The new england journal of medicine Table 1. Characteristics of the Patients at Baseline.* line was −0.53 (95% confidence interval [CI], −0.98 to −0.08; P = 0.02), for a lower viral load by a LY-CoV555 Placebo factor of 3.4 (Table 2). However, smaller differ- Characteristic (N = 309) (N = 143) ences from placebo in the decrease from base- Age line were observed among the patients who re- Median (range) — yr 45 (18–86) 46 (18–77) ceived the 700-mg dose (−0.20; 95% CI, −0.66 to 65 Yr or older — no. (%) 33 (10.7) 20 (14.0) 0.25; P = 0.38) and the 7000-mg dose (0.09; 95% CI, Female sex — no. (%) 171 (55.3) 78 (54.5) −0.37 to 0.55; P = 0.70). Race or ethnic group — no./ total no. (%)† Secondary Viral Outcomes White 269/305 (88.2) 120/138 (87.0) On day 3, among the patients who received the 2800-mg dose of LY-CoV555, the observed differ- Hispanic or Latino 135/309 (43.7) 63/143 (44.1) ence from placebo in the decrease from baseline Black 22/305 (7.2) 7/138 (5.1) in the mean log viral load was −0.64 (95% CI, Body-mass index‡ −1.11 to −0.17) (Table 2). The other two doses of Median 29.4 29.1 LY-CoV555 showed similar improvements in viral ≥30 to <40 — no./total no. (%) 112/304 (36.8) 56/139 (40.3) clearance at day 3, with a difference from pla- ≥40 — no./total no. (%) 24/304 (7.9) 9/139 (6.5) cebo in the change from baseline of −0.42 (95% Risk factors for severe Covid-19 215 (69.6) 95 (66.4) CI, −0.89 to 0.06) for the 700-mg dose and −0.42 — no. (%)§ (95% CI, −0.90 to 0.06) for the 7000-mg dose. Disease status — no. (%) The difference from placebo in the change from baseline for the pooled doses of LY-CoV555 was Mild 232 (75.1) 113 (79.0) −0.49 (95% CI, −0.87 to −0.11). Moderate 77 (24.9) 30 (21.0) Median no. of days since onset 4.0 4.0 Exploratory Measures of Viral Clearance of symptoms In the pooled trial population, an association Mean viral load — Ct value¶ 23.9 23.8 was observed between slower viral clearance and * Covid-19 denotes coronavirus disease 2019. more hospitalization events. Figure 2A presents † Race or ethnic group was reported by the patients, who could choose more the absolute viral load among hospitalized pa- than one category. tients (pooled across randomization strata) as ‡ The body-mass index is the weight in kilograms divided by the square of the well as a box plot of viral loads among nonhos- height in meters. § Risk factors were an age of 65 years or older, a body-mass index of 35 or pitalized patients. On day 7, all the available more, or at least one coexisting illness in certain prespecified categories. measures of viral load among hospitalized pa- ¶ Ct denotes the cycle threshold of the reverse-transcriptase–polymerase-chain- tients were higher than the median values among reaction assay. the nonhospitalized patients. Among the patients with a higher viral load on day 7, the frequency of hospitalization was 12% (7 of 56 patients) is described in Section 6.10 of the statistical analy- among those who had a Ct value of less than sis plan. 27.5, as compared with a frequency of 0.9% (3 of 340 patients) among those with a lower viral Primary Outcome load. (The SARS-CoV-2 N1 gene primer determines By day 11, the majority of patients had a sub- a Ct value that is equivalent to approximately stantial trend toward viral clearance, including 570,000 nucleic acid–based amplification tests those in the placebo group. The observed mean per milliliter with the use of the SARS-CoV-2 decrease from baseline in the log viral load for reference panel of the Food and Drug Administra- the entire population was −3.81 (baseline mean, tion.) Since this difference was not anticipated 6.36; day 11 mean, 2.56); this value corresponded and emerged from post hoc exploratory analysis, to a decrease by more than a factor of 4300 in the it is unclear whether it would be applicable to SARS-CoV-2 burden, for an elimination of more other populations. Figure 2B shows the cumula- than 99.97% of viral RNA. For patients who re- tive probability that patients in each trial group ceived the 2800-mg dose of LY-CoV555, the dif- would have the indicated cycle threshold of viral ference from placebo in the decrease from base- load on day 7. 4 n engl j med nejm.org 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.