Household transmission of SARS-CoV-2 in five US jurisdictions: Comparison of Delta and Omicron variants

Julia M. Baker; Jasmine Y. Nakayama; Michelle O’Hegarty; Andrea McGowan; Richard A. Teran; Stephen M. Bart; Lynn E. Sosa; Jessica Brockmeyer; Kayla English; Katie Mosack; Sanjib Bhattacharyya; Manjeet Khubbar; Nicole R. Yerkes; Brooke Campos; Alina Paegle; John McGee; Robert Herrera; Marcia Pearlowitz; Thelonious W. Williams; Hannah L. Kirking; Jacqueline E. Tate

doi:10.1371/journal.pone.0313680

Peer Review History

Original SubmissionJanuary 16, 2024
20 Aug 2024 Decision Letter - Ranjan K. Mohapatra, Editor PONE-D-24-00274Household transmission of SARS-CoV-2 in five US jurisdictions: comparison of Delta and Omicron variantsPLOS ONE Dear Dr. Baker, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Oct 04 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. Additional Editor Comments: I have received the comments from the reviewers. However, it may further be considered with the following changes. 1. Authors should discuss the novelty of the work in last part of abstract and conclusion. 2. The study was carried out from October 2021 through February 2022 in the US. However, authors have not discussed the application of this work in 2024. 3. Discussion part must be improved. 4. Add limitations of the study after discussion. 5. The important findings of the study should be discussed in conclusion section. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. 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Revision 1
21 Oct 2024 Author Response Please note: Responses to the editor/reviewers are in blue and line numbers refer to the track changes version of the manuscript. Editor Comments: I have received the comments from the reviewers. However, it may further be considered with the following changes. 1. Authors should discuss the novelty of the work in last part of abstract and conclusion. Response: Thank you for your suggestion to better highlight the novelty of this work. In both the abstract and conclusion sections, we have elaborated on how this investigation is unique in its use of a multivariable model to account for the interaction between various index case and household contact characteristics and their role in household transmission risk. This approach more accurately captures the combined role of multiple predictors which contribute to risk in today’s COVID-19 environment. Updates to text: (lines 53-56) “Uniquely, this study adjusted risk estimates for several index case and household contact characteristics and demonstrates that few characteristics strongly dictate risk, likely reflecting the complexity of the biological and social factors which combine to impact SARS-CoV-2 transmission.” (lines 443-447) “This investigation quantified the contribution of several index case and household contact characteristics to transmission risk in households with Delta or Omicron circulating and, uniquely, applied a multivariable model to produce estimates reflecting the complex relationships between variant, index case characteristics, and household contact characteristics. 2. The study was carried out from October 2021 through February 2022 in the US. However, authors have not discussed the application of this work in 2024. Response: Throughout the discussion and conclusion sections, we have added text to elaborate on how this investigation applies to today’s COVID-19 environment and currently circulating strains. We explain that 1) the household transmission study approach will remain useful for rapid evaluation of transmission as SARS-CoV-2 evolves; 2) the patterns observed in this evaluation in the Delta and early Omicron period likely hold true today as Omicron is still circulating (albeit slightly differently as new sub-variants have emerged) and COVID-19 vaccination and infection still occur, contributing to multifactorial components of transmission risk; and 3) the primary predictor of transmission identified in this study, index case symptom status, should be a key characteristic evaluated in current and future variants when estimating their public health impact. Relatedly, we have added several new references describing the importance of household transmission studies for understanding infectious disease transmission (ref #11-12), information on recently circulating SARS-CoV-2 strains (ref #14), and viral characteristics that may be related to symptom status of infections (ref #20-24) Updates to text: (lines 346-349) “These findings emphasize the importance of adjusted models that account for the multifactorial drivers of transmission and the importance of symptom status when predicting transmissibility of currently circulating Omicron sub-lineages or emerging strains.” (lines 351-362) “SARS-CoV-2 variants and sub-lineages have exhibited distinct variation in traits, such as the ability to evade immune defenses or cause severe disease, requiring ongoing assessment of the public health and clinical impact of SARS-CoV-2 over time. Much as household-based studies have elucidated the epidemiology of the ever-changing influenza virus over the last several decades [11,12], they can provide early insight into the transmission of SARS-CoV-2 as the virus evolves. Important strengths of household-based studies are the well-defined cohorts exposed to the index case and the relatively short duration of follow-up required to identify infection [11], facilitating rapid evaluation of emerging variants. The current study adds to the growing body of literature comparing transmission of Omicron to previously circulating variants [5,7,13] and provides baseline data from the early months of Omicron’s emergence for comparison to currently circulating Omicron sub-lineages [14], contributing to our understanding of collective and cumulative changes that occur over the course of the pandemic.” (lines 386-389) “Extrapolating to the more recently circulating Omicron sub-lineages [14], we might expect only small changes in risk given the close genetic relationship of the circulating sub-lineages to the Omicron lineage investigated here and the ongoing COVID-19 vaccination and infection occurring in the population.” (lines 452-454) “Symptom status of the index case was the only consistent and strong predictor of household transmission regardless of variant and may serve as an important clinical characteristic to consider when assessing the public health impact of emerging strains.” 