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Background: People with HIV (PWH) are at elevated risk for atherosclerotic cardiovascular disease (ASCVD). Underrepresented racial and ethnic groups (UREGs) with HIV in the southern U.S. are disproportionately affected, yet whether cardiology specialist care for this at-risk group improves blood pressure and lipid control or prevents cardiovascular events is unknown. Methods: We evaluated a cohort of PWH from UREGs at elevated ASCVD risk without known cardiovascular disease who received HIV-related care from 2015-2018 at four academic medical centers in the Southern United States with follow up through 2020. Primary outcomes were blood pressure control (<140/90 mmHg) and lipid control (LDL-C ≤ 100 mg/dl) over 2 years and time to first major adverse cardiovascular (MACE) event. Statistical analyses were adjusted for cohort/site and patient factors including HIV measures and comorbidities. Results: Among 3972 included PWH (median age 47 years old, 32.6% female) without diagnosed cardiovascular disease, 276 (6.9%) had a cardiology clinic visit. Cardiology clinic visits were not significantly associated with subsequent blood pressure control (adjusted OR 0.78, 95% CI 0.49-1.24, p=0.29) or lipid control (adjusted OR 2.25, 95% CI 0.72-7.01, p=0.16). Over a median follow up of 5 years, patients who had a cardiology clinic visit had higher risk of MACE, overall mortality, and falsification endpoints (hospitalization or death from accident/trauma and pneumonia/sepsis) indicating a higher risk group overall, even after adjusting for measured risk factors. Conclusions: Among UREG PWH at elevated cardiovascular risk, a cardiology clinic visit was not associated with improved cardiovascular risk factors or reduced risk of cardiovascular events. Our study suggests that seeing a cardiologist is not alone sufficient to promote cardiovascular health or prevent cardiovascular events among PWH, but with low confidence given the higher risk among those who had a cardiology visit.
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The mechanisms of postacute medical conditions and unexplained symptoms after SARS-CoV-2 infection [Long Covid (LC)] are incompletely understood. There is growing evidence that viral persistence, immune dysregulation, and T cell dysfunction may play major roles. We performed whole-body positron emission tomography imaging in a well-characterized cohort of 24 participants at time points ranging from 27 to 910 days after acute SARS-CoV-2 infection using the radiopharmaceutical agent [18F]F-AraG, a selective tracer that allows for anatomical quantitation of activated T lymphocytes. Tracer uptake in the postacute COVID-19 group, which included those with and without continuing symptoms, was higher compared with prepandemic controls in many regions, including the brain stem, spinal cord, bone marrow, nasopharyngeal and hilar lymphoid tissue, cardiopulmonary tissues, and gut wall. T cell activation in the spinal cord and gut wall was associated with the presence of LC symptoms. In addition, tracer uptake in lung tissue was higher in those with persistent pulmonary symptoms specifically. Increased T cell activation in these tissues was also observed in many individuals without LC. Given the high [18F]F-AraG uptake detected in the gut, we obtained colorectal tissue for in situ hybridization of SARS-CoV-2 RNA and immunohistochemical studies in a subset of five participants with LC symptoms. We identified intracellular SARS-CoV-2 single-stranded spike protein-encoding RNA in rectosigmoid lamina propria tissue in all five participants and double-stranded spike protein-encoding RNA in three participants up to 676 days after initial COVID-19, suggesting that tissue viral persistence could be associated with long-term immunologic perturbations.
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COVID-19 , Ativação Linfocitária , Tomografia por Emissão de Pósitrons , RNA Viral , SARS-CoV-2 , Linfócitos T , Humanos , COVID-19/imunologia , COVID-19/virologia , COVID-19/patologia , Linfócitos T/imunologia , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Idoso , Pulmão/virologia , Pulmão/patologia , Pulmão/diagnóstico por imagem , Fatores de TempoRESUMO
This state-of-the art review discusses the underlying mechanisms that contribute to atherosclerotic cardiovascular disease, heart failure and arrhythmias among people with human immunodeficiency virus (HIV), risk prediction and prevention, management, and outstanding research questions, including a discussion of how the Randomized Trial to Prevent Vascular Events in HIV may inform clinical practice.
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Doenças Cardiovasculares , Infecções por HIV , Humanos , Infecções por HIV/complicações , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/terapia , Fatores de Risco , Gerenciamento ClínicoRESUMO
Background: Human immunodeficiency virus (HIV) is associated with increased risk of heart failure (HF) but data regarding phenotypes of heart failure and outcomes after HF diagnosis, especially within the safety-net which is where half of people with HIV in the United States receive care, are less clear. Methods: Using an electronic health record cohort of all individuals with HF within a municipal safety-net system from 2001-2019 linked to the National Death Index Plus, we compared HF phenotypes, all-cause mortality, HF hospitalization, and cause of death for individuals with and without HIV. Results: Among people with HF (n=14,829), 697 individuals had HIV (4.7%). Persons with HIV (PWH) were diagnosed with HF ten years younger on average. A higher proportion of PWH had a reduced ejection fraction at diagnosis (37.9% vs 32.7%). Adjusted for age, sex, and risk factors, coronary artery disease on angiography was similar by HIV status. HIV was associated with 55% higher risk of all-cause mortality (HR 1.55; 95% CI 1.37-1.76; P<0.001) and lower odds of HF hospitalization (OR 0.51; 95% CI 0.39-0.66; P<0.001). Among PWH with HF, cause of death was less often attributed to cardiovascular disease (22.5% vs 54.6% uninfected; P<0.001) and more to substance use (17.9% vs 9.3%; P<0.001), consistent with autopsy findings in a subset (n=81). Conclusions: Among people with HF who receive care within a municipal safety-net system, HIV infection is associated with higher mortality, despite lower odds of HF hospitalization, attributable to non-cardiovascular causes including substance-related and HIV-related mortality.
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BACKGROUND: People with HIV (PWH) have lower exercise capacity compared to peers without HIV, which may be explained by chronotropic incompetence (CI), the inability to increase heart rate during exercise. METHODS: The Exercise for Healthy Aging Study included adults ages 50-75 with and without HIV. Participants completed 12 weeks of moderate intensity exercise, before randomization to moderate or high intensity for 12 additional weeks. We compared adjusted heart rate reserve (AHRR; CI <80%) on cardiopulmonary exercise testing by HIV serostatus and change from baseline to 12 and 24 weeks using mixed effects models. RESULTS: Among 32 PWH and 37 controls (median age 56, 7% female, mean BMI 28â kg/m2), 28% of PWH compared to 11% of controls had CI at baseline (p = 0.067). AHRR was lower among PWH (91 vs 101%; difference 10%, 95% CI 1.9-18.9; p = 0.02). At week 12, AHRR normalized among PWH (+8%, 95% CI 4-11; p < 0.001) and was sustained at week 24 (+5, 95%CI 1-9; p = 0.008) compared to no change among controls (95%CI -4 to 4; p = 0.95; pinteraction = 0.004). After 24 weeks of exercise, only 15% PWH and 10% of controls had CI (p = 0.70). CONCLUSIONS: Chronotropic incompetence contributes to reduced exercise capacity among PWH and improves with exercise training.
