A study of the Ad26.COV2.S vaccine candidate for the prevention of SARS-CoV-2-mediated COVID-19 in adults

Number of participants who were seronegative at baseline with first occurrence of molecularly confirmed moderate to severe/critical COVID-19, with onset at least 14 days after the 2nd vaccination, monitored from 14 days after 2nd vaccination (Day 71) to end of study (2 years and 3 months). Moderate defined as one sign or symptom form a list of signs and symptoms, such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of signs and symptoms or severe COVID-19 defined in US Food and Drug Administration (FDA) guidance.

1. Number of participants, regardless of their serostatus, with first occurrence of molecularly confirmed moderate to severe/critical COVID-19, monitored from 1 day after the 1st vaccination (Day 2) to end of study (2 years and 3 months). Moderate defined as one sign or symptom form a list of signs and symptoms, such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of signs and symptoms or severe COVID-19 defined in USA Food and Drug Administration (FDA) guidance.
2. Number of participants, regardless of their serostatus, with first occurrence of molecularly confirmed moderate to severe/critical COVID-19, with onset at least 14 days after 2nd vaccination, monitored from 14 days after the 2nd vaccination (Day 71) to end of study (2 years and 3 months). Moderate defined as one sign or symptom form a list of signs and symptoms, such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of signs and symptoms or severe COVID-19 defined in USA Food and Drug Administration (FDA) guidance.
3. Number of participants who were seronegative at baseline with first occurrence of molecularly confirmed moderate to severe/critical COVID-19, monitored from 1 day after the 1st vaccination (Day 2) to end of study (2 years and 3 months). Moderate defined as one sign or symptom form a list of signs and symptoms, such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of signs and symptoms or severe COVID-19 defined in US Food and Drug Administration (FDA) guidance.
4. Number of participants who were seronegative at baseline with first occurrence of molecularly confirmed moderate to severe/critical COVID-19, with onset at least 14 days after 1st vaccination, monitored from 14 days after the 1st vaccination (Day 15) to end of study (2 years and 3 months). Moderate defined as one sign or symptom form a list of signs and symptoms, such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of signs and symptoms or severe COVID-19 defined in USA Food and Drug Administration (FDA) guidance.
5. Number of participants with first occurrence of COVID-19 requiring medical intervention (such as a composite endpoint of hospitalization, intensive care unit (ICU) admission, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO), linked to objective measures such as decreased oxygenation, X-ray or computed tomographic [CT] findings) linked to any molecularly confirmed, COVID-19, with onset at least 14 days after the 2nd vaccination, monitored from 14 days after the 2nd vaccination (Day 71) to end of study (2 years and 3 months)
6. SARS-CoV-2 viral load assessed by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) in participants with molecularly confirmed, moderate to severe/critical COVID-19, measured during the course of a COVID-19 episode, from 14 days after the 2nd vaccination (Day 71) to end of study (2 years and 3 months). Nasal swabs will be used to detect and/or quantify SARS-CoV-2.
7. Number of participants with first occurrence of molecularly confirmed mild COVID-19, with onset at least 14 days after 2nd vaccination, monitored from 14 days after the 2nd vaccination (Day 71) to end of study (2 years and 3 months. Molecularly confirmed mild COVID-19 is defined as a SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract sample (for example, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other sample. Mild COVID-19 includes: fever, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, cough, chest congestion, runny nose, wheezing, skin rash, eye irritation or discharge, or chills, without shortness of breath or dyspnea.
8. Number of participants with first occurrence of molecularly confirmed COVID-19 defined by the US FDA harmonized case definition, with onset at least 14 days after 2nd vaccination, monitored from 14 days after the 2nd vaccination (Day 71) to end of study (2 years and 3 months). Molecularly confirmed moderate and severe/critical COVID-19 defined as a positive SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract sample (for example, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other sample; and COVID-19 symptoms consistent with those defined by the US FDA harmonized case definition at the time of finalization of this protocol: 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, diarrhea.
