Distinguishing Severe Acute Respiratory Syndrome Coronavirus 2 Persistence and Reinfection: A Retrospective Cohort Study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection is poorly understood, partly because few studies have systematically applied genomic analysis to distinguish reinfection from persistent RNA detection related to initial infection. We aimed to evaluate the characteristics of SARS-CoV-2 reinfection and persistent RNA detection using independent genomic, clinical, and laboratory assessments. METHODS: All individuals at a large academic medical center who underwent a SARS-CoV-2 nucleic acid amplification test (NAAT) ≥45 days after an initial positive test, with both tests between 14 March and 30 December 2020, were analyzed for potential reinfection. Inclusion criteria required having ≥2 positive NAATs collected ≥45 days apart with a cycle threshold (Ct) value <35 at repeat testing. For each included subject, likelihood of reinfection was assessed by viral genomic analysis of all available specimens with a Ct value <35, structured Ct trajectory criteria, and case-by-case review by infectious diseases physicians. RESULTS: Among 1569 individuals with repeat SARS-CoV-2 testing ≥45 days after an initial positive NAAT, 65 (4%) met cohort inclusion criteria. Viral genomic analysis characterized mutations present and was successful for 14/65 (22%) subjects. Six subjects had genomically supported reinfection, and 8 subjects had genomically supported persistent RNA detection. Compared to viral genomic analysis, clinical and laboratory assessments correctly distinguished reinfection from persistent RNA detection in 12/14 (86%) subjects but missed 2/6 (33%) genomically supported reinfections. CONCLUSIONS: Despite good overall concordance with viral genomic analysis, clinical and Ct value-based assessments failed to identify 33% of genomically supported reinfections. Scaling-up genomic analysis for clinical use would improve detection of SARS-CoV-2 reinfections.

Discharge to post-acute care and other predictors of prolonged length of stay during the initial COVID-19 surge: a single site analysis.

BACKGROUND: During the initial surge of coronavirus disease 2019 (COVID-19), health-care utilization fluctuated dramatically, straining acute hospital capacity across the USA and potentially contributing to excess mortality. METHODS: This was an observational retrospective study of patients with COVID-19 admitted to a large US urban academic medical center during a 12-week COVID-19 surge in the Spring of 2020. We describe patterns in length of stay (LOS) over time. Our outcome of interest was prolonged LOS (PLOS), which we defined as 7 or more days. We performed univariate analyses of patient characteristics, clinical outcomes and discharge disposition to evaluate the association of each variable with PLOS and developed a final multivariate model via backward elimination, wherein all variables with a P-value above 0.05 were eliminated in a stepwise fashion. RESULTS: The cohort included 1366 patients, of whom 13% died and 29% were readmitted within 30 days. The LOS (mean: 12.6) fell over time (P < 0.0001). Predictors of PLOS included discharge to a post-acute care (PAC) facility (odds ratio [OR]: 11.9, 95% confidence interval [CI] 2.6-54.0), uninsured status (OR 3.2, CI 1.1-9.1) and requiring intensive care and intubation (OR 18.4, CI 11.5-29.6). Patients had a higher readmission rate if discharged to PAC facilities (40%) or home with home health agency (HHA) services (38%) as compared to patients discharged home without HHA services (26%) (P < 0.0001). CONCLUSION: Patients hospitalized with COVID-19 during a US COVID-19 surge had a PLOS and high readmission rate. Lack of insurance, an intensive care unit stay and a decision to discharge to a PAC facility were associated with a PLOS. Efforts to decrease LOS and optimize hospital capacity during COVID-19 surges may benefit from focusing on increasing PAC and HHA capacity and resources.

Fecal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) RNA Is Associated With Decreased Coronavirus Disease 2019 (COVID-19) Survival.

The clinical significance of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) RNA in stool remains uncertain. We found that extrapulmonary dissemination of infection to the gastrointestinal tract, assessed by the presence of SARS-CoV-2 RNA in stool, is associated with decreased coronavirus disease 2019 (COVID-19) survival. Measurement of SARS-CoV-2 RNA in stool may have utility for clinical risk assessment.

Assessing Cardiovascular Risk in People Living with HIV: Current Tools and Limitations.

