Effectiveness of Evusheld in Immunocompromised Patients: Propensity Score-Matched Analysis.

BACKGROUND: Tixagevimab and Cilgavimab, a combined monoclonal antibody (Evusheld) was granted emergency use authorization for SARS-CoV-2 preexposure prophylaxis in individuals with moderate to severe immunocompromising condition. In this study we used population-based real-world data to evaluate the effectiveness of Evusheld in immunocompromised patients. METHODS: Using the computerized database of the largest healthcare provider in Israel, we identified all adult immunocompromised patients who were eligible to receive Evusheld (the dose used during the study period was 150 mg Tixagevimab and 150 mg Cilgavimab) on 15-February-2022. Patients with a documentation of a prior SARS-CoV-2 infection were excluded. A total of 703 patients who received Evusheld were propensity score-matched, using a ratio of 1:4, with 2812 patients who have not received Evusheld (control group). Patients were followed through 30-June-2022 for up to 90-days for the first documentation of SARS-CoV-2 infection and COVID-19 related hospitalization. RESULTS: Overall, 72 patients in the Evusheld group and 377 patients in the control group had SARS-CoV-2 infection, reflecting and incidence rate of 4.18 and 5.64 per 100 person-months, respectively. HR was 0.75(95%CI,0.58-0.96) for SARS-CoV-2 infection, and 0.41(0.19-0.89) for COVID-19 related hospitalization in the Evusheld group compared to the control group. The magnitude of relative risks reduction of each outcome was greater in non-obese patients (P for interaction = 0.020 and 0.045, respectively). CONCLUSION: This study suggests that Evusheld (150 mg Tixagevimab and 150 mg Cilgavimab) is effective in reducing the risk of SARS-CoV-2 infection and COVID-19 hospitalization in immunocompromised patients. The effectiveness of this dose appears to be greater in non-obese patients.

Development of Autoantibodies Following BNT162b2 mRNA COVID-19 Vaccination and Their Association with Disease Flares in Adult Patients with Autoimmune Inflammatory Rheumatic Diseases (AIIRD) and the General Population: Results of 1-Year Prospective Follow-Up Study.

Development of autoantibodies following BNT162b2 mRNA COVID-19 vaccination and their association with disease flares in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) and the general population: results of 1-year prospective follow-up study. We conducted a prospective study aimed at investigating the incidence of appearance of autoantibodies (antinuclear, antiphospholipid, and rheumatoid factor) in the sera of 463 adult patients with AIIRD compared to 55 controls from the general population prior to, and following the second and third vaccine doses, and at 1-year of follow-up. Pre- and post-vaccination disease activity indices and the association of autoantibodies with rheumatic disease flares and new onset AIIRD were examined. Autoantibody development of any type in AIIRD patients vs. the controls was 4.0% (vs. 6.7%, p = 0.423) following two vaccine doses and 7.6% (vs. 0%, p = 0.152) after three doses. There was no significant difference in sex, age, or disease-type among individuals with and without autoantibody development, regardless of the immunosuppressant use. More patients developed autoantibodies following the third than the second vaccine dose (p = 0.004). Disease flares occurred in 5.8% and 7.2% of AIIRD patients following second and third vaccine doses, respectively, with autoantibody production increasing the risk of flares following the second (p = 0.002) and third (p = 0.004) vaccine doses. BNT162b2 vaccination resulted in the development of autoantibodies in a minority of AIIRD patients and controls. Autoantibody development was associated with disease flares in patients, but no new-onset autoimmunity was observed.

Effectiveness of Paxlovid in Reducing Severe COVID-19 and Mortality in High Risk Patients.

BACKGROUND: Paxlovid was granted emergency use authorization for the treatment of mild to moderate COVID-19, based on the interim analysis of EPIC-HR trial. Paxlovid effectiveness needs to be assessed in a noncontrolled setting. In this study we used population-based real world data to evaluate the effectiveness of Paxlovid. METHODS: The database of the largest healthcare provider in Israel was used to identify all adults aged 18 years or older with first ever positive test for SARS-CoV-2 between January and February 2022, who were at high risk for severe COVID-19 and had no contraindications for Paxlovid use. Patients were included irrespective of their COVID-19 vaccination status. Cox hazard regression was used to estimate the 28 day HR for severe COVID-19 or mortality with Paxlovid examined as time-dependent variable. RESULTS: Overall, 180,351 eligible were included, of them only 4,737 (2.6%) were treated with Paxlovid, and 135,482 (75.1%) had adequate COVID-19 vaccination status. Both Paxlovid and adequate COVID-19 vaccination status were associated with significant decrease in the rate of severe COVID-19 or mortality with adjusted HR 0.54 (95% CI, 0.39-0.75) and 0.20 (95% CI, 0.17-0.22), respectively. Paxlovid appears to be more effective in older patients, immunosuppressed patients, and patients with underlying neurological or cardiovascular disease (interaction p-value <0.05 for all). No significant interaction was detected between Paxlovid treatment and COVID-19 vaccination status. CONCLUSIONS: This study suggests that in the era of omicron and in real life setting Paxlovid is highly effective in reducing the risk of severe COVID-19 or mortality.

Effectiveness of Molnupiravir in High Risk Patients: a Propensity Score Matched Analysis.

BACKGROUND: Molnupiravir was granted emergency use authorization for the treatment of mild to moderate COVID-19. In this study we used population-based real-world data to evaluate the effectiveness of Molnupiravir. METHODS: The database of the largest healthcare provider in Israel was used to identify all adults with first ever positive test for SARS-CoV-2 performed in the community during January-February 2022, who were at high risk for severe COVID-19 and had no contraindications for Molnupiravir use. Patients were included regardless of SARS-CoV-2 vaccination status. A total of 2661 patients who received Molnupiravir were propensity score-matched with 2661 patients who have not received Molnupiravir (control group). Patients were followed through 10 March 2022 for up to 28 days for the first occurrence of the composite severe COVID-19 or COVID-19 specific mortality. RESULTS: The composite outcome occurred in 50 patients in the Molnupiravir group and 60 patients in the control group. Molnupiravir was associated with a nonsignificant reduced risk of the composite outcome HR, 0.83 (95% CI, 0.57-1.21). However, subgroup analyses showed that Molnupiravir was associated with a significant decrease in the risk of the composite outcome in older patients 0.54 (0.34-0.86), in females 0.41 (0.22-0.77), and in patients with inadequate COVID-19 vaccination 0.45 (0.25-0.82). The results were similar when each component of the composite outcome were examined separately. CONCLUSIONS: This study suggests that in the era of omicron and in real life setting Molnupiravir might be effective in reducing the risk of severe COVID-19 and COVID-19 related mortality, particularly in specific subgroups.

Maternal and Neonatal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Immunoglobulin G Levels After the Pfizer-BioNTech Booster Dose for Coronavirus Disease 2019 (COVID-19) Vaccination During the Second Trimester of Pregnancy.

OBJECTIVE: To evaluate maternal and neonatal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) antibody levels at birth after a third (booster) dose of the Pfizer-BioNTech messenger RNA (Pfizer) coronavirus disease 2019 (COVID-19) vaccine during the second trimester of pregnancy, and compare them with those in women who received two vaccine doses during the second trimester. METHODS: We conducted a prospective cohort study of women admitted to the delivery ward at a single center who received the third Pfizer COVID-19 vaccine dose (booster group) at 17-30 weeks of pregnancy and who did not have previous SARS-CoV-2 infection. Maternal and neonatal antibody levels were measured on admission for delivery and in the umbilical cord blood after birth. Antibody levels for the booster group were compared with those in a historical control group of pregnant women who received their second vaccine dose (two-dose group) within the same gestational age window. RESULTS: Between October 2021 and February 2022, antibody levels were measured in 121 women and 109 neonates at a mean±SD of 15.3±3.9 weeks after booster vaccination. Neonatal titers measured two times higher than maternal titers, with inverse correlation between maternal and neonatal titers at birth and time interval from third vaccination. The two-dose group included 121 women and 107 neonates, with antibody levels measured at a mean±SD of 14.6±2.6 weeks after the second dose. Median [interquartile range] maternal antibody titers were higher in the booster group (4,485 [2,569-9,702] AU/mL) compared with the two-dose group (1,122 [735-1,872] AU/mL) (P<.001). Furthermore, neonatal antibody titers were higher in the booster group (8,773 [5,143-18,830] AU/mL) compared with the two-dose group (3,280 [2,087-5,754] AU/mL) (P<.001). CONCLUSION: Maternal and neonatal SARS-CoV-2 IgG antibody titers after second-trimester maternal Pfizer COVID-19 vaccination were significantly higher after the booster dose compared with the two-dose vaccination series. Although there is uncertainty as to whether antibody levels correlate with protection, these data support the importance of booster vaccination during pregnancy to restore maternal and neonatal protection against COVID-19.

Complementary and integrative medicine intervention in front-line COVID-19 clinicians.

OBJECTIVE: To assess the impact of a multidisciplinary complementary and integrative medicine (CIM) intervention on physical and emotional concerns among front-line COVID-19 healthcare providers (HCPs). METHODS: A multimodality CIM treatment intervention was provided by integrative practitioners to HCPs in three isolated COVID-19 departments. HCPs' two main concerns were scored (from 0 to 6) before and following the CIM intervention using the Measure Yourself Concerns and Wellbeing questionnaire. Postintervention narratives identified reflective narratives specifying emotional and/or spiritual keywords. RESULTS: Of 181 HCPs undergoing at least one CIM treatment, 119 (65.7%) completed post-treatment questionnaires. While HCPs listing baseline emotional-related concerns benefited from the CIM intervention, those who did not express emotional or spiritual concerns improved even more significantly following the first session, for both leading concerns (p=0.038) and emotional-related concerns (p=0.023). Nevertheless, it was shown that following subsequent treatments HCPs who expressed emotional and spiritual concerns improved more significantly than those who did not for emotional-related concerns (p=0.017). CONCLUSIONS: A CIM intervention for front-line HCPs working in isolated COVID-19 departments can significantly impact emotional-related concerns, more so after the first treatment and among HCPs not using emotional-spiritual keywords in post-treatment narratives. Referral of HCPs to CIM programmes for improved well-being should avoid referral bias to those not expressing emotional/spiritual concerns.