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.

Association of COVID-19 with New-Onset Alzheimer's Disease.

An infectious etiology of Alzheimer's disease has been postulated for decades. It remains unknown whether SARS-CoV-2 viral infection is associated with increased risk for Alzheimer's disease. In this retrospective cohort study of 6,245,282 older adults (age ≥65 years) who had medical encounters between 2/2020-5/2021, we show that people with COVID-19 were at significantly increased risk for new diagnosis of Alzheimer's disease within 360 days after the initial COVID-19 diagnosis (hazard ratio or HR:1.69, 95% CI: 1.53-1.72), especially in people age ≥85 years and in women. Our findings call for research to understand the underlying mechanisms and for continuous surveillance of long-term impacts of COVID-19 on Alzheimer's disease.

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).

SARS-CoV-2 primary and breakthrough infections in patients with cancer: Implications for patient care.

Initial reports of SARS-CoV-2 caused COVID-19 suggested that patients with malignant diseases were at increased risk for infection and its severe consequences. In order to provide early United States population-based assessments of SARS-CoV-2 primary infections in unvaccinated patients with hematologic malignancies or cancer, and SARS-CoV-2 breakthrough infections in vaccinated patients with hematologic malignancies or cancer, we conducted retrospective studies using two, unique nationwide electronic health records (EHR) databases. Using these massive databases to provide highly statistically significant data, our studies demonstrated that, compared to patients without malignancies, risk for COVID-19 was increased in patients with all cancers and with all hematologic malignancies. Risks varied with specific types of malignancy. Patients with hematologic malignancies or cancer were at greatest risk for COVID-19 during the first year after diagnosis. Risk for infection was increased for patients 65 years and older, compared to younger patients and among Black patients compared to white patients. When patients with hematologic malignancies or cancer were vaccinated against SARS-CoV-2, their risk for breakthrough infections was decreased relative to primary infections but remained elevated relative to vaccinated patients without malignancies. Compared to vaccinated patients without malignancies, vaccinated patients with hematologic malignancy or cancer showed increased risk for infection at earlier post vaccination time points. As with primary infections, risk for breakthrough infections was greatest in patients during their first year of hematologic malignancy or cancer. There were no signs of racial disparities among vaccinated patients with hematologic malignancies or cancer. These results provide the population basis to understand the significance of subsequent immunologic studies showing relative defective and delayed immunoresponsiveness to SARS-CoV-2 vaccines among patients with hematologic malignancies and cancers. These studies further provide the basis for recommendations regarding COVID-19 vaccination, vigilance and maintaining mitigation strategies in patients with hematologic malignancies and cancers.

SARS-CoV-2 primary and breakthrough infections in patients with cancer: Implications for patient care

Initial reports of SARS-CoV-2 caused COVID-19 suggested that patients with malignant diseases were at increased risk for infection and its severe consequences. In order to provide early United States population-based assessments of SARS-CoV-2 primary infections in unvaccinated patients with hematologic malignancies or cancer, and SARS-CoV-2 breakthrough infections in vaccinated patients with hematologic malignancies or cancer, we conducted retrospective studies using two, unique nationwide electronic health records (EHR) databases. Using these massive databases to provide highly statistically significant data, our studies demonstrated that, compared to patients without malignancies, risk for COVID-19 was increased in patients with all cancers and with all hematologic malignancies. Risks varied with specific types of malignancy. Patients with hematologic malignancies or cancer were at greatest risk for COVID-19 during the first year after diagnosis. Risk for infection was increased for patients 65 years and older, compared to younger patients and among Black patients compared to white patients. When patients with hematologic malignancies or cancer were vaccinated against SARS-CoV-2, their risk for breakthrough infections was decreased relative to primary infections but remained elevated relative to vaccinated patients without malignancies. Compared to vaccinated patients without malignancies, vaccinated patients with hematologic malignancy or cancer showed increased risk for infection at earlier post vaccination time points. As with primary infections, risk for breakthrough infections was greatest in patients during their first year of hematologic malignancy or cancer. There were no signs of racial disparities among vaccinated patients with hematologic malignancies or cancer. These results provide the population basis to understand the significance of subsequent immunologic studies showing relative defective and delayed immunoresponsiveness to SARS-CoV-2 vaccines among patients with hematologic malignancies and cancers. These studies further provide the basis for recommendations regarding COVID-19 vaccination, vigilance and maintaining mitigation strategies in patients with hematologic malignancies and cancers.

COVID-19 breakthrough infections, hospitalizations and mortality in fully vaccinated patients with hematologic malignancies: A clarion call for maintaining mitigation and ramping-up research.