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BACKGROUND: Ischemic cardiomyopathy is the leading cause of heart failure (HF). Most patients do not undergo coronary assessment after HF diagnosis. There are no randomized clinical trials of coronary assessment after HF diagnosis. METHODS: Using an electronic health record cohort of all individuals with HF within the San Francisco Health Network from 2001 to 2019, we identified factors associated with coronary assessment. Then, we studied the association of coronary assessment within 30 days of HF diagnosis with all-cause mortality and a composite of mortality and emergent angiography using a target trial emulation observational comparative-effectiveness approach. Target trial emulation is an approach to causal inference based on creating a hypothetical randomized clinical trial protocol and using observational data to emulate the protocol. We used propensity scores for covariate adjustment. We used national death records to improve the ascertainment of mortality and included falsification end points for the cause of death. RESULTS: Among 14 829 individuals with HF (median, 62 years old; 5855 [40%] women), 3987 (26.9%) ever completed coronary assessment, with 2467/13 301 (18.5%) with unknown coronary artery disease status at HF diagnosis assessed. Women, older individuals, and people without stable housing were less likely to complete coronary assessment. Among 5972 eligible persons of whom 627 underwent early elective coronary assessment, coronary assessment was associated with lower mortality (hazard ratio, 0.84 [95% CI, 0.72-0.97]; P=0.025), reduced risk of the composite outcome (hazard ratio, 0.86 [95% CI, 0.73-1.00]), higher rates of revascularization (odds ratio, 7.6 [95% CI, 5.4-10.6]), and higher use of medical therapy (odds ratio, 2.5 [95% CI, 1.7-3.6]), but not the falsification end points. CONCLUSIONS: In a safety-net population, disparities in coronary assessment after HF diagnosis are not fully explained by coronary artery disease risk factors. Early coronary assessment is associated with improved HF outcomes possibly related to higher rates of revascularization and guideline-directed medical therapy but with low certainty that this finding is not attributable to unmeasured confounding.
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Angiografia Coronária , Registros Eletrônicos de Saúde , Insuficiência Cardíaca , Valor Preditivo dos Testes , Provedores de Redes de Segurança , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Idoso , São Francisco/epidemiologia , Fatores de Tempo , Fatores de Risco , Medição de Risco , Causas de Morte , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/diagnóstico por imagem , Prognóstico , Pesquisa Comparativa da EfetividadeRESUMO
In 2023, the Keystone Symposia held the first international scientific conference convening research leaders investigating the pathology of post-acute sequelae of COVID-19 (PASC) or Long COVID, a growing and urgent public health priority. In this report, we present insights from the talks and workshops presented during this meeting and highlight key themes regarding what researchers have discovered regarding the underlying biology of PASC and directions toward future treatment. Several themes have emerged in the biology, with inflammation and other immune alterations being the most common focus, potentially related to viral persistence, latent virus reactivation, and/or tissue damage and dysfunction, especially of the endothelium, nervous system, and mitochondria. In order to develop safe and effective treatments for people with PASC, critical next steps should focus on the replication of major findings regarding potential mechanisms, disentangling pathogenic mechanisms from downstream effects, development of cellular and animal models, mechanism-focused randomized, placebo-controlled trials, and closer collaboration between people with lived experience, scientists, and other stakeholders. Ultimately, by learning from other post-infectious syndromes, the knowledge gained may help not only those with PASC/Long COVID, but also those with other post-infectious syndromes.
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COVID-19 , Síndrome de COVID-19 Pós-Aguda , SARS-CoV-2 , Humanos , COVID-19/terapia , COVID-19/complicações , COVID-19/virologia , SARS-CoV-2/patogenicidade , Tratamento Farmacológico da COVID-19RESUMO
Oral nirmatrelvir/ritonavir is approved as treatment for acute COVID-19, but the effect of treatment during acute infection on risk of Long COVID is unknown. We hypothesized that nirmatrelvir treatment during acute SARS-CoV-2 infection reduces risk of developing Long COVID and rebound after treatment is associated with Long COVID. We conducted an observational cohort study within the Covid Citizen Science (CCS) study, an online cohort study with over 100 000 participants. We included vaccinated, nonhospitalized, nonpregnant individuals who reported their first SARS-CoV-2 positive test March-August 2022. Oral nirmatrelvir/ritonavir treatment was ascertained during acute SARS-CoV-2 infection. Patient-reported Long COVID symptoms, symptom rebound and test-positivity rebound were asked on subsequent surveys at least 3 months after SARS-CoV-2 infection. A total of 4684 individuals met the eligibility criteria, of whom 988 (21.1%) were treated and 3696 (78.9%) were untreated; 353/988 (35.7%) treated and 1258/3696 (34.0%) untreated responded to the Long COVID survey (n = 1611). Among 1611 participants, median age was 55 years and 66% were female. At 5.4 ± 1.3 months after infection, nirmatrelvir treatment was not associated with subsequent Long COVID symptoms (odds ratio [OR]: 1.15; 95% confidence interval [CI]: 0.80-1.64; p = 0.45). Among 666 treated who answered rebound questions, rebound symptoms or test positivity were not associated with Long COVID symptoms (OR: 1.34; 95% CI: 0.74-2.41; p = 0.33). Within this cohort of vaccinated, nonhospitalized individuals, oral nirmatrelvir treatment during acute SARS-CoV-2 infection and rebound after nirmatrelvir treatment were not associated with Long COVID symptoms more than 90 days after infection.
