comment. We prefer to keep ' 'lemon as a separate category from citrus because some studies showed variations ' 'in their nutritional values. This was clarified in the revised manuscript. - ' 'In table 1, the results were expressed in a different format, I suggest having ' 'all the results expressed as N (%). For this purpose, age can be categorized ' 'into 2-3 categories, and same for BMI. \n' "<b>Authors' response: </b>Done as suggested.\n" '<b> </b> - In the multivariate logistic regression, the authors mentioned that ' 'after controlling for covariate, the findings... What are the covariates? The ' 'authors should list the covariates here, and if that includes controlling for ' 'age and gender. \n' "<b>Authors' response:</b> The point raised by the reviewer is now incorporated " 'in the revised manuscript.', 'URL': 'https://f1000research.com/articles/11-639/v1#referee-comment-8464', 'order': 1, 'name': 'referee-comment-8464', 'label': 'Referee Comment', 'group': {'name': 'article-reports', 'label': 'Article Reports'}}, { 'value': '10.5256/f1000research.133852.r140506, Caterina Vicidomini, Istituto di ' 'Biostrutture e Bioimmagini IBB-CNR, Naples, Italy, 28 Jun 2022, version 1, 2 ' 'approved with reservations', 'URL': 'https://f1000research.com/articles/11-639/v1#referee-response-140506', 'order': 2, 'name': 'referee-response-140506', 'label': 'Referee Report', 'group': {'name': 'article-reports', 'label': 'Article Reports'}}, { 'value': '<b>Refat Nimer</b>; \n' '<i>Posted: 02 Jul 2022</i>; We would like to thank the reviewers for careful ' 'and thorough reading of this manuscript and for the thoughtful comments and ' 'constructive suggestions, which helped to improve the quality of this ' 'manuscript. Please find attached a point-by-point response to reviewers’ ' 'concerns. We hope that you find our responses satisfactory and that the ' 'manuscript is now acceptable for publication. \n' '<u>Reviewer #2 (Comments to the Author):</u>&nbsp; In my opinion, this paper ' 'has some limitations including those the authors have described in the text. ' 'The total number and quantity of natural products used by the subjects were ' 'unknown,.. \n' "<b>Authors' response:</b> We agree with the reviewer that the rate of " 'consumption of these natural products was unknown. However, this point was ' 'mentioned in the limitations (highlighted in red). And also, I didn’t find any ' 'information on whether the participants consumed these natural products as ' 'commercial supplements, or if they prepared them from natural sources at home, ' 'for example. \n' '<b>Authors’ response:</b> This study focuses on natural products, not ' 'commercial supplements.&nbsp; However, the point raised by the reviewer is now ' 'incorporated in the revised manuscript. Provide some information on the ' 'recruitment method adopted. \n' "<b>Authors' response:</b> More information was added at “Study design and " 'subjects” section. Specify, at least for the most active products such as ' 'carnation, how it is usually consumed. \n' '<b>&nbsp;</b>\n' '<b>Authors’ response:</b> Your suggestion is now incorporated in the updated ' 'version of the manuscript. Reading the questionnaire, I saw that the authors ' "collected data on potential confounders and comorbidities, but they didn't " 'specify anything on this aspect. Please, add what they considered confounders. ' 'If possible, it would be interesting to evaluate whether, for example, the ' 'cigarette smoking modified the beneficial effect of natural substances ' 'intake. \n' '<b>Authors’ response:</b> COVID-19 was reported to be more severe in people ' 'having high BMI or comorbidities. However, the aim of this study was to explore ' 'the effect of using natural products on the severity of the disease, regardless ' 'of the confounding factors. Therefore, multivariate regression analysis was ' 'applied to control for possible confounding factors such as age, gender, ' 'cigarette smoking, and the number of comorbidities (Table 3). The analysis ' 'without adjusted confounding factors is shown in Table 2. The point raised by ' 'the reviewer is now discussed in the revised manuscript.&nbsp; I know that ' 'there are other natural substances traditionally used to boost the immune ' 'system, but they were not mentioned or considered in the study. Please add a ' 'comment in the text and cite at least the following reference. PMID: 33511704 \n' "<b>Authors’ response: </b>We agree with the reviewer's comment. However, this " 'study covered the broadest range of natural products used by the Jordanian ' 'population. The point raised by the reviewer is now incorporated in the revised ' 'manuscript the last sentence in the introduction) and the proposed reference ' 'was added (ref no. 14).', 'URL': 'https://f1000research.com/articles/11-639/v1#referee-comment-8463', 'order': 3, 'name': 'referee-comment-8463', 'label': 'Referee Comment', 'group': {'name': 'article-reports', 'label': 'Article Reports'}}, { 'value': 'This work was supported by the Deanship of Research, Jordan University of ' 'Science and Technology (Grant number 20210173; to Dr. Refat Nimer). The funders ' 'had no role in study design, data collection and analysis, decision to publish, ' 'or preparation of the manuscript.', 'order': 4, 'name': 'grant-information', 'label': 'Grant Information'}, { 'value': 'This is an open access article distributed under the terms of the Creative ' 'Commons Attribution Licence, which permits unrestricted use, distribution, and ' 'reproduction in any medium, provided the original work is properly cited.', 'order': 0, 'name': 'copyright-info', 'label': 'Copyright'}]}