Clinical trial NCT04895189: Yale COVID-19 Recovery Study
Official title: Yale COVID-19 Recovery Vaccine Study: Measuring Changes in Long Covid Symptoms After Vaccination
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Covid19 Sequelae
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Food and Drug Administration (FDA)
First posted: 2021-05-20
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Study participants will include adults aged 18 and over who either have been diagnosed with COVID-19, hospitalized due to COVID-19, or who have tested positive for SARS-CoV-2 more than 2 months prior to joining the study (PCR, antigen, or a positive T-test or antibody test at any point), and who have proof of the diagnosis, hospitalization, or positive test; who intend to receive the vaccine for SARS-CoV-2, but who have not yet received any doses of the vaccine; and who self report having persistent moderate-to-severe symptoms or disability.

Brief summary: The general purpose of the study is to determine the change in immune responses in people with Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) after vaccination. PASC is a disabling, heterogeneous condition in which people have persistent or emerging symptoms months after an initial SARS-CoV-2 infection, (the virus that causes coronavirus disease 2019, or COVID-19. Specifically, the purpose is to enroll participants suffering from moderate-to-severe PASC prior to vaccination and to measure participants' immune and symptom profiles both before and after vaccination. This study is primarily descriptive.

Detailed description: The investigators are conducting an observational study within Connecticut of adults who have moderate-to-severe PASC and who are planning to receive a vaccine against SARS-CoV-2. The study seeks primarily to describe the heterogeneity in symptoms and immune profile among people with PASC, and once participants have been vaccinated, to determine changes in clinical and immune responses to vaccination and whether there is an association.

Broadly, the study will include 4 surveys to monitor participants' symptom profile and experience with COVID-19 as well as 3 separate biospecimen collection appointments. The surveys and study enrollment will be conducted through REDCap at Yale, a platform that is designed to securely collect survey data from people in a user-friendly design setting. The biospecimen collection will occur at 2 Yale New Haven Health blood draw sites. The biospecimen collection will occur as follows: the first will occur as soon as a participant is enrolled, the second will occur 6 weeks after the participant receives the first dose of a COVID-19 vaccine, and the third will occur 12 weeks after the participant receives the first dose of a COVID-19 vaccine. Participants will be asked to provide 45ccs of blood and a saliva sample (up to 5 mL) for each biospecimen collection. Participants will be able to give a blood sample within a 2-week window (e.g. the collection may be within 5-7 weeks after the participant's first COVID-19 vaccine dose). The survey collection will occur as follows: the first will occur as soon as the participant is enrolled, the second will occur 2 weeks after the participant receives the first dose of a COVID-19 vaccine, the third will occur 6 weeks after the participant receives the first dose of a COVID-19 vaccine, and the fourth will occur 12 weeks after the participant receives the first dose of COVID-19 vaccine. Survey links and reminders will be sent by the Yale research team through REDCap at Yale (via text and/or email) and specimen collection scheduling will be coordinated between the Yale research team and the Yale New Haven Health draw sites.

The study recruitment efforts will be coordinated with YCCI, according to YCCI standards. The investigators will also distribute a study flyer at local Long Covid health clinics and on social media, including Twitter and Facebook. In addition to recruitment efforts at Yale, the investigators' patient partners, Survivor Corps, will be publicizing the study by sharing the study information and eligibility requirements on social media including Facebook and Twitter. Survivor Corps's recruitment efforts will not be coordinated by the Yale research team. There will be a study landing page where potential participants can find information about the study and the study link.

Potential participants will be provided a link for the study enrollment as well as an email address (covidrecovery@yale.edu) to reach out for more information about the study. The study enrollment process will take place on REDCap at Yale and by phone. Participants will complete a brief screening questionnaire to determine study eligibility and to provide an email address and/or phone number. Study coordinators will then reach out, by email to schedule a phone consultation, or directly by phone, as is the participant's preference. During the phone consultation, a study coordinator will read a script designed to inform the participant of the study design and risks to ensure that the participant understands the study prior to consent. The participant will also be asked if the participant has any questions for the study coordinator. Once the phone consultation is complete, the study coordinator will email the participant a link to the e-consent, which will be a REDCap form. Once the participant consents to the study, which will require an e-signature, a study coordinator will sign a REDCap form to acknowledge that the e-consent is complete. An email will automatically be sent to the participant containing the (REDCap) link for the first survey and information as to how to provide the first biospecimen sample. The research team will also contact the participant within the next 2-3 days by phone to provide information regarding the timing and location for biospecimen collection and to answer any questions the participant has.

Participants will provide blood and saliva samples 3 times at any of the study's 2 Yale New Haven Health blood draw sites. While all specimen collection will occur in Connecticut at these sites, people who are not currently patients within the Yale New Haven Health system will still be eligible to participate in the study, so long as the participant is willing and able to travel to one of the blood draw sites 3 times. The Yale study consent will include consenting to providing blood and saliva samples 3 times at a Yale New Haven Health site.

