Safety and Efficacy of Intramuscular Tixagevimab-Cilgavimab in Prevention of COVID-19 in Patients Who Are Immunocompromised.

INTRODUCTION: Patients who are immunocompromised face an increased chance of severe COVID-19 infection compared with patients who are immunocompetent. However, vaccine efficacy for COVID-19 appears to be lower in patients who are immunocompromised. Tixagevimab-cilgavimab are monoclonal antibodies designed to enhance immune defense against COVID-19. Nevertheless, the safety and efficacy of tixagevimab-cilgavimab specifically in patients who are immunocompromised remains unknown. METHODS: The authors conducted a retrospective case study of patients who were immunocompromised and received tixagevimab-cilgavimab between January 3, 2022 to July 31, 2022 at Kaiser Permanente Southern California. All patients were monitored for 180 days following tixagevimab-cilgavimab administration. Patients who were immunocompromised included those with solid tumors, hematologic malignancies, primary immunodeficiencies, recipients of solid organ or hematopoietic stem cell transplants, and patients undergoing treatment with immunosuppressive medications (eg, chemotherapy, high-dose corticosteroids, tumor necrosis factor blockers, and certain biologic agents). RESULTS: A total of 2352 patients who were immunocompromised were included in the study. Among them, 101 patients (4.3%) tested positive for COVID-19, and 13 patients (0.6%) required COVID-19-related hospital admissions. Notably, no deaths were reported within 180 days following tixagevimab-cilgavimab administration. Additionally, 4 patients (0.17%) sought same-day medical care after receiving tixagevimab-cilgavimab. Within 30 days, there were 39 non-COVID-19-related hospital admissions (1.7%) and within 7 days, 11 hospital admissions (0.5%) occurred after tixagevimab-cilgavimab administration. DISCUSSION: Tixagevimab-cilgavimab demonstrated a low incidence of COVID-19 and COVID-19-related hospital admissions in patients who were immunocompromised, with no reported mortality. Furthermore, there were no significant adverse effects associated with the use of these monoclonal antibodies. CONCLUSION: Tixagevimab-cilgavimab exhibited a low incidence of COVID-19 and adverse effects in patients who were immunocompromised.

Incidence, Risk Factors, and Outcomes of COVID-19 Infection in a Large Cohort of Solid Organ Transplant Recipients.

BACKGROUND: Solid organ transplant recipients (SOTr) are at increased risk for severe disease from coronavirus disease 2019 (COVID-19) compared with non-SOTr. METHODS: We performed a retrospective cohort study between March 1, 2020, and March, 30, 2021, in an integrated healthcare system with 4.3 million members aged ≥18 y including 5126 SOTr. Comparisons in COVID-19 mortality, hospitalization, and incidence were made between SOTr and non-SOTr, and between different SOTr organs. Multivariate analysis was performed to identify risk factors for COVID-19 mortality and hospitalization. RESULTS: There were 600 SOTr (kidney, liver, heart, and lung) with COVID-19. Per person-year incidence of COVID-19 among SOTr was 10.0% versus 7.6% among non-SOTr (P < 0.0001). Compared with uninfected SOTr, infected SOTr were older (57.1 ± 14.0 versus 45.7 ± 17.9 y, P < 0.001), predominantly Hispanic/Latino (58.8% versus 38.6%, P < 0.0001), hypertensive (77.0% versus 23.8%; P < 0.0001), and diabetic (49.6% versus 13.0%; P = 0.0009). Compared with non-SOTr, infected SOTr had higher hospitalization (39.5% versus 6.0%; P < 0.0001), intensive care unit admission (29.1% versus 15.5%; P < 0.0001), and mortality (14.7% versus 1.8%; P < 0.0001) from COVID-19. Older age (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.05-1.10), male gender (HR, 1.79; 95% CI, 1.11-2.86), and higher body mass index (HR, 1.04; 95% CI, 1.00-1.09; P = 0.047) were associated with increased mortality from COVID-19, whereas race, diabetes, and number/type of immunosuppressive medications were not. Among the different SOTr, COVID-19 mortality risk was lowest in liver recipients (HR, 0.34; 95% CI, 0.16-0.73) and highest in lung recipients (HR, 1.74; 95% CI, 0.68-4.42). CONCLUSIONS: SOTr have higher rates of hospitalization and mortality from COVID-19 compared with the general population. Among the SOTr, the incidence and outcomes were distinct among different transplantation types.

Prevalence and Characteristics of Chronic Hepatitis C Among Asian Americans Are Distinct From Other Ethnic Groups.

GOAL: The goal of this study was to determine the prevalence and characteristics of chronic hepatitis C (CHC) among Asian Americans compared with other ethnicities. BACKGROUND: Chronic hepatitis C virus (HCV) affects an estimated 2.7 million in the United States, but there are limited data on HCV among Asian Americans. STUDY: A total of 3,369,881 adults over the age of 18 who were patients of the integrated health care system in Southern California and 4903 Asian participants at community hepatitis screenings were included in a cross-sectional study. Variables included HCV serology, HCV genotype, comorbidities, and coinfections. RESULTS: The prevalence of CHC was 1.3% in the general population (8271 adults) and 0.6% among Asians. The prevalence of CHC was significantly higher in the 1945-1965 birth cohort with 2.7% (5876) in the general population and 1.0% (313) among Asians (P<0.001). Asians had the highest rates of hepatitis B coinfection (2.9% vs. 0.2%, P<0.001). The distribution of genotypes among Asians differed from the general population with the most common genotype being 1b (27.5%) and a higher presence of genotype 6 (9.5%) (P<0.001). The presence of cirrhosis was 17.6% in Asians. Disaggregated Asian data showed that CHC was highest among Vietnamese and Cambodian and that genotype 6 was predominant among these 2 subgroups. CONCLUSIONS: The prevalence of chronic HCV was significantly lower in Asians compared with other ethnicities. However, disaggregated data among Asians showed the highest prevalence rates among adults from Vietnam and Cambodia.

