Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for Prevention of Covid-19.

BACKGROUND: The monoclonal-antibody combination AZD7442 is composed of tixagevimab and cilgavimab, two neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that have an extended half-life and have been shown to have prophylactic and therapeutic effects in animal models. Pharmacokinetic data in humans indicate that AZD7442 has an extended half-life of approximately 90 days. METHODS: In an ongoing phase 3 trial, we enrolled adults (≥18 years of age) who had an increased risk of an inadequate response to vaccination against coronavirus disease 2019 (Covid-19), an increased risk of exposure to SARS-CoV-2, or both. Participants were randomly assigned in a 2:1 ratio to receive a single dose (two consecutive intramuscular injections, one containing tixagevimab and the other containing cilgavimab) of either 300 mg of AZD7442 or saline placebo, and they were followed for up to 183 days in the primary analysis. The primary safety end point was the incidence of adverse events after a single dose of AZD7442. The primary efficacy end point was symptomatic Covid-19 (SARS-CoV-2 infection confirmed by means of reverse-transcriptase-polymerase-chain-reaction assay) occurring after administration of AZD7442 or placebo and on or before day 183. RESULTS: A total of 5197 participants underwent randomization and received one dose of AZD7442 or placebo (3460 in the AZD7442 group and 1737 in the placebo group). The primary analysis was conducted after 30% of the participants had become aware of their randomized assignment. In total, 1221 of 3461 participants (35.3%) in the AZD7442 group and 593 of 1736 participants (34.2%) in the placebo group reported having at least one adverse event, most of which were mild or moderate in severity. Symptomatic Covid-19 occurred in 8 of 3441 participants (0.2%) in the AZD7442 group and in 17 of 1731 participants (1.0%) in the placebo group (relative risk reduction, 76.7%; 95% confidence interval [CI], 46.0 to 90.0; P<0.001); extended follow-up at a median of 6 months showed a relative risk reduction of 82.8% (95% CI, 65.8 to 91.4). Five cases of severe or critical Covid-19 and two Covid-19-related deaths occurred, all in the placebo group. CONCLUSIONS: A single dose of AZD7442 had efficacy for the prevention of Covid-19, without evident safety concerns. (Funded by AstraZeneca and the U.S. government; PROVENT ClinicalTrials.gov number, NCT04625725.).

Remdesivir for Severe Coronavirus Disease 2019 (COVID-19) Versus a Cohort Receiving Standard of Care.

BACKGROUND: We compared the efficacy of the antiviral agent, remdesivir, versus standard-of-care treatment in adults with severe coronavirus disease 2019 (COVID-19) using data from a phase 3 remdesivir trial and a retrospective cohort of patients with severe COVID-19 treated with standard of care. METHODS: GS-US-540-5773 is an ongoing phase 3, randomized, open-label trial comparing two courses of remdesivir (remdesivir-cohort). GS-US-540-5807 is an ongoing real-world, retrospective cohort study of clinical outcomes in patients receiving standard-of-care treatment (non-remdesivir-cohort). Inclusion criteria were similar between studies: patients had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, were hospitalized, had oxygen saturation ≤94% on room air or required supplemental oxygen, and had pulmonary infiltrates. Stabilized inverse probability of treatment weighted multivariable logistic regression was used to estimate the treatment effect of remdesivir versus standard of care. The primary endpoint was the proportion of patients with recovery on day 14, dichotomized from a 7-point clinical status ordinal scale. A key secondary endpoint was mortality. RESULTS: After the inverse probability of treatment weighting procedure, 312 and 818 patients were counted in the remdesivir- and non-remdesivir-cohorts, respectively. At day 14, 74.4% of patients in the remdesivir-cohort had recovered versus 59.0% in the non-remdesivir-cohort (adjusted odds ratio [aOR] 2.03: 95% confidence interval [CI]: 1.34-3.08, P < .001). At day 14, 7.6% of patients in the remdesivir-cohort had died versus 12.5% in the non-remdesivir-cohort (aOR 0.38, 95% CI: .22-.68, P = .001). CONCLUSIONS: In this comparative analysis, by day 14, remdesivir was associated with significantly greater recovery and 62% reduced odds of death versus standard-of-care treatment in patients with severe COVID-19. CLINICAL TRIALS REGISTRATION: NCT04292899 and EUPAS34303.