PURPOSE OF REVIEW: To provide the current state of the development and application of cardiovascular disease (CVD) prediction tools in people living with HIV (PLWH). RECENT FINDINGS: Several risk prediction models developed on the general population are available to predict CVD risk, the most notable being the US-based pooled cohort equations (PCE), the Framingham risk functions, and the Europe-based SCORE (Systematic COronary Risk Evaluation). In validation studies in cohorts of PLWH, these models generally underestimate CVD risk, especially in individuals who are younger, women, Black race, or predicted to be at low/intermediate risk. An HIV-specific CVD prediction model, the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) model, is available, but its performance is modest, especially in US-based cohorts. Enhancing CVD prediction with novel biomarkers of inflammation or coronary artery calcification is of interest but has not yet been evaluated in PLWH. Finally, studies on CVD risk prediction are lacking in diverse PLWH globally. While available risk models for CVD prediction in PLWH remain suboptimal, clinicians should remain vigilant of higher CVD risk in this population and should use any of these risk scores for risk stratification to guide preventive interventions. Focus on established traditional risk factors such as smoking remains critical in PLWH. Risk prediction functions tailored to PLWH in diverse settings will enhance clinicians' ability to deliver optimal preventive care.

Immune Correlates of Diffuse Myocardial Fibrosis and Diastolic Dysfunction Among Aging Women With Human Immunodeficiency Virus.

Human immunodeficiency virus (HIV) imparts increased heart failure risk to women. Among women with HIV (WHIV), immune pathways relating to heart failure precursors may intimate targets for heart failure prevention strategies. Twenty asymptomatic, antiretroviral-treated WHIV and 14 non-HIV-infected women matched on age and body mass index underwent cardiac magnetic resonance imaging and immune phenotyping. WHIV (vs non-HIV-infected women) exhibited increased myocardial fibrosis (extracellular volume fraction, 0.34 ± 0.06 vs 0.29 ± 0.04; P = .002), reduced diastolic function (diastolic strain rate, 1.10 ± 0.23 s-1 vs 1.39 ± 0.27 s-1; P = .003), and heightened systemic monocyte activation. Among WHIV, soluble CD163 levels correlated with myocardial fibrosis (r = 0.53; P = .02), while circulating inflammatory CD14+CD16+ monocyte CCR2 expression related directly to myocardial fibrosis (r = 0.48; P = .04) and inversely to diastolic function (r = -0.49; P = .03). Clinical Trials Registration. NCT02874703.

Baseline 10-Year Cardiovascular Risk Scores Predict Cognitive Function in Older Persons, and Particularly Women, Living With Human Immunodeficiency Virus Infection.

BACKGROUND: Cardiovascular disease (CVD) and associated comorbidities increase the risk of cognitive impairment in persons living with human immunodeficiency virus (PLWH). Given the potential composite effect of multiple cardiovascular risk factors on cognition, we examined the ability of the Atherosclerotic Cardiovascular Disease (ASCVD) risk score and the Framingham Heart Study Global CVD risk score (FRS) to predict future cognitive function in older PLWH. METHODS: We constructed linear regression models evaluating the association between baseline 10-year cardiovascular risk scores and cognitive function (measured by a summary z-score, the NPZ-4) at a year 4 follow-up visit. RESULTS: Among 988 participants (mean age, 52 years; 20% women), mean 10-year ASCVD risk score at entry into the cohort was 6.8% (standard deviation [SD], 7.1%) and FRS was 13.1% (SD, 10.7%). In models adjusted only for cognitive function at entry, the ASCVD risk score significantly predicted year 4 NPZ-4 in the entire cohort and after stratification by sex (for every 1% higher ASCVD risk, year 4 NPZ-4 was lower by 0.84 [SD, 0.28] overall, P = .003; lower by 2.17 [SD, 0.67] in women, P = .001; lower by 0.78 [SD, 0.32] in men, P = .016). A similar relationship was observed between FRS and year 4 NPZ-4. In multivariable models, higher 10-year ASCVD risk and FRS predicted lower NPZ-4 in women. CONCLUSIONS: Baseline 10-year ASCVD risk and FRS predicted future cognitive function in older PLWH with well-controlled infection. Cardiovascular risk scores may help to identify PLWH, especially women, who are at risk for worse cognition over time.

Baseline Factors Associated with Mortality in Patients Who Engaged in Buprenorphine Treatment for Opioid Use Disorder: a Cohort Study.

