Definition: serious adverse events (SAEs)	Definition: severe or critical disease
RNA‐based
BNT162b2 – BioNTech/Fosun Pharma/Pfizer
Walsh 2020	An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life‐threatening; requires inpatient hospitalisation or prolongation of existing hospitalisation; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other situations. Medical or scientific judgement should be exercised in deciding whether SAE reporting is appropriate in other situations, such as important medical events that may not be immediately life‐threatening or result in death or hospitalisation, but may jeopardize the participant or may require medical or surgical intervention to prevent 1 of the other outcomes listed in the above definition.	NR
Frenck 2021	An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life‐threatening; requires inpatient hospitalisation or prolongation of existing hospitalisation; results in persistent disability/incapacity; is a congenital anomaly/birth defect.	Diagnosis of severe COVID‐19 included confirmed COVID‐19 and the presence of any of the following: (1) clinical signs at rest indicative of severe systemic illness (e.g. respiratory rate ≥ 30 breaths/min, heart rate ≥ 125 beats/min, SpO2 ≤ 93% on room air at sea level, or PaO2/FiO2 < 300 mmHg; (2) respiratory failure (i.e. needing high‐flow oxygen, non‐invasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation); (3) evidence of shock (i.e. systemic blood pressure < 90 mmHg, diastolic blood pressure < 60 mmHg, or requiring vasopressors); (4) significant acute renal, hepatic, or neurological dysfunction; (5) intensive care unit admission; or (6) death.
Thomas 2021	An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life‐threatening; requires inpatient hospitalisation or prolongation of existing hospitalisation; results in persistent disability/incapacity; is a congenital anomaly/birth defect.	Confirmed severe COVID‐19 required confirmation of COVID‐19 and the presence of ≥ 1 of the following: clinical signs at rest indicative of severe systemic illness (respiratory rate ≥ 30 breaths/min, heart rate ≥ 125 beats/min, SpO2 ≤ 93% on room air at sea level, or PaO2/FiO2 < 300 mmHg); respiratory failure (defined as needing high‐flow oxygen, non‐invasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation); evidence of shock (systolic blood pressure < 90 mmHg, diastolic blood pressure < 60 mmHg, or requiring vasopressors); significant acute renal, hepatic, or neurological dysfunction; intensive care unit admission; death; or a combination of these.
mRNA‐1273 – ModernaTX
Ali 2021	An SAE results in any of the following outcomes: death; is life‐threatening; requires inpatient hospitalisation or prolongation of existing hospitalisation; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; is a congenital anomaly or birth defect; is a medically important event.	NR
El Sahly 2021	An adverse event (including an adverse reaction) is considered an SAE if, in the view of either the investigator or sponsor, it results in any of the following outcomes: death; is life‐threatening; inpatient hospitalisation or prolongation of existing hospitalisation; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; congenital anomaly or birth defect; medically important event.	Confirmed severe COVID‐19 requires any of the following criteria had to be met: clinical signs of severe systemic illness; respiratory rate ≥ 30 breaths/min; heart rate ≥ 125 beats/min; SpO2 ≤ 93% on room air at sea level or PaO2/FIO2 < 300 mmHg, or respiratory failure or acute respiratory distress syndrome (defined as needing high‐flow oxygen, non‐invasive or mechanical ventilation, or extracorporeal membrane oxygenation); evidence of shock (systolic blood pressure < 90 mmHg, diastolic blood pressure < 60 mmHg or requiring vasopressors) or significant acute renal, hepatic or neurological dysfunction or admission to an intensive care unit or death.
CVnCoV – CureVac AG
Kremsner 2021	NR	Severe COVID‐19 was defined by clinical signs at rest that are indicative of severe systemic illness (respiratory rate ≥ 30 breaths/min, heart rate ≥ 125 beats/min, altitude‐adjusted SpO2 ≤ 93% or PaO2/FIO2 < 300 mmHg), respiratory failure, evidence of shock, significant renal, hepatic, or neurological dysfunction, admission to an intensive care unit, or death.
Non‐replicating viral vector
ChAdOx1/SII‐ChAdOx1 nCoV‐19 – AstraZeneca + University of Oxford
Asano 2022	Severity of safety endpoints was assessed according to toxicity grading scales adapted from Food and Drug Administration (FDA) grading guidance	NR
Emary 2021	NR	NR
Falsey 2021	An adverse event that fulfils ≥ 1 of the following criteria: results in death; is immediately life‐threatening; requires in‐participant hospitalisation or prolongation of existing hospitalisation; results in persistent or significant disability or incapacity; is a congenital abnormality or birth defect; is an important medical event that may jeopardize the participant or may require medical treatment to prevent 1 of the outcomes listed above.	Laboratory‐confirmed COVID‐19 (SARS‐CoV‐2 RT‐PCR‐positive symptomatic illness) plus any of the following: clinical signs at rest indicative of severe systemic illness (respiratory rate ≥ 30 breaths/min, heart rate ≥ 125 beats/min, oxygen saturation ≤ 93% on room air at sea level, or PaO2/FIO2 < 300 mmHg); respiratory failure (defined as needing high‐flow oxygen, non‐invasive ventilation, mechanical ventilation or extracorporeal membrane oxygenation); evidence of shock (systolic blood pressure < 90 mmHg, diastolic blood pressure < 60 mmHg, or requiring vasopressors); significant acute renal, hepatic, or neurological dysfunction; admission to an intensive care unit; death.
