Investigating transmission of SARS-CoV-2 using novel face mask sampling: a protocol for an observational prospective study of index cases and their contacts in a congregate setting

Introduction This study aims to measure how transmission of SARS-CoV-2 occurs in communities and to identify conditions that lend to increased transmission focusing on congregate situations. We will measure SARS-CoV-2 in exhaled breath of asymptomatic and symptomatic persons using face mask sampling—a non-invasive method for SARS-CoV-2 detection in exhaled air. We aim to detect transmission clusters and identify risk factors for SARS-CoV-2 transmission in presymptomatic, asymptomatic and symptomatic individuals. Methods and analysis In this observational prospective study with daily follow-up, index cases and their respective contacts are identified at each participating institution. Contact definitions are based on Centers for Disease Control and Prevention and local health department guidelines. Participants will wear masks with polyvinyl alcohol test strips adhered to the inside for 2 hours daily. The strips are applied to all masks used over at least 7 days. In addition, self-administered nasal swabs and (optional) finger prick blood samples are performed by participants. Samples are tested by standard PCR protocols and by novel antigen tests. Ethics and dissemination This study was approved by the Colorado Multiple Institutional Review Board and the WHO Ethics Review Committee. From the data generated, we will analyse transmission clusters and risk factors for transmission of SARS-CoV-2 in congregate settings. The kinetics of asymptomatic transmission and the evaluation of non-invasive tools for detection of transmissibility are of crucial importance for the development of more targeted control interventions—and ultimately to assist with keeping congregate settings open that are essential for our social fabric. Trial registration number ClinicalTrials.gov (#NCT05145803).

-on page 5, lines 11-16, there is some discussion on the role of asymptomatic infections in SARS-CoV-2 transmission. These modelling values should be contrasted with those from systematic reviews reported by Madewell et al (https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2783544) and Qiu et al (https://pubmed.ncbi.nlm.nih.gov/33484843/). -the authors have chosen to use congregant to describe the settings in their study. A minor point but is this more frequently reported as congregate in the literature?

REVIEWER
Korzen, Marcin West Pomeranian University of Technology in Szczecin, Department of Artificial Intelligence and Applied Mathematics REVIEW RETURNED 04-Jul-2022

GENERAL COMMENTS
The paper describes the proposition of future experiments or an initial research stage. I have no objections to the proposed procedures. Research seems to be planned properly and may be very interesting. However, these are only plans without any results and firm conclusions. I do not know how it is seen in this journal, but I think that most scientists expect that one paper presents the closed experiment as a whole in a compact form. In my opinion, here may be the case of a redundant publication, and also the STROBE Statement is incomplete.

VERSION 1 -AUTHOR RESPONSE
Reviewer: 1 Dr. Esteban Ortiz-Prado, Universidad de Las Américas, Universitat de Barcelona, Comments to the Author: The protocol presented by the authors is interesting.
Definitely the fact of knowing the transmission in crowded places and what is the potential role of respirator wearers in 95 and whether the symptomatological status is of significant importance. RESPONSE: We thank the reviewer for this encouraging evaluation.
Reviewer: 2 Prof. Jason Kindrachuk, University of Manitoba, Comments to the Author: Jaenisch and colleagues provide a study protocol for a prospective investigation of SARS-CoV-2 transmission using face mask sampling within congregate settings. It is noted that this protocol was reviewed by the Colorado multiple institutions review board and the WHO ethics review committee. There were no major concerns noted with study design. However, some minor concerns were identified: -it was noted that the sensitivity of the authors' testing method was equal or greater than 10^4 viral particles. -The authors did not note any statistical analysis for laboratory analyses (eg. immune profiling, viral genome copy quantification, etc).

RESPONSE:
The main objectives of the study are centered around the epidemiology transmission.
We have included more information on the planned analytical approach for laboratory analyses: "In addition, the samples and data generated in this study will provide ample opportunity for laboratory analysis such as immune profiling or viral genome copy quantification and sequencing. Specific analyses will depend on the experiments and number of confirmed cases -however, will likely include ANOVA, student t-test, and other analyses. Laboratory data will be examined for normality of distribution as necessary, and the appropriate parametric or non-parametric descriptive analyses will be conducted to determine significant differences." -on page 8, lines 55-57, has the time component defining extended contact been adapted with the increased transmissibilities associated with VOCs?
RESPONSE: Thanks for this interesting question. We had initially defined this according to the CDC definitionand have now checked the latest guidelines by CDC, which still states that the definition of 'close contact' is determined by two factors: a) being less than 6 feet (1.5m) apart, b) for a cumulative total of 15 minutes over 24 hours. If necessary, we would adapt the time component according to new CDC guidelines and have included a sentence accordingly: "... and will be updated to reflect the most recent definition available." -on page 5, lines 11-16, there is some discussion on the role of asymptomatic infections in SARS-CoV-2 transmission. These modelling values should be contrasted with those from systematic reviews reported by Madewell et al (