Index Individuals in SARS-CoV-2 Prevention Research Studies (COVID-19 Index Individuals Companion Study)

Study Overview
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Brief Summary
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Clinical trials of prevention modalities for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and coronavirus disease (COVID-19) and pneumonia are underway under separate protocol(s) for close contacts (i.e., household contacts, [e.g.,3502]) of infectious (index) individuals (3502-01). Characterizing the index individuals within households will ascertain the risk of exposure for the contact participant. These data will be used to strengthen the precision of efficacy estimates. This ancillary observational study will assess the cofactors for infectiousness among index individuals whose close contacts are enrolled in COVID-19 prevention clinical trials. Additionally, this study will assess post-acute sequelae of SARS-CoV-2 infection in index individuals that are more than two weeks past their initial diagnosis.

Detailed Description
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Within households, the incidence of SARS-CoV-2 is high, but the risk of transmission is characterized by exposure cofactors and transmission mitigation strategies. Exposure cofactors are defined as cofactors that influence infectiousness of the index individual such as SARS-CoV-2 viral load, SARS-CoV-2 antibodies, and viable virus (as characterized by subgenomic RNA). Transmission mitigation strategies are defined as modifiable cofactors that influence transmission and currently include physical distancing, social isolation, ventilation, and handwashing. The continued progression of the pandemic has seen an increase in reports of persistent and/or delayed onset of symptoms and complications in patients well past the acute phase of COVID-19 infection. The prevalence and impacts of these post-acute sequelae of SARS-CoV-2 infection (PASC), which may continue for weeks to months after the initial COVID-19 illness, are not well understood. Up to approximately 2,000 eligible index individuals who have close contacts (e.g., uninfected household members) in COVID-19 prevention research studies will be invited to participate. Individuals that enroll within two weeks of their diagnosis will be asked to provide a baseline mid-turbinate nasal swab for SARS-CoV-2 testing and complete questionnaires at baseline and on Days 7 and 14. Through these questionnaires, index individuals will report on the clinical course of their illness and share information about their household environment, including potential exposures there-in and any COVID-19 transmission mitigation strategies implemented (whether intentional or as part of standard home routines). Individuals that enroll more than two weeks after being diagnosed will be asked to provide a mid-turbinate nasal swab for SARS-CoV-2 testing and to complete a questionnaire reporting retrospectively on their COVID-19 illness and household environment. These individuals will also complete a questionnaire reporting on the persistence and/or delayed onset of symptoms and complications that they associate with their COVID-19 illness. Enrolled index individuals will also be invited to participate in the SARS-CoV-2 Antibody Sub-study and provide a dried blood spot specimen (at baseline) for antibody testing. Working closely with prevention research studies, we propose to characterize the index individual level cofactors for SARS-CoV-2 transmission. Each contact between an index individual and close contact is the unit of analysis for the research study. The ascertainment of SARS-CoV-2 status among contacts/household members will be done through the parent prevention research study, e.g., through an existing clinical trials agreement with the CoVPN 3502/R 10933-10987-COV-2069 study.h Across these studies, the investigators aim to assess: Prevalence and incidence of SARS-CoV-2 infection in the close contacts. Reported SARS-CoV-2 transmission mitigation strategies and exposures as assessed in the index individuals (3502-01) and household contact protocols (e.g., 3502) and the correlation between them. Association between the index individual SARS-CoV-2 viral load and subgenomic RNA and infection in the contact participant. Association of the duration of symptomatic COVID-19 in the index individual on the risk of SARS-CoV-2 transmission. Association of SARS-CoV-2 viral genotype in index individual to related SARS-CoV-2 genotype infection in the contact participant Post-acute sequelae of SARS-CoV-2 (PASC) infection in individuals that are weeks to months past their initial SARS-CoV-2 infection. With these combined household data, effective, modifiable cofactors for household transmission can be identified to inform future post-exposure interventions. With the inclusion of data related to viral and host exposure cofactors, the investigators can increase the precision of predictive models of SARS-CoV-2 infection, adjusted for exposure and mitigation strategies. Data collected on PASC will contribute to the characterization of the long term consequences of SARS-CoV-2 infection and Post-acute COVID-19 Syndrome.