Kulkarni 2021	All adverse events were graded for severity using the Division of AIDS (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (corrected version 2.1, July 2017) from the US Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases.	Severe cases as per the WHO clinical progression scale
Madhi 2021b	NR	As defined by WHO ordinal scale
Voysey 2021a	NR	Severe COVID‐19 (WHO clinical progression score ≥ 6)
Gam‐COVID‐Vac (Sputnik V) – Gamaleya Research Institute
Logunov 2021	SAEs were diagnosed on the basis of the event requiring hospital admission.	Moderate or severe COVID‐19: fever > 38.5 °C; respiratory rate > 22 breaths/min; shortness of breath during physical exertion; pneumonia (confirmed by computed tomography of the lungs); oxygen saturation level < 95%.
Ad26.COV2.S – Janssen Pharmaceutical Companies
Sadoff 2021a	NR	NR
Sadoff 2021b	An SAE based on ICH and EU guidelines on pharmacovigilance for medicinal products for human use is any untoward medical occurrence that at any dose: results in death; is life‐threatening (the participant was at risk of death at the time of the event; it does not refer to an event that hypothetically might have caused death if it were more severe); requires inpatient hospitalisation or prolongation of existing hospitalisation; 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; is medically important.	A SARS‐CoV‐2 positive RT‐PCR or molecular test result. Respiratory rate ≥ 30 breaths/min; heart rate ≥ 125 beats/min; oxygen saturation (SpO2) ≤ 93% on room air at sea level, or PaO2/FiO2 < 300 mmHg; respiratory failure; evidence of shock; significant acute renal, hepatic, or neurological dysfunction; admission to the ICU; death
Inactivated virus
BBV152 – Bharat Biotech
Ella 2021a	NR	NR
Ella 2021b	NR	NR
CoronaVac – Sinovac
Zhang 2021	NR	NR
Bueno 2021	Any untoward medical occurrence that: results in death; is life‐threatening (i.e. the subject was, in the opinion of the investigator, at immediate risk  of death from the event as it occurred; it does not refer to an event which hypothetically might have caused death if it were more severe); requires or prolongs subject’s hospitalisation; results in persistent or significant disability/incapacity (i.e. the event causes a substantial disruption of a personal ability to conduct normal life functions); results in a congenital anomaly/birth defect; requires intervention to prevent permanent impairment or damage; is an important and significant medical event that may not be immediately life‐threatening or resulting in death or hospitalisation but, based upon appropriate medical judgement, may jeopardize the subject or may require intervention to prevent 1 of the other outcomes listed above.	NR
Han 2021	NR	NR
Fadlyana 2021	NR	Severe or critical COVID‐19 confirmed by RT‐PCR
Palacios 2020	Any adverse event that results in any of the following outcomes: death; threat to life; there is a risk of death at the time of the event; hospitalisation or extension of hospitalisation; significant or persistent disability; congenital anomaly; any suspicion of transmission of an infectious agent by means of a medication; clinically significant event; any event resulting from the use of drugs that require medical intervention, in order to avoid death, risk to life, significant disability or hospitalisation.	Score ≥ 6 on WHO 10‐point clinical progression scale (hospitalized with severe COVID‐19 through to death)
Tanriover 2021	An SAE is an adverse event that results in any of the following outcomes, whether or not considered related to the study intervention: death; life‐threatening event (i.e. the volunteer was, in the view of the investigator, at immediate risk of death from the event that occurred);  persistent or significant disability or incapacity (i.e. substantial disruption of one’s ability to carry out normal life functions); hospitalisation or prolongation of existing hospitalisation, regardless of length of stay, even if it is a precautionary measure for continued observation (hospitalisation (including inpatient or outpatient hospitalisation for an elective procedure) for a pre‐existing condition that has not worsened unexpectedly does not constitute an SAE); an important medical event (that may not cause death, be life‐threatening, or require hospitalisation) that may, based upon appropriate medical judgement, jeopardise the volunteer, require medical or surgical intervention to prevent 1 of the outcomes listed above, or a combination of these. Examples of such medical events include allergic reaction requiring intensive treatment in an emergency room or clinic, blood dyscrasias, or convulsions that do not result in inpatient hospitalisation.	WHO clinical progression scale ≥ 6: hospitalized, needing oxygen by non‐invasive or high‐flow ventilation or worse
Wu 2021a	Events during the clinical trial that need hospitalisation treatment, prolong hospitalisation time, disability, affect working ability, endanger life or death, cause congenital malformation, etc.	NR
WIBP‐CorV – Sinopharm Wuhan
Al Kaabi 2021	NR	Confirmed COVID‐19 case, meeting any 1 of the following criteria: respiratory distress (respiratory rate ≥ 30 breaths/min); O2 saturation ≤ 93% at rest; PaO2/FiO2 < 300 mmHg (1 mmHg = 0.133 kPa); clinical symptoms progressively worsened, and chest imaging showed > 50% obvious lesion progression within 24–48 hours.
