A binary response, whereby a participant with negative serostatus at baseline is defined as a COVID-19 case if their first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurs ≥ 15 days post second dose of study intervention. Otherwise, a participant is not defined as a COVID-19 case. The primary efficacy analysis was performed once approximately 150 events meeting the primary efficacy outcome measure definition had occurred across the AZD1222 and placebo groups.

The fully vaccinated analysis set (FVS) included all participants in the full analysis set (FAS) who were seronegative at baseline, received 2 doses of study intervention, and who remained on-study 15 days after their second dose without having had a prior SARS-CoV-2 RT-PCR-positive confirmed COVID-19 infection.

An AE is the development of any untoward medical occurrence in a clinical study participant administered medicinal product and which does not necessarily have a causal relationship with this medicinal product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

The safety analysis set included all participants who received at least 1 dose of study intervention from primary analysis data cut which is 1 participant less in placebo group than that from the final data cut.

An SAE is an AE occurring during any study phase that fulfils 1 or more of the following criteria: death; immediately life-threatening; in-participant hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; congenital abnormality or birth defect; an important medical event. AESIs were events of scientific and medical interest specific to the further understanding of the study intervention safety profile and required close monitoring and rapid communication by the investigators to the sponsor. MAAEs are defined as AEs leading to medically-attended visits that were not routine visits for physical examination or vaccination, such as an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Different follow-up time between AZD1222 and Placebo groups (20223 versus 3893 participant years).

The safety analysis set included all participants who received at least 1 dose of study intervention.

Solicited AEs are local or systemic predefined events for assessment of reactogenicity. Solicited AEs were collected in a e-Diary only for participants in the substudy.

The safety analysis set included all participants who received at least 1 dose of study intervention. Only participants included in the substudy were analyzed.

The incidence of the first post-intervention response (negative at baseline to positive post intervention with study intervention) for SARS-CoV-2 nucleocapsid antibodies occurring ≥ 15 days post second dose of study intervention (key secondary endpoint).

The FVS included all participants in the FAS who were seronegative at baseline, received 2 doses of study intervention, and who remained on-study 15 days after their second dose without having had a prior SARS-CoV-2 RT-PCR-positive confirmed COVID-19 infection.

The incidence of the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurring ≥ 15 days post second dose of study intervention using CDC criteria. Participant must present with at least 1 of the following symptoms per CDC criteria: fever, shortness of breath, difficulty breathing, chills, cough, fatigue, muscle aches, body aches, headache, new loss of taste, new loss of smell, sore throat, congestion, runny nose, nausea, vomiting, or diarrhea.

The FVS included all participants in the FAS who were seronegative at baseline, received 2 doses of study intervention, and who remained on-study 15 days after their second dose without having had a prior SARS-CoV-2 RT-PCR-positive confirmed COVID-19 infection.

The incidence of the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurring ≥ 15 days post second dose of study intervention using University of Oxford-defined symptom criteria: new onset of fever (> 100 °Fahrenheit [> 37.8 °Celsius]), cough, shortness of breath, or anosmia/ageusia.

The FVS included all participants in the FAS who were seronegative at baseline, received 2 doses of study intervention, and who remained on-study 15 days after their second dose without having had a prior SARS-CoV-2 RT-PCR-positive confirmed COVID-19 infection.

The incidence of the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurring ≥ 15 days post second dose of study intervention regardless of evidence of prior SARS-CoV-2 infection (key secondary endpoint).

The FVS regardless of prior SARS-COV-2 infection included all participants in the FAS who were seronegative at baseline, received 2 doses of study intervention, and who remained on-study 15 days after their second dose.

The incidence of SARS-CoV-2 RT-PCR-positive severe or critical symptomatic illness occurring ≥ 15 days post second dose of study intervention. The severity of COVID-19 was evaluated in participants with symptoms of COVID-19. Following are the findings regarding severe of critical symptomatic COVID-19: clinical signs at rest indicative of severe systemic illness; respiratory failure; evidence of shock; significant acute renal, hepatic, or neurologic dysfunction; admission to an intensive care unit; and death (key secondary endpoint).

The FVS included all participants in the FAS who were seronegative at baseline, received 2 doses of study intervention, and who remained on-study 15 days after their second dose without having had a prior SARS-CoV-2 RT-PCR-positive confirmed COVID-19 infection.

The incidence of SARS-CoV-2 RT-PCR-positive severe or critical symptomatic illness occurring post first dose of study intervention. The severity of COVID-19 was evaluated in participants with symptoms of COVID-19. Following are the findings regarding severe of critical symptomatic COVID-19: clinical signs at rest indicative of severe systemic illness; respiratory failure; evidence of shock; significant acute renal, hepatic, or neurologic dysfunction; admission to an intensive care unit; and death.

The FAS included all randomized participants who received at least 1 dose of study intervention, irrespective of their protocol adherence and continued participation in the study. Only participants who are seronegative at baseline were analyzed.

The incidence of COVID-19-related emergency department visits occurring ≥ 15 days post second dose of study intervention (key secondary endpoint).

The FVS included all participants in the FAS who were seronegative at baseline, received 2 doses of study intervention, and who remained on-study 15 days after their second dose without having had a prior SARS-CoV-2 RT-PCR-positive confirmed COVID-19 infection.

The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titer/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titer, where 'n' is the number of participants with titer information.

The immunogenicity analysis population included all participants in the safety analysis set who had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only participants included in the substudy were analyzed.

The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. GMFR was calculated as anti-logarithm of Σ (log base 2 transformed (post-vaccination titer/ pre-vaccination titer)/n). Where 'n' is the number of participants with titer information.

The immunogenicity analysis population included all participants in the safety analysis set who had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only participants included in the substudy were analyzed.

The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. The percentage of participants with a post-intervention seroresponse (≥ 4-fold rise in titers from baseline value to 28 days post each dose) to the S and RBD antigens of AZD1222 as measured by MSD serology assay is reported.

The immunogenicity analysis population included all participants in the safety analysis set who had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only participants included in the substudy were analyzed.

The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titer/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titer, where 'n' is the number of participants with titer information.

The immunogenicity analysis population included all participants in the safety analysis set who had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only participants included in the substudy were analyzed.

The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. GMFR was calculated as anti-logarithm of Σ (log base 2 transformed (post-vaccination titer/ pre-vaccination titer)/n). Where 'n' is the number of participants with titer information.

The immunogenicity analysis population included all participants in the safety analysis set who had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only participants included in the substudy were analyzed.

The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. The percentage of participants with a post-intervention seroresponse (≥ 4-fold rise in titers from baseline value to 28 days post each dose) to SARS-CoV-2 neutralizing antibodies of AZD1222 as measured by pseudo-neutralization assay is reported.

The immunogenicity analysis population included all participants in the safety analysis set who had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only participants included in the substudy were analyzed.

The incidence of SARS-CoV-2 RT-PCR-positive symptomatic illness occurring post first dose of study intervention.

The FAS included all randomized participants who received at least 1 dose of study intervention, irrespective of their protocol adherence and continued participation in the study. Only participants who are seronegative at baseline were analyzed.