Official Title
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Characterization of the Index Individual for Contact Participants Enrolled in Clinical Trials of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Prevention Interventions; COVID-19 Prevention Trials Network (CoVPN) 3502-01

Conditions
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SARS-CoV-2 Infection, COVID-19, Coronavirus Infection, SARS (Severe Acute Respiratory Syndrome)

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults 18 and older; children and adolescents 10 years of age and older, at the time of signing the informed assent with parent or guardian consent Willing and able to provide informed consent/assent with parental consent Diagnosis of SARS-CoV-2 infection using a diagnostic test with a positive result, e.g., RT-PCR, antigen test, or other test format (approved or with Emergency Use Authorization issued by the US FDA or by local health authority) and within the eligibility period of the contact's prevention research study, or is currently being assessed for COVID-19 A close contact is being screened for enrollment or has enrolled in a SARS-CoV-2 prevention research study Access to a smart phone or device with internet access to complete a questionnaire or communicate with research study team Exclusion Criteria: Hospitalization (current) No household member enrolling/enrolled in a SARS-CoV-2 prevention research study

Ages Eligible for Study
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Minimum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort A<br>Cohort A comprises individuals that enroll within two weeks of diagnosis of SARS-CoV-2 infection. These individuals will be asked to provide a baseline mid-turbinate nasal swab for SARS-CoV-2 testing and complete questionnaires at baseline and on Days 7 and 14. Through these questionnaires, index individuals will report on the clinical course of their illness and share information about their household environment, including potential exposures there-in and any COVID-19 transmission mitigation strategies implemented (whether intentional or as part of standard home routines). Enrolled Cohort A index individuals will also be invited to participate in the SARS-CoV-2 Antibody Sub-study and provide a dried blood spot specimen (at baseline) for antibody testing. | |
| Cohort B<br>Cohort B comprises individuals that enroll more than two weeks after diagnosis of SARS-CoV-2 infection. These individuals will be asked to provide a mid-turbinate nasal swab for SARS-CoV-2 testing and to complete a questionnaire reporting retrospectively on their COVID-19 illness and household environment. Through this questionnaire, index individuals will report on the clinical course of their illness and share information about their household environment, including potential exposures there-in and any COVID-19 transmission mitigation strategies implemented (whether intentional or as part of standard home routines). These individuals will also complete a questionnaire reporting on the persistence and/or delayed onset of symptoms and complications that they associate with their COVID-19 illness. Enrolled Cohort B index individuals will also be invited to participate in the SARS-CoV-2 Antibody Sub-study and provide a dried blood spot specimen (at baseline) for antibody testing. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence and incidence of SARS-CoV-2 infection in the household contacts of index individuals | Positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test, or equivalent, as assessed in the Index Individuals Companion Study (3502-01) and household contact COVID-19 Prevention Study (3502) protocols | Day 1/Baseline for index individuals (3502-01); assessed weekly across 4 weeks for household contacts (3502) | 
| Characterization of reported SARS-CoV-2 transmission mitigation strategies | Characterization and quantification of reported SARS-CoV-2 transmission mitigation strategies as assessed in the index individuals (3502-01) and household contacts (3502) protocols. Assessment of concordance and/or correlation between index individuals' reporting and household contacts' reporting. | Across 14 days (Day 1/Baseline and Days 7 &14 Questionnaires) for index individuals, or retrospectively for individuals enrolled more than two weeks after diagnosis (3502-01); assessed at baseline and at 4 weeks for household contacts (3502) | 
| Assessment of household exposures | Characterization and quantification of household exposures assessed in the index individuals (3502-01) and household contacts (3502) protocols. Assessment of concordance and/or correlation between index individuals' reporting and household contacts' reporting. | Across 14 days (Day 1/Baseline and Days 7 &14 Questionnaires) for index individuals, or retrospectively for individuals enrolled more than two weeks after diagnosis (3502-01); assessed at baseline and at 4 weeks for household contacts (3502) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SARS-CoV-2 viral load and/or subgenomic RNA | SARS-CoV-2 semiquantitative RT-PCR and subgenomic RNA from the index individuals' mid-turbinate nasal swab (3502-01) | Day 1/Baseline sample (single day) for index individuals (3502-01) | 
| SARS-CoV-2 genotyping within households | SARS-CoV-2 genotyping from a subset of index individuals' (3502-01) and household contacts' (3502) mid-turbinate nasal swab samples. Where feasible (per genotype sample availability), genotype comparisons among index and newly infected household (i.e. contacts) members. | Day 1/Baseline sample (single day) for index individuals; assessed weekly for household contacts, across 4 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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index, cofactors, transmission, prevention, mitigation, viral load, subgenomic RNA, exposure, long COVID, PASC (post-acute sequelae of SARS-CoV-2)