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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.

Background Patients with severe Coronavirus Disease 2019 (COVID-19) have respiratory failure with hypoxemia and acute bilateral pulmonary infiltrates, consistent with acute respiratory distress syndrome (ARDS). It has been suggested that respiratory failure in COVID-19 represents a novel pathologic entity. Research Question How does the lung histopathology described in COVID-19 compare to the lung histopathology described in SARS and H1N1 influenza? Study Design and Methods: We conducted a systematic review to characterize the lung histopathologic features of COVID-19 and compare them against findings of other recent viral pandemics, H1N1 influenza and SARS. We systematically searched MEDLINE and PubMed for studies published up to June 24, 2020 using search terms for COVID-19, H1N1 influenza and SARS with keywords for pathology, biopsy, and autopsy. Using PRISMA-IPD guidelines, our systematic review analysis included 26 articles representing 171 COVID-19 patients; 20 articles representing 287 H1N1 patients; and eight articles representing 64 SARS patients. Results In COVID-19, acute phase diffuse alveolar damage (DAD) was reported in 88% of patients, which was similar to the proportion of cases with DAD in both H1N1 (90%) and SARS (98%). Pulmonary microthrombi were reported in 57% of COVID-19 and 58% of SARS patients, as compared to 24% of H1N1 influenza patients. Interpretation DAD, the histologic correlate of ARDS, is the predominant histopathologic pattern identified in lung pathology from patients with COVID-19, H1N1 influenza and SARS. Microthrombi were reported more frequently in both patients with COVID-19 and SARS as compared to H1N1 influenza. Future work is needed to validate this histopathologic finding and, if confirmed, elucidate the mechanistic underpinnings and characterize any associations with clinically important outcomes.

Rationale: Post-intensive care syndrome (PICS), defined as new or worsening impairment in cognition, mental health, or physical function after critical illness, is an important development in survivors. Although studies to date have focused on the frequency of these impairments, fundamental questions remain unanswered regarding the survivor experience and the impact of the critical illness event on survivor resilience and recovery.Objectives: To examine the association between resilience and neuropsychological and physical function and to contextualize these findings within the survivors' recovery experience. Methods:We conducted a mixed-methods pilot investigation of resilience among 43 survivors from two medical intensive care units (ICUs) within an academic health-care system. We interviewed survivors to identify barriers to and facilitators of recovery in the ICU, on the medical ward, and at home, using qualitative methods. We used a telephone battery of standardized tests to examine resilience, neuropsychological and physical function, and quality of life. We examined PICS in two ways. First, we identified how frequently survivors were impaired in one or more domains 6-12 months postdischarge. Second, we identified how frequently survivors reported that neuropsychological or physical function was worse. Measurements and Main Results:Resilience was low in 28% of survivors, normal in 63% of survivors, and high in 9% of survivors. Resilience was inversely correlated with self-reported executive dysfunction, symptoms of anxiety, depression, and post-traumatic stress disorder, difficulty with self-care, and pain (P , 0.05). PICS was present in 36 survivors (83.7%; 95% confidence interval, 69.3-93.2%), whereas 23 survivors (53.5%; 95% confidence interval, 37.6-68.8%) reported worsening of neuropsychological or physical function after critical illness. We identified challenges along the recovery path of ICU survivors, finding that physical limitations and functional dependence were the most frequent challenges experienced in the ICU, medical ward, and on return to home. Spiritual and family support facilitated recovery. Conclusions:Resilience was inversely correlated with neuropsychological impairment, pain, and difficulty with self-care. PICS was present in most survivors of critical illness, and 54% reported neuropsychological or physical function to be worse, yet resilience was normal or high in most survivors. Survivors experienced many challenges during recovery, while spiritual and family support facilitated recovery.