Impact of direct-acting oral anticoagulants and warfarin on postendoscopic GI bleeding and thromboembolic events in patients undergoing elective endoscopy.

BACKGROUND AND AIMS: An increasing number of patients are undergoing GI endoscopic procedures with active prescriptions for direct oral anticoagulants (DOACs). DOACs have been associated with a higher risk of GI bleeding (GIB) compared with warfarin. Our aims were to compare the risk of postendoscopic GIB and thromboembolic (TE) events among patients on DOACs versus warfarin. METHODS: We conducted a retrospective cohort study of patients aged 18 years or older in a large integrated health care system in Southern California, who had undergone an outpatient GI endoscopic procedure and were taking a DOAC or warfarin between January 1, 2013, and October 1, 2019. We compared bleeding and thrombosis risk in the 30 days after the endoscopic procedure between the warfarin and DOAC groups using multivariate logistic regression analysis adjusted for covariates. RESULTS: Between January 1, 2013, and October 1, 2019, we identified 6765 outpatient GI endoscopic procedures in which patients received preprocedure prescriptions for either a DOAC (1587) or warfarin (5178). Overall, there was no significant difference in postprocedure GIB (odds ratio [OR], 1.165; 95% confidence interval [CI], 0.88-1.55; P = .291) or TE (OR, 0.929; 95% CI, 0.64-1.35; P = .703) between the DOAC and warfarin groups). Subgroup analysis revealed a higher risk of GIB associated with DOAC specifically with EGD procedures (OR, 1.8; 95% CI, 1.15-2.83; P = .011). CONCLUSIONS: There was no significant difference in the overall postendoscopic risk of GIB and TE events among patients with preprocedure use of DOACs compared with patients on warfarin. There may be a higher risk of GIB in patients taking DOACs and undergoing EGD.

Improvement of bone mineral density and markers of proximal renal tubular function in chronic hepatitis B patients switched from tenofovir disoproxil fumarate to tenofovir alafenamide.

Tenofovir alafenamide (TAF) is a novel prodrug that reduces tenofovir plasma levels by 90% compared to tenofovir disoproxil fumarate (TDF), resulting in decreased bone mineral density (BMD) loss and renal toxicity. We aimed to study changes in BMD and markers of renal function of chronic hepatitis B (CHB) patients previously treated with TDF who were switched to TAF in as early as 12 weeks. This was a prospective single-arm open-label study of 75 CHB patients treated with TDF 300 mg daily who were switched to TAF 25 mg daily and followed for 24 weeks. All patients had been treated with TDF for at least 12 months and had HBV DNA <21 IU/mL at the time of switch. BMD and markers of renal function were taken on the day of switch and repeated after 12 and 24 weeks of TAF treatment. Hip and spine bone mineral density significantly increased from baseline to week 12 (+12.9% and +2.4%, respectively, P < 0.01). There were significant decreases in urinary beta-2-microglobulin to creatinine and retinol-binding protein to creatinine ratios by week 12 (P < 0.01 for both). Mean estimated glomerular filtration rate (GFR) did not change. Tubular reabsorption of phosphate was decreased at week 24 (P < 0.05). In conclusion, CHB patients previously treated with TDF experienced significant improvement in bone density and some markers of renal tubular function and as early as 12 weeks after switching to TAF. Bone density changes associated with TDF may not be entirely related to renal handling of phosphate.

Durability of Hepatitis B e Antigen Seroconversion in Chronic Hepatitis B Patients Treated with Entecavir or Tenofovir.

INTRODUCTION: Loss of HBeAg and development of anti-HBe (seroconversion) is seen as a milestone and endpoint in the treatment of HBeAg-positive patients with chronic hepatitis B (CHB). Among patients treated with nucleos(t)ide analogs (NA), recurrent viremia is common after discontinuation of therapy. Entecavir (ETV) and tenofovir (TDF) are highly potent NA. The durability of virological response and HBeAg seroconversion in patients treated with these agents is not well studied. METHODS: We retrospectively studied the outcomes of 54 HBeAg-positive CHB patients who were treated with either ETV (n = 30) or TDF (23) or both (n = 1) that achieved virological response and underwent seroconversion and consolidation therapy before cessation of treatment. RESULTS: Only 4 (7%) patients had sustained virological, serological, and biochemical remission. Thirteen patients (24%) continued to have HBV DNA levels below 2000 IU/mL and normal alanine aminotransferase activity (ALT). Thirty-seven patients (69%) developed HBV DNA >2000 IU/mL, with 20 having elevated ALT. Among these 37 patients, 23 (62%) remained HBeAg negative/anti-HBe positive, 12 (32%) became HBeAg positive, and 2 (5%) were HBeAg and anti-HBe negative. Duration of consolidation therapy did not correlate with low versus high level of virological relapse. CONCLUSIONS: Durability of HBeAg seroconversion associated with ETV or TDF was not superior to that reported in patients treated with less potent NA. Our results, aggregated with others, suggest HBeAg seroconversion should not be considered as a treatment endpoint for most HBeAg-positive patients treated with NA. Future updates of treatment guidelines should reconsider HBeAg seroconversion as an endpoint to therapy.