Characterizing Symptoms and Identifying Biomarkers of Long COVID in People with and without HIV: Protocol for a Remotely-Conducted Prospective Observational Cohort Study.

Abstract

Living with HIV is a risk factor for severe acute COVID-19, but it is unknown whether living with HIV is a risk factor for long COVID. This study aimed to formally and prospectively characterize symptoms, sequelae, and cognition in the 12 months following SARS-CoV-2 infection in people living with HIV (PWH) as compared to HIV-seronegative people. Additionally, PWH and HIV-seronegative people with no history of SARS-CoV-2 infection were enrolled as controls. The study also aimed to identify blood-based biomarkers or patterns of immune dysregulation that associate with long COVID. This prospective observational cohort study enrolled participants into one of four study arms: PWH who had SARS-CoV-2 infection for the first time no more than four weeks prior to enrollment (HIV+COVID+ arm), HIV-seronegative people who had SARS-CoV-2 infection for the first time within 4 weeks of enrollment (HIV-COVID+ arm), PWH who believe they never had SARS-CoV-2 infection (HIV+COVID- arm), and HIV-seronegative people who believe they never had SARS-CoV-2 infection (HIV-COVID- arm). At enrollment, participants in the COVID+ arms recalled their symptoms, mental health status, and quality of life in the month prior to having SARS-CoV-2 infection via comprehensive survey administered by telephone or online. All participants completed the same symptom, mental health, and quality of life surveys at 1, 2, 4, 6, and 12 months post-acute COVID-19 symptom onset or diagnosis, if asymptomatic, (COVID+ arms) or post-enrollment (COVID- arms) online or by telephone. Eleven cognitive assessments were administered by telephone at 1 and 4 months post-symptom onset (COVID+ arms) or post-enrollment (COVID- arms). A mobile phlebotomist met the participant at a location of their choosing for height and weight measurements, orthostatic vital signs, and a blood draw. Participants in the COVID+ arms donated blood 1 and 4 months post-COVID, and participants in the COVID- arms donated blood 0-1 times. Blood was then shipped overnight to the receiving study laboratory. When received, blood was sent to the local Clinical Laboratory Improvement Amendments of 1988 (CLIA)-certified laboratory for real-time testing and processed and stored as frozen plasma, serum, and PBMC for future testing. This project was funded in early 2021, and recruitment began in June 2021. Data analyses will be completed by summer 2023. As of February 2023, 387 participants enrolled in this study with 345 having completed enrollment/baseline surveys together with at least one other completed study event at month 1, 2, 4, 6, or 12. This includes 76 COVID+HIV+, 121 COVID+HIV-, 78 COVID-HIV+ and 70 COVID-HIV- participants. This study will provide longitudinal data to characterize post-COVID recovery over 12 months in PWH and HIV-seronegative people. Additionally, this study will determine whether biomarkers or patterns of immune dsyregulation associate with decreased cognitive function or symptoms of long COVID. ClinicalTrials.gov NCT04958889.