Pathogenesis Of COVID-19 Research Articles

CIAO: a living experiment in interdisciplinary large-scale collaboration facilitated by the Adverse Outcome Pathway framework.

The CIAO project was launched in Spring 2020 to address the need to make sense of the numerous and disparate data available on COVID-19 pathogenesis. Based on a crowdsourcing model of large-scale collaboration, the project has exploited the Adverse Outcome Pathway (AOP) knowledge management framework built to support chemical risk assessment driven by mechanistic understanding of the biological perturbations at the different organizational levels. Hence the AOPs might have real potential to integrate data produced through different approaches and from different disciplines as experienced in the context of COVID-19. In this study, we aim to address the effectiveness of the AOP framework (i) in supporting an interdisciplinary collaboration for a viral disease and (ii) in working as the conceptual mediator of a crowdsourcing model of collaboration. We used a survey disseminated among the CIAO participants, a workshop open to all interested CIAO contributors, a series of interviews with some participants and a self-reflection on the processes. The project has supported genuine interdisciplinarity with exchange of knowledge. The framework provided a common reference point for discussion and collaboration. The diagram used in the AOPs assisted with making explicit what are the different perspectives brought to the knowledge about the pathways. The AOP-Wiki showed up many aspects about its usability for those not already in the world of AOPs. Meanwhile their use in CIAO highlighted needed adaptations. Introduction of new Wiki elements for modulating factors was potentially the most disruptive one. Regarding how well AOPs support a crowdsourcing model of large-scale collaboration, the CIAO project showed that this is successful when there is a strong central organizational impetus and when clarity about the terms of the collaboration is brought as early as possible. Extrapolate the successful CIAO approach and related processes to other areas of science where the AOP could foster interdisciplinary and systematic organization of the knowledge is an exciting perspective.

Tissue plasminogen activator receptor ANXA2 and its complementary regulator anti-inflammatory ANXA1 as prognostic indicators of inflammatory response in COVID-19 pathogenesis

COVID-19 patients demonstrating hyperactive immunologic response appear to have a severe illness with a poor prognosis. This study hypothesizes that the pro-inflammatory Annexin A2 (ANXA2) has role in COVID-19 pathogenesis. In thisobservational study, serum levels of ANXA2 along with interleukin 1 beta (IL1β), IL6, tumour necrosis factor-alpha (TNFα), and anti-inflammatory ANXA1 were determined by sandwich ELISA in 20 each control, mild, moderate, and severe COVID-19 subjects.The ANXA2 levels (130 ng/mL, p < 0.001) were significantly elevated in severe COVID-19 subjects, compared to mild, moderate and controls. Similarly, all the other pro-inflammatory biomarkers levels were also significantly correlated with disease severity (p < 0.0001). However, ANXA1 showed significantly negative correlation with disease severity (p < 0.0001). Furthermore, the pro-inflammatory ANXA2 showed utility in mortality prediction with 86% sensitivity and specificity, and 57% positive predictive value at a serum threshold of 94 ng/mL. Overall,ANXA2 and ANXA1 along with IL1β, IL6, TNFα, would be beneficial biomarkers in assessing the COVID-19 severity and mortality prediction.

Evolution of Status of Trace Elements and Metallothioneins in Patients with COVID-19: Relationship with Clinical, Biochemical, and Inflammatory Parameters.

The inflammatory reaction and pathogenesis of COVID-19 may be modulated by circulating trace elements (Iron (Fe), Zinc (Zn), Copper (Cu), Manganese (Mn)) and Metallothioneins (MTs). Thus, the present study aimed to investigate their relationship with clinical, biochemical, and inflammatory parameters in patients with COVID-19 at the early Intensive Care Unit (ICU) phase. Critically ill patients (n = 86) were monitored from the first day of ICU admission until the third day of stay. Serum samples were used to assess mineral levels via Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and MT levels via differential pulse voltammetry. Levels of Cu and MTs were significantly decreased after 3 days (p < 0.05), increasing the prevalence of Cu-deficient values from 50% to 65.3% (p = 0.015). Fe and Zn were shown to have a predictive value for mortality and severity. The present study suggests trace element deficiency may be a risk factor during early ICU treatment of COVID-19, as it is related to different biochemical and clinical parameters, indicating a possible beneficial effect of restoring proper levels of these micronutrients.

