Risk for diagnosis or treatment of mood or anxiety disorders in adults after SARS-CoV-2 infection, 2020-2022.

COVID-19 is associated with increased risks for mood or anxiety disorders, but it remains uncertain how the association evolves over time or which patient groups are most affected. We conducted a retrospective cohort study using a nationwide database of electronic health records to determine the risk of depressive or anxiety disorder diagnoses after SARS-CoV-2 infection by 3-month blocks from January 2020 to April 2022. The study population comprised 822,756 patients (51.8% female; mean age 42.8 years) with COVID-19 and 2,034,353 patients with other respiratory tract infections (RTIs) (53.5% female, mean age 30.6 years). First time diagnoses of depressive or anxiety disorders 14 days to 3 months after infection, as well as new or new plus recurrent prescriptions of antidepressants or anxiolytics, were compared between propensity score matched cohorts using Kaplan-Meier survival analysis, including hazard ratio (HR) and 95% confidence interval (CI). Risk of a new diagnosis or prescription was also stratified by age, sex, and race to better characterize which groups were most affected. In the first three months of the pandemic, patients infected with SARS-CoV-2 had significantly increased risk of depression or anxiety disorder diagnosis (HR 1.65 [95% CI, 1.30-2.08]). October 2021 to January 2022 (HR, 1.12 [95% CI, 1.06-1.18]) and January to April 2022 (HR, 1.08 [95% CI, 1.01-1.14]). Similar temporal patterns were observed for antidepressant and anxiolytic prescriptions, when the control group was patients with bone fracture, when anxiety and depressive disorders were considered separately, when recurrent depressive disorder was tested, and when the test period was extended to 6 months. COVID-19 patients ≥65 years old demonstrated greatest absolute risk at the start of the pandemic (6.8%), which remained consistently higher throughout the study period (HR, 1.20 [95% CI, 1.13-1.27]), and overall, women with COVID-19 had greater risk than men (HR 1.35 [95% CI 1.30-1.40]).

Association of semaglutide with reduced incidence and relapse of cannabis use disorder in real-world populations: a retrospective cohort study.

Cannabis is the most frequently used illicit drug in the United States with more than 45 million users of whom one-third suffer from a cannabis use disorder (CUD). Despite its high prevalence, there are currently no FDA-approved medications for CUD. Patients treated with semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA) approved for treating type 2 diabetes (T2D) and for weight management have reported reduced desire to drink and smoke. Preclinical studies have shown that semaglutide decreased nicotine and alcohol consumption. Preclinical and preliminary clinical evidence of semaglutide's potential beneficial effects on various substance use disorders led us to evaluate if it pertained to CUD. In this retrospective cohort study of electronic health records (EHRs) from the TriNetX Analytics Network, a global federated health research network of approximately 105.3 million patients from 61 large healthcare organizations in the US, we aimed to assess the associations of semaglutide with both incident and recurrent CUD diagnosis compared to non-GLP-1RA anti-obesity or anti-diabetes medications. Hazard ratio (HR) and 95% confidence intervals (CI) of incident and recurrent CUD were calculated for 12-month follow-up by comparing propensity-score matched patient cohorts. The study population included 85,223 patients with obesity who were prescribed semaglutide or non-GLP-1RA anti-obesity medications, with the findings replicated in 596,045 patients with T2D. In patients with obesity (mean age 51.3 years, 65.6% women), semaglutide compared with non-GLP-1RA anti-obesity medications was associated with lower risk for incident CUD in patients with no prior history CUD (HR: 0.56, 95% CI: 0.42-0.75), and recurrent CUD diagnosis in patients with a prior history CUD (HR: 0.62, 95% CI: 0.46-0.84). Consistent reductions were seen for patients stratified by gender, age group, race and in patients with and without T2D. Similar findings were replicated in the study population with T2D when comparing semaglutide with non-GLP-1RA anti-diabetes medications for incident CUD (HR: 0.40, 95% CI: 0.29-0.56) and recurrent CUD (HR: 0.66, 95% CI: 0.42-1.03). While these findings provide preliminary evidence of the potential benefit of semaglutide in CUD in real-world populations, further preclinical studies are warranted to understand the underlying mechanism and randomized clinical trials are needed to support its use clinically for CUD.