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COVID-19 , Síndrome de COVID-19 Pós-Aguda , Feminino , Humanos , Pessoa de Meia-Idade , Masculino , Ritonavir , Estudos de Coortes , SARS-CoV-2RESUMO
Background: People with HIV (PWH) have lower exercise capacity compared to HIV-uninfected peers, which may be explained by chronotropic incompetence (CI), the inability to increase heart rate during exercise. Methods: The Exercise for Healthy Aging Study included adults ages 50-75 with and without HIV. Participants completed 12 weeks of moderate intensity exercise, before randomization to moderate or high intensity for 12 additional weeks. We compared adjusted heart rate reserve (AHRR; CI <80%) on cardiopulmonary exercise testing by HIV serostatus, and change from baseline to 12 and 24 weeks using mixed effects models. Results: Among 32 PWH and 37 controls (median age 56, 7% female, mean BMI 28 kg/m2), 28% of PWH compared to 11% of controls had CI at baseline (p=0.067). AHRR was lower among PWH (91 vs 102%; difference 11%, 95% CI 2.5-19.7; p=0.01). At week 12, AHRR normalized among PWH (+8%, 95% CI 4-11; p<0.001) and was sustained at week 24 (+5, 95%CI 1-9; p=0.008) compared to no change among controls (95%CI -4 to 4; p=0.95; pinteraction=0.004). After 24 weeks of exercise, only 15% PWH and 10% of controls had CI (p=0.70). Conclusions: Chronotropic incompetence contributes to reduced exercise capacity among PWH and improves with exercise training.
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BACKGROUND: Persistent symptoms among some persons who develop COVID-19 has led to the hypothesis that SARS-CoV-2 may, in some form or location, persist for long periods following acute infection. Several studies have shown data in this regard but are limited by non-representative and small study populations, short duration since acute infection, and lack of a true-negative comparator group to assess assay specificity. METHODS: We evaluated adults with RNA-confirmed COVID-19 at multiple time points following acute infection (pandemic-era participants) and adults with specimens collected prior to 2020 (pre-pandemic era). Using once-thawed plasma, we employed the Simoa® (Quanterix) single molecule array detection platform to measure SARS-CoV-2 spike, S1, and nucleocapsid antigens. RESULTS: Compared to 250 pre-pandemic participants who had 2% assay positivity, detection of any SARS-CoV-2 antigen was significantly more frequent among 171 pandemic-era participants at three different time periods in the post-acute phase of infection. The absolute difference in SARS-CoV-2 plasma antigen prevalence was +11% (95% CI: +5.0% to +16%) at 3.0-6.0 months post-onset of COVID-19; +8.7% (95% CI: +3.1% to +14%) at 6.1 to 10.0 months; and +5.4% (95% CI: +0.42% to +10%) at 10.1-14.1 months. Hospitalization for acute COVID-19 and, among the non-hospitalized, worse self-reported health during acute COVID-19 were associated with greater post-acute phase antigen detection. CONCLUSIONS: Compared to uninfected persons, there is an excess prevalence of SARS-CoV-2 antigenemia in SARS-CoV-2-infected individuals up to 14 months after acute COVID-19. These findings motivate an urgent research agenda regarding the short-term and long-term clinical manifestations of this viral persistence.
