COVID-19 vaccination, all-cause mortality, and hospitalization for cancer: 30-month cohort study in an Italian province

"Materials and Methods

This cohort study... included the population aged 11 years or older residing in the province of Pescara, Italy, on January 1st 2021. The aim was to compare the overall mortality and incidence of cancer in the vaccinated vs. the unvaccinated...

Results

All cancer hospitalizations

Overall, 3134 subjects had a hospital admission with a cancer diagnosis during the follow-up (1.10% of the sample). The rate of hospitalization for cancer of any site was 0.85% in the unvaccinated group, and 1.15% in the group vaccinated with at least one dose (p<0.001). At multivariate analyses, the likelihood of cancer hospitalization was higher in the subjects who received at least one dose, compared to the unvaccinated (HR: 1.23; 1.11-1.37). Similar results were observed for the vaccinated with at least three doses (HR: 1.09; 1.02-1.16)...

Cancer hospitalizations by site

At univariate analyses, the vaccinated subjects showed higher rates of cancer admission for colon-rectum, breast, bladder, and all hematological cancers (the latter only for the comparison with the group "≥1 dose"). The multivariate models largely confirmed the univariate analyses. Vaccination with at least one dose was significantly associated with a higher risk of hospitalization for colon-rectum cancer (HR: 1.34; 1.00-1.80), breast cancer (HR: 1.54; 1.10-2.16), and bladder cancer (HR: 1.62; 1.07-2.45). After three or more vaccine doses, similar results were observed for breast cancer (HR: 1.36; 1.08-1.72), and for bladder cancer (HR: 1.43; 1.08-1.88)...

Discussion

Clearly, the 40% risk reduction in all-cause mortality observed in our study, exceeds the impact that could be expected from the reduction of COVID-19 related mortality, which was estimated to cause less than 30% of the excess mortality registered in a number of countries. However, as previously reported for these and other vaccines, this discrepancy was likely caused by the healthy vaccine bias, as the vaccinated individuals are well known to be more likely, as compared with the unvaccinated ones, to present further unmeasured characteristics which might protect them from death...

The theoretical arguments supporting a potential tumorigenic action of the mRNA anti-SARS-CoV-2 vaccines have been reported in four reviews, which gathered evidence from studies on the biological responses to vaccination in animals and humans. According to these authors, vaccination may promote or expedite the oncogenic multi-hit process through the following mechanisms: (1) pro-inflammatory and tumorigenic effects triggered by the vaccine mRNA and vaccine-induced Spike protein, both systemically and on mucosal surfaces such as the gut; (2) pro-inflammatory action of LNPs, whose biodistribution was reported for almost every organ; (3) altered translation of cellular microRNA; (4) reduced Interferon type 1 activity; and finally (5) lymphopenia, also observed by Sing et al, possibly related to an untimely cytokine signal which inactivates T-cells. Notably, the lymphopenia and the pro-inflammatory action of mRNA were also reported for SARS-CoV-2 infection.

In fact, a number of publications reported various manifestations related to a deregulation of the immune system following vaccination against SARS-CoV-2. For instance, the mRNA vaccines were found to be associated with immune-mediated adverse events such as Herpes Zoster flares, immune thrombocytopenia and other autoimmune hematological disorders, and also neurological, otolaryngology, renal, skin, ocular, and thyroid manifestations. Additionally, the Adenovirus vector vaccine was found to induce thrombocytopenia, thrombosis, and capillary leak syndrome. Lastly, a final hypothesis in need of validation has been proposed, to date, by two preprint papers. Namely, the BNT162b2 and mRNA-1273 vaccines could be contaminated with detectable quantities of DNA, which are likely to promote oncogenesis."