RESUMO
The devastating complications of coronavirus disease 2019 (COVID19) result from the dysfunctional immune response of an individual following the initial severe acute respiratory syndrome coronavirus 2 (SARSCoV2) infection. Multiple toxic stressors and behaviors contribute to underlying immune system dysfunction. SARSCoV2 exploits the dysfunctional immune system to trigger a chain of events, ultimately leading to COVID19. The authors have previously identified a number of contributing factors (CFs) common to myriad chronic diseases. Based on these observations, it was hypothesized that there may be a significant overlap between CFs associated with COVID19 and gastrointestinal cancer (GIC). Thus, in the present study, a streamlined dotproduct approach was used initially to identify potential CFs that affect COVID19 and GIC directly (i.e., the simultaneous occurrence of CFs and disease in the same article). The nascent character of the COVID19 core literature (~1yearold) did not allow sufficient time for the direct effects of numerous CFs on COVID19 to emerge from laboratory experiments and epidemiological studies. Therefore, a literaturerelated discovery approach was used to augment the COVID19 core literaturebased 'direct impact' CFs with discoverybased 'indirect impact' CFs [CFs were identified in the nonCOVID19 biomedical literature that had the same biomarker impact pattern (e.g., hyperinflammation, hypercoagulation, hypoxia, etc.) as was shown in the COVID19 literature]. Approximately 2,250 candidate direct impact CFs in common between GIC and COVID19 were identified, albeit some being variants of the same concept. As commonality proof of concept, 75 potential CFs that appeared promising were selected, and 63 overlapping COVID19/GIC potential/candidate CFs were validated with biological plausibility. In total, 42 of the 63 were overlapping direct impact COVID19/GIC CFs, and the remaining 21 were candidate GIC CFs that overlapped with indirect impact COVID19 CFs. On the whole, the present study demonstrates that COVID19 and GIC share a number of common risk/CFs, including behaviors and toxic exposures, that impair immune function. A key component of immune system health is the removal of those factors that contribute to immune system dysfunction in the first place. This requires a paradigm shift from traditional Western medicine, which often focuses on treatment, rather than prevention.
Assuntos
COVID-19/epidemiologia , Neoplasias Gastrointestinais/epidemiologia , COVID-19/etiologia , COVID-19/imunologia , Neoplasias Gastrointestinais/etiologia , Neoplasias Gastrointestinais/imunologia , Humanos , Fatores de Risco , SARS-CoV-2/fisiologia , Fatores SocioeconômicosRESUMO
The devastating complications of coronavirus disease 2019 (COVID-19) result from an individual's dysfunctional immune response following the initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple toxic stressors and behaviors contribute to underlying immune system dysfunction. SARS-CoV-2 exploits the dysfunctional immune system to trigger a chain of events ultimately leading to COVID-19. We have previously identified many contributing factors (CFs) (representing toxic exposure, lifestyle factors and psychosocial stressors) common to myriad chronic diseases. We hypothesized significant overlap between CFs associated with COVID-19 and inflammatory bowel disease (IBD), because of the strong role immune dysfunction plays in each disease. A streamlined dot-product approach was used to identify potential CFs to COVID-19 and IBD. Of the fifty CFs to COVID-19 that were validated for demonstration purposes, approximately half had direct impact on COVID-19 (the CF and COVID-19 were mentioned in the same record; i.e., CF---âCOVID-19), and the other half had indirect impact. The nascent character of the COVID-19 core literature (â¼ one year old) did not allow sufficient time for the direct impacts of many CFs on COVID-19 to be identified. Therefore, an immune system dysfunction (ID) literature directly related to the COVID-19 core literature was used to augment the COVID-19 core literature and provide the remaining CFs that impacted COVID-19 indirectly (i.e., CF---âimmune system dysfunction---âCOVID-19). Approximately 13000 potential CFs for myriad diseases (obtained from government and university toxic substance lists) served as the starting point for the dot-product identification process. These phrases were intersected (dot-product) with phrases extracted from a PubMed-derived IBD core literature, a nascent COVID-19 core literature, and the COVID-19-related immune system dysfunction (ID) core literature to identify common ID/COVID-19 and IBD CFs. Approximately 3000 potential CFs common to both ID and IBD, almost 2300 potential CFs common to ID and COVID-19, and over 1900 potential CFs common to IBD and COVID-19 were identified. As proof of concept, we validated fifty of these â¼3000 overlapping ID/IBD candidate CFs with biologic plausibility. We further validated 24 of the fifty as common CFs in the IBD and nascent COVID-19 core literatures. This significant finding demonstrated that the CFs indirectly related to COVID-19 -- identified with use of the immune system dysfunction literature -- are strong candidates to emerge eventually as CFs directly related to COVID-19. As discussed in the main text, many more CFs common to all these core literatures could be identified and validated. ID and IBD share many common risk/contributing factors, including behaviors and toxic exposures that impair immune function. A key component to immune system health is removal of those factors that contribute to immune system dysfunction in the first place. This requires a paradigm shift from traditional Western medicine, which often focuses on treatment, rather than prevention.
RESUMO
Inflammatory bowel disease (IBD) incidence has been increasing steadily, most dramatically in the Western developed countries. Treatment often includes lifelong immunosuppressive therapy and surgery. There is a critical need to reduce the burden of IBD and to discover medical therapies with better efficacy and fewer potential side-effects. Repurposing of treatments originally studied in other diseases with similar pathogenesis is less costly and time intensive than de novo drug discovery. This study used a treatment repurposing methodology, the literature-related discovery and innovation (LRDI) text mining system, to identify potential treatments (developed for non-IBD diseases) with sufficient promise for extrapolation to treatment of IBD. By searching for desirable patterns of twenty key biomarkers relevant to IBD (e.g., inflammation, reactive oxygen species, autophagy, barrier function), the LRDI-based query retrieved approximately 9500 records from Medline. The most recent 350 records were further analyzed for proof-of-concept. Approximately 18% (64/350) met the criteria for discovery (not previously studied in IBD human or animal models) and relevance for application to IBD treatment. Many of the treatments were compounds derived from herbal remedies, and the majority of treatments were being studied in cancer, diabetes, and central nervous system disease, such as depression and dementia. As further validation of the search strategy, the query identified ten treatments that have just recently begun testing in IBD models in the last three years. Literature-related discovery and innovation text mining contains a unique search strategy with tremendous potential to identify treatments for repurposing. A more comprehensive query with additional key biomarkers would have retrieved many thousands more records, further increasing the yield of IBD treatment repurposing discovery.