Sequels of COVID-19: An integrative literature review

The strong affinity between the Spike protein of the SARS-CoV-2 virus and the angiotensin-converting enzyme 2 receptor is postulated as one of the main reasons for the high viral transmission rate, leading the WHO to declare COVID-19 as a Public Health Emergency of International Concern and to adopt measures to contain viral spread. Moreover, due to the virus’s pathophysiological mechanism, non-specific symptoms, atypical progression, especially in the elderly and immunocompromised, and a faster and more lethal progression are observed. Additionally, as knowledge about the natural history of the virus infection has advanced, persistent symptoms and/or sequelae causing organic dysfunctions and negatively impacting patients’ quality of life have been noted. In light of this, the objective of this article was to present an integrative review of the main sequels of COVID-19 in the years 2021 and 2022. To achieve this, full articles were searched in the Scientific Electronic Library Online, Biblioteca Virtual em Saúde, and PubMed research databases, in both Portuguese and English languages, using the PRISMA methodology (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), resulting in the selection of 14 articles. Among the results, the following stand out: the pathogenesis of persistent COVID-19 is based on the theory of immune phenomena secondary to infection, abnormal immune response, and the presence of the virus in immunologically privileged sites; prevalent complications include fatigue, dyspnea, subjective cognitive impairment, neurological sequelae, central nervous system inflammatory diseases, and post-viral olfactory dysfunction; evidence of a causal relationship between COVID-19 and subacute thyroiditis was presented; a higher number of complications and hospitalizations were demonstrated in vitamin D-deficient patients; as well as the presence of neuropsychiatric symptoms in the healthcare professional population. In conclusion, a scarcity of studies directly addressing COVID-19 sequelae was noted, highlighting the need for further research to create more specific diagnostic protocols.

Covid-19 In A Patient With Pemphigus: A Case Report

Background: Pemphigus disease, especsially Pemphigus Vulgaris (PV), is an autoimmune disease resulting in blisters on the skin and mucosa due to autoantibodies attacking desmogleins (DSG) 1 and 3. Autoimmunity development in PV may be idiopathic or induced by neoplasms, drugs, infections, or inflammatory processes. Besides affecting the respiratory tract, COVID-19 may also affect other systems, such as the skin. The pathogenesis of autoimmune diseases and COVID-19 have similarities, which is an overreaction of the immune system. Purpose: To report a case about the association between PV autoimmune disease and COVID-19. Case: A 30-year-old woman presented with full-body pain and ulcers. Three days before the skin lesions, the patient complained of a mild cough, and the SARS-CoV-2 examination was positive. The patient was treated with systemic and topical corticosteroids along with broad-spectrum antivirals. The patient was discharged with an improved lesion condition and a negative SARS-CoV-2 PCR on day 5 of treatment. Discussion: Prolonged viral infection or viral infection itself, such as COVID-19 can cause immune system dysregulation leading to autoimmune skin lesions with different mechanisms. The use of corticosteroids or immunosuppressants in autoimmune diseases increases the risk of COVID-19 infection in a pandemic. Conclusion: In the COVID-19 pandemic, COVID-19 and autoimmune diseases such as pemphigus vulgaris are interrelated with the presence of immune dysregulation leading to skin lesions

Airway Epithelial-Derived Immune Mediators in COVID-19.