BACKGROUND: Opioid agonist therapy (OAT) has been shown to reduce mortality in patients with opioid use disorder (OUD), yet mortality in individuals receiving OAT remains higher than in an age- and gender-matched population. OBJECTIVE: To identify baseline risk factors in patients who engaged in buprenorphine treatment that are associated with this elevated risk of death. DESIGN: We performed a retrospective cohort study from January 1, 2007, to December 31, 2018, using a centralized clinical data registry within a multi-hospital health system in Boston, MA, USA. PARTICIPANTS: All adult patients who had ≥ 2 consecutive encounters with sublingual buprenorphine on the active medication list from January 1, 2007, to December 31, 2018. MAIN MEASURES: We abstracted several sociodemographic, clinical, and healthcare use characteristics from the clinical data registry. The primary outcome was all-cause mortality and the secondary outcome was opioid overdose-related mortality. We performed multivariable cox regression to identify baseline characteristics independently associated with these outcomes. KEY RESULTS: Of 5948 patients in the cohort, the majority were white (80.7%) and male (59.7%), with a mean age of 38.2 years. The all-cause mortality rate was 24.0 deaths per 1000 person-years. Baseline characteristics independently associated with an increased hazard of all-cause mortality included homelessness (adjusted hazard ratio [aHR] = 1.39; 95% confidence interval [CI] = 1.09, 1.78), an opioid on the active medication list (aHR = 1.28; 95% CI = 1.08, 1.52), and entry into the cohort during an inpatient hospitalization (aHR = 1.43; 95% CI = 1.18, 1.73). Homelessness was also associated with an increased hazard of opioid overdose-related mortality (aHR = 1.77; 95% CI = 1.25, 2.50). CONCLUSIONS: We identified several novel and potentially modifiable predictors of mortality among patients engaging in buprenorphine treatment who remain at an increased risk of death compared with the general population. Understanding these risk factors can assist healthcare providers in risk stratification and inform the design of targeted interventions to improve outcomes in a high-risk patient population.

Impact of Smoking Cessation Interventions Initiated During Hospitalization Among HIV-Infected Smokers.

INTRODUCTION: Smoking is a key determinant of mortality among people living with HIV (PLWH). METHODS: To better understand the effects of smoking cessation interventions in PLWH, we conducted a pooled analysis of four randomized controlled trials of hospital-initiated smoking interventions conducted through the Consortium of Hospitals Advancing Research on Tobacco (CHART). In each study, cigarette smokers were randomly assigned to usual care or a smoking cessation intervention. The primary outcome was self-reported past 30-day tobacco abstinence at 6-month follow-up. Abstinence rates were compared between PLWH and participants without HIV and by treatment arm, using both complete-case and intention-to-treat analyses. Multivariable logistic regression was used to determine the effect of HIV status on 6-month tobacco abstinence and to determine predictors of smoking cessation within PLWH. RESULTS: Among 5550 hospitalized smokers, there were 202 (3.6%) PLWH. PLWH smoked fewer cigarettes per day and were less likely to be planning to quit than smokers without HIV. At 6 months, cessation rates did not differ between intervention and control groups among PLWH (28.9% vs. 30.5%) or smokers without HIV (36.1% vs. 34.1%). In multivariable regression analysis, HIV status was not significantly associated with smoking cessation at 6 months. Among PLWH, confidence in quitting was the only clinical factor independently associated with smoking cessation (OR 2.0, 95% CI = 1.4 to 2.8, p < .01). CONCLUSIONS: HIV status did not alter likelihood of quitting smoking after hospital discharge, whether or not the smoker was offered a tobacco cessation intervention, but power was limited to identify potentially important differences. IMPLICATIONS: PLWH had similar quit rates to participants without HIV following a hospital-initiated smoking cessation intervention. The findings suggest that factors specific to HIV infection may not influence response to smoking cessation interventions and that all PLWH would benefit from efforts to assist in quitting smoking. TRIAL REGISTRATION: (1) Using "warm handoffs" to link hospitalized smokers with tobacco treatment after discharge: study protocol of a randomized controlled trial: NCT01305928. (2) Web-based smoking cessation intervention that transitions from inpatient to outpatient: NCT01277250. (3) Effectiveness of smoking-cessation interventions for urban hospital patients: NCT01363245. (4) Effectiveness of Post-Discharge Strategies for Hospitalized Smokers (HelpingHAND2): NCT01714323.

