Man’s death from COVID-19 vaccine highlights benefit-risk balance

A recent investigation has confirmed that the death of a 27-year-old man from the UK, Jack Last, in 2021 was directly linked to a side effect of the Oxford/AstraZeneca COVID-19 vaccine, which he received before government guidelines deemed him eligible.

But was Last’s doctor really to blame? According to The Independent, the investigation into Last’s death found the hospital system that administered the shot had been “forced to expand the number of people receiving the Oxford/AstraZeneca jab amid fears over vaccine wastage at the height of the pandemic.”^[]

What physicians are saying

Robert Hopkins Jr., MD, a professor at the University of Arkansas for Medical Sciences and current chair of the US National Vaccine Advisory Committee, remembers that when vaccines against the virus first became available, it was challenging to ensure that all doses out of the multidose vials were used.

“Thinking back through the 35-plus years of my career, I really can't think of any time where we've been in a situation where we've been pressured to try to make sure we use every dose and had to plan for the same exigency, so to speak,” he tells MDLinx.

As for a situation in which a hospital has a surplus of vaccine at a time of worldwide shortage, as happened in Last’s case, “A vaccine expiring doesn't do anybody any good, Dr. Hopkins says. “If you give a vaccine and get it into arms, you're much better than taking a chance of having the infection.”

An improper assessment of risk vs benefit

Vaccines against COVID-19 undoubtedly had and continue to have a positive impact around the world, saving an estimated 14.4 to 19.8 million lives in the first year of their availability, according to a study in the Lancet Infectious Diseases.^[]

All medical interventions come with risks of complications, however, and the COVID-19 vaccines are no different. Shortly after countries started rolling out the shots in late 2020 and early 2021, reports emerged about unusual blood clotting accompanied by low platelet counts. These effects occurred in a small number of people generally within 2 weeks of receiving their first dose of the vaccine developed jointly by the University of Oxford and AstraZeneca. On April 7, 2021, the European Medicines Agency (EMA) concluded that the risk should be listed as a very rare side effect on the label, at a time when some countries had started suspending use of the shot or moving to alternatives.^[]

A subsequent investigation into Last’s death kept the blame on the vaccine, despite missteps by his doctor and the hospital where he sought care. Bad timing also contributed. As The Independent reported, had Last’s vaccination been delayed to a later date, he would have been vaccinated at a time when UK authorities were recommending other shots that carried less risk of blood clotting for people younger than 30.^[]

Early vaccine issues

For the Oxford/AstraZeneca vaccine, the condition combining thrombosis and low platelet counts came to be known as vaccine-induced immune thrombotic thrombocytopenia (VITT) or thrombosis with thrombocytopenia syndrome (TTS). A greater risk was confirmed in subsequent studies, including one using data from three Nordic countries published in JAMA Network Open.^[] The events were rare, however, with the Nordic study estimating an excess of 4.9 thrombocytopenic events and 1.6 cerebral venous thrombosis events per 100,000 doses.

That study also showed that risks of those types of events were less consistent with the mRNA-based vaccines from Pfizer/BioNTech and Moderna, which Last would have been offered if he had waited to get vaccinated just a week longer. On April 7, 2021, the UK government announced that people under 30 would be offered an alternative to the Oxford/AstraZeneca vaccine due to concerns of blood clots, according to a BBC report.^[]

In the context of the clinic

Those risks have to be put into context for your patients as the world continues to grapple with the spread of the SARS-CoV-2 virus. In a BMJ study using UK data that spanned the time period of the Last case (December 2020 to April 2021), researchers found that risks of thrombocytopenia, venous thromboembolism, CVST, and rare arterial thrombotic events were indeed increased after receipt of the Oxford/AstraZeneca vaccine, but not nearly as much as after a positive SARS-CoV-2 test.^[]

In contrast, there are additional studies indicating that COVID-19 vaccination, on balance, may be protecting the heart. A study in Nature Communications, which assessed the cardiovascular safety of the vaccines among about 46 million adults in England, indicated that risks of a variety of outcomes like acute MI, ischemic stroke, pulmonary embolism, and deep venous thrombosis were either similar or lower after use of the Oxford/AstraZeneca or mRNA shots compared with no vaccination.^[]

The CDC recommends that everyone 6 months and older get an updated COVID-19 vaccine, noting that doing so protects against severe illness, hospitalization, and death.^[] The World Health Organization (WHO) also provides recommendations on vaccination and states that people should “take whatever vaccine is made available to you, even if you have already had COVID-19.”^[]

That was true early in the vaccine rollout and remains true moving forward, according to Dr. Hopkins. “The vaccines that we had available early on and throughout the COVID-19 pandemic and going forward now are clearly safer than the risk of having COVID-19 infection,” he says, underscoring that there are no risk-free products in medicine. “Adverse events do happen. And we've got to make sure that when we're assessing these products, that we make sure that those adverse events are far, far less common than the beneficial effects from the vaccine.”