Association of COVID-19 with endocarditis in patients with cocaine or opioid use disorders in the US.

The incidence of endocarditis in the US is increasing, driven in part by the rise in intravenous drug use, mostly opioids and stimulant drugs (cocaine and methamphetamine). Recent reports have documented that individuals with COVID-19 are at increased risk for cardiovascular diseases. However, it is unknown whether COVID-19 is associated with increased risk for endocarditis in patients with opioid or stimulant use disorders. This is a retrospective cohort study based on a nationwide database of electronic health records (EHRs) of 109 million patients in the US, including 736,502 patients with a diagnosis of opioid use disorder (OUD) and 379,623 patients with a diagnosis of cocaine use disorder (CocaineUD). Since Metamphetamine use disorder is not coded we could not analyze it. We show that the incidence rate of endocarditis among patients with OUD or CocaineUD significantly increased from 2011 to 2022 with acceleration during 2021-2022. COVID-19 was associated with increased risk of new diagnosis of endocarditis among patients with OUD (HR: 2.23, 95% CI: 1.92-2.60) and with CocaineUD (HR: 2.24, 95% CI: 1.79-2.80). Clinically diagnosed COVID-19 was associated with higher risk of endocarditis than lab-test confirmed COVID-19 without clinical diagnosis. Hospitalization within 2 weeks following COVID-19 infection was associated with increased risk of new diagnosis of endocarditis. The risk for endocarditis did not differ between patients with and without EHR-recorded vaccination. There were significant racial and ethnic differences in the risk for COVID-19 associated endocarditis, lower in blacks than in whites and lower in Hispanics than in non-Hispanics. Among patients with OUD or CocaineUD, the 180-day hospitalization risk following endocarditis was 67.5% in patients with COVID-19, compared to 58.7% in matched patients without COVID-19 (HR: 1.21, 95% CI: 1.07-1.35). The 180-day mortality risk following the new diagnosis of endocarditis was 9.2% in patients with COVID-19, compared to 8.0% in matched patients without COVID-19 (HR: 1.16, 95% CI: 0.83-1.61). This study shows that COVID-19 is associated with significantly increased risk for endocarditis in patients with opioid or cocaine use disorders. These results highlight the need for endocarditis screening and for linkage to infectious disease and addiction treatment in patients with opioid or cocaine use disorders who contracted COVID-19. Future studies are needed to understand how COVID-19 damages the heart and the vascular endothelium among people who misuse opioids or cocaine (presumably also methamphetamines).

Comorbidity-driven multi-modal subtype analysis in mild cognitive impairment of Alzheimer's disease.

BACKGROUND: Mild cognitive impairment (MCI) is a heterogeneous condition with high individual variabilities in clinical outcomes driven by patient demographics, genetics, brain structure features, blood biomarkers, and comorbidities. Multi-modality data-driven approaches have been used to discover MCI subtypes; however, disease comorbidities have not been included as a modality though multiple diseases including hypertension are well-known risk factors for Alzheimer's disease (AD). The aim of this study was to examine MCI heterogeneity in the context of AD-related comorbidities along with other AD-relevant features and biomarkers. METHODS: A total of 325 MCI subjects with 32 AD-relevant comorbidities and features were considered. Mixed-data clustering is applied to discover and compare MCI subtypes with and without including AD-related comorbidities. Finally, the relevance of each comorbidity-driven subtype was determined by examining their MCI to AD disease prognosis, descriptive statistics, and conversion rates. RESULTS: We identified four (five) MCI subtypes: poor-, average-, good-, and best-AD prognosis by including comorbidities (without including comorbidities). We demonstrated that comorbidity-driven MCI subtypes differed from those identified without comorbidity information. We further demonstrated the clinical relevance of comorbidity-driven MCI subtypes. Among the four comorbidity-driven MCI subtypes there were substantial differences in the proportions of participants who reverted to normal function, remained stable, or converted to AD. The groups showed different behaviors, having significantly different MCI to AD prognosis, significantly different means for cognitive test-related and plasma features, and by the proportion of comorbidities. CONCLUSIONS: Our study indicates that AD comorbidities should be considered along with other diverse AD-relevant characteristics to better understand MCI heterogeneity.

