Serological response to vaccination in post-acute sequelae of COVID.

BACKGROUND: Individuals with post-acute sequelae of COVID (PASC) may have a persistence in immune activation that differentiates them from individuals who have recovered from COVID without clinical sequelae. To investigate how humoral immune activation may vary in this regard, we compared patterns of vaccine-provoked serological response in patients with PASC compared to individuals recovered from prior COVID without PASC. METHODS: We prospectively studied 245 adults clinically diagnosed with PASC and 86 adults successfully recovered from prior COVID. All participants had measures of humoral immunity to SARS-CoV-2 assayed before or after receiving their first-ever administration of COVID vaccination (either single-dose or two-dose regimen), including anti-spike (IgG-S and IgM-S) and anti-nucleocapsid (IgG-N) antibodies as well as IgG-S angiotensin-converting enzyme 2 (ACE2) binding levels. We used unadjusted and multivariable-adjusted regression analyses to examine the association of PASC compared to COVID-recovered status with post-vaccination measures of humoral immunity. RESULTS: Individuals with PASC mounted consistently higher post-vaccination IgG-S antibody levels when compared to COVID-recovered (median log IgG-S 3.98 versus 3.74, P < 0.001), with similar results seen for ACE2 binding levels (median 99.1 versus 98.2, P = 0.044). The post-vaccination IgM-S response in PASC was attenuated but persistently unchanged over time (P = 0.33), compared to in COVID recovery wherein the IgM-S response expectedly decreased over time (P = 0.002). Findings remained consistent when accounting for demographic and clinical variables including indices of index infection severity and comorbidity burden. CONCLUSION: We found evidence of aberrant immune response distinguishing PASC from recovered COVID. This aberrancy is marked by excess IgG-S activation and ACE2 binding along with findings consistent with a delayed or dysfunctional immunoglobulin class switching, all of which is unmasked by vaccine provocation. These results suggest that measures of aberrant immune response may offer promise as tools for diagnosing and distinguishing PASC from non-PASC phenotypes, in addition to serving as potential targets for intervention.

Blood pressure variability supersedes heart rate variability as a real-world measure of dementia risk.

Blood pressure variability (BPV) and heart rate variability (HRV) have been associated with Alzheimer's Disease and Related Dementias (ADRD) in rigorously controlled studies. However, the extent to which BPV and HRV may offer predictive information in real-world, routine clinical care is unclear. In a retrospective cohort study of 48,204 adults (age 54.9 ± 17.5 years, 60% female) receiving continuous care at a single center, we derived BPV and HRV from routinely collected clinical data. We use multivariable Cox models to evaluate the association of BPV and HRV, separately and in combination, with incident ADRD. Over a median 3 [2.4, 3.0] years, there were 443 cases of new-onset ADRD. We found that clinically derived measures of BPV, but not HRV, were consistently associated with incident ADRD. In combined analyses, only patients in both the highest quartile of BPV and lowest quartile of HRV had increased ADRD risk (HR 2.34, 95% CI 1.44-3.81). These results indicate that clinically derived BPV, rather than HRV, offers a consistent and readily available metric for ADRD risk assessment in a real-world patient care setting. Thus, implementation of BPV as a widely accessible tool could allow clinical providers to efficiently identify patients most likely to benefit from comprehensive ADRD screening.

Subclinical hepatic fibrosis is associated with coronary microvascular dysfunction by myocardial perfusion reserve index: a retrospective cohort study.

