1130: Neutralizing antibody LY-CoV555 hastens SARS-CoV-2 viral clearance in outpatients    

1. A single intravenous infusion of the neutralizing antibody LY-CoV555 2800 mg can accelerate the natural fall in viral load over time among outpatients with recently diagnosed mild or moderate COVID-19, reported a phase 2 study published in The New England Journal of Medicine.
2. The interim analysis revealed that patients who received LY-CoV555 had fewer hospitalizations and a lower symptom burden compared to those given placebo, with the effects most marked in high-risk cohorts.
3. The ongoing Blocking Viral Attachment and Cell Entry With SARS-CoV-2 Neutralizing Antibodies (BLAZE-1) trial randomized 452 outpatients with recently diagnosed mild or moderate COVID-19 to a single intravenous infusion of neutralizing antibody LY-CoV555 700 mg (101 patients), 2800 mg (107 patients), or 7000 mg (101 patients), or placebo (143 patients) from June 17 through August 21, 2020.
4. The primary outcome was change from baseline in SARS-CoV-2 viral load at day 11 following positive test results.
5. Patients received their treatments within a median of 4 days after symptom onset. At the time of randomization, over 80% of the patients had only mild symptoms.
6. At the time of analysis, by day 11, the majority of patients showed a trend toward viral clearance, including those on placebo.
7. On days 2 to 6, patients who received LY-CoV555 were shown to have a slightly lower severity of symptoms compared to those given placebo.
8. Among patients in the LY-CoV555 group, 1.6% had a COVID-19-related hospitalization or visit to an emergency department compared to 6.3% of patients in the placebo group.
9. In the pooled trial population, there was an association between slower viral clearance and more hospitalization events.Among patients with a higher viral load on day 7, the frequency of hospitalization was 12% among those who had a cycle threshold (Ct) value <27.5 compared to a frequency of 0.9% among those with a lower viral load.
10. No serious adverse events were reported.
11. There was an unanticipated observation in this trial - patients with a higher viral load on day 7 appeared to have a higher rate of hospitalization in comparison with those with better clearance of viral RNA on day 7. It was consistent with delayed viral clearance that was observed in patients with more severe disease.
12. On day 7, no hospitalized patient had a viral load below the median value of the population. If prospectively confirmed in future studies, this finding would point to the potential for an agent that decreases the viral load to reduce the rate of hospitalization.

[NEJM, DG Alerts]

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA