Recent developments in the immunopathology of COVID-19.

There has been an important change in the clinical characteristics and immune profile of Coronavirus disease 2019 (COVID-19) patients during the pandemic thanks to the extensive vaccination programs. Here, we highlight recent studies on COVID-19, from the clinical and immunological characteristics to the protective and risk factors for severity and mortality of COVID-19. The efficacy of the COVID-19 vaccines and potential allergic reactions after administration are also discussed. The occurrence of new variants of concerns such as Omicron BA.2, BA.4, and BA.5 and the global administration of COVID-19 vaccines have changed the clinical scenario of COVID-19. Multisystem inflammatory syndrome in children (MIS-C) may cause severe and heterogeneous disease but with a lower mortality rate. Perturbations in immunity of T cells, B cells, and mast cells, as well as autoantibodies and metabolic reprogramming may contribute to the long-term symptoms of COVID-19. There is conflicting evidence about whether atopic diseases, such as allergic asthma and rhinitis, are associated with a lower susceptibility and better outcomes of COVID-19. At the beginning of pandemic, the European Academy of Allergy and Clinical Immunology (EAACI) developed guidelines that provided timely information for the management of allergic diseases and preventive measures to reduce transmission in the allergic clinics. The global distribution of COVID-19 vaccines and emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with reduced pathogenic potential dramatically decreased the morbidity, severity, and mortality of COVID-19. Nevertheless, breakthrough infection remains a challenge for disease control. Hypersensitivity reactions (HSR) to COVID-19 vaccines are low compared to other vaccines, and these were addressed in EAACI statements that provided indications for the management of allergic reactions, including anaphylaxis to COVID-19 vaccines. We have gained a depth knowledge and experience in the over 2 years since the start of the pandemic, and yet a full eradication of SARS-CoV-2 is not on the horizon. Novel strategies are warranted to prevent severe disease in high-risk groups, the development of MIS-C and long COVID-19.

COVID-19 disease in hospitalized young adults in India and China: Evaluation of risk factors predicting progression across two major ethnic groups.

Data pertaining to risk factor analysis in coronavirus disease 2019 (COVID-19) is confounded by the lack of data from an ethnically diverse population. In addition, there is a lack of data for young adults. This study was conducted to assess risk factors predicting COVID-19 severity and mortality in hospitalized young adults. A retrospective observational study was conducted at two centers from China and India on COVID-19 patients aged 20-50 years. Regression analysis to predict adverse outcomes was performed using parameters including age, sex, country of origin, hospitalization duration, comorbidities, lymphocyte count, and National Early Warning Score 2 (NEWS2) score at admission. A total of 420 patients (172 East Asians and 248 South Asians) were included. The predictive model for intensive care unit (ICU) admission with variables NEWS2 Category II and higher, diabetes mellitus, liver dysfunction, and low lymphocyte counts had an area under the curve (AUC) value of 0.930 with a sensitivity of 0.931 and a specificity of 0.784. The predictive model for mortality with NEWS2 Category III, cancer, and decreasing lymphocyte count had an AUC value of 0.883 with a sensitivity of 0.903 and a specificity of 0.701. A combined predictive model with bronchial asthma and low lymphocyte count, in contrast, had an AUC value of 0.768 with a sensitivity of 0.828 and a specificity of 0.719 for NEWS2 score (5 or above) at presentation. NEWS2 supplemented with comorbidity profile and lymphocyte count could help identify hospitalized young adults at risk of adverse COVID-19 outcomes.

Risk factors for severe and critically ill COVID-19 patients: A review.

The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an unprecedented global social and economic impact, and high numbers of deaths. Many risk factors have been identified in the progression of COVID-19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type I interferon secretion capacity, and pregnancy. Possible complications include acute kidney injury, coagulation disorders, thoromboembolism. The development of lymphopenia and eosinopenia are laboratory indicators of COVID-19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high-sensitivity C-reactive protein, proinflammatory cytokines such as interleukin (IL)-6, IL-1ß, Krebs von den Lungen-6 (KL-6), and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of severity of COVID-19.

Complications of implanted port catheters and peripherally inserted central catheters in chemotherapy-treated cancer patients: A meta-analysis.

BACKGROUND: One of the most significant advancements in nursing technology for cancer patients has been the development of implantable port catheters and peripherally inserted central venous catheters. They create an essential, dependable route for subjects to receive chemotherapy, long-term infusions and nutritional care, and provide a site for regular blood draws. OBJECTIVES: We performed a meta-analysis to evaluate the complications of implanted port catheters and peripherally inserted central catheters in chemotherapy-treated cancer patients. MATERIAL AND METHODS: A systematic literature search up to April 2022 was performed and a total of 11,801 articles have been retrieved. Of these, 5017 concerned peripherally inserted central catheters and 6784 implanted port catheters to administer chemotherapy. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (95% CIs) were calculated to assess the complications of implanted port catheters and peripherally inserted central catheters in chemotherapy-treated cancer patients using dichotomous and contentious methods with randomor fixed-effects models. RESULTS: Peripherally inserted central catheters had significantly higher incidence of occlusion complications (OR: 5.43, 95% CI: 3.46-8.52, p < 0.001), longer durations of local infection (OR: 2.94, 95% CI: 2.17-4.00, p < 0.001), higher incidence of catheter-related infection (OR: 2.13, 95% CI: 1.19-3.83, p = 0.01), higher rate of malposition (OR: 6.46, 95% CI: 2.93-14.27, p < 0.001), higher rates of catheter-related thrombosis (OR: 2.71, 95% CI: 1.90-3.87, p < 0.001), higher incidence of phlebitis complications (OR: 6.67, 95% CI: 2.94-15.11, p < 0.001), higher incidence of accidental removal (OR: 3.38, 95% CI: 1.97-5.81, p < 0.001), and a shorter catheter lifespan (MD: -233.16, 95% CI: -449.52--16.80, p = 0.03) in subjects undergoing chemotherapy compared to those in whom implanted port catheters were used. CONCLUSION: Implantable port catheter has advantages over peripherally inserted central catheter in decreasing cancer patients' complications. The outcomes provide evidence for practitioners to select which type of central venous catheters is better for cancer chemotherapy subject.

IL-13 Regulates Orai1 Expression in Human Bronchial Smooth Muscle Cells and Airway Remodeling in Asthma Mice Model via LncRNA H19.

Background: Increased proliferation and hypertrophy of airway smooth muscle cells (ASMCs) contribute substantially to airway remodeling in asthma. Interleukin (IL)-13 regulates ASMC proliferation by increasing Orai1 expression, the pore-forming subunit of store-operated Ca2+ entry (SOCE). The underlying mechanisms of this effect are not fully understood. Methods: Bioinformatic analysis identified an interaction between microRNA 93-5p (miR-93-5p) and long non-coding RNA (lncRNA) H19, and between miR-93-5p and Orai1. RNA interference was used to investigate H19 knockdown on IL-13-induced proliferation and migration of in vitro cultured human bronchial smooth muscle cells (hBSMCs). Functional relevance of H19 in airway inflammation and airway remodeling was investigated in murine models of acute and chronic asthma. Results: IL-13 concentration-dependently increased the expression of H19 and Orai1 and decreased the expression of miR-93-5p in hBSMCs. H19 knockdown partly reversed the effects of IL-13 on the expression of miR-93-5p and Orai1 and attenuated the proliferation and migration of hBSMCs promoted by IL-13. IL-13-promoted expression of Orai1 was attenuated by miR-93-5p mimic and increased by miR-93-5p inhibitor. IL-13-promoted proliferation of hBSMCs was increased by miR-93-5p inhibitor but not affected by miR-93-5p mimic, whereas IL-13-promoted migration of hBSMCs was increased by miR-93-5p inhibitor and attenuated by miR-93-5p mimic. The inhibiting effect of H19 knockdown on IL-13-induced Orai1 expression and the proliferation and migration of hBSMCs was counteracted by miR-93-5p inhibitor but only marginally or not impacted by miR-93-5p mimic. The expression of H19 and Orai1 was higher in the lungs of asthmatic mice than in control mice. In asthmatic mice, H19 siRNA reduced Orai1 expression, inflammatory cell infiltration, goblet cell hyperplasia, collagen deposition and smooth muscle mass in the lungs. Conclusion: H19 may mediate the effects of IL-13 on Orai1 expression by inhibition of miR-93-5p in hBSMCs. H19 may be a therapeutic target for airway inflammation and airway remodeling.

Dropouts From Sublingual Immunotherapy and the Transition to Subcutaneous Immunotherapy in House Dust Mite-Sensitized Allergic Rhinitis Patients.

Purpose: Both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are effective in reducing symptoms and medication scores and inducing long-term efficacy in patients with allergic rhinitis (AR). However, SLIT has been associated with poor patient adherence. This study investigates the factors impacting dropout rates from SLIT in house dust mite (HDM)-sensitized AR patients. Methods: A retrospective study was performed to analyze dropout rates and reasons in AR patients receiving Dermatophagoides farinae (Der f) SLIT with a follow-up period of 2 years. Results: A total of 719 HDM-sensitized AR patients received Der f-SLIT. Dropout rates increased with time and most occurred after 1 year of SLIT. By month 24, 654 (91%) patients had discontinued SLIT. The dropout rates by month 24 were 100, 90.1, and 91.1% in children <5 years old, children aged 5-18 years old, and adults ≥ 18 years old, respectively. Combination with allergic asthma and mono- or multi-sensitization to other aeroallergens did not affect the dropout rates. The most common self-reported reasons for dropouts were refusal of continuation, dissatisfaction with the efficacy, transition to SCIT, and adverse effects. Refusal of continuation increased with age, whereas transition to SCIT decreased with age. Ninety-seven cases transitioned from SLIT to SCIT, and the transition rates increased with time. Comorbid allergic asthma did not affect the transition rates. However, multi-sensitization was associated with a slightly higher rate of transition to SCIT. The most common reason for the transition was dissatisfaction with the efficacy (54.6%), which was only reported by patients older than 5 years. For children who began SLIT at younger than 5 years old, the most common reason (81.2%) for transition was age reaching 5 years. Conclusions: HDM-SLIT has a very high dropout rate, which is mainly due to refusal of continuation and dissatisfaction with the efficacy. Transitioning from SLIT to SCIT may help keep these patients on AIT and thus increase adherence and long-term efficacy.

Recent advances and developments in COVID-19 in the context of allergic diseases.

BACKGROUND: Since the first reports of coronavirus disease 2019 (COVID-19) in Wuhan, China, in December 2019, there have been 198 million confirmed cases worldwide as of August 2021. The scientific community has joined efforts to gain knowledge of the newly emerged virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the immunopathological mechanisms leading to COVID-19, and its significance for patients with allergies and asthma. METHODS: Based on the current literature, recent advances and developments in COVID-19 in the context of allergic diseases were reviewed. RESULTS AND CONCLUSIONS: In this review, we discuss the prevalence of COVID-19 in subjects with asthma, attacks of hereditary angioedema, and other allergic diseases during COVID-19. Underlying mechanisms suggest a protective role of allergy in COVID-19, involving eosinophilia, SARS-CoV-2 receptors expression, interferon responses, and other immunological events, but further studies are needed to fully understand those associations. There has been significant progress in disease evaluation and management of COVID-19, and allergy care should continue during the COVID-19 pandemic. The European Academy of Allergy & Clinical Immunology (EAACI) launched a series of statements and position papers providing recommendations on the organization of the allergy clinic, handling of allergen immunotherapy, asthma, drug hypersensitivity, allergic rhinitis, and other allergic diseases. Treatment of allergies using biologics during the COVID-19 pandemic has also been discussed. Allergic reactions to the COVID-19 vaccines, including severe anaphylaxis, have been reported. Vaccination is a prophylactic strategy that can lead to a significant reduction in the mortality and morbidity associated with SARS-CoV-2 infection, and in this review, we discuss the proposed culprit components causing rare adverse reactions and recommendations to mitigate the risk of anaphylactic events during the administration of the vaccines.

IL-23 enhances the malignant properties of hepatoma cells by attenuation of HNF4α.

Chronic infection with hepatitis B virus (HBV) is one of the major risk factors for hepatocellular carcinoma. HBV infection can induce the expression of IL-23. However, the effects of IL-23 on carcinogenesis are rare and contradictory. To investigate the potential role of IL-23 on malignant properties of hepatoma cells, in the present study, first, we confirmed that HBV drove infected hepatoma cells to produce more IL-23. And then we found that at low concentration, human recombinant IL-23 (hrIL-23) enhanced malignant properties of hepatoma cells through increasing the proportion of stem/progenitor cells, promoting proliferation and colony formation, reducing apoptosis and inducing motility and invasivity of them. Hepatocyte nuclear factor 4 alpha (HNF4α), which is essential for liver development and hepatocyte function, was found to be downregulated in HBV integrated or transiently transfected hepatoma cells. Its expression was also decreased in cells treated by hrIL-23 or by HepG2.215 culture supernatant and this decrease could be abolished by supplementation of anti-IL-23p19 antibody. Hence, it is speculated that HBV related IL-23 can enhance malignant properties of hepatoma cells through attenuation of HNF4α. The findings identified a potential target of interventional strategies for treating hepatitis B patients through manipulation of the IL-23.

Overexpression of GRP78 enhances survival of CHO cells in response to serum deprivation and oxidative stress.

Chinese hamster ovary (CHO) cells are regarded as one of the most commonly used mammalian hosts, which decreases the productivity due to loss in culture viability. Overexpressing antiapoptosis genes in CHO cells was developed as a means of limiting cell death upon exposure to environmental insults. Glucose-regulated protein 78 (GRP78) is traditionally regarded as a major ER chaperone that participates in protein folding and other cell processes. It is also a potent antiapoptotic protein and plays a critical role in cell survival, proliferation, and metastasis. In this study, the impact of GRP78 on CHO cells in response to environmental insults such as serum deprivation and oxidative stress was investigated. First, it was confirmed that CHO cells were very sensitive to environmental insults. Then, GRP78 overexpressing CHO cell line was established and exposed to serum deprivation and H2O2. Results showed that GRP78 engineering increased the viability and decreased the apoptosis of CHO cells. The survival advantage due to GRP78 engineering could be mediated by suppression of caspase-3 involved in cell death pathways in stressed cells. Besides, GRP78 engineering also enhanced yields of antibody against transferrin receptor in CHO cells. GRP78 should be a potential application in the biopharmaceutical industries.

GRP78 Impairs Production of Lipopolysaccharide-Induced Cytokines by Interaction with CD14.

The 78-kDa glucose-regulated protein (GRP78) is a stress-inducible chaperone that resides primarily in the endoplasmic reticulum. GRP78 has been described to be released at times of cellular stress and as having extracellular properties that are anti-inflammatory or favor the resolution of inflammation. In the current study, we confirmed that GRP78 impaired the production of lipopolysaccharide-induced pro-inflammatory cytokines in GRP78-treated bone-marrow-derived dendritic cells (DCs). To explore the underlying mechanism, first of all, GRP78 was checked to be bound to the plasma membrane. Interestingly, such binding promoted endocytosis of toll-like receptor (TLR) 4 and reduction in TLR4 on the plasma surface had a key role in desensitization of GRP78-treated DCs to lipopolysaccharide. Given that cluster of differentiation (CD)14 is a crucial regulator of TLR4 endocytosis, interaction of GRP78 with CD14 was investigated next. Data showed that GRP78 co-localized with CD14 on the plasma membrane and glutathione-S-transferase-GRP78 precipitated CD14. In CD14 knockout mice, down-regulation of tumor necrosis factor-α and reduction in TLR4 on the plasma surface were abrogated in GRP78-treated DCs. Overall, these data suggested that GRP78 mediates endocytosis of TLR4 by targeting CD14 to favor the resolution of inflammation.

BIP induces mice CD19(hi) regulatory B cells producing IL-10 and highly expressing PD-L1, FasL.

Many studies have shown that B cells possess a regulatory function in mouse models of autoimmune diseases. Regulatory B cells can modulate immune response through many types of molecular mechanisms, including the production of IL-10 and the expression of PD-1 Ligand and Fas Ligand, but the microenvironmental factors and mechanisms that induce regulatory B cells have not been fully identified. BIP (binding immunoglobulin protein), a member of the heat shock protein 70 family, is a type of evolutionarily highly conserved protein. In this article, we have found that IL-10(+), PD-L1(hi) and FasL(hi) B cells are discrete cell populations, but enriched in CD19(hi) cells. BIP can induce IL-10-producing splenic B cells, IL-10 secretion and B cells highly expressing PD-L1 and FasL. CD40 signaling acts in synergy with BIP to induce regulatory B cells. BIP increased surface CD19 molecule expression intensity and IL-10(+), PD-L1(hi) and FasL(hi) B cells induced by BIP share the CD19(hi) phenotype. Furthermore, B cells treated with BIP and anti-CD40 can lead to suppression of T cell proliferation and the effect is partially IL-10-dependent and mainly BIP-induced. Taken together, our findings identify a novel function of BIP in the induction of regulatory B cells and add a new reason for the therapy of autoimmune disorders or other inflammatory conditions.

Effect of caesarean section on maternal and foetal outcomes in acute fatty liver of pregnancy: a systematic review and meta-analysis.

Several studies have reported a positive association between caesarean section for expeditious pregnancy termination and perinatal outcomes in acute fatty liver of pregnancy (AFLP); however, the risks remain unclear and independent studies have reported conflicting findings. In this meta-analysis, we aimed to confirm the relationship between caesarean section and perinatal outcomes in AFLP. The PubMed, Embase, and China National Knowledge Infrastructure databases were searched (until July 17, 2015) for observational clinical studies focusing on the association between caesarean section and perinatal outcomes in AFLP. Data were extracted and processed independently by 2 authors. We also compared caesarean section with vaginal delivery to further investigate this relationship. We observed that 2 of the 3 primary outcomes in caesarean section exhibited positive effects-the maternal mortality rate was 44% lower (relative risk [RR], 0.56 [0.41-0.76]) and perinatal mortality rate was also reduced (RR, 0.52 [0.38-0.71]), compared to those for vaginal delivery. We did not find any associations between caesarean section and perinatal outcomes in AFLP in terms of neonatal mortality type and maternal multiple organ complications. These findings emphasise the significant prognostic value and clinical implications of caesarean section in AFLP, and suggest that the adverse outcomes should be reduced.