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The associations between longitudinal dynamics and the breadth of SARS-CoV-2 neutralizing antibody (nAb) response with various Long COVID phenotypes before vaccination are not known. The capacity of antibodies to cross-neutralize a variety of viral variants may be associated with ongoing pathology and persistent symptoms. We measured longitudinal neutralizing and cross-neutralizing antibody responses to pre- and post-SARS-CoV-2 Omicron variants in participants infected early in the COVID-19 pandemic, before widespread rollout of SARS-CoV-2 vaccines. Cross-sectional regression models adjusted for clinical covariates and longitudinal mixed-effects models were used to determine the impact of the breadth and rate of decay of neutralizing responses on the development of Long COVID symptoms, as well as Long COVID phenotypes. We identified several novel relationships between SARS-CoV-2 antibody neutralization and the presence of Long COVID symptoms. Specifically, we show that, although nAb responses to the original, infecting strain of SARS-CoV-2 were not associated with Long COVID in cross-sectional analyses, cross-neutralization ID50 levels to the Omicron BA.5 variant approximately 4 months following acute infection was independently and significantly associated with greater odds of Long COVID and with persistent gastrointestinal and neurological symptoms. Longitudinal modeling demonstrated significant associations in the overall levels and rates of decay of neutralization capacity with Long COVID phenotypes. A higher proportion of participants had antibodies capable of neutralizing Omicron BA.5 compared with BA.1 or XBB.1.5 variants. Our findings suggest that relationships between various immune responses and Long COVID are likely complex but may involve the breadth of antibody neutralization responses.
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COVID-19 , Síndrome de COVID-19 Pós-Aguda , Humanos , Anticorpos Neutralizantes , Vacinas contra COVID-19 , Estudos Transversais , Pandemias , SARS-CoV-2 , Anticorpos AntiviraisRESUMO
Background Postacute sequelae of COVID-19 (PASC) and HIV are both associated with reduced exercise capacity, but whether SARS-CoV-2 or PASC are associated with exercise capacity among people with HIV (PWH) is unknown. We hypothesized that PWH with PASC would have reduced exercise capacity from chronotropic incompetence. Methods and Results We conducted cross-sectional cardiopulmonary exercise testing within a COVID recovery cohort that included PWH with and without prior SARS-CoV-2 infection and people without HIV with prior SARS-CoV-2 infection (controls). We evaluated associations of HIV, SARS-CoV-2, and PASC with exercise capacity (peak oxygen consumption) and chronotropy (adjusted heart rate reserve). We included 83 participants (median age, 54 years; 35% women; 37 PWH): 23 out of 37 (62%) PWH and all 46 controls had prior SARS-CoV-2 infection, and 11 out of 23 (48%) PWH and 28 out of 46 (61%) without HIV had PASC. Peak oxygen consumption was reduced among PWH versus controls (80% predicted versus 99%, P=0.005), a difference of 5.5 mL/kg per minute (95% CI, 2.7-8.2; P<0.001). Chronotropic incompetence was more prevalent among PWH (38% versus 11%, P=0.002), with lower adjusted heart rate reserve (60% versus 83%, P<0.0001) versus controls. Among PWH, SARS-CoV-2 coinfection and PASC were not associated with exercise capacity. Chronotropic incompetence was more common among PWH with PASC: 7 out of 11 (64%) with PASC versus 7 out of 26 (27%) without PASC (P=0.04). Conclusions Exercise capacity and chronotropy are lower among PWH compared with individuals with SARS-CoV-2 infection without HIV. Among PWH, SARS-CoV-2 infection and PASC were not strongly associated with reduced exercise capacity. Chronotropic incompetence may be a common underrecognized mechanism of exercise intolerance among PWH, especially those with cardiopulmonary PASC.