The airway epithelium, which lines the conducting airways, is central to the defense of the lungs against inhaled particulate matter and pathogens such as SARS-CoV-2, the virus that causes COVID-19. Recognition of pathogens results in the activation of an innate and intermediate immune response which involves the release of cytokines and chemokines by the airway epithelium. This response can inhibit further viral invasion and influence adaptive immunity. However, severe COVID-19 is characterized by a hyper-inflammatory response which can give rise to clinical presentations including lung injury and lead to acute respiratory distress syndrome, viral pneumonia, coagulopathy, and multi-system organ failure. In response to SARS-CoV-2 infection, the airway epithelium can mount a maladaptive immune response which can delay viral clearance, perpetuate excessive inflammation, and contribute to the pathogenesis of severe COVID-19. In this article, we will review the barrier and immune functions of the airway epithelium, how SARS-CoV-2 can interact with the epithelium, and epithelial-derived cytokines and chemokines and their roles in COVID-19 and as biomarkers. Finally, we will discuss these immune mediators and their potential as therapeutic targets in COVID-19.

Renin-Angiotensin System Components and Arachidonic Acid Metabolites as Biomarkers of COVID-19.

Through the ACE2, a main enzyme of the renin-angiotensin system (RAS), SARS-CoV-2 gains access into the cell, resulting in different complications which may extend beyond the RAS and impact the Arachidonic Acid (ArA) pathway. The contribution of the RAS through ArA pathways metabolites in the pathogenesis of COVID-19 is unknown. We investigated whether RAS components and ArA metabolites can be considered biomarkers of COVID-19. We measured the plasma levels of RAS and ArA metabolites using an LC-MS/MS. Results indicate that Ang 1-7 levels were significantly lower, whereas Ang II levels were higher in the COVID-19 patients than in healthy control individuals. The ratio of Ang 1-7/Ang II as an indicator of the RAS classical and protective arms balance was dramatically lower in COVID-19 patients. There was no significant increase in inflammatory 19-HETE and 20-HETE levels. The concentration of EETs was significantly increased in COVID-19 patients, whereas the DHETs concentration was repressed. Their plasma levels were correlated with Ang II concentration in COVID-19 patients. In conclusion, evaluating the RAS and ArA pathway biomarkers could provide helpful information for the early detection of high-risk groups, avoid delayed medical attention, facilitate resource allocation, and improve patient clinical outcomes to prevent long COVID incidence.

Analysis of the Relationship between Serum Magnesium Levels and Severity of COVID-19 Patients

Magnesium (Mg) plays an important role in the homeostasis functions of the lungs and heart for humankind. However, there is limited information concerning the importance of such an electrolyte mineral to COVID-19 pathogenesis. The Mg level is not primarily considered for the analysis of infectious diseases in the laboratory. The purpose of this study was to analyze the relationship between Mg levels and COVID-19 patient severity at Dr. Wahidin Sudirohusodo Hospital, Makassar. This research was a retrospective study with a cross-sectional design. Samples were prepared from 186 patients. Serum Mg levels were measured using an ABX Pentra 400C analyzer and the patients diagnosed with COVID-19 were then classified into abnormal and normal magnesemia. Based on the severity of COVID-19, patients were then categorized into severe and non-severe. The obtained data were then statistically analyzed using the Kolmogorov-Smirnov test, Mann-Whitney test, Chi-Square, and odd ratio with a significant level of p &lt;0.05. The mean values of serum Mg levels of severe COVID-19 patients (2.53±2.03 mg/dL) were not significantly different compared to those of non-severe COVID-19 patients (2.12±0.83 mg/dL) with p=0.712. Patients with abnormal magnesemia had a 2.625 times higher risk of severe COVID-19 (95% CI = 1.499 – 4.757, p-value=0.001) compared to those with normal magnesemia. There was a significant relationship between serum Mg levels and the severity of COVID-19 patients at Dr. Wahidin Sudirohusodo Hospital. Patients with abnormal Mg levels had a 2.625 times higher risk of severe COVID-19. Magnesium concentration is an important parameter, which must be monitored in the laboratory analyses of COVID-19 patients.

