Introduction. The term "heterologous immunity" is actively discussed in foreign literature. Heterologous immunity is a term that describes the phenomenon when infection with one specific pathogen (microorganism) affects the innate or adaptive immune response to an unrelated microorganism [1]. In the world scientific community, there is also the term "heterologous non-specific effects of vaccines" (in other words, "off-target effects") – this is their effect on the body's immune response, which is different from their intended purpose. There is growing evidence that vaccines can affect diseases other than those for which they were designed [2,3,4, p.195]. Around the world, children receive several vaccinations against diphtheria and tetanus, including three to four doses during the first year of life (depending on the country of residence) and one dose between the ages of 4 and 6 years. In addition, a low antigenic dose in the form of ADT-m-toxoid is also administered at the age of 9 to 16 years. Numerous cross-reactive T and B cell epitopes between antigens have also been detected in vaccines against tetanus, diphtheria and pertussis and SARS-CoV-2 [5p.1055].
The aim of the study. To assess the level of humoral immunity against tetanus toxin in school-aged children with infectious diseases (except tetanus) during the COVID-19 pandemic as a possible marker of disease severity.
Materials and methods. During the performance of the work, the rules of patient safety and ethical principles of scientific medical research with human participation were observed (2000). The Commission on Bioethics granted permission to conduct this study (Protocol No. 61 of 13.11.2020). Parents (legal representatives) of the patients gave an informed concert in writing form to conduct this study. 124 children aged 6 to 18 years were examined: 62 patients with laboratory-confirmed SARS-CoV-2 infection, 32 patients with other infectious diseases (except tetanus) and negative laboratory tests for COVID-19, and 30 children without signs of the disease (control group). All children underwent a determination of the level of immunoglobulin G (Ig G) against tetanus toxin by enzyme-linked immunosorbent assay (Òetanus Elisa Ig G, Vircell, Spain). This technique is based on the determination of the index of antibodies of class G [6, p.33] to tetanus toxin by comparing the optical density of a particular serum sample to the cut off average value of optical density. The result was assessed as negative (no specific antibodies to tetanus toxin), positive (specific antibodies to the above toxin are present). Some laboratory indicators (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), WBC (white blood cells), procalcitonin, cortisol, D-dimer and duration of hyperthermia were evaluated. Statistical analysis was carried out using the "Stat Plus" program. The results were considered statistically significant at p<0.05.
Results. The median age of all children was 11.06±3.90 years. There was no significant difference in sex (p=0.388, x2=2.33) and age composition (p=0.092) in the study groups.
In patients of the control group, in 96.43% of cases, immunoglobulins G to the tetanus toxin were present in the blood serum, in patients with COVID-19 the presence of specific immunoglobulins G was detected only in 36.96%, in patients with other infectious diseases – in 87.50% of cases (P<0,001, x2=33,94).
The ratio of leukocyte count, ESR, D-dimer, CRP and duration of hyperthermia,
days in the presence (absence) of specific immunoglobulins G against tetanus toxin is shown in Table 1.
Table 1. The ratio of leukocyte count, ESR, D-dimer, CRP and duration of hyperthermia in the presence (absence) of specific immunoglobulins G against tetanus toxin
The ratio of procalcitonin and cortisol levels in the presence (absence) of specific immunoglobulins G against tetanus toxin is shown in Table 2.
Table 2. The ratio of duration of hyperthermia, procalcitonin and cortisol levels in the presence (absence) of specific immunoglobulins G against tetanus toxin
Conclusions. The lowest number of children with anti-tetanus antibodies was in children with SARS-CoV-2 infection. In children with absence of immunoglobulins G to tetanus toxin, there is a significant increase in pro-inflammatory markers, such as the number of leukocytes, ESR, CRP, procalcitonin, as well as the levels of cortisol and D-dimer and the duration of hyperthermia, which indicate a more severe course of the infectious process.
Key words: tetanus, children, infection, severity, immunity, COVID-19
References
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4. Schnoeller C., Roux X., Sawant D., Raze D., Olszewska W., Locht C. et al. Attenuated Bordetella pertussis vaccine protects against respiratory syncytial virus disease via an IL-17-dependent mechanism. Am J Respir Crit Care Med. 2014;189(2):194-202. DOI: 10.1164/rccm.201307-1227OC.
5. Mysore V., Cullere X., Settles M.L., Ji X., Kattan M.W., Desjardins M. et al. (2021). Protective heterologous T cell immunity in COVID-19 induced by the trivalent MMR and Tdap vaccine antigens. Med. 2021; 2(9), 1050-1071. e7 DOI: 10.1016/j.medj.2021.08.004.
6. Health counseling, genetic background, and safety against tetanus in women referring to premarital center. Health Biotechnology and Biopharma (HBB), 2021; 4(4): 32-42. DOI: 10.22034/HBB.2021.04
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