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COVID-19 , Infecções por HIV , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Síndrome de COVID-19 Pós-Aguda , Tolerância ao Exercício/fisiologia , Estudos Transversais , SARS-CoV-2 , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologiaRESUMO
The etiologic mechanisms of post-acute medical morbidities and unexplained symptoms (Long COVID) following SARS-CoV-2 infection are incompletely understood. There is growing evidence that viral persistence and immune dysregulation may play a major role. We performed whole-body positron emission tomography (PET) imaging in a cohort of 24 participants at time points ranging from 27 to 910 days following acute SARS-CoV-2 infection using a novel radiopharmaceutical agent, [18F]F-AraG, a highly selective tracer that allows for anatomical quantitation of activated T lymphocytes. Tracer uptake in the post-acute COVID group, which included those with and without Long COVID symptoms, was significantly higher compared to pre-pandemic controls in many anatomical regions, including the brain stem, spinal cord, bone marrow, nasopharyngeal and hilar lymphoid tissue, cardiopulmonary tissues, and gut wall. Although T cell activation tended to be higher in participants imaged closer to the time of the acute illness, tracer uptake was increased in participants imaged up to 2.5 years following SARS-CoV-2 infection. We observed that T cell activation in spinal cord and gut wall was associated with the presence of Long COVID symptoms. In addition, tracer uptake in lung tissue was higher in those with persistent pulmonary symptoms. Notably, increased T cell activation in these tissues was also observed in many individuals without Long COVID. Given the high [18F]F-AraG uptake detected in the gut, we obtained colorectal tissue for in situ hybridization SARS-CoV-2 RNA and immunohistochemical studies in a subset of participants with Long COVID symptoms. We identified cellular SARS-CoV-2 RNA in rectosigmoid lamina propria tissue in all these participants, ranging from 158 to 676 days following initial COVID-19 illness, suggesting that tissue viral persistence could be associated with long-term immunological perturbations.
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Background: Though ischemic cardiomyopathy is the leading cause of heart failure (HF), most patients do not undergo coronary assessment after heart failure diagnosis. In a safety-net population, referral patterns have not been studied, and it is unknown whether coronary assessment is associated with improved HF outcomes. Methods: Using an electronic health record cohort of all individuals with HF within San Francisco Health Network from 2001-2019, we identified factors associated with completion of coronary assessment (invasive coronary angiography, nuclear stress, or coronary computed tomographic angiography). Then we emulated a randomized clinical trial of elective coronary assessment with outcomes of all-cause mortality and a composite outcome of mortality and emergent angiography. We used propensity scores to account for differences between groups. We used national death records to improve ascertainment of mortality. Results: Among 14,829 individuals with HF (median 62 years old, 5,855 [40%] women), 3,987 (26.9%) ever completed coronary assessment, with 2,467 (18.5%) assessed out of 13,301 with unknown CAD status at HF diagnosis. Women and older individuals were less likely to complete coronary assessment, with differences by race/ethnicity, medical history, substance use, housing, and echocardiographic findings. Among 5,972 eligible for inclusion in the "target trial," 627 underwent early elective coronary assessment and 5,345 did not. Coronary assessment was associated with lower mortality (HR 0.84; 95% CI 0.72-0.97; p=0.025), reduced risk of the composite outcome, higher rates of revascularization, and higher use of medical therapy. Conclusions: In a safety-net population, disparities in coronary assessment after HF diagnosis are not fully explained by CAD risk factors. Our target trial emulation suggests coronary assessment is associated with improved HF outcomes possibly related to higher rates of revascularization and GDMT use, but with low certainty that this is finding is not attributable to unmeasured confounding.
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OBJECTIVES: We sought to characterize atherosclerotic cardiovascular disease (ASCVD) risk and metrics of cardiovascular health in persons with HIV (PWH) eligible for primary prevention of ASCVD. DESIGN: A cross-sectional study of PWH 40âyears and older without documented ASCVD who received care at three HIV clinics in San Francisco from 2019 to 2022. METHODS: We used ICD-10 codes and electronic health record data to assess ASCVD risk and cardiovascular health, as defined by the American Heart Association's Life's Essential 8 (LE8) metrics for nicotine exposure, BMI, lipids, glucose, and blood pressure (BP). RESULTS: Among 2567 PWH eligible for primary prevention of ASCVD, the median age was 55âyears, 14% were women, and 95% were on antiretroviral therapy. Seventy-seven percent had undergone complete assessment of ASCVD risk factors, and 50% of these patients had intermediate-high ASCVD risk (≥7.5%). Of those with hypertension, 39% were prescribed an antihypertensive. Among those eligible, 43% were prescribed a statin. The mean LE8 cardiovascular health score [0--100 (best health)] was 55.1 for nicotine exposure, 71.3 for BMI, 70.4 for lipids, 81.2 for blood glucose, 56.0 for BP, with an average score of 66.2 across the five metrics. Patients with Medicare insurance, black patients, and those with sleep apnea and chronic kidney disease had on average lower cardiovascular health scores; patients with undetectable viral loads had higher cardiovascular health scores. CONCLUSION: We highlight opportunities for improving primary prevention of ASCVD among PWH, especially in the areas of guideline-based therapy, nicotine exposure, and BP control.