The underlying molecular mechanisms and biomarkers between periodontitis and COVID-19

ObjectiveEmerging evidence shows the clinical consequences of patient with COVID-19 and periodontitis are not promising, and periodontitis is a risk factor. Periodontitis and COVID-19 probably have a relationship. Hence, this study aimed to identify the common molecular mechanism that may help to devise potential therapeutic strategies in the future.Material and methodsWe analyzed two RNA-seq datasets for differential expressed genes, enrichment of biological processes, transcription factors (TFs) and deconvolution-based immune cell types in periodontitis, COVID-19 and healthy controls. Relationships between TFs and mRNA were established by Pearson correlation analysis, and the common TFs-mRNA regulatory network and nine co-upregulated TFs of the two diseases was obtained. The RT-PCR detected the TFs.ResultsA total of 1616 and 10201 differentially expressed gene (DEGs) from periodontitis and COVID-19 are found. Moreover, nine shared TFs and common biological processes associated with lymphocyte activation involved in immune response were identified across periodontitis and COVID-19. The cell type enrichment revealed elevated plasma cells among two diseases. The RT-PCR further confirmed the nine TFs up-regulation in periodontitis.ConclusionThe pathogenesis of periodontitis and COVID-19 is closely related to the expression of TFs and lymphocyte activation, which can provide potential targets for treatment.

Rational Design of Highly Potent SARS-CoV-2 nsp14 Methyltransferase Inhibitors.

The search for new drugs against COVID-19 and its causative agent, SARS-CoV-2, is one of the major trends in the current medicinal chemistry. Targeting capping machinery could be one of the therapeutic concepts based on a unique mechanism of action. Viral RNA cap synthesis involves two methylation steps, the first of which is mediated by the nsp14 protein. Here, we rationally designed and synthesized a series of compounds capable of binding to both the S-adenosyl-l-methionine and the RNA-binding site of SARS-CoV-2 nsp14 N7-methyltransferase. These hybrid molecules showed excellent potency, high selectivity toward various human methyltransferases, nontoxicity, and high cell permeability. Despite the outstanding activity against the enzyme, our compounds showed poor antiviral performance in vitro. This suggests that the activity of this viral methyltransferase has no significant effect on virus transcription and replication at the cellular level. Therefore, our compounds represent unique tools to further explore the role of the SARS-CoV-2 nsp14 methyltransferase in the viral life cycle and the pathogenesis of COVID-19.

Culinary spices and herbs in managing early and long-COVID-19 complications: A comprehensive review.

Human race is preparing for the upsurge and aftermath of COVID-19 pandemic complicated by novel variants, new waves, variable mortality rate, and post-COVID complications. Despite use of repurposed drugs, symptomatic treatments and licensing of multiple vaccines, the daily number of cases and rate of transmission are significant. Culinary spices and herbs have been historically used in pandemic and non-pandemic times to reduce respiratory viral burden. Specific food items and culinary spices can boost the levels of protective immunity and also offer therapeutic benefits against impervious bugs via well-known as well as less-known but scientifically testable mechanisms. Here, we analyzed the phytochemicals profile of Ayurvedic herbs and inferred from the clinical trials/observational studies to provide a focused and succinct perspective on the relevance of "food-based" traditional decoction to moderate COVID-19 disease and long-COVID via modulation of immunity and reinstatement of homeostasis. We also underscore the druggable targets in pathogenesis of COVID-19 which are relevant to the ongoing clinical trials using spices and herbs. This information will provide a strong scientific rationale for standardization of the traditional herbs-based therapies and adopting the use of herbs, spices, and their formulations for reducing SARS-CoV-2 transmission, long-COVID symptoms, and COVID-19 disease progression.

