Researching COVID to enhance recovery (RECOVER) pregnancy study: Rationale, objectives and design
Authors: Metz Torri D. , Clifton Rebecca G. , Gallagher Richard , Gross Rachel S. , Horwitz Leora I. , Jacoby Vanessa L. , Martin-Herz Susanne P. , Peralta-Carcelen Myriam , Reeder Harrison T. , Beamon Carmen J. , Chan James , Chang A. Ann , Costantine Maged M. , Fitzgerald Megan L. , Foulkes Andrea S. , Gibson Kelly S. , Güthe Nick , Habli Mounira , Hackney David N. , Hoffman Matthew K. , Hoffman M. Camille , Hughes Brenna L. , Katz Stuart D. , Laleau Victoria , Mallett Gail , Mendez-Figueroa Hector , Monzon Vanessa , Palatnik Anna , Palomares Kristy T. S. , Parry Samuel , Pettker Christian M. , Plunkett Beth A. , Poppas Athena , Reddy Uma M. , Rouse Dwight J. , Saade George R. , Sandoval Grecio J. , Schlater Shannon M. , Sciurba Frank C. , Simhan Hyagriv N. , Skupski Daniel W. , Sowles Amber , Thaweethai Tanayott , Thomas Gelise L. , Thorp John M. , Tita Alan T. , Weiner Steven J. , Weigand Samantha , Yee Lynn M. , Flaherman Valerie J. ,   on behalf of the RECOVER Initiative
Published: December 2023

Importance
Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER-Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads.

Methods
RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators.

Discussion
RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero.

Clinical Trials.gov Identifier
Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.