Cardiovascular Risk Prediction Functions Underestimate Risk in HIV Infection.

BACKGROUND: Cardiovascular disease (CVD) risk is elevated in HIV-infected individuals, with contributions from both traditional and nontraditional risk factors. The accuracy of established CVD risk prediction functions in HIV is uncertain. We sought to assess the performance of 3 established CVD risk prediction functions in a longitudinal cohort of HIV-infected men. METHODS: The FHS (Framingham Heart Study) functions for hard coronary heart disease (FHS CHD) and atherosclerotic CVD (FHS ASCVD) and the American College of Cardiology/American Heart Association ASCVD function were applied to the Partners HIV cohort. Risk scores were calculated between January 1, 2006, and December 31, 2008. Outcomes included CHD (myocardial infarction or coronary death) for the FHS CHD function and ASCVD (myocardial infarction, stroke, or coronary death) for the FHS ASCVD and American College of Cardiology/American Heart Association ASCVD functions. We investigated the accuracy of CVD risk prediction for each function when applied to the HIV cohort using comparison of Cox regression coefficients, discrimination, and calibration. RESULTS: The HIV cohort was comprised of 1272 men followed for a median of 4.4 years. There were 78 (6.1%) ASCVD events; the 5-year incidence rate was 16.4 per 1000 person-years. Discrimination was moderate to poor as indicated by the low c statistic (0.68 for FHS CHD, 0.65 for American College of Cardiology/American Heart Association ASCVD, and 0.67 for FHS ASCVD). Observed CVD risk exceeded the predicted risk for each of the functions in most deciles of predicted risk. Calibration, or goodness of fit of the models, was consistently poor, with significant χ2P values for all functions. Recalibration did not significantly improve model fit. CONCLUSIONS: Cardiovascular risk prediction functions developed for use in the general population are inaccurate in HIV infection and systematically underestimate risk in a cohort of HIV-infected men. Development of tailored CVD risk prediction functions incorporating traditional CVD risk factors and HIV-specific factors is likely to result in more accurate risk estimation to guide preventative CVD care.

Heart failure and adverse heart failure outcomes among persons living with HIV in a US tertiary medical center.

BACKGROUND: Persons living with HIV (PLHIV) have an increased risk of heart failure (HF). However, little is known about outcomes among PLHIV with HF. The study aim was to compare HF outcomes among PLHIV with HF versus individuals without HIV with HF. METHODS: Our cohort included 2,308 individuals admitted with decompensated HF. We compared baseline characteristics, 30-day HF readmission, and cardiovascular (CV) and all-cause mortality. Within PLHIV, we assessed outcomes stratified between CD4 count and viral load (VL), and tested the association between traditional and HIV-specific parameters with 30-day HF readmission. RESULTS: There were 374 (16%) PLHIV with HF. Among PLHIV, 92% were on antiretroviral therapy and 63% had a VL <200 copies/mL. Groups were similar with respect to age, sex, race/ethnicity, and CV risk factors. In follow-up, PLHIV had increased 30-day HF readmission (49% vs 32%) and CV (26% vs 13.5%) and all-cause mortality rates (38% vs 22%). Among PLHIV, cocaine use, HIV-specific parameters (CD4, VL), and coronary artery disease were predictors of 30-day HF readmission. Specifically, among PLHIV, those with detectable VL had higher 30-day HF readmission and CV mortality, whereas PLHIV with undetectable VL had a similar 30-day HF readmission rate and CV mortality to uninfected controls with HF. Similar outcomes were observed across strata of left ventricular ejection fraction and by CD4. CONCLUSIONS: PLHIV with a low CD4 count or detectable VL have an increased 30-day HF readmission rate as well as increased CV and all-cause mortality. In contrast, PLHIV with a higher CD4 count and undetectable VL have similar HF outcomes to uninfected controls.

Sleep Apnea and Heart Failure With a Reduced Ejection Fraction Among Persons Living With Human Immunodeficiency Virus.