Comparing the expression of MiR-223-NLRP3-IL-1β axis and serum IL-1β levels in patients with severe COVID-19 and healthy individuals

Background and aimThe hyperactive nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key factor for cytokine storm, chronic inflammation, and mortality in infected patients. On the subject of the regulation of the NLRP3-inflammasome activation, micro-ribonucleic acid (RNA)-223 (miR-223), among the major RNA molecules, has been thus far investigated in some inflammatory diseases along with interleukin-1 beta (IL-1β) and NLRP3. Against this background, the present study aimed to compare healthy individuals and patients with severe COVID-19 with reference to the alterations in the expression of the miR-223, NLRP3, and IL-1β axis and the serum IL-1β levels. MethodsIn total, 40 patients with severe COVID-19, admitted to the Infectious Ward of Razi Hospital, Ahvaz, Iran, who were homogenous in terms of age (40 years old) and gender, were selected based on the inclusion and exclusion criteria. The real-time polymerase chain reaction (RT-PCR) technique was then applied to assess the expression of the miR-223, NLRP3, and IL-1β genes, and enzyme-linked immunosorbent assay (ELISA) was then utilized to evaluate the serum IL-1β levels, using patients’ blood samples. Moreover, inflammatory biochemical markers of the participants were collected and recorded ResultsAccording to the study results, the IL-1β expression was 3.9 times higher in the patients with COVID-19, compared with the control group (p = 0.0005). The NLRP3 expression was also 6.04 times greater in the infected patients, compared with the healthy individuals (p < 0.0001). On the other hand, the miR-223 expression was 5.37 times lower in the case group, compared with the controls (p = 0.04). ConclusionThe study findings indicated the potential role of miR-223 and the dysregulation of NLRP3 inflammasome followed by IL-1β, as a regulatory factor in the pathogenesis of COVID-19, like that in other inflammatory diseases.

COVID-19 Disease in Pediatric Solid Organ Transplantation from Alpha to Omicron: A High Monocyte Count in the Preceding Three Months Portends a Risk for Severe Disease.

Planning for future resurgences in SARS-CoV-2 infection is necessary for providers who care for immunocompromised patients. to determine factors associated with COVID-19 disease severity in immunosuppressed children. a case series of children with solid organ transplants diagnosed with SARS-CoV-2 infection between 15 March 2020 and 31 March 2023. a single pediatric transplant center. all children with a composite transplant (liver, pancreas, intestine), isolated intestine transplant (IT), isolated liver transplant LT), or simultaneous liver kidney transplant (SLK) with a positive PCR for SARS-CoV-2. SARS-CoV-2 infection. We hypothesized that children on the most immunosuppression, defined by the number of immunosuppressive medications and usage of steroids, would have the most severe disease course and that differential white blood cell count in the months preceding infection would be associated with likelihood of having severe disease. The hypothesis being tested was formulated during data collection. The primary study outcome measurement was disease severity defined using WHO criteria. 77 children (50 LT, 24 intestine, 3 SLK) were infected with SARS-CoV-2, 57.4 months from transplant (IQR 19.7-87.2). 17% were ≤1 year post transplant at infection. 55% were male, 58% were symptomatic and ~29% had severe disease. A high absolute lymphocyte count at diagnosis decreased the odds of having severe COVID-19 disease (OR 0.29; CI 0.11-0.60; p = 0.004). Conversely, patients with a high absolute monocyte count in the three months preceding infection had increased odds of having severe disease (OR 30.49; CI 1.68-1027.77; p = 0.033). Steroid use, higher tacrolimus level, and number of immunosuppressive medications at infection did not increase the odds of having severe disease. The significance of a high monocyte count as predictor of severe disease potentially confirms the importance of monocytic inflammasome-driven inflammation in COVID-19 pathogenesis. Our data do not support reducing immunosuppression in the setting of infection. Our observations may have important ramifications in resource management as vaccine- and infection-induced immunity wanes.

Tocilizumab; A Potential Remedy Against The Ever-Evolving Threat Of Coronavirus-2 (SARS-Cov-2).

