COVID-19 in patients with gastrointestinal stromal tumors: Recommendations for management and vaccination

The coronavirus disease 2019 (COVID-19) pandemic profoundly affected the management and treatment of patients with malignancies. Based on the progress reported in the literature, we reviewed the recommendations for treatment and vaccination in patients with gastrointestinal stromal tumor (GIST) during COVID-19. We focus on whether there is a risk and what could be the possible effects of vaccinating patients with GIST/cancer. Since the situation is quickly changing, and the health services have been severely disrupted, the diagnosis, treatment and recommendations for vaccination of these patients against COVID-19 are still not updated. The approval of vaccines in the pandemic gave hope that we would soon be able to return to a more normal life. However, the oncology community needs to adapt and provide the most effective treatment and care models for patients with rare cancer, such as GIST. Collecting data on the impact of vaccination in patients with GIST/cancer also will be beneficial in expanding knowledge about the future planning of treatment strategies and optimizing care in the event of a subsequent pandemic.     

Alpha-fetoprotein secretion in a craniopharyngioma. Are craniopharyngiomas part of the germ cell tumor family?

A 14-months-old girl was admitted to our hospital because of excessive irritability and abnormal eye movements over the last two months. Brain CT and MRI revealed a suprasellar cystic and partially solid mass with calcifications. The laboratory investigation revealed increased serum levels of AFP. These findings were suggestive for a brain germ cell tumor. Therefore, systemic chemotherapy was started. After two courses there was a reduction in the levels of AFP but the tumor size remained unchanged. Subtotal tumor excision was performed that revealed the presence of a craniopharyngioma. One month later there was enlargement of the cystic part of the tumor, while serum AFP was elevated. The child received again systemic chemotherapy and placement of a reservoir into the cystic part of the tumor. Analysis of the intracystic flouid revealed the presence of beta-HCG and AFP. Following that the patient received brachytherapy with intracavity yttrium placement. Three months later repeated MRI showed a decrease in the size of the cystic part, while the solid part remained unchanged. Thus, the solid part was treated by radiosurgery. One year later the patient was stable but with complete loss of vision. These observations support the theory of a germ cell tumor family, in which craniopharyngioma and germ cell tumor present the two sides of the same entity, while between them a wide variety of tumors, with variable type of secretion of AFP and/or beta-HCG, may exist.     

Effectiveness and safety of COVID-19 vaccines in patients with diabetes as a factor for vaccine hesitancy

Diabetes mellitus is one of the most common comorbid conditions encountered in patients with severe acute respiratory syndrome coronavirus 2 infection accompanied by significantly increased mortality, prolonged hospital stay, and requirement of invasive mechanical ventilation. This review aims to present the effectiveness and safety profile of available coronavirus disease 2019 (COVID-19) vaccines in people with diabetes as a potential cause of hesitancy for vaccination. Data from published research proves a robust immune response following immunization for COVID-19 in diabetic patients with substantial production of virus-neutralizing antibodies; however, the observed immune response was unequivocally weaker than that in individuals without diabetes. This observation was further enhanced by the findings that worse glycemic control was associated with more suppressed antibody production. In contrast, individuals with optimal glycemic control performed similarly to healthy controls. In addition to the need for strict glucose monitoring and adequate diabetes treatment, those findings reinforce the concept of diabetes-induced secondary immune deficiency and necessitate the application of booster doses to diabetic patients with priority. Nevertheless, after vaccination, reported adverse events were not different from those in the general population. No increase in severe adverse events was documented. While single case reports detected transient increases in blood glucose post-vaccination, more extensive trials could not replicate such a relationship.     

Mucosal COVID-19 vaccines: Risks,benefits and control of the pandemic

Based on mucosal immunization to promote both mucosal and systemic immune responses, next-generation coronavirus disease 2019 (COVID-19) vaccines would be administered intranasally or orally. The goal of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines is to provide adequate immune protection and avoid severe disease and death. Mucosal vaccine candidates for COVID-19 including vector vaccines, recombinant subunit vaccines and live attenuated vaccines are under development. Furthermore, subunit protein vac-cines and virus-vectored vaccines have made substantial progress in preclinical and clinical settings, resulting in SARS-CoV-2 intranasal vaccines based on the previously successfully used nasal vaccines. Additional to their ability to trigger stable, protective immune responses at the sites of pathogenic infection, the development of ‘specific’ mucosal vaccines targeting coronavirus antigens could be an excellent option for preventing future pandemics. However, their efficacy and safety should be confirmed.     

Gastrointestinal mucosal immunity and COVID-19

As the gastrointestinal tract may also be a crucial entry or interaction site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the role of the gut mucosal immune system as a first-line physical and immunological defense is critical. Furthermore, gastrointestinal involvement and symptoms in coronavirus disease 2019 (COVID-19) patients have been linked to worse clinical outcomes. This review discusses recent data on the interactions between the virus and the immune cells and molecules in the mucosa during the infection. By carrying out appropriate investigations, the mucosal immune system role in SARS-CoV-2 infection in therapy and prevention can be established. In line with this, COVID-19 vaccines that stimulate mucosal immunity against the virus may have more advantages than the others.     

Pandemic control - do's and don'ts from a control theory perspective

Managing a pandemic is a difficult task. Pandemics are part of the dynamics of nonlinear systems with multiple different interactive features that co-adapt to each other (such as humans, animals, and pathogens). The target of controlling such a nonlinear system is best achieved using the control system theory developed in engineering and applied in systems biology. But is this theory and its principles actually used in controlling the current coronavirus disease-19 pandemic? We review the evidence for applying principles in different aspects of pandemic control related to different goals such as disease eradication, disease containment, and short- or long-term economic loss minimization. Successful policies implement multiple measures in concordance with control theory to achieve a robust response. In contrast, unsuccessful policies have numerous failures in different measures or focus only on a single measure (only testing, vaccines, etc.). Successful approaches rely on predictions instead of reactions to compensate for the costs of time delay, on knowledge-based analysis instead of trial-and-error, to control complex nonlinear systems, and on risk assessment instead of waiting for more evidence. Iran is an example of the effects of delayed response due to waiting for evidence to arrive instead of a proper risk analytical approach. New Zealand, Australia, and China are examples of appropriate application of basic control theoretic principles and focusing on long-term adaptive strategies, updating measures with the evolution of the pandemic.