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.

Breakthrough SARS-CoV-2 Infections, Hospitalizations, and Mortality in Vaccinated Patients With Cancer in the US Between December 2020 and November 2021.

Importance: Limited data have been presented to examine breakthrough SARS-CoV-2 infections, hospitalizations, and mortality in vaccinated patients with cancer in the US. Objectives: To examine the risk of breakthrough SARS-CoV-2 infection, hospitalizations, and mortality in vaccinated patients with cancer between December 2020 and November 2021. Design, Setting, and Participants: Retrospective cohort study of electronic health records (EHRs) of vaccinated patients from a multicenter and nationwide database in the US during the period of December 2020 through November 2021. The study population comprised patients who had documented evidence of vaccination (2 doses of Moderna or Pfizer-BioNTech or single dose of Janssen/Johnson & Johnson vaccines) in their EHRs from December 2020 to November 2021 and had no SARS-CoV-2 infection prior to vaccination. Exposures: The 12 most common cancers combined and separately; recent vs no recent encounter for cancer; and breakthrough SARS-CoV-2 infection. Main Outcomes and Measures: Time trends of incidence proportions of breakthrough SARS-CoV-2 infections from December 2020 to November 2021 in vaccinated patients with all cancer; cumulative risks of breakthrough infections in vaccinated patients for all cancer and 12 common cancer types; hazard ratios (HRs) and 95% CIs of breakthrough infections between propensity score-matched patients with vs without cancer and between propensity score-matched patients with cancer who had a recent medical encounter for cancer vs those who did not; overall risks, HRs, and 95% CIs of hospitalizations and mortality in patients with cancer who had breakthrough infections vs those who did not. Results: Among 45 253 vaccinated patients with cancer (mean [SD] age, 68.7 [12.4] years), 53.5% were female, 3.8% were Asian individuals, 15.4% were Black individuals, 4.9% were Hispanic individuals, and 74.1% were White individuals. Breakthrough SARS-CoV-2 infections in patients with cancer increased from December 2020 to November 2021 and reached 52.1 new cases per 1000 persons in November 2021. The cumulative risk of breakthrough infections in patients with all cancer was 13.6%, with highest risk for pancreatic (24.7%), liver (22.8%), lung (20.4%), and colorectal (17.5%) cancers, and lowest risk for thyroid (10.3%), endometrial (11.9%), and breast (11.9%) cancers, vs 4.9% in the noncancer population (P < .001). Patients with cancer had significantly increased risk for breakthrough infections vs patients without cancer (HR, 1.24; 95% CI, 1.19-1.29), with greatest risk for liver (HR, 1.78; 95% CI, 1.38-2.29), lung (HR, 1.73; 95% CI, 1.50-1.99), pancreatic (HR, 1.64; 95% CI, 1.24-2.18), and colorectal (HR, 1.53; 95% CI, 1.32-1.77) cancers and lowest risk for thyroid (HR, 1.07; 95% CI, 0.88-1.30) and skin (HR, 1.17; 95% CI, 0.99-1.38) cancers. Patients who had medical encounters for cancer within the past year had higher risk for breakthrough infections than those who did not (HR, 1.24; 95% CI, 1.18-1.31). Among patients with cancer, the overall risk for hospitalizations and mortality was 31.6% and 3.9%, respectively, in patients with breakthrough infections, vs 6.7% and 1.3% in those without breakthrough infections (HR for hospitalization: 13.48; 95% CI, 11.42-15.91; HR for mortality: 6.76; 95% CI, 4.97-9.20). Conclusions and Relevance: This cohort study showed significantly increased risks for breakthrough infection in vaccinated patients with cancer, especially those undergoing active cancer care, with marked heterogeneity among specific cancer types. Breakthrough infections in patients with cancer were associated with significant and substantial risks for 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.

Sustaining Student Engagement - Successes and Challenges of a Virtual STEM Program for High School Students.

Case Western Reserve University's School of Medicine and Comprehensive Cancer Center coordinate in-depth research immersion STEM programs to engage high school students in biomedical research and encourage pursuit of careers in health-related research and clinical care. Due to COVID-19, the 2020 programs were delivered entirely virtually. Student and faculty perceptions of the virtual experience were evaluated using surveys and focus groups. Ninety percent of students felt the virtual program met expectations. Student rankings for programmatic components that could remain virtual in future years showed a preference for highly interactive activities, especially mentorship and dialogue-based activities like discussions of science in the news. Ninety-seven percent of faculty agreed students' scientific knowledge improved. Faculty commented that certain research projects (e.g., data analysis, literature reviews) were highly appropriate for a virtual program, but that the lack of hands-on laboratory activities was challenging. Increased individual attention, flexibility, and independence were hailed as strengths of the virtual program. These findings identify activities that sustain student interest in biomedical, healthcare, and cancer related research using a virtual medium and indicate mentorship and interactive discussion-based activities enhance virtual education. Moreover, the results support incorporation of interactive online pedagogical approaches to enhance student engagement virtually and in-person.