COVID-19 breakthrough infections and hospitalizations among vaccinated patients with dementia in the United States between December 2020 and August 2021.

INTRODUCTION: There is lack of data on COVID-19 breakthrough infections in vaccinated patients with dementia in the United States. METHODS: This is a retrospective cohort study of 262,847 vaccinated older adults (age 73.8 ± 6.81 years old) between December 2020 and August 2021. RESULTS: Among the fully vaccinated patients with dementia, the overall risk of COVID-19 breakthrough infections ranged from 8.6% to 12.4%. Patients with dementia were at increased risk for breakthrough infections compared with patients without dementia, with the highest odds for patients with Lewy body dementia (LBD) (adjusted odds ratio or AOR: 3.06, 95% confidence interval or CI [1.45 to 6.66]), followed by vascular dementia (VD) (AOR: 1.99, 95% CI [1.42 to 2.80]), Alzheimer's disease (AD) (1.53, 95% CI [1.22 to 1.92]), and mild cognitive impairment (MCI) (AOR: 1.78, 95% CI [1.51 to 2.11]). The incidence rate of breakthrough infections among fully vaccinated patients with dementia increased since December 2020 and accelerated after May 2021. The overall risk for hospitalization after breakthrough infections in patients with dementia was 39.5% for AD, 46.2% for VD, and 30.4% for MCI. DISCUSSION: These results highlight the need to continuously monitor breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and outcomes in vaccinated patients with dementia.

Cardiac and mortality outcome differences between methadone, buprenorphine and naltrexone prescriptions in patients with an opioid use disorder.

IMPORTANCE: More than 109,000 Americans died of drug overdose in 2022, with 81,231 overdose deaths involving opioids. Methadone, buprenorphine and naltrexone are the most widely used medications for opioid use disorders (MOUD) and the most effective intervention for preventing overdose deaths. However, there is a concern that methadone results in long QT syndrome, which increases the risk for fatal cardiac arrythmias. Currently few studies have systematically evaluated both the short-term and long-term differences in cardiac and mortality outcomes between MOUD. OBJECTIVES: To compare the risks of cardiac arrythmias, long QT syndrome and overall mortality between patients with opioid use disorders (OUD) who were prescribed methadone, buprenorphine or naltrexone. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study based on a multicenter and nationwide database of electronic health records (EHRs) in the United States. The study population was comprised of 144,141 patients who had medical encounters for OUD in 2016-2022, were prescribed MOUD within 1 month following a medical encounter for OUD diagnosis and had no diagnosis of cardiac arrythmias or long QT syndrome before any MOUD prescription. The study population was divided into three cohorts: (1) Methadone cohort (n = 40,938)-who were only prescribed methadone. (2) Buprenorphine cohort (n = 80,055)-who were only prescribed buprenorphine. (3) Naltrexone cohort (n = 5,738)-who were only prescribed naltrexone. EXPOSURES: methadone, buprenorphine, or naltrexone. MAIN OUTCOMES AND MEASURES: Cardiac arrythmias, long QT syndrome, and death. Hazard ratio (HR) and 95% confidence interval (CI) of outcomes at six different follow-up time frames (1-month, 3-month, 6-month, 1-year, 3-year, and 5-year) by comparing propensity-score matched cohorts using Kaplan-Meier survival analysis. RESULTS: Patients with OUD who were prescribed methadone had significantly higher risks of cardiac arrhythmias, long QT syndrome and death compared with propensity-score matched patients with OUD who were prescribed buprenorphine or naltrexone. For the 1-month follow-up, the overall risk for cardiac arrythmias was 1.03% in the Methadone cohort, higher than the 0.87% in the matched Buprenorphine cohort (HR: 1.20, 95% CI: 1.04-1.39); The overall risk for long QT syndrome was 0.35% in the Methadone cohort, higher than the 0.15% in the matched Buprenorphine cohort (HR: 2.40, 95% CI: 1.75-3.28); The overall mortality was 0.59% in the Methadone cohort, higher than the 0.41% in the matched Buprenorphine cohort (HR: 1.48, 95% CI: 1.21-1.81). The increased risk persisted for 5 years: cardiac arrhythmias (HR: 1.31, 95% CI: 1.23-1.38), long QT syndrome (HR: 3.14, 95% CI: 2.76-3.58), death (HR: 1.50, 95% CI: 1.41-1.59). CONCLUSIONS AND RELEVANCE: Methadone was associated with a significantly higher risk for cardiac and mortality outcomes than buprenorphine and naltrexone. These findings are relevant to the development of guidelines for medication selection when initiating MOUD treatment and inform future medication development for OUD that minimizes risks while maximizing benefits.

