The Sisonke Phase 3b clinical trial of the Johnson & Johnson COVID-19 vaccine, during which an impressive nearly 290,000 frontline South African health workers were vaccinated in less than two months, has reported positive levels of vaccine safety in The New England Journal of Medicine, writes MedicalBrief.
“The rate of adverse events with vaccination is low, and thromboembolic events have occurred mainly in persons with risk factors for thromboembolism,” says the 2 June 2021 letter to the journal editor by 11 leading medical researchers from six organisations in South Africa and the United States.
The authors include Professor Glenda Gray and Professor Linda-Gail Bekker, and the institutions are: Fred Hutchinson Cancer Research Center in the US; South African Medical Research Council; University of Cape Town; University of the Witwatersrand; the Centre for the AIDS Programme of Research in South Africa in Durban; and Right to Care in Johannesburg.
In a nutshell, 2% of the health workers reported adverse events but 81% of these were mild to moderate reactogenicity events.
Among 30 health workers, 12 had COVID-19 within 28 days after vaccination; 12 had allergic reactions, and six had neurologic conditions. Arterial, venous thrombotic or embolic events were reported in five health care workers with known risk factors, with one fatality.
All in all, according to a Supplementary Index published with the NEMJ article, there were seven deaths in the study. “Four participants aged 55, 56, 58 and 62 died of COVID-19 disease within 21 days of vaccination.”
“One participant already mentioned died of a pulmonary embolism, one of gastrointestinal bleeding from oesophageal varices and portal hypertension, and one from advanced HIV-Tuberculosis co-infection, renal failure and Escherichia coli septicaemia.”
In a 4 June 2021 article for Health24, journalist Zakiyah Ebrahim pointed out that the Sisonke study had noted no cases of the rare blood clotting condition – vaccine-induced immune thrombotic thrombocytopenia or VITT. Some 28 cases had been identified in vaccinated individuals in other countries.
Co-author Professor Ian Sanne, an infectious diseases specialist and CEO of Right to Care, told Health24 that VITT was the very specific immune-driven occurrence responsible for the temporary pause of the use of the vaccine in the US, European Union and South Africa.
The cause is of uncertain origin but its incidence – 1.7 events per 100,000 people vaccinated – “is infinitely lower than the complications of COVID infection”, Sanne told Health24.
The global J&J clinical trial, in which SA participated, reported in February that the J&J vaccine prevented all cases of hospitalisations and deaths related to COVID-19.
The Sisonke study
The Sisonke study, described on its website as “a pragmatic, real world Phase 3b clinical trial of the single-dose COVID-19 vaccine candidate among frontline healthcare workers in South Africa, is a collaboration between the National Department of Health, SA Medical Research Council, Desmond Tutu Health Foundation, CAPRISA, Janssen and Johnson & Johnson.
“It allows the government to make the Ad26.COV2.S COVID-19 vaccine (JnJ vaccine) immediately available to healthcare workers using a research programme. Sisonke is not the same as a clinical trial. Rather it is a way that research can help to make a vaccine available while the licensing process takes place.”
The government launched the initiative, the website says, “because it would be unethical to withhold a vaccine known to be safe and effective”. The South African Health Products Regulatory Authority (SAHPRA) approved the use of the vaccine for the trial while processing the full licensing.
Thromboembolic Events in the South African Ad26.COV2.S Vaccine Study
Simbarashe Takuva and Azwidhwi Takalani of the Fred Hutchinson Cancer Research Center in Seattle, United States; Glenda Gray and Ameena Goga of the South African Medical Research Council; Linda Gail-Bekker, Jonny Peter, Vernon Louw and Jessica Opie of the University of Cape Town; Nigel Garrett of the Centre for the AIDS Programme of Research in South Africa; Barry Jacobson of the University of the Witwatersrand, and Ian Sanne of Right to Care in Johannesburg.
Published in The New England Journal of Medicine on 2 June 2021.
Rare thromboembolic events have been observed during the vaccination rollout, which have prompted cautionary pauses in vaccinations by some regulatory authorities, including the South Africa Health Products Regulatory Authority.
Here, we report interim safety data from the first 288,368 participants who were vaccinated with Ad26.COV2.S in the Sisonke study – an open label, single-group, phase 3b implementation study to monitor the effectiveness of the single-dose Ad26.COV2.S vaccine among 500,000 health care workers in South Africa (ClinicalTrials.gov number NCT04838795).
Enrolment in the study began on 17 February 2021, and as of 12 April 2021 a total of 288,368 health care workers had received the Ad26.COV2.S vaccine, among whom 5,898 (2%) reported adverse events.
The majority (81%) of adverse events reported were expected mild-to-moderate reactogenicity events.
Fifty health care workers had adverse events that met the criteria of being serious or of special interest; a full list of these events is provided in Table 1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org [See also the link below]. Among these 50 workers, 12 (24%) had coronavirus disease 2019 (COVID-19), which occurred within 28 days after vaccination; 12 (24%) had allergic reactions, of which one met the criteria for anaphylaxis; and 6 (12%) had neurologic conditions, including a 40-year-old man who received a diagnosis of Guillain-Barré syndrome and a 53-year-old woman with Bell’s palsy.
Five arterial, venous thrombotic, or embolic events were reported in 5 health care workers with known risk factors for thromboembolism (1.7 events per 100,000 participants).
One case of pulmonary embolus occurred 23 days after vaccination in a 63-year-old woman who was overweight and had hypertension, diabetes mellitus, and a history of venous thrombosis; this event was fatal.
A second case occurred in a 64-year-old woman who received a diagnosis of cor pulmonale 17 days after vaccination; this case had features consistent with chronic and recurrent pulmonary emboli. Two cerebrovascular accidents (infarcts on imaging) were reported – one case involved a 45-year-old woman who had underlying rheumatic heart disease and a history of human immunodeficiency virus infection, cerebrovascular accident, and aortic valve replacement, in whom left-sided weakness developed the day after vaccination, and the other case involved a 38-year-old woman who had given birth to twins 9 months before vaccination and presented with features of transient ischemic attack 8 days after vaccination.
A 65-year-old woman with chronic diabetes mellitus had deterioration and blurring of vision 8 days after vaccination and received a diagnosis of retinal vein occlusion and macular hemorrhage. To date, no case of vaccine-induced immune thrombotic thrombocytopenia has been documented.
In South Africa, since the start of the pandemic, COVID-19 has been reported in 1.58 million persons, including more than 55,000 health care workers. The rate of adverse events with vaccination is low, and thromboembolic events have occurred mainly in persons with risk factors for thromboembolism.
* Supported by Janssen Vaccines and Prevention and the South African Medical Research Council.
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