Discussion:
Fusobacterium species are Gram-negative anaerobic bacilli which are normally a constituent of the oropharynx, gastrointestinal tract, and female genital flora. Overall, Fusobacterium species are a rare cause of bacteremia, accounting for < 0.001% of all bacteremia and < 1% of anaerobic bacteremia cases among adults5. Fusobacterium bacteremia generally affects males more than females6,7, with the primary infection source typically being the respiratory tract, abdomen, or pelvis6,8. With respect to the hepatic abscesses associated with Fusobacterium species, oropharyngeal disease or intestinal sources of infections including diverticulitis have been postulated as the potential initial portal of entry7. Our patient had periodontal disease, but no evidence of oropharyngeal infections was noted.
Was this bacteremia event a coincidence or a complication related to vaccination? F. nucleatum is an adhesive bacterium. It can co-aggregate with various microbial species in the oral cavity, and plays a key role in dental plaque formation7,9. In healthy individuals, there is an established homeostasis between immunity and oral cavity microorganisms that do not cause diseases. Once disseminated outside the oral cavity and under dysbiosis, F. nucleatum induces exacerbated inflammation, thus turning into a pathogen10,11. Regulatory T cells (Tregs) have been known to act on the balance of immunopathogenesis of periodontal lesions. When Tregs function was inhibited, it increased alveolar bone loss and inflammatory cell migration, and as such, the tissue damage associated with periodontitis was noted12. Furthermore, F. nucleatum stimulates Toll-like receptor 4 (TLR4)-mediated inflammatory responses in the placentas of pregnant mice, causing fetal demise. Suppression of inflammation protects the fetuses, even in the presence of bacterial colonization13. However, the exact molecular immunological pathway against F. nucleatum is not fully understood. Therefore, we supposed that our patient experienced both wanted and unwanted immunogenicity and the disruption of symbiont status after vaccination, which led to F. nucleatum bacteremia.
Fever developed off and on in our patient about 1 week after vaccination. All laboratory data initially showed no abnormality, and he was treated as having an adverse effect post-vaccination. Then, on day 3 of his second admission, the blood culture that was obtained during his first hospitalization grew F. nucleatum . The Oxford AstraZeneca chimpanzee adenovirus-vectored vaccine, ChAdOx1 nCoV-19, has appeared to be effective and safe for SARS-CoV-2 immunization14. The incidence of objectively measured fever was low in the 18–55 years standard-dose group (12 [24%] of 49), and no fevers were recorded in either the 56–69 years or older standard-dose groups within 7 days after the prime vaccination with ChAdOx1 nCoV-1914. Therefore, the diagnosis of systemic adverse reactions post-vaccination should be determined carefully by a clinical physician, especially fever occurrence during an unexpected period among the elderly patient group.
During the COVID-19 pandemic, the normal processes of clinical inference and diagnosis were disrupted and delayed treatment of bacteremia has been noted15. Although F. nucleatum bacteremia associated with coronavirus disease was reported recently during the COVID-19 pandemic16, to the best of our knowledge, this is the first case report of F. nucleatum bacteremia with hepatic abscess in an immunocompetent patient post-anti-COVID-19 vaccine administration. The exact relationship between host immunological reaction and the pathogenesis of bacteremia is difficult to identify at present, so further research is needed to elucidate this interaction.