Researching COVID to Enhance Recovery (RECOVER) adult study protocol: Rationale, objectives, and design

IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. METHODS: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. DISCUSSION: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options. REGISTRATION: NCT05172024

Researching COVID to enhance recovery (RECOVER) adult study protocol: Rationale, objectives, and design

Abstract: Importance: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. Methods: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility– and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross– validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. Discussion: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options

Researching COVID to Enhance Recovery (RECOVER) adult study protocol: Rationale, objectives, and design.

ImportanceSARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis.MethodsRECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms.DiscussionRECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options.RegistrationNCT05172024

Crustal redistribution, crust–mantle recycling and Phanerozoic evolution of the continental crust

We here attempt a global scale mass balance of the continental crust during the Phanerozoic and especially the Cenozoic (65 Ma). Continental crust is mostly recycled back into the mantle as a result of the subduction of sediment in trenches (1.65 km3/a), by the subduction of eroded forearc basement (1.3 km3/a) and by the delamination of lower crustal material from orogenic plateaus (ca. 1.1 km3/a). Subduction of rifted crust in continent-continent collision zones (0.4 km3/a), and dissolved materials fixed into the oceanic crust (ca. 0.4 km3/a) are less important crustal sinks. At these rates the entire continental crust could be reworked in around 1.8 Ga. Nd isotope data indicate that ca. 80% of the subducted continental crust is not recycled by melting at shallow levels back into arcs, but is subducted to depth into the upper mantle. Continent- continent collision zones do not generally form new crust, but rather cause crustal loss by subduction and as a result of their physical erosion, which exports crust from the orogen to ocean basins where it may be subducted. Regional sedimentation rates suggest that most orogens have their topography eliminated within 100-200 million years. We estimate that during the Cenozoic the global rivers exported an average of 1.8 km3/a to the oceans, approximately balancing the subducted loss. Accretion of sediment to active continental margins is a small contribution to crustal construction (ca. 0.3 km3/a). Similarly, continental large igneous provinces (flood basalts) represent construction of only around 0.12 km3/a, even after accounting for their intrusive roots. If oceanic plateaus are accreted to continental margins then they would average construction rates of 1.1 km3/a, meaning that to keep constant crustal volumes, arc magmatism would have to maintain production of around 3.8 km3/a (or 94 km3/Ma/km of trench). This slightly exceeds the rates derived from sparse seismic experiments in oceanic arc systems. Although the crust appears to be in a state of rough equilibrium during the Phanerozoic, 200-300 million years cycles in sealevel may be governed in part by periods of crustal growth and destruction. During the Cenozoic the crustal volume may be running a long term loss of \u3c1.8 km3/a, meaning that arc production rates could be as low at 2.0 km3/a (50 km3/Ma/km), if sealevel fall approaches 175 m since 65 Ma. Periods of orogeny cause crustal thickening and enhanced loss via subduction and delamination, effectively increasing the size of the ocean basins and thus freeboard. © 2009 Elsevier B.V