Table 2. Vaccine Efficacy against Covid-19 with Onset at Least 14 Days and at Least 28 Days after the Administration of Vaccine or Placebo (Per-Protocol at-Risk Population).^*.

Variable	≥14 Days after Administration†					≥28 Days after Administration‡
	Ad26.COV2.S (N=19,514)		Placebo (N=19,544)		Vaccine Efficacy (95% CI)	Ad26.COV2.S (N=19,306)		Placebo (N=19,178)		Vaccine Efficacy (95% CI)
	no. of cases	person-yr	no. of cases	person-yr	%	no. of cases	person-yr	no of cases	person-yr	%
Moderate to severe–critical Covid-19	116	3116.6	348	3096.1	66.9 (59.0–73.4)	66	3102.0	193	3070.7	66.1 (55.0–74.8)
18−59 yr	95	2106.8	260	2095.0	63.7 (53.9–71.6)	52	2097.6	152	2077.0	66.1 (53.3–75.8)
≥60 yr	21	1009.8	88	1001.2	76.3 (61.6–86.0)	14	1004.4	41	993.6	66.2 (36.7–83.0)
Symptomatic Covid-19 of any severity	117	3116.5	351	3095.9	66.9 (59.1–73.4)	66	3102.0	195	3070.5	66.5 (55.5–75.1)
Mild	1	3116.5	3	3095.9	NC§	0	3102.0	2	3070.5	NC§
Moderate	102	3116.6	288	3096.1	64.8 (55.8–72.2)	61	3102.0	159	3070.7	62.0 (48.7–72.2)
Severe–critical	14	3125.1	60	3122.0	76.7 (54.6–89.1)	5	3106.2	34	3082.6	85.4 (54.2–96.9)
Severity-adjusted symptomatic Covid-19¶	117	3116.5	351	3095.9	68.1 (60.3–74.3)	66	3102.0	195	3070.5	69.0 (56.7–77.6)
18−59 yr	95	2106.8	260	2095.0	65.8 (56.2–73.1)	52	2097.6	152	2077.0	69.3 (57.4–77.7)
≥60 yr	22	1009.6	91	1001.0	74.5 (57.9–84.3)	14	1004.4	43	993.5	67.9 (38.2–82.8)
Moderate to severe–critical Covid-19, including noncentrally confirmed cases	173	3113.9	509	3089.1	66.3 (59.9–71.8)	113	3100.3	324	3065.9	65.5 (57.2–72.4)
Covid-19, according to FDA harmonized definition‖	114	3116.6	345	3,096.3	67.2 (59.3–73.7)	65	3102.0	193	3070.6	66.7 (55.6–75.2)
Moderate to severe–critical Covid-19, according to Cox proportional-hazards model**	116	3116.6	348	3,096.1	66.9 (59.1–73.2)	66	3102.0	193	3070.7	66.2 (55.3–74.4)

^*All cases of coronavirus disease 2019 (Covid-19) were centrally confirmed unless stated otherwise and occurred in participants who had been seronegative at baseline and negative on reverse-transcriptase–polymerase-chain-reaction (RT-PCR) testing before 14 or 28 days after the administration of vaccine or placebo, for the respective end points, and were therefore at risk for Covid-19. The follow-up time for each participant was defined as the time from the administration of vaccine or placebo to the onset of Covid-19 or the last available trial measurement (January 22, 2021). Adjusted 95% confidence intervals are shown for moderate and severe–critical Covid-19, severe–critical Covid-19, severity-adjusted Covid-19, and moderate to severe–critical Covid-19, including non–centrally confirmed cases; unadjusted 95% confidence intervals are shown for other end points. The adjusted confidence interval was calculated with implementation of type I error control for multiple testing. Adjusted confidence intervals are presented for the end points that were prespecified for inferential evaluation at the primary analysis and on reaching the associated minimal required number of cases for that end point. Mild cases of Covid-19 were defined as a positive result on RT-PCR testing and the presence of at least one of the following symptoms: fever (body temperature, ≥38.0°C), sore throat, malaise, headache, myalgia, gastrointestinal symptoms, cough, chest congestion, runny nose, wheezing, skin rash, eye irritation or discharge, chills, loss of taste or smell, red or bruised looking feet or toes, or shaking chills or rigors. Moderate cases were defined as a positive RT-PCR test and either the presence of at least two of the following symptoms: fever (≥38.0°C), heart rate of at least 90 beats per minute, shaking chills or rigors, sore throat, cough, malaise, headache, myalgia, gastrointestinal symptoms, loss of taste or smell, or red or bruised-looking feet or toes; or the presence at least one of the following symptoms: respiratory rate of at least 20 breaths per minute, abnormal oxygen saturation (but >93% while the patient was breathing ambient air at sea level), clinical or radiologic evidence of pneumonia, radiologic evidence of deep-vein thrombosis, or shortness of breath or difficulty breathing. Severe–critical cases were defined as a positive RT-PCR test and the presence of at least one of the following features: clinical signs at rest that were indicative of severe systemic illness (respiratory rate of ≥30 breaths per minute, heart rate of ≥125 beats per minute, oxygen saturation of ≤93% while the patient was breathing ambient air at sea level, or partial pressure of oxygen divided by the fraction of inspired oxygen, <300 mm Hg); respiratory failure (defined as the use of high-flow oxygen, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation); shock; clinically meaningful acute renal, hepatic, or neurologic dysfunction; intensive care unit admission; or death.

^†The at-risk population for this analysis excluded participants who were RT-PCR–positive between days 1 and 14 after the administration of vaccine or placebo.

^‡The at-risk population for this analysis excluded participants who were RT-PCR–positive between days 1 and 28 after the administration of vaccine or placebo.

^§The vaccine efficacy was not calculated (NC) if fewer than 6 cases were observed for an end point.

^¶Shown is the weighted version of the estimates of vaccine efficacy against mild, moderate, and severe–critical Covid-19.¹⁸

^‖The Food and Drug Administration (FDA) harmonized definition of Covid-19 was defined as a positive RT-PCR test and the presence of Covid-19 symptoms consistent with the FDA harmonized definition at the time that the protocol was written: fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, or diarrhea.

^**A supportive analysis with the use of a Cox proportional-hazards regression model of the time to moderate to severe–critical Covid-19 was used to estimate vaccine efficacy.