Cardiovascular risk of gabapentin and pregabalin in patients with diabetic neuropathy.

BACKGROUND: Gabapentin and pregabalin are commonly prescribed medications to treat pain in patients with diabetic neuropathy. Gabapentin and pregabalin can cause fluid retention, which is hypothesized to be associated with cardiovascular diseases. However, whether long-term use of gabapentin and pregabalin is associated with adverse cardiovascular diseases remains unknown. This study aims to examine the association between gabapentin use, pregabalin use and several adverse cardiovascular events. METHODS: This retrospective cohort study used propensity score matching within patient electronic health records (EHRs) from a multicenter database with 106 million patients from 69 health care organizations in the US. The study population comprised 210,064 patients who had a diagnosis of diabetic neuropathy and were prescribed diabetic neuropathy medications in their EHRs. The exposure cohort comprised patients who were prescribed gabapentin or pregabalin to treat diabetic neuropathy. The comparison cohort comprised patients who were not prescribed either gabapentin or pregabalin but were prescribed other drugs to treat diabetic neuropathy. The outcomes of interest were myocardial infarcts, strokes, heart failure, peripheral vascular disease, and venous thromboembolic events. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for 3-month and 5-year risk for adverse cardiovascular events between the propensity score-matched cohorts. RESULTS: Both gabapentin and pregabalin were associated with increased risk of 5-year adverse cardiovascular events compared with the comparison group. In patients prescribed gabapentin, the highest risk was observed for deep venous thrombosis (HR: 1.58, 95% CI 1.37-1.82), followed by pulmonary embolism (HR: 1.5, 95% CI 1.27-1.76), peripheral vascular disease (HR: 1.37, 95% CI 1.27-1.47), stroke (HR: 1.31, 95% CI 1.2-1.43), myocardial infarction (HR: 1.25, 95% CI 1.14-1.38) and heart failure (HR: 1.14, 95% CI 1.07-1.21). In patients prescribed pregabalin, the highest risk was observed for deep venous thrombosis (HR: 1.57, 95% CI 1.31-1.88), followed by peripheral vascular disease (HR: 1.35, 95% CI 1.22-1.49), myocardial infarction (HR: 1.29, 95% CI 1.13-1.47), pulmonary embolism (HR: 1.28, 95% CI 1.04-1.59), stroke (HR: 1.26, 95% CI 1.12-1.42), and heart failure (HR: 1.2, 95% CI 1.11-1.3). There were significant associations between short-term (3 month) gabapentin use and heart failure, myocardial infarction, peripheral vascular disease, deep venous thrombosis, and pulmonary embolism. Short-term (3 month) pregabalin use was associated with deep venous thrombosis, peripheral vascular disease. CONCLUSION: In patients with diabetic neuropathy who were prescribed gabapentin and pregabalin, there is an increased risk for heart failure, myocardial infarction, peripheral vascular disease, stroke, deep venous thrombosis, and pulmonary embolism with long-term use. Our findings suggest that increased risk for adverse cardiovascular events, along with other side effects, the efficacy of pain control and the degree of tolerance of the patient, should be considered when prescribing gabapentin and pregabalin long-term in patients with diabetic neuropathy.

