Idiopathic pulmonary fibrosis (IPF), which shares a radiographic pattern with the usual interstitial pneumonia (UIP), is a specific form of chronic and progressive interstitial lung disorder resulting in persistent fibrosis and impaired lung function. Most of the patients suffer from dyspnea which adversely affects health-related quality of life (HRQOL). The underlying etiology of the disease is not yet understood, but research done on the subject reveals that aberrant repair mechanisms and dysregulated immune responses may be the cause. It can affect any age group but predominantly affects patients who are above 50 years of age. It has been observed that in addition to age, the reasons are also related to smoking, pollution, and inhalation of harmful elements. As the cause of IPF is still unknown and there is no cure yet, presently, it is treated to delay lung function loss with antifibrotic medications, nintedanib, and pirfenidone. However, both nintedanib and perfenidone have side effects which affect different patients in different ways and with different levels of severity, thereby making the treatment even more challenging for medical practitioners. The present systematic review aims at studying the efficacy of pirfenidone and nintedanib in relieving symptoms and in extending survival in patients. A detailed search was done in relevant articles listed in PubMed, ScienceDirect, and the New England Journal of Medicine between 2018 and 2023. It was observed that the most accepted way of measuring the progression of IPF is the evaluation of pulmonary function by assessing the forced vital capacity (FVC). Several studies have shown that the decline in FVC over a period of 6-12 months is directly associated with a higher mortality rate. The outcomes were similar in both male and female irrespective of age, gender, and ethnicity. However, some patients being treated with pirfenidone and nintedanib experienced various side-effects which were mainly gastrointestinal like diarrhea, dyspepsia, and vomiting. In the case of pirfenidone, some patients also experienced photosensitivity and skin rashes. In cases where the side-effects are extremely severe and are more threatening than the disease itself, the treatment has to be discontinued. The survival rate in patients with IPF is marked by a median of 3-5 years that is even lower than many cancers; hence, the treatment should be started as soon as the disease is detected. However, further research is needed to establish the etiology of IPF and to establish treatments that can stop its progression.

SARS-CoV-2 infection (COVID-19) induces dysregulated production of pro- and anti-inflammatory cytokines, called the cytokine storm, leading to the development of severe pneumonia and ARDS. We aimed to examine the dynamic cytokine response on different days of the disease in adult COVID-19 patients.
Our study included 142 patients (with SARS-CoV-2 PCR-positive nasopharyngeal samples) with varying disease severity and admitted on different days of the disease. We examined the presence and mean levels of TNF-α and IL-10 and did a correlation and logistic regression analysis.
TNF-α levels were high in all patients, with mean levels being the highest on day 5 of the disease. IL-10 was high only in a quarter of the patients. The levels of IL-10 were also the highest on day 5, which was significantly different from the mean levels on the other days of the disease. Average IL-10 levels were not any higher than the normal range on the other days. We found a significant positive correlation between the levels of TNF-α and IL-10 during the first week of the infection. In the second week, the positive correlation was no longer significant, and starting from day 10, there was even a slight negative correlation. IL-10 level increase showed prognostic significance for severe, but not the critical forms of the disease.
The uncontrolled immune response to SARS-CoV-2 in the second week of the disease can be the result of dysregulated production of endogenous anti-inflammatory cytokines. This leads to a severe disease course and a possible unfavorable outcome.

Introduction: Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome (ARDS) and life-threatening multi-organ failure with increased levels of inflammatory mediators and viral load; however, little is known about its pathophysiology. Methods: To better understand the cellular status of COVID-19-induced ARDS, we performed single-cell RNA sequencing on peripheral blood samples from patients with COVID-19-induced ARDS. Single-cell RNA sequencing combined with bioinformatics analysis was used to study dynamic changes in cell composition and transcriptional profiles. Results: The single-cell RNA sequencing data revealed significant phenotypic differences between patients with COVID-19-induced ARDS and controls, mainly in monocytes, and CD8+ T and B cells. B-cell and monocyte abundances were significant in COVID-19-induced ARDS patients compared to controls, while CD8+ T cells were depleted. These data suggest that there is an imbalance between lymphocytes and monocytes in the blood of COVID-19-induced ARDS patients. In addition, cytokine interactions between T cells, monocytes and B cells are enhanced as evidenced by the intercellular communication analysis. In particular, T cell subsets target receptors on other cells via CCL5 and may play an important role in patients with COVID-19-induced ARDS. Conclusion: Our analysis suggested that a dysregulated adaptive immune response exists in patients with COVID-19-induced ARDS. Overall, we provided a cellular picture of the peripheral immune response in patients with COVID-19-induced ARDS.