9. Burden of Disease (BOD) based on first occurrence of molecularly confirmed symptomatic COVID-19 (including mild, moderate, or severe/critical COVID-19) with onset at least 14 days after 2nd vaccination, monitored from 14 days after the 2nd vaccination (Day 71) to end of study (2 years and 3 months).
10. Number of participants with serologic conversion, determined by Enzyme-Linked Immunosorbent Assay (ELISA) and/or SARS-CoV-2 immunoglobulin assay that is dependent on the SARS-CoV-2 nucleocapsid (N) protein, between baseline (Day 1) and 14 days, 6 months, and 1 year after the 2nd vaccination
11. Number of participants with first occurrence of SARS-CoV-2 infection that is either serologically and/or molecularly confirmed, with onset at least 14 days after 2nd vaccination, monitored from 14 days after the 2nd vaccination (Day 71) to end of study (2 years and 3 months).
12. Number of participants with serious adverse events (SAEs) monitored from Day 1 to end of study (2 years and 3 months). An SAE is any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product.
13. Number of participants with medically-attended adverse events (MAAEs), monitored from Day 1 to 6 months after 2nd vaccination (up to 34 weeks). MAAEs are defined as AEs with medically-attended visits including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason. Routine study visits will not be considered medically-attended visits. New onset of chronic diseases will be collected as part of MAAEs.
14. Number of participants with medically-attended adverse events (MAAEs) leading to study discontinuation, monitored from Day 1 to end of study (2 years and 3 months). MAAEs are defined as AEs with medically-attended visits including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason. Routine study visits will not be considered medically-attended visits. New onset of chronic diseases will be collected as part of MAAEs.
15. Number of participants with solicited local adverse events (AEs) with onset in the 7 day- period after the first or second vaccination, assessed up to day 8 (7 days after first vaccination on Day 1) and up to Day 64 (7 days after second vaccination on Day 57). Participants will be asked to note in the e-Diary occurrences of injection site pain/tenderness, erythema, and swelling at the study vaccine injection site daily for 7 days post each vaccination (day of each vaccination and the subsequent 7 days).
16. Number of participants with solicited systemic AEs with onset in the 7-day period after the first or second vaccination, measured up to Day 8 (7 days after first vaccination on Day 1) and up to Day 64 (7 days after second vaccination on Day 57). Participants will be instructed on how to record daily temperature using a thermometer provided for home use. Participants should record the temperature in the e-Diary in the evening of the day of each vaccination, and then daily for the next 7 days approximately at the same time each day. If more than 1 measurement is made on any given day, the highest temperature of that day will be recorded in the e-Diary. Fever is defined as endogenous elevation of body temperature >= 38.0 degrees Celsius or >= 100.4 degrees Fahrenheit, as recorded in at least one measurement. Participants will also be instructed on how to note signs and symptoms in the e-Diary on a daily basis for 7 days post each vaccination (day of each vaccination and the subsequent 7 days), for the following events: fatigue, headache, nausea, myalgia.
17. Number of participants with unsolicited local adverse events (AEs) with onset in the 28-day period after the first or second vaccination, measured up to Day 29 (28 days after first vaccination on Day 1), and up to Day 85 (28 days after second vaccination on Day 58). Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant diary.
18. SARS-CoV-2 binding antibodies assessed by ELISA (as a measure for humoral immune response) for up to 2 years and 3 months.

Removed 01/02/2021:
19. SARS-CoV-2 neutralizing antibody titers assessed by Virus Neutralization Assay (VNA) (as a measure for humoral immune response) for up to 2 years and 3 months.

Added 20/04/2021:
19. Number of participants with first occurrence of Molecularly confirmed Moderate to Severe/Critical COVID-19 and who were Seronegative at baseline, monitored from 28 days after the first vaccination (day 29) to end of study (2 years and 3 months). Moderate defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of sign and symptoms or severe COVID-19 defined in FDA guidance.
20. Number of participants with Asymptomatic infection detected by reverse Transcriptase-Polymerase chain reaction (RT-PCR) for up to 2 years and 3 months. Number of participants with asymptomatic infection as assessed by RT-PCR will be reported.