Potential long-term effect of tumor necrosis factor inhibitors on dementia risk: A propensity score matched retrospective cohort study in US veterans.

INTRODUCTION: Tumor necrosis factor (TNF) inhibitors are widely used to treat rheumatoid arthritis (RA) and their potential to retard Alzheimer's disease (AD) progression has been reported. However, their long-term effects on the dementia/AD risk remain unknown. METHODS: A propensity scored matched retrospective cohort study was conducted among 40,207 patients with RA within the US Veterans Affairs health-care system from 2000 to 2020. RESULTS: A total of 2510 patients with RA prescribed TNF inhibitors were 1:2 matched to control patients. TNF inhibitor use was associated with reduced dementia risk (hazard ratio [HR]: 0.64, 95% confidence interval [CI]: 0.52-0.80), which was consistent as the study period increased from 5 to 20 years after RA diagnosis. TNF inhibitor use also showed a long-term effect in reducing the risk of AD (HR: 0.57, 95% CI: 0.39-0.83) during the 20 years of follow-up. CONCLUSION: TNF inhibitor use is associated with lower long-term risk of dementia/AD among US veterans with RA.

COVID-19 and dementia: Analyses of risk, disparity, and outcomes from electronic health records in the US.

INTRODUCTION: At present, there is limited data on the risks, disparity, and outcomes for COVID-19 in patients with dementia in the United States. METHODS: This is a retrospective case-control analysis of patient electronic health records (EHRs) of 61.9 million adult and senior patients (age ≥ 18 years) in the United States up to August 21, 2020. RESULTS: Patients with dementia were at increased risk for COVID-19 compared to patients without dementia (adjusted odds ratio [AOR]: 2.00 [95% confidence interval (CI), 1.94-2.06], P < .001), with the strongest effect for vascular dementia (AOR: 3.17 [95% CI, 2.97-3.37], P < .001), followed by presenile dementia (AOR: 2.62 [95% CI, 2.28-3.00], P < .001), Alzheimer's disease (AOR: 1.86 [95% CI, 1.77-1.96], P < .001), senile dementia (AOR: 1.99 [95% CI, 1.86-2.13], P < .001) and post-traumatic dementia (AOR: 1.67 [95% CI, 1.51-1.86] P < .001). Blacks with dementia had higher risk of COVID-19 than Whites (AOR: 2.86 [95% CI, 2.67-3.06], P < .001). The 6-month mortality and hospitalization risks in patients with dementia and COVID-19 were 20.99% and 59.26%, respectively. DISCUSSION: These findings highlight the need to protect patients with dementia as part of the strategy to control the COVID-19 pandemic.

Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population.

Alcohol use disorders are among the top causes of the global burden of disease, yet therapeutic interventions are limited. Reduced desire to drink in patients treated with semaglutide has raised interest regarding its potential therapeutic benefits for alcohol use disorders. In this retrospective cohort study of electronic health records of 83,825 patients with obesity, we show that semaglutide compared with other anti-obesity medications is associated with a 50%-56% lower risk for both the incidence and recurrence of alcohol use disorder for a 12-month follow-up period. Consistent reductions were seen for patients stratified by gender, age group, race and in patients with and without type 2 diabetes. Similar findings are replicated in the study population with 598,803 patients with type 2 diabetes. These findings provide evidence of the potential benefit of semaglutide in AUD in real-world populations and call for further randomized clinicl trials.

Association of semaglutide with risk of suicidal ideation in a real-world cohort.