Analyses of Risk, Racial Disparity, and Outcomes Among US Patients With Cancer and COVID-19 Infection.

Importance: Patients with specific cancers may be at higher risk than those without cancer for coronavirus disease 2019 (COVID-19) and its severe outcomes. At present, limited data are available on the risk, racial disparity, and outcomes for COVID-19 illness in patients with cancer. Objectives: To investigate how patients with specific types of cancer are at risk for COVID-19 infection and its adverse outcomes and whether there are cancer-specific race disparities for COVID-19 infection. Design, Setting, and Participants: This retrospective case-control analysis of patient electronic health records included 73.4 million patients from 360 hospitals and 317 000 clinicians across 50 US states to August 14, 2020. The odds of COVID-19 infections for 13 common cancer types and adverse outcomes were assessed. Exposures: The exposure groups were patients diagnosed with a specific cancer, whereas the unexposed groups were patients without the specific cancer. Main Outcomes and Measures: The adjusted odds ratio (aOR) and 95% CI were estimated using the Cochran-Mantel-Haenszel test for the risk of COVID-19 infection. Results: Among the 73.4 million patients included in the analysis (53.6% female), 2 523 920 had at least 1 of the 13 common cancers diagnosed (all cancer diagnosed within or before the last year), and 273 140 had recent cancer (cancer diagnosed within the last year). Among 16 570 patients diagnosed with COVID-19, 1200 had a cancer diagnosis and 690 had a recent cancer diagnosis of at least 1 of the 13 common cancers. Those with recent cancer diagnosis were at significantly increased risk for COVID-19 infection (aOR, 7.14 [95% CI, 6.91-7.39]; P < .001), with the strongest association for recently diagnosed leukemia (aOR, 12.16 [95% CI, 11.03-13.40]; P < .001), non-Hodgkin lymphoma (aOR, 8.54 [95% CI, 7.80-9.36]; P < .001), and lung cancer (aOR, 7.66 [95% CI, 7.07-8.29]; P < .001) and weakest for thyroid cancer (aOR, 3.10 [95% CI, 2.47-3.87]; P < .001). Among patients with recent cancer diagnosis, African Americans had a significantly higher risk for COVID-19 infection than White patients; this racial disparity was largest for breast cancer (aOR, 5.44 [95% CI, 4.69-6.31]; P < .001), followed by prostate cancer (aOR, 5.10 [95% CI, 4.34-5.98]; P < .001), colorectal cancer (aOR, 3.30 [95% CI, 2.55-4.26]; P < .001), and lung cancer (aOR, 2.53 [95% CI, 2.10-3.06]; P < .001). Patients with cancer and COVID-19 had significantly worse outcomes (hospitalization, 47.46%; death, 14.93%) than patients with COVID-19 without cancer (hospitalization, 24.26%; death, 5.26%) (P < .001) and patients with cancer without COVID-19 (hospitalization, 12.39%; death, 4.03%) (P < .001). Conclusions and Relevance: In this case-control study, patients with cancer were at significantly increased risk for COVID-19 infection and worse outcomes, which was further exacerbated among African Americans. These findings highlight the need to protect and monitor patients with cancer as part of the strategy to control the pandemic.

When hematologic malignancies meet COVID-19 in the United States: Infections, death and disparities.

Scientific data is limited on the risks, adverse outcomes and racial disparities for COVID-19 illness in individuals with hematologic malignancies in the United States. To fill this void, we screened and analyzed a nation-wide database of patient electronic health records (EHRs) of 73 million patients in the US (up to September 1st) for COVID-19 and eight major types of hematologic malignancies. Patients with hematologic malignancies had increased odds of COVID-19 infection compared with patients without hematologic malignancies for both all-time diagnosis (malignancy diagnosed in the past year or prior) (adjusted Odds ratio or AOR: 2.27 [2.17-2.36], p < 0.001) and recent diagnosis (malignancy diagnosed in the past year) (AOR:11.91 [11.31-12.53], p < 0.001), with strongest effect for recently diagnosed acute lymphoid leukemia (AOR: 31.03 [25.87-37.27], p < 0.001), essential thrombocythemia (AOR: 20.65 [19.10-22.32], p < 0.001), acute myeloid leukemia (AOR: 18.94 [15.79-22.73], p < 0.001), multiple myeloma (AOR: 14.21 [12.72-15.89], p < 0.001). Among patients with hematologic malignancies, African Americans had higher odds of COVID-19 infection than Caucasians with largest racial disparity for multiple myeloma (AOR: 4.23 [3.21-5.56], p < 0.001). Patients with recently diagnosed hematologic malignancies had worse outcomes (hospitalization: 51.9%, death: 14.8%) than COVID-19 patients without hematologic malignancies (hospitalization: 23.5%, death: 5.1%) (p < 0.001) and hematologic malignancy patients without COVID-19 (hospitalization: 15.0%, death: 4.1%) (p < 0.001).