Background Most research on SARS-CoV-2 variants focuses on initial symptomatology with limited data on longer-term sequelae. We sought to characterize the prevalence and differences in prolonged symptoms at three months post SARS-CoV-2-infection across the three major variant time-periods (pre-Delta, Delta, and Omicron). Methods This multicenter prospective cohort study of adults with acute illness tested for SARS-CoV-2 compared fatigue severity, fatigue symptoms, individual and organ system-based symptoms, and presence of ≥3 total symptoms across variants among COVID-positive and COVID-negative participants 3 months after their initial SARS-CoV-2 diagnosis. Variant periods were defined by dates with ≥50% dominant strain. We performed a sensitivity analysis using ≥90% dominance threshold and multivariable logistic regression modeling to estimate the independent effects of each variant adjusting for socio-demographic characteristics, baseline health, and vaccine status. Results The study included 3,223 participants (2,402 COVID-positive and 821 COVID-negative). Among the COVID-positive cohort, 463 (19.3%) were pre-Delta, 1,198 (49.9%) during Delta, and 741 (30.8%) during Omicron. Prolonged severe fatigue was highest in the pre-Delta COVID-positive cohort compared with Delta and Omicron cohorts (16.7% vs 11.5% vs 12.3%, respectively; p = 0.017), as was presence of ≥3 prolonged symptoms (28.4% vs 21.7% vs 16.0%; p < 0.001). No difference was seen in the COVID-negative cohort between variant time-periods. In multivariable models, there was no difference in severe fatigue between variants. There was decreased odds of having ≥3 symptoms in Omicron compared with other variants; this was not significant after adjusting for vaccination status. Conclusions Prolonged symptoms following SARS-CoV-2 infection were more common among participants infected during the pre-Delta period compared with Delta and Omicron periods; however, these differences were no longer significant after adjusting for vaccination status. This suggests a potential beneficial effect of vaccination on the risk of developing long-term symptoms.

ImportanceLong-term sequelae after symptomatic SARS-CoV-2 infection may impact well-being, yet existing data primarily focus on discrete symptoms and/or health care use.ObjectiveTo compare patient-reported outcomes of physical, mental, and social well-being among adults with symptomatic illness who received a positive vs negative test result for SARS-CoV-2 infection.Design, Setting, and ParticipantsThis cohort study was a planned interim analysis of an ongoing multicenter prospective longitudinal registry study (the Innovative Support for Patients With SARS-CoV-2 Infections Registry [INSPIRE]). Participants were enrolled from December 11, 2020, to September 10, 2021, and comprised adults (aged ≥18 years) with acute symptoms suggestive of SARS-CoV-2 infection at the time of receipt of a SARS-CoV-2 test approved by the US Food and Drug Administration. The analysis included the first 1000 participants who completed baseline and 3-month follow-up surveys consisting of questions from the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29; 7 subscales, including physical function, anxiety, depression, fatigue, social participation, sleep disturbance, and pain interference) and the PROMIS Short Form–Cognitive Function 8a scale, for which population-normed T scores were reported.ExposuresSARS-CoV-2 status (positive or negative test result) at enrollment.Main Outcomes and MeasuresMean PROMIS scores for participants with positive COVID-19 tests vs negative COVID-19 tests were compared descriptively and using multivariable regression analysis.ResultsAmong 1000 participants, 722 (72.2%) received a positive COVID-19 result and 278 (27.8%) received a negative result; 406 of 998 participants (40.7%) were aged 18 to 34 years, 644 of 972 (66.3%) were female, 833 of 984 (84.7%) were non-Hispanic, and 685 of 974 (70.3%) were White. A total of 282 of 712 participants (39.6%) in the COVID-19–positive group and 147 of 275 participants (53.5%) in the COVID-19–negative group reported persistently poor physical, mental, or social well-being at 3-month follow-up. After adjustment, improvements in well-being were statistically and clinically greater for participants in the COVID-19–positive group vs the COVID-19–negative group only for social participation (β = 3.32; 95% CI, 1.84-4.80; P < .001); changes in other well-being domains were not clinically different between groups. Improvements in well-being in the COVID-19–positive group were concentrated among participants aged 18 to 34 years (eg, social participation: β = 3.90; 95% CI, 1.75-6.05; P < .001) and those who presented for COVID-19 testing in an ambulatory setting (eg, social participation: β = 4.16; 95% CI, 2.12-6.20; P < .001).Conclusions and RelevanceIn this study, participants in both the COVID-19–positive and COVID-19–negative groups reported persistently poor physical, mental, or social well-being at 3-month follow-up. Although some individuals had clinically meaningful improvements over time, many reported moderate to severe impairments in well-being 3 months later. These results highlight the importance of including a control group of participants with negative COVID-19 results for comparison when examining the sequelae of COVID-19.