Concerns over reports of suicidal ideation associated with semaglutide treatment, a glucagon-like peptide 1 receptor (GLP1R) agonist medication for type 2 diabetes (T2DM) and obesity, has led to investigations by European regulatory agencies. In this retrospective cohort study of electronic health records from the TriNetX Analytics Network, we aimed to assess the associations of semaglutide with suicidal ideation compared to non-GLP1R agonist anti-obesity or anti-diabetes medications. The hazard ratios (HRs) and 95% confidence intervals (CIs) of incident and recurrent suicidal ideation were calculated for the 6-month follow-up by comparing propensity score-matched patient groups. The study population included 240,618 patients with overweight or obesity who were prescribed semaglutide or non-GLP1R agonist anti-obesity medications, with the findings replicated in 1,589,855 patients with T2DM. In patients with overweight or obesity (mean age 50.1 years, 72.6% female), semaglutide compared with non-GLP1R agonist anti-obesity medications was associated with lower risk for incident (HR = 0.27, 95% CI = 0.200.32-0.600.36) and recurrent (HR = 0.44, 95% CI = 0.32-0.60) suicidal ideation, consistent across sex, age and ethnicity stratification. Similar findings were replicated in patients with T2DM (mean age 57.5 years, 49.2% female). Our findings do not support higher risks of suicidal ideation with semaglutide compared with non-GLP1R agonist anti-obesity or anti-diabetes medications.

Liver abnormalities following SARS-CoV-2 infection in children 1 to 10 years of age.

OBJECTIVE: Beginning in October 2021 in the USA and elsewhere, cases of severe paediatric hepatitis of unknown aetiology were identified in young children. While the adenovirus and adenovirus-associated virus have emerged as leading aetiological suspects, we attempted to investigate a potential role for SARS-CoV-2 in the development of subsequent liver abnormalities. DESIGN: We conducted a study using retrospective cohorts of deidentified, aggregated data from the electronic health records of over 100 million patients contributed by US healthcare organisations. RESULTS: Compared with propensity score matched children with other respiratory infections, children aged 1-10 years with COVID-19 had a higher risk of elevated transaminases (HR (95% CI) 2.16 (1.74 to 2.69)) or total bilirubin (HR (95% CI) 3.02 (1.91 to 4.78)), or new diagnoses of liver diseases (HR (95% CI) 1.67 (1.21 to 2.30)) from 1 to 6 months after infection. Patients with pre-existing liver abnormalities, liver abnormalities surrounding acute infection, younger age (1-4 years) or illness requiring hospitalisation all had similarly elevated risk. Children who developed liver abnormalities following COVID-19 had more pre-existing conditions than those who developed abnormalities following other infections. CONCLUSION: These results indicate that SARS-CoV-2 may prime the patient for subsequent development of liver infections or non-infectious liver diseases. While rare (~1 in 1000), SARS-CoV-2 is a risk for subsequent abnormalities in liver function or the diagnosis of diseases of the liver.

Sex-Specific Heterogeneity of Mild Cognitive Impairment Identified Based on Multi-Modal Data Analysis.

BACKGROUND: Mild cognitive impairment (MCI), a prodromal phase of Alzheimer's disease (AD), is heterogeneous with different rates and risks of progression to AD. There are significant gender disparities in the susceptibility, prognosis, and outcomes in patients with MCI, with female being disproportionately negatively impacted. OBJECTIVE: The aim of this study was to identify sex-specific heterogeneity of MCI using multi-modality data and examine the differences in the respective MCI subtypes with different prognostic outcomes or different risks for MCI to AD conversion. METHODS: A total of 325 MCI subjects (146 women, 179 men) and 30 relevant features were considered. Mixed-data clustering was applied to women and men separately to discover gender-specific MCI subtypes. Gender differences were compared in the respective subtypes of MCI by examining their MCI to AD disease prognosis, descriptive statistics, and conversion rates. RESULTS: We identified three MCI subtypes: poor-, good-, and best-prognosis for women and for men, separately. The subtype-wise comparison (for example, poor-prognosis subtype in women versus poor-prognosis subtype in men) showed significantly different means for brain volumetric, cognitive test-related, also for the proportion of comorbidities. Also, there were substantial gender differences in the proportions of participants who reverted to normal function, remained stable, or converted to AD. CONCLUSION: Analyzing sex-specific heterogeneity of MCI offers the opportunity to advance the understanding of the pathophysiology of both MCI and AD, allows stratification of risk in clinical trials of interventions, and suggests gender-based early intervention with targeted treatment for patients at risk of developing AD.

