Table 1 Summary of included studies

1

Bae et al., 2021

Adverse Reactions Following the First Dose of ChAdOx1 nCoV-19 Vaccine and BNT162b2 Vaccine for Healthcare Workers in South Korea

To report the adverse reactions following the first dose of two types of vaccines against coronavirus disease 2019 (COVID-19) in healthcare workers (HCWs) in South Korea.

South Korea

March 5 and March 26, 2021.

Cross-sectional

A mobile self-report questionnaire

Healthcare workers involved in general patient care

In our prospective survey, vaccine-associated adverse reactions were more commonly reported in the ChAdOx1 group than in the BNT162b2 group. Females and younger age groups experienced vaccine-associated adverse reactions more frequently.

2

Jeon et al., 2021

Adverse Events Following Immunization Associated with Coronavirus Disease 2019 Vaccination Reported in the Mobile Vaccine Adverse Events Reporting System

To investigate the adverse events following immunization (AEFIs) for COVID-19 among healthcare workers (HCWs).

Republic of Korea.

March 3 to March 22, 2021

A retrospective,single-center cohort study

The MVAERS project developed a mobile web page to systematically capture spontaneous reporting of AEFIs.

HCWs who had completed the first dose of the ChAdOx1 nCov-19 vaccine.

The AEFIs associated with the ChAdOx1 nCoV-19 vaccine were tolerable, and the use of the MVAERS was helpful in monitoring the AEFIs. The use of MVAERS will help in sharing accurate and ample information about vaccination against COVID-19.

3

Pottegård et al., 2021

Arterial events, venous thromboembolism, thrombocytopenia, and bleeding after vaccination with Oxford-AstraZeneca ChAdOx1-S in Denmark and Norway: population based cohort study

To assess rates of cardiovascular and hemostatic events in the first 28 days after vaccination with the Oxford-AstraZeneca vaccine ChAdOx1-S in Denmark and Norway and to compare them with rates observed in the general populations.

Denmark

Norway

9 February 2021 to 11 March 2021

Population-based cohort study

Complete follow-up based on computerized Danish healthcare registries, with full population coverage and daily updates.

All people aged 18–65 years who received a first vaccination with ChAdOx1-S

Among recipients of ChAdOx1-S, increased rates of venous thromboembolic events, including cerebral venous thrombosis, were observed. For the remaining safety outcomes, results were largely reassuring, with slightly higher rates of thrombocytopenia/coagulation disorders and bleeding, which could be influenced by increased surveillance of vaccine recipients. The absolute risks of venous thromboembolic events were, however, small, and the findings should be interpreted in the light of the proven beneficial effects of the vaccine, the context of the given country, and the limitations to the generalizability of the study findings.

4

Kim et al., 2021

Adverse events in healthcare workers after the first dose of ChAdOx1 nCoV-19 or BNT162b2 mRNA COVID-19 vaccination: a single center experience

To investigate adverse events (AEs) of the first dose of each vaccine, any symptom was collected daily for seven days after vaccination in a tertiary hospital.

South Korea

Began on March 5, 2021, and lasted for 7 days

Prospective cohort

Symptoms were recorded using a self-report form.

Healthcare workers (HCWs)

Reported AEs were more common in recipients with ChAdOx1 nCoV-19 than in those with BNT162b2. However, most of the reported AEs were mild to moderate in severity. Sufficient explanation and preparation for expected AEs required to promote widespread vaccination.

5

Vasileiou et al., 2021

Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study

To investigate the association between the mass roll-out of the first doses of these COVID-19 vaccines and hospital admissions for COVID-19.

Scotland

Dec 8, 2020, and Feb 22, 2021

Open, real-time prospective observational cohort study

Using a unique dataset ( of the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19—EAVEII—database) consisting of linked vaccination, primary care, laboratory testing (from the Electronic Communication of Surveillance in Scotland (ECOSS),8, hospital admission, and mortality data

People in Scotland who were registered in Surveillance of COVID-19 EAVE II—database

People in Scotland who were registered in Surveillance of COVID-19 EAVE II—database

6

Menni et al., 2021

Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study

Aimed to investigate the safety and effectiveness of these vaccines in a UK community setting.