Remdesivir Versus Standard-of-Care for Severe Coronavirus Disease 2019 Infection: An Analysis of 28-Day Mortality.

BACKGROUND: Remdesivir is approved by the US Food and Drug Administration for the treatment of patients hospitalized with coronavirus disease 2019 (COVID-19) and has been shown to shorten time to recovery and improve clinical outcomes in randomized trials. METHODS: This was the final day 28 comparative analysis of data from a phase 3, randomized, open-label study comparing 2 remdesivir regimens (5 vs 10 days, combined for this analysis [remdesivir cohort]) and a real-world retrospective longitudinal cohort study of patients receiving standard-of-care treatment (nonremdesivir cohort). Eligible patients, aged ≥18 years, had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), oxygen saturation ≤94% on room air or required supplemental oxygen, with pulmonary infiltrates. Propensity score matching (up to 1:10 ratio) was used to ensure comparable populations. We assessed day 14 clinical recovery (determined using a 7-point ordinal scale) and day 28 all-cause mortality (coprimary endpoints). RESULTS: A total of 368 (remdesivir) and 1399 (nonremdesivir) patients were included in the matched analysis. The day 14 clinical recovery rate was significantly higher among the remdesivir versus the nonremdesivir cohort (65.2% vs 57.1%; odds ratio [OR], 1.49; 95% confidence interval [CI], 1.16-1.90; P = 0.002). The day 28 mortality rate was significantly lower in the remdesivir cohort versus the nonremdesivir cohort (12.0% vs 16.2%; OR, 0.67; 95% CI, 0.47-.95; P = .03). CONCLUSIONS: Remdesivir was associated with significantly higher rates of day 14 clinical recovery, and lower day 28 mortality, compared with standard-of-care treatment in hospitalized patients with COVID-19. These data, taken together, support the use of remdesivir to improve clinical recovery and decrease mortality from SARS-CoV-2 infection.

Clinical characteristics and outcomes of COVID-19 in people living with HIV in Belgium: A multicenter, retrospective cohort.

The aim of this study was to describe the clinical characteristics and outcomes of coronavirus disease 2019 (COVID-19) among people living with HIV (PLWH) in Belgium. We performed a retrospective multicenter cohort analysis of PLWH with either laboratory-confirmed, radiologically diagnosed, or clinically suspected COVID-19 between February 15, 2020 and May 31, 2020. The primary endpoint was outcome of COVID-19. Secondary endpoints included rate of hospitalization and length of hospital stay and rate of Intensive Care Unit (ICU) admission and mechanical ventilation. One hundred and one patients were included in this study. Patients were categorized as having either laboratory-confirmed (n = 65), radiologically-diagnosed (n = 3), or clinically suspected COVID-19 (n = 33). The median age was 51.3 years (interquartile range [IQR] 41.3-57.3) and 44% were female. Ninety-four percent of patients were virologically suppressed and 67% had a CD4+ cell count more than or equal to 500 cells/µl. Overall, 46% of patients required hospitalization and the median length of hospital stay was 6 days (IQR 3-15). Age more than or equal to 50 years, Black Sub-Saharan African patients, and being on an integrase strand transfer inhibitor-based regimen were associated with being hospitalized. ICU admission and mechanical ventilation was required for 15% and 10% of all patients respectively. Overall, 9% of patients died while 78 (77%) patients made a full recovery. HIV patients with COVID-19 experienced a high degree of hospitalization despite having elevated CD4+ cell counts and a high rate of virologic suppression. Matched case-control studies are warranted to measure the impact that HIV may have on patients with COVID-19.