The heart-liver axis is of growing importance. Previous studies have identified independent association of liver dysfunction and fibrosis with adverse cardiac outcomes, but mechanistic pathways remain uncertain. We sought to understand the relations between the degree of hepatic fibrosis identified by the Fibrosis-4 (Fib-4) risk score and comprehensive cardiac MRI (CMR) measures of subclinical cardiac disease. We conducted a retrospective single-center cohort study of patients between 2011 and 2021. We identified consecutive patients who underwent a comprehensive CMR imaging protocol including contrast enhanced with stress/rest perfusion, and lacked pre-existing cardiovascular disease or perfusion abnormalities on CMR. We examined the association of hepatic fibrosis, using the Fib-4 score, with subclinical cardiac disease on CMR while adjusting for cardiometabolic traits. Given known associations of hepatic disease and coronary microvascular dysfunction, we prioritized analyses with the myocardial perfusion reserve index (MPRI), a marker of coronary microvascular function. Of the 66 patients in our study cohort, 54 were female (81%) and the mean age was 53.7 ± 15.3 years. We found that higher Fib-4 was associated with reduction in the MPRI (ß [SE] - 1.12 [0.46], P = 0.02), after adjusting for cardiometabolic risk factors. Importantly, Fib-4 was not significantly associated with any other CMR phenotypes including measures of cardiac remodeling, inflammation, fibrosis, or dysfunction. We found evidence that hepatic fibrosis associated with coronary microvascular dysfunction, in the absence of overt associations with any other subclinical cardiac disease measures. These findings highlight a potentially important precursor pathway leading to development of subsequent heart-liver disease.

Apparent Risks of Postural Orthostatic Tachycardia Syndrome Diagnoses After COVID-19 Vaccination and SARS-Cov-2 Infection.

Postural orthostatic tachycardia syndrome (POTS) has been previously described after SARS-CoV-2 infection; however, limited data is available on the relation of POTS with COVID-19 vaccination. Here we show in a cohort of 284,592 COVID-19 vaccinated individuals using a sequence-symmetry analysis, that the odds of POTS are higher 90 days after vaccine exposure than 90 days prior to exposure, and that the odds for POTS are higher than referent conventional primary care diagnoses, but lower than the odds of new POTS diagnosis after SARS-CoV-2 infection. Our results identify a possible association between COVID-19 vaccination and incidence of POTS. Notwithstanding the probable low incidence of POTS after COVID-19 vaccination, particularly when compared to SARS-Cov-2 post-infection odds which were five times higher, our results suggest that further studies, are needed to investigate the incidence and etiology of POTS occurring after COVID-19 vaccination.

Demographic and clinical characteristics associated with variations in antibody response to BNT162b2 COVID-19 vaccination among healthcare workers at an academic medical centre: a longitudinal cohort analysis.

OBJECTIVES: We sought to understand the demographic and clinical factors associated with variations in longitudinal antibody response following completion of two-dose regiment of BNT162b2 vaccination. DESIGN: This study is a 10-month longitudinal cohort study of healthcare workers and serially measured anti-spike protein IgG (IgG-S) antibody levels using mixed linear models to examine their associations with participant characteristics. SETTING: A large, multisite academic medical centre in Southern California, USA. PARTICIPANTS: A total of 843 healthcare workers met inclusion criteria including completion of an initial two-dose course of BNT162b2 vaccination, complete clinical history and at least two blood samples for analysis. Patients had an average age of 45±13 years, were 70% female and 7% with prior SARS-CoV-2 infection. RESULTS: Vaccine-induced IgG-S levels remained in the positive range for 99.6% of individuals up to 10 months after initial two-dose vaccination. Prior SARS-CoV-2 infection was the primary correlate of sustained higher postvaccination IgG-S levels (partial R2=0.133), with a 1.74±0.11 SD higher IgG-S response (p<0.001). Female sex (beta 0.27±0.06, p<0.001), younger age (0.01±0.00, p<0.001) and absence of hypertension (0.17±0.08, p=0.003) were also associated with persistently higher IgG-S responses. Notably, prior SARS-CoV-2 infection augmented the associations of sex (-0.42 for male sex, p=0.08) and modified the associations of hypertension (1.17, p=0.001), such that infection-naïve individuals with hypertension had persistently lower IgG-S levels whereas prior infected individuals with hypertension exhibited higher IgG-S levels that remained augmented over time. CONCLUSIONS: While the IgG-S antibody response remains in the positive range for up to 10 months following initial mRNA vaccination in most adults, determinants of sustained higher antibody levels include prior SARS-CoV-2 infection, female sex, younger age and absence of hypertension. Certain determinants of the longitudinal antibody response appear significantly modified by prior infection status. These findings offer insights regarding factors that may influence the 'hybrid' immunity conferred by natural infection combined with vaccination.