COVID-19, or coronavirus infection, is an acute respiratory illness caused by the corona virus that can develop into a life-threatening form of ARDS. Extracorporeal membrane oxygenation (ECMO) is a highly effective treatment for life-threatening instances. One of the many complications associated with ECMO was bleeding. COVID patients are at risk for intracerebral bleeding due to several factors, including the drug\'s action on ACE2 receptors, leading to hypertension, as well as hypercoagulability, dysregulated immune response, DIC, and the use of anticoagulants.

UNASSIGNED: Myofasciitis is a heterogeneous group of diseases pathologically characterized by inflammatory cell infiltration into the fascia. Endothelial activation plays a critical role in the pathogenesis of the inflammatory response. However, the expression of cellular adhesion molecules (CAMs) in myofasciitis has not been investigated.
UNASSIGNED: Data on clinical features, thigh magnetic resonance imaging, and muscle pathology were collected from five patients with myofasciitis. Immunohistochemical (IHC) staining and Western blot (WB) of the muscle biopsies from patients and healthy controls were performed.
UNASSIGNED: Increased levels of serum pro-inflammatory cytokines, including IL-6, TNF-α, and IL-2R, were detected in four patients. IHC staining and WB indicated significantly increased expression of cell adhesion molecules in blood vessels or inflammatory cells within the perimysium in muscle and fascia tissues of patients with myofasciitis compared to controls.
UNASSIGNED: The up-regulation of CAMs in myofasciitis indicates endothelial activation, which may be potential therapy targets for the treatment of myofasciitis.

Acute kidney injury (AKI) is a common consequence of sepsis with a mortality rate of up to 40%. The pathogenesis of septic AKI is complex and involves several mechanisms leading to exacerbated inflammatory response associated with renal injury. A large body of evidence suggests that inflammation is tightly linked to AKI through bidirectional interaction between renal and immune cells. Preclinical data from our and other laboratories have identified in complement system activation a crucial mediator of AKI. Partial recovery following AKI could lead to long-term consequences that predispose to chronic dysfunction and may also accelerate the progression of preexisting chronic kidney disease. Recent findings have revealed striking morphological and functional changes in renal parenchymal cells induced by mitochondrial dysfunction, cell cycle arrest via the activation of signaling pathways involved in aging process, microvascular rarefaction, and early fibrosis. Although major advances have been made in our understanding of the pathophysiology of AKI, there are no available preventive and therapeutic strategies in this field. The identification of ideal clinical biomarkers for AKI enables prompt and effective therapeutic strategy that could prevent the progression of renal injury and promote repair process. Therefore, the use of novel biomarkers associated with clinical and functional criteria could provide early interventions and better outcome. Several new drugs for AKI are currently being investigated; however, the complexity of this disease might explain the failure of pharmacological intervention targeting just one of the many systems involved. The hypothesis that blood purification could improve the outcome of septic AKI has attracted much attention. New relevant findings on the role of polymethylmethacrylate-based continuous veno-venous hemofiltration in septic AKI have been reported. Herein, we provide a comprehensive literature review on advances in the pathophysiology of septic AKI and potential therapeutic approaches in this field.