Guo 2021	NR
Protein subunit
NVX‐CoV2373 – Novavax
Dunkle 2021	NR	Severe refers to ≥ 1 of the following: tachypnoea ≥ 30 breaths/min at rest; resting heart rate ≥ 125 beats/min; SpO2 ≤ 93% on room air or PaO2/FiO2 < 300 mmHg; high‐flow O2 therapy or non‐invasive ventilation/non‐invasive positive pressure ventilation (e.g. continuous positive airway pressure or bilevel positive airway pressure; mechanical ventilation or extracorporeal membrane oxygenation; ≥ 1 major organ system dysfunction or failure to be defined by diagnostic testing/clinical syndrome/interventions, including any of the following – acute respiratory failure, including acute respiratory distress syndrome, acute renal failure, acute hepatic failure, acute right or left heart failure, septic or cardiogenic shock (with shock defined as systolic blood pressure < 90 mmHg or diastolic blood pressure < 60 mmHg), acute stroke (ischaemic or haemorrhagic), acute thrombotic event; acute myocardial infarction, deep vein thrombosis, pulmonary embolism, requirement for: vasopressors, systemic corticosteroids, or haemodialysis; admission to an intensive care unit; death.
Formica 2021	NR	NR
Heath 2021	An SAE is defined as any event that results in death, is immediately life‐threatening, requires inpatient hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.	Tachypnoea ≥ 30 breaths/min at rest; resting heart rate ≥ 125 beats/min; SpO2 ≤ 93% on room air or PaO2/FiO2 < 300 mmHg; high‐flow O2 therapy or non‐invasive ventilation/non‐invasive positive pressure ventilation (e.g. continuous positive airway pressure or bilevel positive airway pressure; mechanical ventilation or extracorporeal membrane oxygenation; ≥ 1 major organ system dysfunction or failure to be defined by diagnostic testing/clinical syndrome/interventions, including any of the following – acute respiratory failure, including acute respiratory distress syndrome, acute renal failure, acute hepatic failure, acute right or left heart failure, septic or cardiogenic shock (with shock defined as systolic blood pressure < 90 mmHg or diastolic blood pressure < 60 mmHg), acute stroke (ischaemic or haemorrhagic), acute thrombotic event; acute myocardial infarction, deep vein thrombosis, pulmonary embolism, requirement for: vasopressors, systemic corticosteroids, or haemodialysis; admission to an intensive care unit; death.
Shinde 2021	NR	Severe refers to ≥ 1 of the following: tachypnoea ≥ 30 breaths/min at rest; resting heart rate ≥ 125 beats/min; SpO2 ≤ 93% on room air or PaO2/FiO2 < 300 mmHg; high‐flow O2 therapy or non‐invasive ventilation/non‐invasive positive pressure ventilation (e.g. continuous positive airway pressure or bilevel positive airway pressure; mechanical ventilation or extracorporeal membrane oxygenation; ≥ 1 major organ system dysfunction or failure to be defined by diagnostic testing/clinical syndrome/interventions, including any of the following – acute respiratory failure, including acute respiratory distress syndrome, acute renal failure, acute hepatic failure, acute right or left heart failure, septic or cardiogenic shock (with shock defined as systolic blood pressure < 90 mmHg or diastolic blood pressure < 60 mmHg), acute stroke (ischaemic or haemorrhagic), acute thrombotic event; acute myocardial infarction, deep vein thrombosis, pulmonary embolism, requirement for: vasopressors, systemic corticosteroids, or haemodialysis; admission to an intensive care unit; death.
FINLAY‐FR‐2 – Instituto Finlay de Vacunas
Toledo‐Romani 2021	NR	Severe systemic confirmed COVID‐19 disease (serious or critical), defined by 1 of the following criteria: polypnoea; x‐ray infiltration/condensation, pulmonary echography; oxygen saturation ≤ 90% or assisted mechanical ventilation (serious disease), acute respiratory distress syndrome or evidence of septic shock (critical disease).
Heterologous vaccination
Liu 2021	Any untoward medical occurrence that: results in death; is life‐threatening; requires inpatient hospitalisation or prolongation of existing hospitalisation; results in persistent or significant disability/incapacity; consists of a congenital anomaly or birth defect.	NR