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Aterosclerose , Doenças Cardiovasculares , Infecções por HIV , Inibidores de Hidroximetilglutaril-CoA Redutases , Idoso , Humanos , Feminino , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Masculino , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/induzido quimicamente , Estudos Transversais , Nicotina , Medição de Risco , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Medicare , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Aterosclerose/complicações , Aterosclerose/epidemiologia , Fatores de Risco , LipídeosRESUMO
IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. METHODS: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. DISCUSSION: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options. REGISTRATION: NCT05172024.
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COVID-19 , Humanos , COVID-19/epidemiologia , Estudos Observacionais como Assunto , Síndrome de COVID-19 Pós-Aguda , Estudos Prospectivos , Estudos Retrospectivos , SARS-CoV-2 , Adolescente , Adulto , Estudos Multicêntricos como AssuntoRESUMO
Some individuals do not return to baseline health following SARS-CoV-2 infection, leading to a condition known as long COVID. The underlying pathophysiology of long COVID remains unknown. Given that autoantibodies have been found to play a role in severity of SARS-CoV-2 infection and certain other post-COVID sequelae, their potential role in long COVID is important to investigate. Here, we apply a well-established, unbiased, proteome-wide autoantibody detection technology (T7 phage-display assay with immunoprecipitation and next-generation sequencing, PhIP-Seq) to a robustly phenotyped cohort of 121 individuals with long COVID, 64 individuals with prior COVID-19 who reported full recovery, and 57 pre-COVID controls. While a distinct autoreactive signature was detected that separated individuals with prior SARS-CoV-2 infection from those never exposed to SARS-CoV-2, we did not detect patterns of autoreactivity that separated individuals with long COVID from individuals fully recovered from COVID-19. These data suggest that there are robust alterations in autoreactive antibody profiles due to infection; however, no association of autoreactive antibodies and long COVID was apparent by this assay.
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COVID-19 , Síndrome de COVID-19 Pós-Aguda , Humanos , SARS-CoV-2 , Autoanticorpos , AutoantígenosRESUMO
BACKGROUND: Mechanisms underlying persistent cardiopulmonary symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (postacute sequelae of coronavirus disease 2019 [COVID-19; PASC] or "long COVID") remain unclear. This study sought to elucidate mechanisms of cardiopulmonary symptoms and reduced exercise capacity. METHODS: We conducted cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring among adults >1 year after SARS-CoV-2 infection, compared those with and those without symptoms, and correlated findings with previously measured biomarkers. RESULTS: Sixty participants (median age, 53 years; 42% female; 87% nonhospitalized; median 17.6 months after infection) were studied. At CPET, 18/37 (49%) with symptoms had reduced exercise capacity (<85% predicted), compared with 3/19 (16%) without symptoms (P = .02). The adjusted peak oxygen consumption (VO2) was 5.2 mL/kg/min lower (95% confidence interval, 2.1-8.3; P = .001) or 16.9% lower percent predicted (4.3%-29.6%; P = .02) among those with symptoms. Chronotropic incompetence was common. Inflammatory markers and antibody levels early in PASC were negatively correlated with peak VO2. Late-gadolinium enhancement on CMR and arrhythmias were absent. CONCLUSIONS: Cardiopulmonary symptoms >1 year after COVID-19 were associated with reduced exercise capacity, which was associated with earlier inflammatory markers. Chronotropic incompetence may explain exercise intolerance among some with "long COVID."