Neutralizing Antibody in Outpatients with Covid-19 measure of viral neutralization, since viral RNA Table 3. Hospitalization.* may persist for some time even in the absence of replication-competent virus. Since the severity of Key Secondary LY-CoV555 Placebo Incidence illness is primarily driven by lung injury from Outcome SARS-CoV-2 infection in the lower respiratory no. of patients/total no. % tract, the viral load in the air spaces would be a Hospitalization 9/143 6.3 better reflection of the injury response than the viral load in nasopharyngeal secretions. However, 700 mg, 1/101 1.0 assessments of the lower respiratory tract were 2800 mg, 2/107 1.9 not practical owing to precautions that were re- 7000 mg, 2/101 2.0 quired in treating these highly infectious patients. Pooled doses, 1.6 Therefore, the nasopharyngeal viral swab was 5/309 the most pragmatic way of getting a sense of viral * Data for patients who presented to the emergency department are included in load as a surrogate marker of the viral load in this category. the lungs and to correlate with clinical outcomes. However, the nasopharyngeal viral load has not been validated as a predictor of clinical disease 0 course. An unanticipated observation in this trial was Delta Value (95% CI) that patients with a higher viral load on day 7 Day 2 −0.79 (−1.35 to −0.24) −2 Day 3 −0.57 (−1.12 to −0.01) had a higher rate of hospitalization than those Day 4 −1.04 (−1.60 to −0.49) Placebo with better clearance of viral RNA on day 7, a Day 5 −0.73 (−1.28 to −0.17) finding that was consistent with the delayed vi- Day 6 −0.79 (−1.35 to −0.23) ral clearance that was observed in patients with −4 Day  −0.50 (−1.06 to 0.07) 20,22,23 LY-CoV555 Day  −0.65 (−1.28 to −0.02) more severe disease. On day 7, no hospital- Change from Baseline Day 9 −0.15 (−0.75 to 0.45) ized patient had a viral load that was below the (pooled) Day  −0.32 (−0.94 to 0.29) median value of the population. If this observa- −6 Day  −0.44 (−1.02 to 0.15) tion is prospectively confirmed in future studies, it would suggest the potential for an agent that 1 2 3 4 5 6 7 8 9 10 11 lowers the viral load to reduce the rate of hospi- Trial Day talization. Figure 3. Symptom Scores from Day 2 to Day 11. To examine the potential of LY-CoV555 to im- Shown is the difference in the change from baseline (delta value) in symp- prove Covid-19 clinical outcomes, we evaluated tom scores between the LY-CoV555 group and the placebo group from day the effect of LY-CoV555 therapy on the frequency 2 to day 11. The symptom scores ranged from 0 to 24 and included eight of hospitalization, an important outcome given domains, each of which was graded on a scale of 0 (no symptoms) to 3 the association between hospitalization and sub- (severe symptoms). The I bars represent 95% confidence intervals. Details 23,24 about the symptom-scoring methods are provided in the Supplementary sequent mortality in patients with Covid-19. Appendix. On day 29, the percentage of patients who were hospitalized was 1.6% in the LY-CoV555 group and 6.3% in the placebo group. In a post hoc fect on symptoms and suggests a mechanistic analysis that was focused on high-risk subgroups link between a lower viral load and a lower fre- (an age of ≥65 years or a BMI of ≥35), the percent- quency of hospitalization. Although the differenc- age of hospitalization was 4.2% in the LY-CoV555 es in the effects of the three doses of LY-CoV555 group and 14.6% in the placebo group. were not clear, the 2800-mg dose was the only The data regarding symptoms (as measured one to show evidence of accelerated viral clear- by the change from baseline in the symptom ance. Nevertheless, further studies should con- score) were also consistent with the hospitaliza- tinue to assess the efficacy of lower doses. tion results, with findings that supported a pos- The safety profile of patients who received sible reduction in symptom severity as early as LY-CoV555 was similar to that of placebo-treated day 2 in the LY-CoV555 group. This effect was patients. These data indicate that the treatment maintained over time and across doses, which is safe. In this interim analysis, the patients who further supports the validity of a treatment ef- received LY-CoV555 had fewer hospitalizations n engl j med nejm.org 7 The New England Journal of Medicine Downloaded from nejm.org on November 19, 2020. For personal use only. No other uses without permission. Copyright © 2020 Massachusetts Medical Society. All rights reserved.