There remains good evidence that reducing saturated fat reduces morbidity in patients with CVD. This advice is consistent for most manifestations of CVD, with the addition of Mediterranean dietary advice and increased omega 3 fats for those who have had a myocardial infarction.

Key Points Question Is subcutaneous treatment with casirivimab and imdevimab associated with improved 28-day clinical outcomes compared with nontreatment, and is it clinically similar to intravenously administered casirivimab and imdevimab for outpatients with COVID-19? Findings In this cohort study of 1959 propensity-matched outpatients with mild to moderate COVID-19 symptoms, the 28-day rate of hospitalization or death was 3.4% vs 7.0% for those receiving subcutaneous treatment vs nontreatment. In a second cohort analysis of 2185 outpatients, the 28-day rate of hospitalization or death was 2.8% vs 1.7% for subcutaneous vs intravenous treatment. Meaning Subcutaneous casirivimab and imdevimab was associated with reduced hospitalization and death compared with nontreatment and showed similar outcomes compared with intravenous casirivimab and imdevimab in outpatients with COVID-19.

IMPORTANCE The effectiveness of monoclonal antibodies (mAbs), casirivimab and imdevimab, and sotrovimab, for patients with mild to moderate Covid-19 from the Delta variant is unknown. OBJECTIVE To evaluate the effectiveness of mAbs for the Delta variant compared to no treatment, and the comparative effectiveness between mAbs. DESIGN, SETTING, AND PARTICIPANTS Two parallel studies among patients who met Emergency Use Authorization criteria for mAbs from July 14, 2021 to September 29, 2021: i.) prospective observational cohort study comparing mAb treatment to no mAb treatment and, ii.) Bayesian adaptive randomized trial comparing the effectiveness of casirivimab-imdevimab versus sotrovimab. In the observational study, we compared eligible patients who received mAb at an outpatient infusion center at UPMC, to nontreated patients with a positive SARS-CoV-2 test. In the comparative effectiveness trial, we randomly allocated casirivimab-imdevimab or sotrovimab to patients presenting to infusion centers and emergency departments, per system therapeutic interchange policy. EXPOSURE Intravenous mAb per their EUA criteria. MAIN OUTCOMES AND MEASURES For the observational study, risk ratio estimates for hospitalization or death by 28 days were compared between mAb treatment to no mAb treatment using propensity matched models. For the comparative effectiveness trial, the primary outcome was hospital-free days (days alive and free of hospital) within 28 days, where patients who died were assigned -1 day) in a Bayesian cumulative logistic model, adjusted for treatment location, age, sex, and time. Inferiority was defined as a 99% posterior probability of an odds ratio <1. Equivalence was defined as a 95% posterior probability that the odds ratio is within a given bound. RESULTS Among 3,558 patients receiving mAb, the mean age was 54 (SD 18 years), 1,511 (43%) were treated in an infusion center, and 450 (13%) were hospitalized or died by day 28. In propensity matched models, mAb treatment was associated with reduced risk of hospitalization or death compared to no treatment (risk ratio (RR)=0.40, 95% CI: 0.28-0.57). Both casirivimab and imdevimab (RR=0.31, 95% CI: 0.20-0.50), and sotrovimab (RR=0.60, 95% CI: 0.37-1.00) reduced hospitalization or death compared to no mAb treatment. Among patients allocated randomly to casirivimab and imdevimab (n=2,454) or sotrovimab (n=1,104), the median hospital-free days were 28 (IQR 28-28) for both groups, 28-day mortality was 0.5% (n=12) and 0.6% (n=7), and hospitalization by day 28 was 12% (n=291) and 12% (n=140), respectively. Compared to casirivimab and imdevimab, the median adjusted odds ratio for hospital-free days was 0.88 (95% credible interval, 0.70-1.11) for sotrovimab. This odds ratio yielded 86% probability of inferiority of sotrovimab versus casirivimab and imdevimab, and 79% probability of equivalence. CONCLUSIONS AND RELEVANCE In non-hospitalized patients with mild to moderate Covid-19 due to the Delta variant, casirivimab and imdevimab and sotrovimab were both associated with a reduced risk of hospitalization or death. The comparative effectiveness of mAbs appeared similar, though prespecified criteria for statistical inferiority or equivalence were not met. TRIAL REGISTRATION ClinicalTrials.gov: NCT04790786

DESIGN, SETTING, AND PARTICIPANTSThis study comprised 2 parallel studies: (1) a propensity score-matched cohort study of mAb treatment vs no mAb treatment and (2) a randomized comparative effectiveness trial of casirivimab-imdevimab and sotrovimab. The cohort consisted of patients who received mAb treatment at the University of Pittsburgh Medical Center outpatient infusion centers and emergency departments from July 14 to September 29, 2021. Participants were patients with a positive SARS-CoV-2 test result who were eligible to receive mAbs according to emergency use authorization criteria.EXPOSURE For the trial, patients were randomized to either intravenous casirivimab-imdevimab or sotrovimab according to a system therapeutic interchange policy. MAIN OUTCOMES AND MEASURESFor the cohort study, risk ratio (RR) estimates for the primary outcome of hospitalization or death by 28 days were compared between mAb treatment and no mAb treatment using propensity score-matched models. For the comparative effectiveness trial, the primary outcome was hospital-free days (days alive and free of hospitalization) within 28 days after mAb treatment, where patients who died were assigned −1 day in a bayesian cumulative logistic model adjusted for treatment location, age, sex, and time. Inferiority was defined as a 99% posterior probability of an odds ratio (OR) less than 1. Equivalence was defined as a 95% posterior probability that the OR was within a given bound. RESULTSA total of 3069 patients (1023 received mAb treatment: mean [SD] age, 53.2 [16.4] years; 569 women [56%]; 2046 had no mAb treatment: mean [SD] age, 52.8 [19.5] years; 1157 women [57%]) were included in the prospective cohort study, and 3558 patients (mean [SD] age, 54 [18] years; 1919 women [54%]) were included in the randomized comparative effectiveness trial. In propensity score-matched models, mAb treatment was associated with reduced risk of hospitalization or death (RR, 0.40; 95% CI, 0.28-0.57) compared with no treatment. Both (continued)