There has been limited data presented to characterize and quantify breakthrough SARS-CoV-2 infections, hospitalizations, and mortality in vaccinated patients with hematologic malignancies (HM). We performed a retrospective cohort study of patient electronic health records of 514,413 fully vaccinated patients from 63 healthcare organizations in the US, including 5956 with HM and 508,457 without malignancies during the period from December 2020 to October 2021. The breakthrough SARS-CoV-2 infections in patients with HM steadily increased and reached 67.7 cases per 1000 persons in October 2021. The cumulative risk of breakthrough infections during the period in patients with HM was 13.4%, ranging from 11.0% for acute lymphocytic leukemia to 17.2% and 17.4% for multiple myeloma and chronic myeloid leukemia respectively, all higher than the risk of 4.5% in patients without malignancies (p < 0.001). No significant racial disparities in breakthrough infections were observed. The overall hospitalization risk was 37.8% for patients with HM who had breakthrough infections, significantly higher than 2.2% for those who had no breakthrough infections (hazard ratio or HR: 34.49, 95% CI: 25.93-45.87). The overall mortality risk was 5.7% for patients with HM who had breakthrough infections, significantly higher than the 0.8% for those who had no breakthrough infections (HR: 10.25, 95% CI: 5.94-17.69). In summary, this study shows that among the fully vaccinated population, patients with HM had significantly higher risk for breakthrough infections compared to patients without cancer and that breakthrough infections in patients with HM were associated with significant clinical outcomes including hospitalizations and mortality.

COVID-19 breakthrough infections, hospitalizations and mortality in fully vaccinated patients with hematologic malignancies: A clarion call for maintaining mitigation and ramping-up research

There has been limited data presented to characterize and quantify breakthrough SARS-CoV-2 infections, hospitalizations, and mortality in vaccinated patients with hematologic malignancies (HM). We performed a retrospective cohort study of patient electronic health records of 514,413 fully vaccinated patients from 63 healthcare organizations in the US, including 5956 with HM and 508,457 without malignancies during the period from December 2020 to October 2021. The breakthrough SARS-CoV-2 infections in patients with HM steadily increased and reached 67.7 cases per 1000 persons in October 2021. The cumulative risk of breakthrough infections during the period in patients with HM was 13.4%, ranging from 11.0% for acute lymphocytic leukemia to 17.2% and 17.4% for multiple myeloma and chronic myeloid leukemia respectively, all higher than the risk of 4.5% in patients without malignancies (p < 0.001). No significant racial disparities in breakthrough infections were observed. The overall hospitalization risk was 37.8% for patients with HM who had breakthrough infections, significantly higher than 2.2% for those who had no breakthrough infections (hazard ratio or HR: 34.49, 95% CI: 25.93–45.87). The overall mortality risk was 5.7% for patients with HM who had breakthrough infections, significantly higher than the 0.8% for those who had no breakthrough infections (HR: 10.25, 95% CI: 5.94–17.69). In summary, this study shows that among the fully vaccinated population, patients with HM had significantly higher risk for breakthrough infections compared to patients without cancer and that breakthrough infections in patients with HM were associated with significant clinical outcomes including hospitalizations and mortality.

Increased risk for COVID-19 breakthrough infection in fully vaccinated patients with substance use disorders in the United States between December 2020 and August 2021.

Individuals with substance use disorders (SUDs) are at increased risk for COVID-19 infection and for adverse outcomes of the infection. Though vaccines are highly effective against COVID-19, their effectiveness in individuals with SUDs might be curtailed by compromised immune status and a greater likelihood of exposures, added to the waning vaccine immunity and the new SARS-CoV-2 variants. In a population-based cohort study, we assessed the risk, time trends, outcomes and disparities of COVID-19 breakthrough infection in fully vaccinated SUD patients starting 14 days after completion of vaccination. The study included 579,372 individuals (30,183 with a diagnosis of SUD and 549,189 without such a diagnosis) who were fully vaccinated between December 2020 and August 2021, and had not contracted COVID-19 infection prior to vaccination. We used the TriNetX Analytics network platform to access de-identified electronic health records from 63 health care organizations in the US. Among SUD patients, the risk for breakthrough infection ranged from 6.8% for tobacco use disorder to 7.8% for cannabis use disorder, all significantly higher than the 3.6% in non-SUD population (p<0.001). Breakthrough infection risk remained significantly higher after controlling for demographics (age, gender, ethnicity) and vaccine types for all SUD subtypes, except for tobacco use disorder, and was highest for cocaine and cannabis use disorders (hazard ratio, HR=2.06, 95% CI: 1.30-3.25 for cocaine; HR=1.92, 95% CI: 1.39-2.66 for cannabis). When we matched SUD and non-SUD individuals for lifetime comorbidities and adverse socioeconomic determinants of health, the risk for breakthrough infection no longer differed between these populations, except for patients with cannabis use disorder, who remained at increased risk (HR=1.55, 95% CI: 1.22-1.99). The risk for breakthrough infection was higher in SUD patients who received the Pfizer than the Moderna vaccine (HR=1.49, 95% CI: 1.31-1.69). In the vaccinated SUD population, the risk for hospitalization was 22.5% for the breakthrough cohort and 1.6% for the non-breakthrough cohort (risk ratio, RR=14.4, 95% CI: 10.19-20.42), while the risk for death was 1.7% and 0.5% respectively (RR=3.5, 95% CI: 1.74-7.05). No significant age, gender and ethnic disparities for breakthrough infection were observed in vaccinated SUD patients. These data suggest that fully vaccinated SUD individuals are at higher risk for breakthrough COVID-19 infection, and this is largely due to their higher prevalence of comorbidities and adverse socioeconomic determinants of health compared with non-SUD individuals. The high frequency of comorbidities in SUD patients is also likely to contribute to their high rates of hospitalization and death following breakthrough infection.