A severe consequence of SARS-CoV-2 infection that manifests as systemic inflammation and multi-organ involvement is called Multisystem Inflammatory Syndrome in Children (MIS-C). This review examines the possible relationship between gut barrier integrity, the microbiome, dysregulation of interleukin 6 (IL-6) signaling, and MIS-C. Clinical and biochemical features of MIS-C are comparable to those of other hyper-inflammatory syndromes, suggesting a dysregulated immune response. One possible explanation for the systemic inflammation seen in MIS-C patients is the SARS-CoV-2-induced dysregulation of the IL-6 signaling pathway. In addition, new data suggest a reciprocal link between gut barrier integrity and IL-6. SARS-CoV-2 exhibits bacteriophage-like behavior, highlighting the role of bacteria as a reservoir for the virus and emphasizing the importance of understanding the bacteriophagic mechanism of the virus in fecal–oral transmission. The increased translocation of viral products and bacterial toxins may result from disrupting the intestinal barrier and cause systemic inflammation. On the other hand, systemic inflammation can weaken the integrity of the intestinal barrier, which feeds back into the loop of immunological dysregulation. In the context of MIS-C, understanding the interaction between SARS-CoV-2 infection, IL-6, and gut barrier integrity may shed light on the etiology of the disease and guide treatment options. Since children with gut dysbiosis may be more susceptible to MIS-C, it is critical to reinforce their microbiome through probiotics supplementation, and plant-fiber-rich diets (prebiotics). Early antibiotic treatment and the use of zonulin antagonists should also be considered.

Repeated inoculation with messenger RNA (mRNA) vaccines elicits immunoglobulin G4 (IgG4) antibody production. Such an increase in the concentration of specific and non-specific IgG4 antibodies allows the growth of some types of cancer by blocking the activation of effector immune cells. This work proposes the hypothesis that cancer growth may be indirectly promoted by increased concentrations of non-specific IgG4 antibodies by the following mechanisms: 1) IgG4 antibodies can bind to anti-tumor IgG1 antibodies and block their interaction with receptors located on effector cells, thus preventing the destruction of cancer cells, 2) IgG4 can interact with fragment crystallizable gamma receptor IIb (FcγRIIB) inhibitory receptors, thus reducing effector functions of innate immune cells, and 3) targeting of specific epitopes by IgG4 could be oncogenic by inducing the production of a microenvironment that can promote cancer development. This article reviews the supporting literature and suggests several experimental protocols to evaluate this hypothesis in the context of repeated inoculation with mRNA vaccines. Additionally, this work proposes some management options aimed at reducing the unfavorable molecular consequences that could mediate cancer development when encountering high concentrations of IgG4 antibodies.

An increase in immunoglobulin G4 (IgG4) levels is typically associated with immunological tolerance states and develops after prolonged exposure to antigens. Accordingly, IgG4 is considered an anti-inflammatory antibody with a limited ability to trigger efficient immune responses. Additionally, IgG4 reduces allergic reactions by blocking immunoglobulin E (IgE) activity. In the case of COVID-19, it has been reported that the repeated administration of some vaccines induces high IgG4 levels. The latest research data have revealed a surprising IgE anti-receptor binding domain response after both natural infection and several SARS-CoV-2 vaccines. The presence of IgG4 and IgE in COVID-19 disease suggests that the virus may induce an “allergic-like” response to evade immune surveillance, leading to a shift from T helper 1 (Th1) to T helper 2 (Th2) cells, which promotes tolerance to the virus and potentially contributes to chronic infection. The spike protein from vaccines could also induce such a response. Interestingly, “allergen-like” epitopes and IgE responses have been reported for other viruses, such as influenza, human immunodeficiency virus (HIV), and respiratory syncytial virus (RSV). The impact of this viral-induced tolerance will be discussed, concerning long COVID and the protective efficacy of vaccines.

The COVID-19 pandemic of 2020 shook the world with its unprecedented scale, affecting over 700 million people and causing nearly 7 million deaths globally. In response, rapid and extraordinary measures were taken, including the development and distribution of COVID-19 vaccines at an unprecedented pace. However, the speed and magnitude of the response have raised questions about the efficacy and ethics of certain measures. To address these concerns, we present a non-comprehensive list of contentious issues that merit discussion and investigation by the scientific and medical communities. These issues encompass public education, ethical considerations, legal implications, policy decisions, regulatory oversight, gaps in scientific knowledge, and concerns related to mass vaccination efforts. By examining these topics, we aim to improve future crisis responses and maintain public trust and participation in vaccination programs. It is essential to learn from the successes and shortcomings of the COVID-19 response to better prepare for future health crises and ensure the safety and well-being of communities worldwide.