London, UK

Boston, MA, USA

Lund, Sweden

Uppsala, Sweden

Dec 8, 2020, and March 10, 2021

A prospective observational study “COHORT”

Self-reported information related to SARS-CoV-2 infection by App was developed by health data company ZOE Global, with input from King’s College London (London, UK)

Individuals older than 18 years can sign up to the app without any restrictions. Individuals can also record information for dependents younger than 18 years.

Systemic and local side-effects after BNT162b2 and ChAdOx1 nCoV-19 vaccination occur at frequencies lower than reported in phase 3 trials. Both vaccines decrease the risk of SARS-CoV-2 infection after 12 days.

7

Bernal et al., 2021

Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on COVID-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study

To estimate the real-world effectiveness of the Pfizer-BioNTech BNT162b2 and Oxford-AstraZeneca ChAdOx1-S vaccines against confirmed COVID-19 symptoms (including the UK variant of concern B.1.1.7), admissions to hospital, and deaths.

England

8 December 2020 and 19 February 2021

Test negative case-control study

Laboratory findings and/or based on PCR test

All adults aged 70 years or older in England (>7.5 million people) were eligible for inclusion.

Vaccination with either one dose of BNT162b2 or ChAdOx1-S was associated with a significant reduction in symptomatic COVID-19 in older adults, and with further protection against severe disease. Both vaccines showed similar effects. Protection was maintained for the duration of follow-up (>6 weeks). A second dose of BNT162b2 was associated with further protection against symptomatic disease. A clear effect of the vaccines against the B.1.1.7 variant was found.

8

Althaus et al., 2021

Antibody-mediated procoagulant platelets in SARS-CoV-2-vaccination associated immune thrombotic thrombocytopenia

To report pathological and immunological findings in 8 patients who developed vaccine-induced immune thrombotic thrombocytopenia (VITT) after administration of SARS-CoV-2 vaccine ChAdOx1 nCoV-19.

London, UK

February 1 and April 6, 2021.

Cohort study

Clinical or laboratory findings and/or based on computed tomography, ultrasound imaging or in case of death by autopsy.

8 patients were referred to different university hospitals with neurological or hematological symptoms after vaccination with ChAdOx1 nCoV-19

Sera from VITT patients contain high titer antibodies against platelet factor 4 (PF4) (OD 2.59±0.64). PF4 antibodies in VITT patients induced significant increase in procoagulant markers (P-selectin and phosphatidylserine externalization) compared to healthy volunteers and healthy vaccinated volunteers. The generation of procoagulant platelets was PF4 and heparin dependent. We demonstrate the contribution of antibody-mediated platelet activation in the pathogenesis of VITT.

9

Folegatti et al., 2020

Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomized controlled trial

To assess the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of SARS-CoV-2.

Five centers in the UK

April 23 to May 21, 2020

A preliminary report of a phase 1/2, single-blind, randomized controlled trial

Humoral responses at baseline and following vaccination were assessed using a standardized total IgG ELISA against trimeric SARS-CoV-2 spike protein, a multiplexed immunoassay, three live SARS-CoV-2 neutralization assays (a 50% plaque reduction neutralization assay [PRNT50]; a microneutralization assay [MNA50, MNA80, and MNA90]; and Marburg VN), and a pseudo-virus neutralization assay. Cellular responses were assessed using an ex-vivo interferon-γ enzyme-linked immune-spot assay.

Healthy adults aged 18–55 years with no history of laboratory confirmed SARS-CoV-2 infection or of COVID-19-like symptoms

ChAdOx1 nCoV-19 showed an acceptable safety profile, and homologous boosting increased antibody responses. These results, together with the induction of both humoral and cellular immune responses, support large-scale evaluation of this candidate vaccine in an ongoing phase 3 program.

10

Greinacher et al., 2021

Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination

To assess the clinical and laboratory features of 11 patients in Germany and Austria in whom thrombosis or thrombocytopenia had developed after vaccination with ChAdOx1 nCov-19.

Germany

Austria

Mid-February 2021 to March 15, 2021

Case series

Clinical and laboratory findings by using a standard enzyme-linked immunosorbent assay

Patients in Germany and Austria in whom thrombosis or thrombocytopenia had developed after vaccination with ChAdOx1 nCov-19.

Vaccination with ChAdOx1 nCov-19 can result in the rare development of immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, which clinically mimics autoimmune heparin-induced thrombocytopenia.