Madam, Coronavirus-2 (SARS-CoV-2) is a novel positive single-strand RNA virus that is the causative agent of COVID-19, which originated in Wuhan, China, at the end of December 2019. Since the beginning of 2020, this virus has taken the world by storm, brought the globe to an absolute crawl for the last two years, and overburdened healthcare facilities in numerous countries. The Coronavirus-2 (SARS-CoV-2) virus is transmitted via aerosolized droplets, and once the virus finds itself inside the host's body, it undergoes an incubation period between 6-7 days. After the viral incubation period passes, the patient suffers from fever, cough, dyspnea, myalgia, and, in severe cases, hypoxia that requires hospitalization and mechanical ventilation.1 The pathogenesis of COVID-19 involves the dysregulation of the host immune response, which may lead to the development of acute respiratory distress syndrome in the host. The dysfunction of the host's immune response involves the hyperactivation of the humoral pathway, resulting in the overproduction of interleukin-6. Elevated levels of Interleukin-6 may lead to the development of numerous pathologies like respiratory failure, shock, and multiorgan dysfunction. This derangement of the host immune response would act as a potential target for several therapeutic agents to relieve COVID-19 symptoms.2 One such therapeutic agent is Toculimizab, which is a recombinant humanized anti-interleukin 6 receptor monoclonal antibody that functions by binding to membrane IL-6 R, thus preventing the formation of the complex with IL-6 and blocking the signal transmission. It is used in several inflammatory immune diseases such as Systemic Sclerosis, Giant Cell Arteritis, Takayasu Arteritis, etc. Tocilizumab has been shown to improve the hyperinflammatory and hypercoagulable state of COVID- 19 patients by reducing the circulating inflammatory biomarkers.3 To support the use and clinical efficacy of Tocilizumab in the hospitalized patient, a 2021 metaanalysis by Kyriakopoilous C. et al. showed the effects of Tocilizumab on mortality amongst Hospitalized COVID-19 patients and to see whether mechanical ventilation would be necessary once Tocilizumab was administered. This research was a combination of observational studies and randomized control trials. The results revealed a reduction in mortalities among 27,004 hospitalized COVID-19 patients. In the meta-analysis observational studies, there was an overall 31% decrease in mortality In the randomized control trials, there was an 11% decrease in mortality, along with a 19% decrease in the need for mechanical ventilation, showing that Tocilizumab was beneficial for all hospitalized patients.4 Continued...

Cytokine response and damages in the lungs of aging Syrian hamsters on a high-fat diet infected with the SARS-CoV-2 virus.

Hypertriglyceridemia, obesity, and aging are among the key risk factors for severe COVID-19 with acute respiratory distress syndrome (ARDS). One of the main prognostic biomarkers of ARDS is the level of cytokines IL-6 and TNF-α in the blood. In our study, we modeled hyperglyceridemia and hypercholesterolemia on 18-month-old Syrian hamsters (Mesocricetus auratus). By 18 months, the animals showed such markers of aging as weight stabilization with a tendency to reduce it, polycystic liver disease, decreased motor activity, and foci of alopecia. The high-fat diet caused an increase in triglycerides and cholesterol, as well as fatty changes in the liver. On the third day after infection with the SARS-CoV-2 virus, animals showed a decrease in weight in the groups with a high-fat diet. In the lungs of males on both diets, there was an increase in the concentration of IFN-α, as well as IL-6 in both males and females, regardless of the type of diet. At the same time, the levels of TNF-α and IFN-γ did not change in infected animals. Morphological studies of the lungs of hamsters with SARS-CoV-2 showed the presence of a pathological process characteristic of ARDS. These included bronchointerstitial pneumonia and diffuse alveolar damages. These observations suggest that in aging hamsters, the immune response to pro-inflammatory cytokines may be delayed to a later period. Hypertriglyceridemia, age, and gender affect the severity of COVID-19. These results will help to understand the pathogenesis of COVID-19 associated with age, gender, and disorders of fat metabolism in humans.