Refining Safe Contrast Limits for Preventing Acute Kidney Injury After Percutaneous Coronary Intervention.

Background Contrast-associated acute kidney injury (CA-AKI) is associated with substantial morbidity and may be prevented by using less contrast during percutaneous coronary intervention (PCI). However, tools for determining safe contrast volumes are limited. We developed risk models to tailor safe contrast volume limits during PCI. Methods and Results Using data from all PCIs performed at 18 hospitals from January 2015 to March 2018, we developed logistic regression models for predicting CA-AKI, including simpler models ("pragmatic full," "pragmatic minimum") using only predictors easily derivable from electronic health records. We prospectively validated these models using PCI data from April 2018 to December 2018 and compared them to preexisting safe contrast models using the area under the receiver operating characteristic curve (AUC). The model derivation data set included 20 579 PCIs with 2102 CA-AKI cases. When applying models to the separate validation data set (5423 PCIs, 488 CA-AKI cases), prior safe contrast limits (5*Weight/Creatinine, 2*CreatinineClearance) were poor measures of safety with accuracies of 53.7% and 56.6% in predicting CA-AKI, respectively. The full, pragmatic full, and pragmatic minimum models performed significantly better (accuracy, 73.1%, 69.3%, 66.6%; AUC, 0.80, 0.76, 0.72 versus 0.59 for 5 * Weight/Creatinine, 0.61 for 2*CreatinineClearance). We found that applying safe contrast limits could meaningfully reduce CA-AKI risk in one-quarter of patients. Conclusions Compared with preexisting equations, new multivariate models for safe contrast limits were substantially more accurate in predicting CA-AKI and could help determine which patients benefit most from limiting contrast during PCI. Using readily available electronic health record data, these models could be implemented into electronic health records to provide actionable information for improving PCI safety.

Practice Patterns and Patient Outcomes After Widespread Adoption of Remote Heart Failure Care.

BACKGROUND: An unprecedented shift to remote heart failure outpatient care occurred during the coronavirus disease 2019 (COVID-19) pandemic. Given challenges inherent to remote care, we studied whether remote visits (video or telephone) were associated with different patient usage, clinician practice patterns, and outcomes. METHODS: We included all ambulatory cardiology visits for heart failure at a multisite health system from April 1, 2019, to December 31, 2019 (pre-COVID) or April 1, 2020, to December 31, 2020 (COVID era), resulting in 10 591 pre-COVID in-person, 7775 COVID-era in-person, 1009 COVID-era video, and 2322 COVID-era telephone visits. We used multivariable logistic and Cox proportional hazards regressions with propensity weighting and patient clustering to study ordering practices and outcomes. RESULTS: Compared with in-person visits, video visits were used more often by younger (mean 64.7 years [SD 14.5] versus 74.2 [14.1]), male (68.3% versus 61.4%), and privately insured (45.9% versus 28.9%) individuals (P<0.05 for all). Remote visits were more frequently used by non-White patients (35.8% video, 37.0% telephone versus 33.2% in-person). During remote visits, clinicians were less likely to order diagnostic testing (odds ratio, 0.20 [0.18-0.22] video versus in-person, 0.18 [0.17-0.19] telephone versus in-person) or prescribe ß-blockers (0.82 [0.68-0.99], 0.35 [0.26-0.47]), mineralocorticoid receptor antagonists (0.69 [0.50-0.96], 0.48 [0.35-0.66]), or loop diuretics (0.67 [0.53-0.85], 0.45 [0.37-0.55]). During telephone visits, clinicians were less likely to prescribe ACE (angiotensin-converting enzyme) inhibitor/ARB (angiotensin receptor blockers)/ARNIs (angiotensin receptor-neprilysin inhibitors; 0.54 [0.40-0.72]). Telephone visits but not video visits were associated with higher rates of 90-day mortality (1.82 [1.14-2.90]) and nonsignificant trends towards higher rates of 90-day heart failure emergency department visits (1.34 [0.97-1.86]) and hospitalizations (1.36 [0.98-1.89]). CONCLUSIONS: Remote visits for heart failure care were associated with reduced diagnostic testing and guideline-directed medical therapy prescription. Telephone but not video visits were associated with increased 90-day mortality.