Background The prevalence, incidence, and interrelationships of persistent symptoms after SARS-CoV-2 infection (Long COVID) vary. There are limited data on specific phenotypes of persistent symptoms. Using latent class analysis (LCA) modeling, we sought to identify whether specific phenotypes of COVID-19 were present three months and six months after acute infection. Methods This was a multicenter, prospective study of symptomatic adults tested for SARS-CoV-2 with prospectively collected data on general symptoms and fatigue-related symptoms up to six-months post-diagnosis. Using LCA, we identified symptomatically homogenous groups among participants with COVID-19 (COVID-positive) and among others without COVID-19 (COVID-negative) at each time period for both general and fatigue-related symptoms. Results Among 5,963 baseline participants (4,504 COVID-positive and 1,459 COVID-negative), 4,056 had three-month and 2,856 had six-month data at the time of analysis. We identified four distinct phenotypes of post-COVID conditions at three- and six-months for both general and fatigue-related symptoms; minimal symptom groups represented 70% of participants at three and six months. When compared with the COVID-negative cohort, COVID-positive participants had higher occurrence of loss of taste and smell, as well cognition problems. There was substantial class-switching over time; those in one symptom class at three months were equally likely to remain or enter a new phenotype at six months. Conclusions We identified distinct classes of post-COVID phenotypes for general and fatigue-related symptoms. Most participants had minimal or no symptoms at three and six months follow-up. Significant proportions of participants changed symptom groups over time, suggesting that symptoms present during the acute illness may differ from prolonged symptoms and that post-COVID conditions may have a more dynamic nature than previously recognized. Trial Registration NCT04610515

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Background While prior work examining SARS-CoV-2 variants of concern focused on hospitalization and death, less is known about differences in clinical presentation. We compared the prevalence of acute symptoms across pre-Delta, Delta, and Omicron. Methods We conducted an analysis of the INSPIRE Registry, a cohort study enrolling symptomatic SARS-CoV-2 positive participants. We determined the association between pre-Delta, Delta, and Omicron time periods and the prevalence of 21 COVID-19 acute symptoms. Results We enrolled 4,113 participants from December 2020 – June 2022. Pre-Delta vs Delta vs Omicron participants had increasing sore throat (40.9%, 54.6%, 70.6%; p < .001), cough (50.9%, 63.3%, 66.7%; p < .001), and runny noses (48.9%, 71.3%, 72.9%; p < .001). We observed reductions during Omicron in chest pain (31.1%, 24.2%, 20.9%; p < .001), shortness of breath (42.7%, 29.5%, 27.5%; p < .001), loss of taste (47.1%, 61.8%, 19.2%; p < .001), and loss of smell (47.5%, 55.6%, 20.0%; p < .001). After adjustment, those infected during Omicron had significantly higher odds of sore throat vs pre-Delta: OR 2.76 (95% CI: 2.26-3.35) and Delta, OR 1.96 (95% CI: 1.69-2.28). Conclusions Participants infected during Omicron were more likely to report symptoms of common respiratory viruses, such as sore throat, and less likely to report loss of smell and taste.

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Background We interviewed college students who engage in prescription stimulant misuse and diversion to better understand perspectives on prevention and intervention strategies. Methods Trained student researchers at one southern California university completed 32 face-to-face interviews with students who had a history of misuse and/or diversion. Participants provided insights on programs, policies, and practices that have the potential to deter behavior. Data were analyzed inductively via thematic analysis. Results Students were often misinformed or unaware of existing programs, policies and practices. Additionally, some students felt their behaviors would not be detected, whereas other students felt the fear of being detected would lead them to change their behaviors. Harm reduction and treatment-based approaches to address misuse were also recommended. Conclusions Our findings emphasize the importance of better educating students about, and enforcing, existing policies. In addition, the need to better inform students of existing campus programs is warranted.

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