The COVID-19 pandemic has created a major alteration in the medical literature including the sepsis discussion. From the outset of the pandemic, various reports have indicated that although there are some unique features pertinent to COVID-19, many of its acute manifestations are similar to sepsis caused by other pathogens. As a consequence, the old definitions now require consideration of this new etiologic agent, namely SARS-CoV-2. Although the pathogenesis of COVID-19 has not been fully explained, the data obtained so far in hospitalized patients has revealed that serum cytokine and chemokine levels are high in severe COVID-19 patients, similar to those found with sepsis. COVID-19 may involve multiple organ systems. In addition to the lungs, the virus has been isolated from blood, urine, faeces, liver, and gallbladder. Results from autopsy series in COVID-19 patients have demonstrated a wide range of findings, including vascular involvement, congestion, consolidation, and hemorrhage as well as diffuse alveolar damage in lung tissue consistent with acute respiratory distress syndrome (ARDS). The presence of viral cytopathic-like changes, infiltration of inflammatory cells (mononuclear cells and macrophages), and viral particles in histopathological samples are considered a consequence of both direct viral infection and immune hyperactivation. Thromboembolism and hyper-coagulopathy are other components in the pathogenesis of severe COVID-19. Although the pathogenesis of hypercoagulability is not fully understood, it has been pointed out that all three components of Virchow’s triad (endothelial injury, stasis, and hypercoagulable state) play a major role in contributing to clot formation in severe COVID-19 infection. In severe COVID-19 cases, laboratory parameters such as hematological findings, coagulation tests, liver function tests, D-dimer, ferritin, and acute phase reactants such as CRP show marked alterations, which are suggestive of a cytokine storm. Another key element of COVID-19 pathogenesis in severe cases is its similarity or association with hemophagocytic lymphohistiocytosis (HLH). SARS-CoV-2 induced cytokine storm has significant clinical and laboratory findings overlapping with HLH. Viral sepsis has some similarities but also some differences when compared to bacterial sepsis. In bacterial sepsis, systemic inflammation affecting multiple organs is more dominant than in COVID-19 sepsis. While bacterial sepsis causes an early and sudden onset clinical deterioration, viral diseases may exhibit a relatively late onset and chronic course. Consideration of severe COVID-19 disease as a sepsis syndrome has relevance and may assist in terms of determining treatments that will modulate the immune response, limit intrinsic damage to tissue and organs, and potentially improve outcome.

OBJECTIVE: Recent evidence suggests a multilevel inflammatory syndrome as a driving factor in some of the most severely ill coronavirus disease 2019 patients with overlapping features to other hyperinflammatory or autoimmune diseases. Therefore, plasma exchange is considered as potential therapy in these patients.
OBJECTIVE: We characterize the longitudinal therapeutic efficacy and safety profile of plasma exchange in critically ill patients with clinical and laboratory evidences of coronavirus disease 2019-related immunopathology.
METHODS: A retropsective case-control study of critically ill coronavirus disease 2019 patients treated with plasma exchange at Heidelberg University Hospital between March and December 2020. Plasma exchange-treated patients were compared with coronavirus disease 2019 patients on standard therapy matched for age, gender, disease severity, and features of hyperinflammatory syndrome.
METHODS: Mortality rate and course of clinical and laboratory parameters in response to plasma exchange were assessed in coronavirus disease 2019 patients and in patients on standard care. A plasma volume of 50 mL per kg body weight or a maximum of 4 L was exchanged.
RESULTS: In total, 28 critically ill coronavirus disease 2019 patients were treated with a median of three plasma exchange procedures per patient. No relevant complications occurred during plasma exchange therapy. Inflammatory and biochemical markers of end-organ damage and endothelial activation were significantly reduced following plasma exchange together with normalization of body temperature, improved pulmonary function, and reduced vasopressor demand. Most importantly, these improvements were maintained after the last plasma exchange. In contrast, no such effects were observed in the control group, although baseline clinical and laboratory parameters were comparable. Kaplan-Meier analysis showed improved 30-day survival in the plasma exchange group compared with the control group (67.9% vs 42.9%; p = 0.044). In a multivariable analysis, the hazard ratio for death was 0.27 (95% CI, 0.11-0.68; p = 0.005) with plasma exchange versus standard care.
CONCLUSIONS: Our data provide further evidence for plasma exchange as a novel therapeutic strategy in a subset of critically ill coronavirus disease 2019 patients by potentially reversing the complex coronavirus disease 2019 immunopathology. Randomized controlled trials are underway to confirm these positive results.