Background: Sleep apnea (SA) is common and has prognostic significance among broad groups of patients with heart failure (HF). There are no data characterizing the presence, associations, and prognostic significance of SA among persons living with human immunodeficiency virus (PLHIV) with HF. Methods: We conducted a single-center study of PLHIV with HF with reduced ejection fraction (HFrEF; left ventricular ejection fraction [LVEF] <50%) and analyzed the relationship of SA with 30-day HF hospital readmission rate. Results: Our cohort included 1124 individuals admitted with HFrEF; 15% were PLHIV, and 92% were on antiretroviral therapy. SA was noted in 28% of PLHIV and 26% of uninfected controls. Compared to uninfected controls with HFrEF and SA, PLHIV with HFrEF and SA had a lower body mass index, lower LVEF, a higher pulmonary artery systolic pressure (PASP), were more likely to have obstructive rather than central SA (P < .05 for all). In a multivariable model, PASP, low CD4 count, high viral load (VL), and SA parameters (apnea-hypopnea index, CPAP use and duration) were predictors of 30-day HF readmission rate. Each 1-hour increase in CPAP use was associated with a 14% decreased risk of 30-day HF readmission among PLHIV. Conclusions: Compared to uninfected controls, PLHIV were more likely to have obstructive SA than central SA. Apnea severity, low CD4 count, high VL, and cocaine use were positively associated with 30-day HF hospital readmission rate, whereas CPAP use and increased duration of CPAP use conferred protection.

The association between HIV and atherosclerotic cardiovascular disease in sub-Saharan Africa: a systematic review.

BACKGROUND: Sub-Saharan Africa (SSA) has confronted decades of the HIV epidemic with substantial improvements in access to life-saving antiretroviral therapy (ART). Now, with improved survival, people living with HIV (PLWH) are at increased risk for non-communicable diseases (NCDs), including atherosclerotic cardiovascular disease (CVD). We assessed the existing literature regarding the association of CVD outcomes and HIV in SSA. METHODS: We used the PRISMA guidelines to perform a systematic review of the published literature regarding the association of CVD and HIV in SSA with a focus on CVD surrogate and clinical outcomes in PLWH. RESULTS: From January 2000 until March 2017, 31 articles were published regarding CVD outcomes among PLWH in SSA. Data from surrogate CVD outcomes (n = 13) suggest an increased risk of CVD events among PLWH in SSA. Although acute coronary syndrome is reported infrequently in SSA among PLWH, limited data from five studies suggest extensive thrombus and hypercoagulability as contributing factors. Additional studies suggest an increased risk of stroke among PLWH (n = 13); however, most data are from immunosuppressed ART-naïve PLWH and thus are potentially confounded by the possibility of central nervous system infections. CONCLUSIONS: Given ongoing gaps in our current understanding of CVD and other NCDs in PLWH in SSA, it is imperative to ascertain the burden of CVD outcomes, and to examine strategies for intervention and best practices to enhance the health of this vulnerable population.

Persistent Immune Activation and Carotid Atherosclerosis in HIV-Infected Ugandans Receiving Antiretroviral Therapy.

BACKGROUND: Human immunodeficiency virus (HIV) infection and associated immune activation predict the risk of cardiovascular disease in resource-rich areas. Less is known about these relationships in sub-Saharan Africa. METHODS: Beginning in 2005, we enrolled subjects in southwestern Uganda into a cohort at the time of antiretroviral therapy (ART) initiation. Multiple immune activation measures were assessed before and 6 months after ART initiation. Beginning in 2013, participants aged >40 years underwent metabolic profiling, including measurement of hemoglobin A1c and lipid levels and carotid ultrasonography. We fit regression models to identify traditional and HIV-specific correlates of common carotid intima media thickness (CCIMT). RESULTS: A total of 105 participants completed carotid ultrasonography, with a median completion time of 7 years following ART initiation. Age, low-density lipoprotein cholesterol level, and pre-ART HIV load were correlated with CCIMT. No association was found between CCIMT and any pre-ART biomarkers of immune activation. However, in multivariable models adjusted for cardiovascular disease risk factors, lower absolute levels of soluble CD14 and interleukin 6 and greater declines in the CD14 level and kynurenine-tryptophan ratio after 6 months of ART predicted a lower CCIMT years later (P < .01). CONCLUSIONS: Persistent immune activation despite ART-mediated viral suppression predicts the future atherosclerotic burden among HIV-infected Ugandans. Future work should focus on clinical correlates of these relationships, to elucidate the long-term health priorities for HIV-infected people in the region.

Epidemiology of coronary heart disease in patients with human immunodeficiency virus.