Ischemic stroke after COVID-19 bivalent vaccine administration in patients aged 65 years and older: analysis of nation-wide patient electronic health records in the United States.

Importance: The Centers for Disease Control and Prevention (CDC) announced in January 2023 that they were investigating a potential connection between administration of the Pfizer novel coronavirus disease-2019 (COVID-19) bivalent vaccine booster and ischemic stroke (IS). Objective: To explore the relationship between Pfizer bivalent booster administration and IS in older patients in the United States and compare it to other COVID-19 vaccines. Design: A retrospective cohort study was conducted to compare hazard of IS among patients aged 65 years or over who received the Pfizer bivalent, Moderna bivalent, or Pfizer/Moderna monovalent COVID-19 booster vaccine 1-21 and 22-42 days after vaccination. Setting: Patient data were collected from TriNetX, a cloud-based analytics platform that includes electronic health record data from over 90 million unique patients in the United States. Participants: Patients in the United States aged 65 years or over at the time of administration of a Pfizer bivalent (n = 43,216), Moderna bivalent (n = 4,267), or Pfizer/Moderna monovalent (n = 100,583) booster were included for analysis. Cohorts were propensity-score matched by demographic factors and risk factors for IS and severe COVID-19. Exposures: Pfizer bivalent, Moderna bivalent, or Pfizer/Moderna monovalent COVID-19 booster administration. Main outcomes: The hazard ratio (HR) and 95% confidence interval (CI) for IS in the cohorts at 1-21 and 22-42 days after administration. Results: After matching, the Pfizer bivalent cohort included 4,267 patients, with an average age of 73.7 years (44.43% male, 76.59% white). The Moderna bivalent cohort included 4,267 patients, with an average age of 74.0 years (44.08% male, 77.39% white). There was no significant difference in the hazard of IS encounters between the Pfizer bivalent versus Moderna bivalent cohorts at 1-21- or 22-42-days post-administration: HR = 0.59 (0.31, 1.11), 0.73 (0.33, 1.60). The hazard for IS was lower in the Pfizer bivalent cohort than in the Pfizer/Moderna monovalent cohort at both timepoints: HR = 0.24 (0.19, 0.29), 0.25 (0.20, 0.31). Conclusions and relevance: Older adults administered the Pfizer bivalent booster had similar hazard for IS encounters compared to those administered the Moderna bivalent booster vaccine, but lower hazard than those administered the Pfizer/Moderna monovalent boosters.

Ischemic stroke after COVID-19 bivalent vaccine administration in patients aged 65 years and older in the United States.

The Centers for Disease Control and Prevention announced in January 2023 a potential connection between administration of the Pfizer novel coronavirus disease-2019 (COVID-19) bivalent vaccine booster and ischemic stroke (IS). A retrospective cohort study was conducted to compare the hazard of IS in patients aged 65 years and over administered the Pfizer bivalent booster versus those administered the Pfizer/Moderna monovalent or Moderna bivalent boosters. De-identified patient electronic health data were collected from TriNetX, a cloud-based analytics platform that includes data from over 90 million unique patients in the United States. Patients aged 65 years and over at the time of administration of a Pfizer bivalent, Moderna bivalent, or Pfizer/Moderna monovalent booster were included for analysis. Cohorts were propensity-score matched. The hazard ratios (HR) and 95% confidence intervals (CI) for IS between matched cohorts at 1-21 and 22-42 days after booster administration were calculated. There was reduced hazard of IS in the Pfizer bivalent cohort compared to the monovalent cohort at both timepoints: 1-21 days after vaccination (HR: 0.54, 95% CI: 0.47-0.62), and 22-42 days after vaccination (HR: 0.62, 95% CI: 0.54-0.72) (n = 79,036 patients per cohort). There was reduced hazard of IS in the Pfizer bivalent cohort compared to the Moderna bivalent cohort at 1-21 days after vaccination (HR: 0.75, 95% CI: 0.58-0.96) (n = 26,962 patients per cohort). This analysis provides no evidence that the Pfizer bivalent vaccine is associated with increased hazard of IS compared to the monovalent or Moderna bivalent vaccines.