ImportanceSARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals.ObjectiveTo develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections.Design, Setting, and ParticipantsProspective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling.ExposureSARS-CoV-2 infection.Main Outcomes and MeasuresPASC and 44 participant-reported symptoms (with severity thresholds).ResultsA total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months.Conclusions and RelevanceA definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.

Ischemia/reperfusion (I/R) injury in the kidney is a major cause of acute kidney injury (AKI) in humans and is associated with significantly high mortality. To identify genes that modulate kidney injury and repair, we conducted genome-wide expression analysis in the rat kidneys after I/R and found that the mRNA levels of fibrinogen (Fg)␣, Fg␤, and Fg␥ chains significantly increase in the kidney and remain elevated throughout the regeneration process. Cellular characterization of Fg␣ and Fg␥ chain immunoreactive proteins shows a predominant expression in renal tubular cells and the localization of immunoreactive Fg␤ chain protein is primarily in the renal interstitium in healthy and regenerating kidney. We also show that urinary excretion of Fg is massively increased after kidney damage and is capable of distinguishing human patients with acute or chronic kidney injury (n ‫؍‬ 25) from healthy volunteers (n ‫؍‬ 25) with high sensitivity and specificity (area under the receiver operating characteristic of 0.98). Furthermore, we demonstrate IntroductionKidney disease is a major public health concern receiving increased global attention owing to the significantly increased prevalence and high mortality rates. 1,2 Renal ischemia/reperfusion (I/R) accounts for a significant number of acute kidney injury (AKI) cases in humans. Studies suggest that damage to the renal microvascular architecture and deterioration of the angiogenic response constitutes the early steps in the complex multiple pathways involved in both early and chronic ischemic renal injury. 3 Restoration of blood flow to the site of injured tissue is crucial for developing a successful repair response that involves the surviving dedifferentiated cells spreading over the denuded basement membrane, undergoing mitogenesis and ultimately redifferentiating to re-establish and restore functional integrity of the nephron. 4,5 Although these processes are well described at the pathologic level, very little is known about the cellular and molecular mechanisms of action of blood proteins within the kidney and their contribution to pathogenesis of renal disease.Fibrinogen (Fg), a 340-kDa dimeric blood protein, is made up of 2 sets of 3 different polypeptide chains, Fg␣, Fg␤, and Fg␥, that span a length of 50 kb on chromosome 4 in region q28. 6 Although the primary site for Fg synthesis is shown to be liver, extrahepatic synthesis of Fg by epithelial cells of intestine, 7 cervix, 8 and lung 9,10 has been reported, suggesting that it may function in other structural and functional capacities. Furthermore, endogenous expression of Fg␣ and Fg␤ chain mRNA has been shown in the normal rat kidneys, levels of which significantly increase at 2 hours after the onset of brain death injury, 11,12 potentially restoring hemostasis by supporting extracellular matrix and wound repair processes after injury. 12 In addition to its major role in blood clotting and circulation via interaction with platelets, 13 Fg has been recognized as an important regulator of inflammation, 14 wound ...

Fibrinogen (Fg) is significantly up-regulated in the kidney after acute kidney injury (AKI). We evaluated the performance of Fg as a biomarker for early detection of AKI. In rats and mice with kidney tubular damage induced by ischemia/reperfusion (I/R) or cisplatin administration, respectively; kidney tissue and urinary Fg increased significantly and correlated with histopathological injury, urinary kidney injury molecule-1 (KIM-1) and N-acetyl glucosaminidase (NAG) corresponding to the progression and regression of injury temporally. In a longitudinal follow-up of 31 patients who underwent surgical repair of abdominal aortic aneurysm, urinary Fg increased earlier than SCr in patients who developed postoperative AKI (AUC-ROC = 0.72). Furthermore, in a cohort of patients with biopsy-proven AKI (n = 53), Fg immunoreactivity in the tubules and interstitium increased remarkably and was able to distinguish patients with AKI from those without AKI (n = 59). These results suggest that immunoreactivity of Fg in the kidney, as well as urinary excretion of Fg, serves as a sensitive and early diagnostic translational biomarker for detection of AKI.

Human embryonic stem (hES) cells hold great promise in regenerative medicine. Although hES cells have unlimited self-renewal potential, they tend to differentiate spontaneously in culture. TRA-1-81 is a biomarker of undifferentiated hES cells. Quantitative characterization of TRA-1-81 expression level in a single cell helps capture the "turn-on" signal and understand the mechanism of early differentiation. Here we report on our examination of TRA-1-81 distribution and association on a hES cell membrane using an atomic force microscope (AFM). Our results suggest that aggregated distribution of TRA-1-81 antigen is characteristic for undifferentiated hES cells. We also evaluated the TRA-1-81 expression level at ~17800 epitopes and ~700 epitopes per cell on an undifferentiated cell and a spontaneously differentiated cell, respectively. The method in this study can be adapted in examining other surface proteins on various cell types, thus providing a general tool for investigating protein distribution and association at the single cell level.