Cancer patients who received mRNA vaccines for COVID-19 have significantly higher long-term survival rates than their unvaccinated counterparts, according to a broad scale. Bulgarian studyproviding some of the most extensive follow-up data to date for oncology patients after COVID.
The research, published in the European Journal of Cancer, tracked nearly 1,800 patients with solid tumors who were hospitalized with COVID-19 and survived the acute phase of the infection. The group was followed over a five-year period, making it the longest observational study of its kind.
Bulgaria’s low uptake of vaccination, around 30% during the pandemic, the lowest in Europe, gave the researchers remarkably distinct control groups. The country also recorded one of the highest death rates from COVID-19 in the world, ranking second globally to Peru in deaths per capita.
According to associate professor Trifon Valkov, a specialist in infectious diseases, this context enabled a rare analytical opportunity.
“The COVID-19 vaccines turned out to be a powerful tool, allowing many people to overcome the infection much more easily, often with minimal symptoms. They do not completely prevent the infection, but significantly mitigate its severity. This raised the question of the long-term effects in the most vulnerable groups of patients,” Valkov told Euractiv.
Previous large-scale studies in Western Europe, the United States and China have examined similar questions, but usually in populations with high vaccination coverage, particularly among vulnerable groups.
“What we have done is unprecedented,” added Professor Radka Argirova, a virologist involved in the study. “There has been no comparable research with a five-year follow-up and such detailed analyzes of therapies, tumor location and survival among oncology patients.”
The next phase of the research will examine other chronic conditions, such as diabetes and cardiovascular disease, which are very prevalent in Bulgaria.
Survival advantage associated with mRNA vaccines
The findings show that patients immunized with mRNA vaccines have significantly longer survival than unvaccinated individuals and those who received vector-based vaccines. This survival advantage persists years after infection, even after adjusting for age, sex, and cancer type.
The effect appears particularly pronounced in patients undergoing modern immunotherapy, especially immune checkpoint inhibitors.
The researchers suggest that vaccination may confer a long-term protective benefit that extends beyond the prevention of severe COVID-19, by potentially positively interacting with the immune system in the context of cancer treatment.
However, results vary by type of cancer. Patients with lung and gastrointestinal tumors continue to show poorer long-term survival despite vaccination, highlighting the continued vulnerability of certain groups. But still, there were positive signs.
Argirova pointed to the tumor microenvironment as a possible explanation for the observed effects. Data from lung cancer patients, for example, show a median survival of 43 months among vaccinated individuals compared with 35 months in the unvaccinated group.
“Our analysis covers chemotherapy, immunotherapy and targeted therapy. Across all tumor sites we examined, vaccinated patients show the strongest and most durable benefit, even where statistical significance is not always reached. The trend is clear,” she said.
She added that Bulgaria is becoming an increasingly important environment for such research. “There is no other country with such low COVID-19 vaccination coverage. This makes Bulgaria particularly valuable scientifically, as it allows for meaningful comparisons. Countries with 90-95% coverage simply cannot conduct this type of study,” Argirova noted. Lead authors of the study include oncologist and medical geneticist Georgi Dimitrov, associate professor Trifon Valkov and professor Radka Argirova.
Hypothesis: immune reactivation in the tumor microenvironment
Researchers hypothesize that mRNA vaccines may affect the tumor microenvironment, which is a complex cellular network that suppresses immune responses and enables tumor survival.
“The immune system is often capable of recognizing and destroying tumor cells. However, within the tumor microenvironment, immune-competent cells are suppressed and unable to perform their function, effectively allowing the tumor to persist,” Valkov explained.
Early studies suggested that vaccination against COVID-19 could increase the infiltration of immune cells into this microenvironment, potentially restoring immune control over tumor progression.
“We didn’t expect the magnitude of the results,” Valkov said. “We observed a multifold improvement in survival among patients vaccinated with mRNA vaccines compared to unvaccinated patients with the same malignancies.”
He added that the statistically significant survival benefit was particularly true for patients immunized with mRNA vaccines. “Years after vaccination, the difference in survival between vaccinated and unvaccinated patients with the same type of cancer becomes striking,” he said.
The investment gap limits further research
Despite the promising findings, the researchers warn that Bulgaria lacks the resources to conduct more in-depth studies.
“Look, at this stage we just have data that we compare and draw conclusions from. However, statistics alone cannot explain the pathogenesis behind these observations. Why do vaccinated patients live longer? What exactly is happening? This should be the next step. It would be extremely interesting,” Valkov told Euractiv.
At the same time, he admitted that such research is currently not feasible in Bulgaria, as it requires highly specialized equipment and a well-coordinated multidisciplinary team, which is very difficult to assemble locally. “These types of studies are related to the purchase of very expensive equipment, and I don’t have much faith that the state would finance such a project,” he said.
The researchers’ main hypothesis is that the RNA delivered to the body through the vaccine remains unrecognized by the tumor microenvironment. Therefore, it may be able to stimulate antigen formation within these cells, leading to increased infiltration of immunocompetent cells into the tumor.
“These are just our hypotheses. This still needs to be broken down, examined in detail and fully clarified. This is impossible for a three-person team, unless institutions stand behind them,” said Valkov, adding that such research could be possible with European funding if supported by the government.
“Medicine in the 21st century is no longer medicine of the organism, nor of organs and tissues; it is already medicine at the subcellular level. And it is really very, very interesting to understand or verify what exactly is happening at that subcellular level and why this phenomenon is observed especially with this type of vaccine,” he told Euractiv.
(VA, BM)
