1. Compared to placebo, intramuscular AZD7442 had a relative risk reduction of 76.7% for symptomatic incident coronavirus disease 2019 (COVID-19).
2. At least one adverse event occurred in 35.3% of the AZD7442 group and 34.2% of the placebo group, these events were often mild or moderate in severity.
Evidence Rating Level: 1 (Excellent)
Study Rundown: The COVID-19 pandemic has had a devastating impact on global health, with the approval of mRNA vaccines playing a critical role in prevention. Monoclonal antibodies are an important alternative for patients who are contraindicated from receiving currently available COVID-19 vaccines. Accordingly, AZD7442 is a combination of two human SARS-CoV-2-neutralizing monoclonal antibodies derived from patients infected with COVID-19 which can be injected intramuscularly. This randomized control trial compared the safety and efficacy of a single intramuscular dose of AZD7442 to a placebo control as pre-exposure prophylaxis to COVID-19. Symptomatic RT-PCR-positive illness occurred significantly less in the treatment group compared to the placebo group. The rate of adverse events was higher in the treatment group but was statistically insignificant. The most common adverse event was an injection-site reaction. This trial was limited by the low number of events in the smaller subgroups there compromising the ability to extrapolate results to important subgroups. The unblinding of some participants due to participants wanting to receive the COVID-19 vaccine.
In-Depth [randomized control trial]: This randomized control trial compared the safety and efficacy of one intramuscular 300 mg dose of AZD7442 (n=3,460) to a placebo control (n=1,737) for preventing COVID-19 infection. The primary outcome was symptomatic and RT-PCR-positive COVID-19 within six-month follow-up. Symptomatic COVID-19 occurred in eight (0.2%) participants in the AZD7442 group and 17 participants (1.0%) in the placebo group (Relative Risk Reduction [RRR], 76.7%; 95% Confidence interval [CI], 46.0 to 90.9, p<0.001). At the median six-month follow-up, there was a lower incidence of COVID-19 in the AZD7442 group as compared to controls, with a relative risk reduction of 82.8% (95% CI, 65.8 to 91.4). The risk reduction was seen across all subgroups analyzed by age, sex, race/ethnicity, BMI, increased risk of COVID-19 exposure, and risk factors for severe covid-19. Additionally, 1,221 participants (35.3%) in the AZD7442 experienced at least one adverse event, compared to 593 participants (34.2%) in the placebo group. The most common adverse event was injection site reaction. All of the cases of severe or critical COVID-19 (n=5) and COVID-19-related deaths (n=2) occurred in the placebo group. Serum levels of AZD7442 remained at elevated levels 6 months after administration. Finally, viral genotypes for seven of 11 symptomatic participants in the treatment group and 13 out of 31 symptomatic participants in the placebo group. In total,11 of these symptomatic participants had variants of concern. In summary, AZD7442 may be effective as pre-exposure prophylaxis for COVID-19 in patients who are immunocompromised, contraindicated to receive the vaccinations, or cannot mount a sufficient response to the vaccination.
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