3. Discussion part must be improved. Response: Thank you for the suggestion to enhance the discussion section. We have substantially modified the text throughout to address the other comments received (please see other responses). In addition, we have included two new paragraphs which detail the benefit of household transmission studies and interpret the finding that transmission is substantially higher when the index case is symptomatic. We feel the discussion section now highlights and interprets the results of this investigation more completely. Updates to text: (lines 351-362) “SARS-CoV-2 variants and sub-lineages have exhibited distinct variation in traits, such as the ability to evade immune defenses or cause severe disease, requiring ongoing assessment of the public health and clinical impact of SARS-CoV-2 over time. Much as household-based studies have elucidated the epidemiology of the ever-changing influenza virus over the last several decades [11,12], they can provide early insight into the transmission of SARS-CoV-2 as the virus evolves. Important strengths of household-based studies are the well-defined cohorts exposed to the index case and the relatively short duration of follow-up required to identify infection [11], facilitating rapid evaluation of emerging variants. The current study adds to the growing body of literature comparing transmission of Omicron to previously circulating variants [5,7,13] and provides baseline data from the early months of Omicron’s emergence for comparison to currently circulating Omicron sub-lineages [14], contributing to our understanding of collective and cumulative changes that occur over the course of the pandemic.” (lines 405-417) “In both Delta and Omicron households, we found household contacts of symptomatic index cases to be twice as likely to become infected compared to contacts of asymptomatic index cases. This strong, consistent association may be representative of viral and individual characteristics. Individuals infected with newer SARS-CoV-2 variants tend to have higher viral loads [20] and emit more airborne virus relative to those infected with variants that circulated early in the COVID-19 pandemic [21]. There is not strong evidence, however, of differences in COVID-19 disease symptomatology in recent variants [22], which may account for the lack of association between symptom status and variant in this analysis. Within a host, increased individual-level immunity from vaccination and/or previous infections may result in reduced severity or duration of symptoms [23,24] that, in turn, reduce the infectiousness of the individual. Interestingly, index case vaccination status was not found to be significantly associated with transmission when included in the adjusted model; however, this may be because the impact of vaccination was partly accounted for in symptom status.” 4. Add limitations of the study after discussion. Response: A substantial limitations section is already included in the discussion section, however, we have demarcated it with a new sub-header, “Limitations” to distinguish it from the rest of the text. Updates to text: (line 419) “Limitations” 5. The important findings of the study should be discussed in conclusion section. Response: We have more clearly highlighted the study’s main findings in the conclusion section and clarified the impact of these findings on COVID-19 today and into the future as the virus evolves. Updates to text: (lines 450-458) “After adjusting for multiple factors, only time since household contact’s last COVID-19 vaccine dose was observed to differ modestly by variant and few factors substantially impacted risk. Symptom status of the index case was the only consistent and strong predictor of household transmission regardless of variant and may serve as an important clinical characteristic to consider when assessing the public health impact of emerging strains.” Reviewers' comments: 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 Response: Thank you. ________________________________________ 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Response: Thank you. ________________________________________ 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 Response: Thank you. ________________________________________ 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 Response: Thank you. ________________________________________ 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 manuscript is technically sound and the analyzed and interpreted data supported the conclusion. Experiments were conducted with appropriate sample size of replication and control. In addition statistics data was done properly and sketched in graphics. The manuscript write-up is written in clearly with no grammatical error. Response: We appreciate your thoughtful evaluation. Reviewer #2: The manuscript offers a significant contribution to the field of public health, addressing an important global health issue. The authors present a well-structured study that is methodologically sound, and theoretically grounded and contributes new insights. I recommend that the paper be accepted for publication. Response: Thank you for your review. ________________________________________ 6. 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: Yes: Asefa Deressa, Research Adviser Reviewer #2: Yes: Lawrence Sena Tuglo Response: Thank you very much for your time and consideration. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0313680.r002
30 Oct 2024 Decision Letter - Ranjan K. Mohapatra, Editor Household transmission of SARS-CoV-2 in five US jurisdictions: comparison of Delta and Omicron variants PONE-D-24-00274R1 Dear Dr. Baker, 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, 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, Ranjan K. Mohapatra, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Authors have improved the manuscript as suggested. It may be accepted for publication after plagiarism check. Reviewers' comments: https://doi.org/10.1371/journal.pone.0313680.r003
Formally Accepted
5 Nov 2024 Acceptance Letter - Ranjan K. Mohapatra, Editor PONE-D-24-00274R1 PLOS ONE Dear Dr. Baker, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, 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 customercare@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. Ranjan K. Mohapatra Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0313680.r004

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