As a growing number of patients infected with human immunodeficiency virus (HIV) have access to antiretroviral therapy and achieve virologic suppression, the focus of clinical care is shifting from treating the infectious complications of advanced immunodeficiency to managing and preventing chronic disease. The aging of the HIV-positive population and increased rates of chronic disease complications in the setting of HIV infection have increased the impact of noncommunicable diseases such as coronary heart disease (CHD). The effect of HIV on CHD is independent of traditional cardiovascular risk factors and antiretroviral medications and is likely due in part to the chronic inflammation and immune activation underlying HIV infection. This article describes the current state of epidemiologic knowledge on CHD in HIV infection. It highlights key studies in the field and summarizes epidemiologic data with respect to traditional and novel CHD risk factors, specialized clinical subgroups, and broader cardiovascular outcomes.

Cardiovascular Risk Estimation Is Suboptimal in People With HIV.

BACKGROUND: Established cardiovascular disease (CVD) risk prediction functions may not accurately predict CVD risk in people with HIV. We assessed the performance of 3 CVD risk prediction functions in 2 HIV cohorts. METHODS AND RESULTS: CVD risk scores were calculated in the Mass General Brigham and Kaiser Permanente Northern California HIV cohorts, using the American College of Cardiology/American Heart Association atherosclerotic CVD function, the FHS (Framingham Heart Study) hard coronary heart disease function and the Framingham Heart Study hard CVD function. Outcomes were myocardial infarction or coronary death for FHS hard coronary heart disease function; and myocardial infarction, stroke, or coronary death for American College of Cardiology/American Heart Association and FHS hard CVD function. We calculated regression coefficients and assessed discrimination and calibration by sex; predicted to observed risk of outcome was also compared. In the combined cohort of 9412, 158 (1.7%) had a coronary heart disease event, and 309 (3.3%) had a CVD event. Among women, CVD risk was generally underestimated by all 3 risk functions. Among men, CVD risk was underestimated by the American College of Cardiology/American Heart Association and FHS hard CVD function, but overestimated by the FHS hard coronary heart disease function. Calibration was poor for women using the FHS hard CVD function and for men using all functions. Discrimination in all functions was good for women (c-statistics ranging from 0.78 to 0.90) and moderate for men (c-statistics ranging from 0.71 to 0.72). CONCLUSIONS: Established CVD risk prediction functions generally underestimate risk in people with HIV. Differences in model performance by sex underscore the need for both HIV-specific and sex-specific functions. Development of CVD risk prediction models tailored to HIV will enhance care for aging people with HIV.

Precision Phenotyping for Curating Research Cohorts of Patients with Post-Acute Sequelae of COVID-19 (PASC) as a Diagnosis of Exclusion.

Scalable identification of patients with the post-acute sequelae of COVID-19 (PASC) is challenging due to a lack of reproducible precision phenotyping algorithms and the suboptimal accuracy, demographic biases, and underestimation of the PASC diagnosis code (ICD-10 U09.9). In a retrospective case-control study, we developed a precision phenotyping algorithm for identifying research cohorts of PASC patients, defined as a diagnosis of exclusion. We used longitudinal electronic health records (EHR) data from over 295 thousand patients from 14 hospitals and 20 community health centers in Massachusetts. The algorithm employs an attention mechanism to exclude sequelae that prior conditions can explain. We performed independent chart reviews to tune and validate our precision phenotyping algorithm. Our PASC phenotyping algorithm improves precision and prevalence estimation and reduces bias in identifying Long COVID patients compared to the U09.9 diagnosis code. Our algorithm identified a PASC research cohort of over 24 thousand patients (compared to about 6 thousand when using the U09.9 diagnosis code), with a 79.9 percent precision (compared to 77.8 percent from the U09.9 diagnosis code). Our estimated prevalence of PASC was 22.8 percent, which is close to the national estimates for the region. We also provide an in-depth analysis outlining the clinical attributes, encompassing identified lingering effects by organ, comorbidity profiles, and temporal differences in the risk of PASC. The PASC phenotyping method presented in this study boasts superior precision, accurately gauges the prevalence of PASC without underestimating it, and exhibits less bias in pinpointing Long COVID patients. The PASC cohort derived from our algorithm will serve as a springboard for delving into Long COVID's genetic, metabolomic, and clinical intricacies, surmounting the constraints of recent PASC cohort studies, which were hampered by their limited size and available outcome data.