Circulating levels of inflammatory cytokines and angiogenesis-related growth factors in patients with osteoarthritis after COVID-19.

The disease COVID-19, caused by SARS-CoV-2 infection, has a systemic effect and is associated with a number of pathophysiological mechanisms that mobilize a wide range of biomolecules. Cytokines and growth factors (GFs) are critical regulators of tissue damage or repair in osteoarthritis (OA) and are being recognized as key players in the pathogenesis of COVID-19. A clear understanding of the long-term consequences of SARS-CoV-2 infection, especially in patients with concomitant chronic diseases, is limited and needs to be elucidated. The study aimed to evaluate the degree of inflammation and levels of pro-angiogenic and hypoxic factors, as well as heat shock proteins HSP60 and HSP70 in plasma, of patients with OA after recovery from COVID-19. The research involved patients of an orthopedic specialty clinic aged 39 to 80 diagnosed with knee OA. All examined patients were divided into three groups: the Control group included conditionally healthy donors, group OA included patients with knee OA mainly stage II or III and the group of OA and COVID-19 included patients with OA who had COVID-19. The plasma levels of pro-inflammatory molecules IL-1β, IL-6, TNF-α, NF-κB, angiogenic factors VEGF, FGF-2, PDGF, hypoxic factor HIF-1α and molecular chaperones HSP60 and HSP70 were measured by enzyme-linked immunosorbent assay. The study showed that in both groups of patients, with OA and convalescent COVID-19, there was an increase in the plasma level of IL-1β and a decrease in TNF-α and NF-κB levels when compared to healthy controls. Systemic deregulation of the cytokine profile was accompanied by reduction in plasma levels of pro-angiogenic growth factors, most pronounced in cases of VEGF and PDGF. This analysis did not reveal any significant difference in the plasma level of HIF-1α. A decrease in the level of stress protein HSP60 in the blood of patients with OA, as well as those patients who have had SARS-CoV-2 infection, has been established. The results suggest the potential role pro-inflammatory cytokines and angiogenesis-related growth factors in pathogenesis of both joint pathologies and long-term systemic post-COVID-19 disorders.

Exploring Key Biomarkers and Common Pathogenesis of Seven Digestive System Cancers and Their Correlation with COVID-19.

Digestive system cancer and COVID-19 significantly affect the digestive system, but the mechanism of interaction between COVID-19 and the digestive system cancers has not been fully elucidated. We downloaded the gene expression of COVID-19 and seven digestive system cancers (oral, esophageal, gastric, colorectal, hepatocellular, bile duct, pancreatic) from GEO and identified hub differentially expressed genes. Multiple verifications, diagnostic efficacy, prognostic analysis, functional enrichment and related transcription factors of hub genes were explored. We identified 23 common DEGs for subsequent analysis. CytoHubba identified nine hub genes (CCNA2, CCNB1, CDKN3, ECT2, KIF14, KIF20A, KIF4A, NEK2, TTK). TCGA and GEO data validated the expression and excellent diagnostic and prognostic ability of hub genes. Functional analysis revealed that the processes of cell division and the cell cycle were essential in COVID-19 and digestive system cancers. Furthermore, six related transcription factors (E2F1, E2F3, E2F4, MYC, TP53, YBX1) were involved in hub gene regulation. Via in vitro experiments, CCNA2, CCNB1, and MYC expression was verified in 25 colorectal cancer tissue pairs. Our study revealed the key biomarks and common pathogenesis of digestive system cancers and COVID-19. These may provide new ideas for further mechanistic research.