BACKGROUND: The outbreak of Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection has become a global health emergency. We aim to decipher SARS-CoV-2 infected cell types, the consequent host immune response and their interplay in lung of COVID-19 patients.
METHODS: We analyzed single-cell RNA sequencing (scRNA-seq) data of bronchoalveolar lavage fluid (BALF) samples from 10 healthy donors, 6 severe COVID-19 patients and 3 mild recovered patients. The expressions of SARS-CoV-2 receptors (ACE2 and TMPRSS2) were examined among different cell types. The immune cells infiltration patterns, their expression profiles, and interplays between immune cells and SARS-CoV-2 target cells were further investigated.
RESULTS: Compared to healthy controls, ACE2 and TMPRSS2 expressions were significantly higher in lung epithelial cells of COVID-19 patients, in particular club and ciliated cells. SARS-CoV-2 activated pro-inflammatory genes and interferon/cytokine signaling in these cells. In severe COVID-19 patients, significantly higher neutrophil, but lower macrophage in lung was observed along with markedly increased cytokines expression compared with healthy controls and mild patients. By contrast, neutrophil and macrophage returned to normal level whilst more T and NK cells accumulation were observed in mild patients. Moreover, SARS-CoV-2 infection altered the community interplays of lung epithelial and immune cells: interactions between the club and immune cells were higher in COVID-19 patients compared to healthy donors; on the other hand, immune-immune cells interactions appeared the strongest in mild patients.
CONCLUSIONS: SARS-CoV-2 could infect lung epithelium, alter communication patterns between lung epithelial cells and immune system, and drive dysregulated host immune response in COVID-19 patients.
BACKGROUND: This project was supported by National Key R&D Program of China (No. 2018YFC1315000/2018YFC1315004), Science and Technology Program Grant Shenzhen (JCYJ20170413161534162), HMRF Hong Kong (17160862), RGC-CRF Hong Kong (C4039-19G), RGC-GRF Hong Kong (14163817), Vice-Chancellor\'s Discretionary Fund CUHK and CUHK direct grant, Shenzhen Virtual University Park Support Scheme to CUHK Shenzhen Research Institute.

OBJECTIVE: Epigenetic modification is an important part of the pathogenesis of inflammatory bowel disease (IBD). Some studies proved that p62 was involved in inflammatory response and upregulated in IBD patients, and histone modification plays an important role in regulating p62 expression. SETD8, a histone H4K20 methyltransferase, has been reported downregulated in some inflammatory diseases. Here, we investigated the role of SETD8 in the development of IBD and its underlying mechanisms.
METHODS: An inflammatory cell model was established to elucidate whether SETD8 involved in inflammatory response in macrophages. Three percent dextran sodium sulfate-induced colitis murine model injection with SETD8 inhibitor was used in our study to investigate whether SETD8 inhibition can affect the progress of IBD. The expression of SETD8 and p62 was measured by qRT-PCR and western blot. The mRNA level of inflammatory cytokines was analyzed by qRT-PCR. In addition, chromatin immunoprecipitation-PCR was performed to identify the mechanism by which SETD8 regulates p62.
RESULTS: SETD8 expression obviously decreased in vitro, in vivo models and in IBD patients. In lipopolysaccharide-activated RAW264.7 cells, knockdown of SETD8 significantly increased the mRNA expression of inducible nitric oxide synthase, cyclooxygenase-2, TNF-α, IL-6, IL-1β, and MCP-1. Based on the dataset, we verified that p62 was a target gene of SETD8 and chromatin immunoprecipitation-PCR assay identified that silence of SETD8 distinctly decreases the H4K20me1 enrichment in the promoter of p62. Moreover, silencing of p62 partly reverses the SETD8 inhibition-mediated pro-inflammatory effect in vitro. Finally, SETD8 pharmacological inhibitor (UNC0379) aggravated the disease progression in dextran sodium sulfate-induced murine colitis.
CONCLUSIONS: Our findings elucidate an epigenetic mechanism by which SETD8 regulates the p62 expression and restrains the inflammatory response in colitis. Our result suggests that targeting SETD8 may be a promising therapy for IBD.