This research will foster a community spirit with participants, producing a collaboration based on relationships, not merely transactions. The Survivor Corps group has joined this effort and will ensure that the study includes the participant perspective and abide by the study's principles. Survivor Corps is an independent group of people who experienced long-term effects of SARS-CoV-2 infection and seek to generate knowledge about people with prolonged recoveries. The Patient-Led Research Collaborative has also joined this effort to provide a PASC participant perspective on the study's participant-facing communication and surveys. Patient-Led Research is also an independent group of people who experienced long-term effects of SARS-CoV-2 infection and seek to generate knowledge about people with prolonged recoveries.

The study will utilize REDCap at Yale to screen for eligibility, conduct e-consent, and to collect survey information. The data will reside within the secure platform and will be transferred to Yale via a secure file transfer service. The data will then reside on secure servers at Yale.

Eligibility criteria: Inclusion Criteria:

1. Fluent in English or Spanish
2. Age 18 years and over
3. Test positive for SARS-CoV-2 (defined as a patient who reports receiving any screening or diagnostic test used to detect the presence of SARS-CoV-2 including any FDA-approved or authorized molecular or antigen-based assay) at least 2 months prior to the start of this study OR test positive for antibodies to SARS-CoV-2 at any point OR receive a positive T-test at any point OR receive a clinical diagnoses of COVID-19 at any point OR was hospitalized due to COVID-19 at any point
4. Self-report moderate to severe symptoms or disability due to PASC
5. Self-report planning to receive a vaccine against SARS-CoV-2
6. Self-report has not yet received any doses of a vaccine against SARS-CoV-2

Exclusion Criteria:

1. Unable to provide informed consent
2. Unable to provide 3 blood and saliva samples at one of the 2 participating Yale New Haven Health blood draw sites on a Monday or Wednesday morning (before 12 pm).
3. Does not have access to a hand-held device or computer that would allow for digital participation in the study
4. Do not have and do not want to set up an email address
5. Individuals who are prisoners

Primary outcomes:
measure: Surveys 2-4 Effect of Vaccination
timeFrame: The measure will be reported both longitudinally, over the 3 months following the participant post-vaccination (reporting the result at 2 weeks, 6 weeks, and 12 weeks post-vaccination), and as a cross-sectional result at the end of the study (week 12).
measure: Immune Assay Findings
timeFrame: The measure will be reported both longitudinally, over the 3 months following the participant post-vaccination (reporting the result at 2 weeks, 6 weeks, and 12 weeks post-vaccination), and as a cross-sectional result at the end of the study (week 12).
Secondary outcomes:
measure: Surveys 1-4 Overall Change in Symptoms
timeFrame: The measure will be reported both longitudinally, over the 3 months following the participant post-vaccination (reporting the result at 2 weeks, 6 weeks, and 12 weeks post-vaccination), and as a cross-sectional result at the end of the study (week 12).
measure: Surveys 2-4 Change in Symptom Severity
timeFrame: The measure will be reported both longitudinally, over the 3 months following the participant post-vaccination (reporting the result at 2 weeks, 6 weeks, and 12 weeks post-vaccination), and as a cross-sectional result at the end of the study (week 12).
measure: Surveys 2-4 Change in Symptom Frequency
timeFrame: The measure will be reported both longitudinally, over the 3 months following the participant post-vaccination (reporting the result at 2 weeks, 6 weeks, and 12 weeks post-vaccination), and as a cross-sectional result at the end of the study (week 12).
measure: Surveys 2-4 Change in Symptom Duration
timeFrame: The measure will be reported both longitudinally, over the 3 months following the participant post-vaccination (reporting the result at 2 weeks, 6 weeks, and 12 weeks post-vaccination), and as a cross-sectional result at the end of the study (week 12).
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
Study officials:
affiliation: Director, Center for Outcomes Research and Evaluation (CORE)
name: Harlan Krumholz, MD, SM
role: PRINCIPAL_INVESTIGATOR
References:
citation: Grady CB, Bhattacharjee B, Silva J, Jaycox J, Lee LW, Silva Monteiro V, Sawano M, Massey D, Caraballo C, Gehlhausen JR, Tabachnikova A, Mao T, Lucas C, Pena-Hernandez MA, Xu L, Tzeng TJ, Takahashi T, Herrin J, Guthe DB, Akrami A, Assaf G, Davis H, Harris K, McCorkell L, Schulz WL, Griffin D, Wei H, Ring AM, Guan L, Dela Cruz C, Krumholz HM, Iwasaki A. Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naive individuals with Long COVID. Commun Med (Lond). 2025 May 9;5(1):163. doi: 10.1038/s43856-025-00829-3.