Vascular thrombosis after single dose Ad26.COV2.S vaccine in healthcare workers in South Africa: open label, single arm, phase 3B study (Sisonke study)

Barry Frank Jacobson; Elise Schapkaitz; Azwi Takalani; Pradeep Frank Rowji; Vernon Louw; Jessica Opie; Linda Gail Bekker; Nigel Garrett; Ameena Goga; Tarylee Reddy; Nonhlanhla Yende Zuma; Ian Sanne; Ishen Seocharan; Jonny Peter; Michelle Robinson; Shirley Collie; Amber Khan; Simbarashe Takuva; Glenda Gray

doi:10.1136/bmjmed-2022-000302

Vascular thrombosis after single dose Ad26.COV2.S vaccine in healthcare workers in South Africa: open label, single arm, phase 3B study (Sisonke study)

BMJ Med. 2023 Mar 23;2(1):e000302. doi: 10.1136/bmjmed-2022-000302. eCollection 2023.

Authors

Barry Frank Jacobson¹, Elise Schapkaitz¹, Azwi Takalani², Pradeep Frank Rowji³, Vernon Louw⁴, Jessica Opie⁴, Linda Gail Bekker⁵, Nigel Garrett⁵, Ameena Goga^{6

7}, Tarylee Reddy⁸, Nonhlanhla Yende Zuma⁹, Ian Sanne¹⁰, Ishen Seocharan⁸, Jonny Peter¹¹, Michelle Robinson¹², Shirley Collie¹³, Amber Khan¹, Simbarashe Takuva^{14

15}, Glenda Gray⁶

Affiliations

¹ Molecular Medicine and Haematology, University of the Witwatersrand Johannesburg Faculty of Health Sciences, Johannesburg, South Africa.
² Hutchinson Centre Research Institute of South Africa (HCRISA), Chris Hani Baragwanath Hospital, Johannesburg, South Africa.
³ The Southern African Society of Thrombosis and Haemostasis, Neurology Association of South Africa, Johannesburg, South Africa.
⁴ Division of Haematology, University of Cape Town, Cape Town, South Africa.
⁵ Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa.
⁶ HIV and Other Infectious Diseases Research Unit, South African Medical Research Council, Cape Town, South Africa.
⁷ Paediatrics and Child Health, University of Pretoria, Pretoria, South Africa.
⁸ Biostatistics Research Unit, South African Medical Research Council Durban, Durban, South Africa.
⁹ Nelson R Mandela School of Medicine, Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa.
¹⁰ Clinical HIV Research Unit, University of the Witwatersrand Johannesburg Faculty of Science, Johannesburg, South Africa.
¹¹ Division of Allergology and Clinical Immunology, University of Cape Town Lung Institute, Cape Town, South Africa.
¹² Right To Care, City of Johannesburg, Johannesburg, South Africa.
¹³ Discovery Health, Sandton, South Africa.
¹⁴ School of Health Systems and Public Health, University of Pretoria Faculty of Health Sciences, Pretoria, South Africa.
¹⁵ Perinatal HIV Research Unit, University of the Witwatersrand Johannesburg Faculty of Health Sciences, Johannesburg, South Africa.

Abstract

Objective: To assess the rates of vascular thrombotic adverse events in the first 35 days after one dose of the Ad26.COV2.S vaccine (Janssen/Johnson & Johnson) in healthcare workers in South Africa and to compare these rates with those observed in the general population.

Design: Open label, single arm, phase 3B study.

Setting: Sisonke study, South Africa, 17 February to 15 June 2021.

Participants: The Sisonke cohort of 477 234 healthcare workers, aged ≥18 years, who received one dose of the Ad26.COV2.S vaccine.

Main outcome measures: Observed rates of venous arterial thromboembolism and vaccine induced immune thrombocytopenia and thrombosis in individuals who were vaccinated, compared with expected rates, based on age and sex specific background rates from the Clinical Practice Research Datalink GOLD database (database of longitudinal routinely collected electronic health records from UK primary care practices using Vision general practice patient management software).

Results: Most of the study participants were women (74.9%) and median age was 42 years (interquartile range 33-51). Twenty nine (30.6 per 100 000 person years, 95% confidence interval 20.5 to 44.0) vascular thrombotic events occurred at a median of 14 days (7-29) after vaccination. Of these 29 participants, 93.1% were women, median age 46 (37-55) years, and 51.7% had comorbidities. The observed to expected ratios for cerebral venous sinus thrombosis with thrombocytopenia and pulmonary embolism with thrombocytopenia were 10.6 (95% confidence interval 0.3 to 58.8) and 1.2 (0.1 to 6.5), respectively. Because of the small number of adverse events and wide confidence intervals, no conclusions were drawn between these estimates and the expected incidence rates in the population.

Conclusions: Vaccine induced immune thrombocytopenia and thrombosis after one dose of the Ad26.COV2.S vaccine was found in only a few patients in this South African population of healthcare workers. These findings are reassuring if considered in terms of the beneficial effects of vaccination against covid-19 disease. These data support the continued use of this vaccine, but surveillance is recommended to identify other incidences of venous and arterial thromboembolism and to improve confidence in the data estimates.

Trial registration: ClinicalTrials.gov NCT04838795.

Keywords: COVID-19; Clinical trial; Hematologic diseases; Thromboembolism.

Associated data

ClinicalTrials.gov/NCT04838795