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.

s_cid=mm7045e1_w † † COVID-19 was confirmed with laboratory detection of SARS-CoV-2 by reverse transcription-polymerase chain reaction or antigen test. § § Patients with MIS-C as the reason for hospitalization included patients who met the clinical case definition for MIS-C (clinically severe illness requiring hospitalization in a person aged <21 years with fever, laboratory evidence of inflammation, multisystem [≥2] organ involvement and no alternative plausible diagnosis, and evidence of current or recent SARS-CoV-2 infection by reverse transcription polymerase chain reaction, serology or antigen test, or COVID-19 exposure within the 4 weeks preceding symptom onset [https:// emergency.cdc.gov/han/2020/han00432.asp]) and were hospitalized for diagnosis and management of MIS-C, based on chart review.

Ventricular shunts are the most common neurosurgical procedure performed in the United States. This hydrocephalus treatment is often complicated by infection of the device with biofilm-forming bacteria. In this review, we discuss the pathogenesis of shunt infection, as well as the implications of the biofilm formation on treatment and prevention of these infections. Many questions remain, including the contribution of glia and the impact of inflammation on developmental outcomes following infection. Immune responses within the CNS must be carefully regulated to contain infection while minimizing bystander damage; further study is needed to design optimal treatment strategies for these patients.

ABSTRACTCentral nervous system catheter infections are a serious complication in the treatment of hydrocephalus. These infections are commonly caused byStaphylococcus epidermidisandStaphylococcus aureus, both known to form biofilms on the catheter surface. Our objective was to generate a novel murine model of central nervous system catheter-associated biofilm infection using a clinicalS. aureusisolate and characterize the nature of the inflammatory response during biofilm growth. Silicone catheters were precoated withS. aureusto facilitate bacterial attachment, whereupon infected or sterile catheters were stereotactically inserted into the lateral ventricle of the brain in C57BL/6 mice and evaluated at regular intervals through day 21 postinsertion. Animals tolerated the procedure well, with no clinical signs of illness or bacterial growth seen in the control group. Bacterial titers associated with central nervous system catheters were significantly elevated compared to those from the surrounding parenchyma, consistent with biofilm formation and minimal planktonic spread of infection. Catheter-associated bacterial burdens progressively increased, with maximal colonization achieved at day 7 postinfection. Analysis of inflammatory infiltrates by fluorescence-activated cell sorting (FACS) revealed significant macrophage and neutrophil influx, which peaked at days 3 and 5 to 7, respectively. In contrast, there were no detectable immune infiltrates associated with tissues surrounding sterile catheters. Biofilm infection led to significant increases in chemokine (CXCL1 and CCL2) and proinflammatory cytokine (interleukin 17 [IL-17]) expression in tissues surrounding infected central nervous system catheters. Based on these results, we propose this approach is a valid animal model for further investigations of catheter-associated central nervous system shunt infections.

During the COVID-19 pandemic, we have witnessed profound health inequities suffered by Black, Indigenous, and People of Color (BIPOC). These manifested as differential access to testing early in the pandemic, rates of severe disease and death 2-3 times higher than White Americans, and now, significantly lower vaccine uptake compared with their share of the population affected by COVID-19. This article explores the impact of these COVID-19 inequities (and the underlying cause, structural racism) on vaccine acceptance in BIPOC populations, ways to establish trustworthiness of healthcare institutions, increase vaccine access for BIPOC communities, and inspire confidence in COVID-19 vaccines.