Longitudinal whole blood transcriptomic analysis characterizes neutrophil activation and interferon signaling in moderate and severe COVID-19

A maladaptive inflammatory response has been implicated in the pathogenesis of severe COVID-19. This study aimed to characterize the temporal dynamics of this response and investigate whether severe disease is associated with distinct gene expression patterns. We performed microarray analysis of serial whole blood RNA samples from 17 patients with severe COVID-19, 15 patients with moderate disease and 11 healthy controls. All study subjects were unvaccinated. We assessed whole blood gene expression patterns by differential gene expression analysis, gene set enrichment, two clustering methods and estimated relative leukocyte abundance using CIBERSORT. Neutrophils, platelets, cytokine signaling, and the coagulation system were activated in COVID-19, and this broad immune activation was more pronounced in severe vs. moderate disease. We observed two different trajectories of neutrophil-associated genes, indicating the emergence of a more immature neutrophil phenotype over time. Interferon-associated genes were strongly enriched in early COVID-19 before falling markedly, with modest severity-associated differences in trajectory. In conclusion, COVID-19 necessitating hospitalization is associated with a broad inflammatory response, which is more pronounced in severe disease. Our data suggest a progressively more immature circulating neutrophil phenotype over time. Interferon signaling is enriched in COVID-19 but does not seem to drive severe disease.

Inflammatory markers and COVID-19 disease progression

BackgroundThe COVID-19 pandemic has resulted in a global humanitarian crisis. Despite ongoing research, transmission risks and many disease characteristics remained unclear. Most patients have displayed elevated levels of certain inflammatory markers, which we sought to investigate further in relation to disease severity. The aim of this study was to examine the correlation between inflammatory markers and the severity of COVID-19 among patients. MethodsWe conducted a cross-sectional study from April to September 2020, involving 143 COVID-19 PCR-positive patients from Ziauddin Hospital. Electronic patient records provided data on demographics, clinical status, and laboratory results. ResultsThe majority of PCR-positive patients were elderly males with comorbidities such as diabetes and hypertension. Almost all patients exhibited increased levels of various inflammatory markers, with procalcitonin (97.2%) being the most common. Statistically significant differences were observed in the levels of TLC (p = 0.005), CRP (p = 0.001), LDH (p = 0.001), Ferritin (p = 0.001), D-dimer (p = 0.001), and procalcitonin (p = 0.028), in relation to COVID-19 severity. ConclusionsThe data suggest a significant association between levels of inflammatory markers and COVID-19 severity. All markers, except procalcitonin, demonstrated a significant correlation with disease severity. These results could enhance our understanding of COVID-19 pathogenesis and help predict and manage severe cases.

Relationship of thrombospondin-1 and thrombospondin-2 with hematological, biochemical and inflammatory markers in COVID-19 patients

Abstract Objectives Roles of thrombospondin-1 (TSP-1) and thrombospondin-2 (TSP-2) in tissue repair and inflammation are well-documented, but the association of their serum expressions with the pathogenesis of COVID-19 remains unclear. We investigate the roles of TSP-1 and TSP-2 in COVID-19. Methods 106 SARS-CoV-2 infected patients and 23 healthy people were enrolled in our study. COVID-19 patients were divided into two groups as non-severe and severe. TSP-1 and TSP-2 concentrations were measured with an enzyme-linked Immunosorbent Assay, and blood markers were analyzed with routine laboratory techniques. Results COVID-19 patients had significantly higher TSP-1 and TSP-2 levels than healthy controls. TSP-1 and TSP-2 positively correlated with inflammatory markers, including ESR, CRP, PCT, ferritin, and biochemical parameters such as ALT, AST, BUN, CK, and LDH. In addition, TSP-1 and TSP-2 were negatively correlated with hematological markers such as LYM, EOS, and HGB. Receiver operating characteristic analyses revealed that COVID-19 may be predicted with TSP-1 levels over 189.94 ng/mL and TSP-2 levels higher than 0.70 ng/mL. Conclusions Our analysis suggests that TSP-1 and TSP-2 expressions at the systemic level may have clinical importance for COVID-19.