Patient Use and Clinical Practice Patterns of Remote Cardiology Clinic Visits in the Era of COVID-19.

Importance: The COVID-19 pandemic has led to an unprecedented shift in ambulatory cardiovascular care from in-person to remote visits. Objective: To understand whether the transition to remote visits is associated with disparities in patient use of care, diagnostic test ordering, and medication prescribing. Design, Setting, and Participants: This cross-sectional study used electronic health records data for all ambulatory cardiology visits at an urban, multisite health system in Los Angeles County, California, during 2 periods: April 1, 2019, to December 31, 2019 (pre-COVID) and April 1 to December 31, 2020 (COVID-era). Statistical analysis was performed from January to February 2021. Exposure: In-person or remote ambulatory cardiology clinic visit at one of 31 during the pre-COVID period or COVID-era period. Main Outcomes and Measures: Comparison of patient characteristics and frequencies of medication ordering and cardiology-specific testing across 4 visit types (pre-COVID in-person (reference), COVID-era in-person, COVID-era video, COVID-era telephone). Results: This study analyzed data from 87 182 pre-COVID in-person, 74 498 COVID-era in-person, 4720 COVID-era video, and 10 381 COVID-era telephone visits. Across visits, 79 572 patients were female (45.0%), 127 080 patients were non-Hispanic White (71.9%), and the mean (SD) age was 68.1 (17.0) years. Patients accessing COVID-era remote visits were more likely to be Asian, Black, or Hispanic individuals (24 934 pre-COVID in-person visits [28.6%] vs 19 742 COVID-era in-person visits [26.5%] vs 3633 COVID-era video visits [30.4%] vs 1435 COVID-era telephone visits [35.0%]; P < .001 for all comparisons), have private insurance (34 063 pre-COVID in-person visits [39.1%] vs 25 474 COVID-era in-person visits [34.2%] vs 2562 COVID-era video visits [54.3%] vs 4264 COVID-era telephone visits [41.1%]; P < .001 for COVID-era in-person vs video and COVID-era in-person vs telephone), and have cardiovascular comorbidities (eg, hypertension: 37 166 pre-COVID in-person visits [42.6%] vs 31 359 COVID-era in-person visits [42.1%] vs 2006 COVID-era video visits [42.5%] vs 5181 COVID-era telephone visits [49.9%]; P < .001 for COVID-era in-person vs telephone; and heart failure: 14 319 pre-COVID in-person visits [16.4%] vs 10 488 COVID-era in-person visits [14.1%] vs 1172 COVID-era video visits [24.8%] vs 2674 COVID-era telephone visits [25.8%]; P < .001 for COVID-era in-person vs video and COVID-era in-person vs telephone). After adjusting for patient and visit characteristics and in comparison with pre-COVID in-person visits, during video and telephone visits, clinicians had lower odds of ordering any medication (COVID-era in-person: odds ratio [OR], 0.62 [95% CI, 0.60-0.64], COVID-era video: OR, 0.22 [95% CI, 0.20-0.24]; COVID-era telephone: OR, 0.14 [95% CI, 0.13-0.15]) or tests, such as electrocardiograms (COVID-era in-person: OR, 0.60 [95% CI, 0.58-0.62]; COVID-era video: OR, 0.03 [95% CI, 0.02-0.04]; COVID-era telephone: OR, 0.02 [95% CI, 0.01-0.03]) or echocardiograms (COVID-era in-person: OR, 1.21 [95% CI, 1.18-1.24]; COVID-era video: OR, 0.47 [95% CI, 0.42-0.52]; COVID-era telephone: OR, 0.28 [95% CI, 0.25-0.31]). Conclusions and Relevance: Patients who were Asian, Black, or Hispanic, had private insurance, and had at least one of several cardiovascular comorbidities used remote cardiovascular care more frequently in the COVID-era period. Clinician ordering of diagnostic testing and medications consistently decreased when comparing pre-COVID vs COVID-era and in-person vs remote visits. Further studies are needed to clarify whether these decreases represent a reduction in the overuse of tests and medications vs an underuse of indicated testing and prescribing.