11

Wolf et al., 2021

Thrombocytopenia and Intracranial Venous Sinus Thrombosis after “COVID-19 Vaccine AstraZeneca” Exposure

To describe the clinical manifestations and the concerning management of patients with cranial venous sinus thrombosis following first exposure to the “COVID-19 vaccine AstraZeneca”.

Germany

Began in early March 2021,

Case reports

The clinical, laboratory, and imaging findings and the results of endovascular and medicinal interventions were analyzed

Three women with intracranial venous sinus thrombosis after their first vaccination with “COVID-19 vaccine AstraZeneca” were encountered.

Early observations insinuate that the exposure to the “COVID-19 vaccine AstraZeneca” might trigger the expression of antiplatelet antibodies, resulting in a condition with thrombocytopenia and venous thrombotic events (e.g., intracranial venous sinus thrombosis). These patients’ treatment should address the thrombo-embolic manifestations, the coagulation disorder, and the underlying immunological phenomena.

12

Schultz et al., 2021

Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination

To report findings in five patients who presented with venous thrombosis and thrombocytopenia 7 to 10 days after receiving the first dose of the ChAdOx1 nCoV-19 adenoviral vector vaccine against coronavirus disease 2019 (COVID-19).

London, UK

March 20, 2021, to March 30, 2021,

Case Reports

Clinical and laboratory findings

Five patients who presented with venous thrombosis and thrombocytopenia 7 to 10 days after receiving the first dose of the ChAdOx1 nCoV-19

Because the five cases occurred in a population of more than 130,000 vaccinated persons, we propose that they represent a rare vaccine-related variant of spontaneous heparin-induced thrombocytopenia that we refer to as vaccine-induced immune thrombotic thrombocytopenia.

13

Scully et al., 2021

Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination

To report findings in 23 patients who presented with thrombosis and thrombocytopenia 6 to 24 days after receiving the first dose of the ChAdOx1 nCoV-19 vaccine (AstraZeneca).

London, UK

N/A

Cohort study

Clinical and laboratory findings by testing for anti-PF4 antibodies was performed by means of enzyme-linked immunosorbent assays (ELISAs) at six reference laboratories in the UK and testing for anti-PF4 antibodies was performed by means of various techniques used locally for HIT testing at individual centers.

Patients were identified for the investigation of suspected vaccine-induced thrombosis and thrombocytopenia (i.e., vaccine-induced immune thrombotic thrombocytopenia, or VITT).

Vaccination against SARS-CoV-2 remains critical for control of the COVID-19 pandemic. A pathogenic PF4 dependent syndrome, unrelated to the use of heparin therapy, can occur after the administration of the ChAdOx1 nCoV-19 vaccine. Rapid identification of this rare syndrome is important because of the therapeutic implications.

14

Tiede et al., 2021

Prothrombotic immune thrombocytopenia after COVID-19 vaccine

To report five cases of prothrombotic immune thrombocytopenia after exposure to the ChAdOx1 vaccine

Germany

8th March and 4th April 2021

Consecutive single-center cohort

Clinical and laboratory findings

The patients were women between 41 and 67 years of age and presented 5 to 11 days after their first vaccination with AZD1222 (2.5×1010 particles).

an unexpected autoimmune prothrombotic disorder is described after vaccination with AZD1222. It is characterized by thrombocytopenia and anti-PF4 antibodies binding to platelets in AZD1222 dependent manner. Initial clinical experience suggests a risk of unusual and severe thromboembolic events.

15

Tobiaqy et al., 2021

Analysis of thrombotic adverse reactions of COVID-19 AstraZeneca vaccine reported to Eudra vigilance database

To identify and analyze the thrombotic adverse reactions associated with Oxford-AstraZeneca vaccine

Saudi Arabia

February 17 and March 12, 2021.

Retrospective descriptive study “COHORT”

Spontaneous reports submitted to EV database

People who were registered in the EV database in relation to COVID-19 vaccine AstraZeneca

With 17 million people having had the AstraZeneca vaccine, these are extremely rare events The EMA’s Pharmacovigilance Risk Assessment Committee (18 March 2021) concluded that the vaccine was safe, effective and the benefits outweighed the risks. Conducting further analyses based on more detailed thrombotic adverse event reports, including patients’ characteristics and comorbidities, may enable assessment of the causality with higher specificity.