Background: Lung injury and STAT1 deficit induce EGFR overexpression in SARS-CoV-2 infection. Patients & methods: A phase I/II trial was done to evaluate the safety and preliminary effect of nimotuzumab, an anti-EGFR antibody, in COVID-19 patients. Patients received from one to three infusions together with other drugs included in the national guideline. Results: 41 patients (31 severe and 10 moderate) received nimotuzumab. The median age was 62 years and the main comorbidities were hypertension, diabetes and cardiovascular disease. The antibody was very safe and the 14-day recovery rate was 82.9%. Inflammatory markers decreased over time. Patients did not show signs of fibrosis. Conclusion: Nimotuzumab is a safe antibody that might reduce inflammation and prevent fibrosis in severe and moderate COVID-19 patients. Clinical Trial Registration: RPCEC00000369 ( rpcec.sld.cu ).
We herein report, by using confocal immunofluorescence, the colocalization of the SARS-CoV-2 nucleocapsid within neurons, astrocytes, oligodendrocytes and microglia in three deceased COVID-19 cases, of between 78 and 85 years of age at death. The viral nucleocapsid was detected together with its ACE2 cell entry receptor, as well as the NLRP3 inflammasome in cerebral cortical tissues. It is noteworthy that NLRP3 was colocalized with CD68 + macrophages in the brain and lung of the deceased, suggesting the critical role of this type of inflammasome in SARS-CoV-2 lesions of the nervous system/lungs and supporting its potential role as a therapeutic target.
INTRODUCTION Bile acids are signaling molecules with immune, metabolic and intestinal microbiota control actions. In high serum concentrations they increase infl ammatory response from the liver-gut axis, until causing multiorgan failure and death; therefore, they may be associated with COVID-19's clinical progression, as a consequence of tissue and metabolic damage caused by SARS-CoV-2. While this topic is of considerable clinical interest, to our knowledge, it has not been studied in Cuba. OBJECTIVE Study and preliminarily characterize patients admitted with a diagnosis of COVID-19 and high levels of serum bile acids.METHODS A preliminary exploratory study was carried out with descriptive statistical techniques in 28 COVID-19 patients (17 women, 11 men; aged 19-92 years) who exhibited high levels of serum bile acids (≥10.1 μmol/L) on admission to the Dr. Luis Díaz Soto Central Military Hospital in Havana, Cuba, from September through November 2021. RESULTSOn admission patients presented hypocholesterolemia (13/28; 46.4%), hyperglycemia (12/28; 43.0%) and hyper gamma-glutamyl transpeptidase (23/28; 84.2%). Median blood glucose (5.8 mmol/L) and cholesterol (4.1 mmol/L) were within normal ranges (3.2-6.2 mmol/L and 3.9-5.2 mmol/L, respectively). Severe or critical stage was the most frequent (13/28) and median serum bile acids (31.6 μmol/L) and gamma-glutamyl transferase (108.6 U/L) averaged well above their respective normal ranges (serum bile acids: 0-10 μmol/L; GGT: 9-36 U/L). Arterial hypertension was the most frequent comorbidity (19/28; 67.9%).CONCLUSIONS Severe or critical stage predominated, with serum bile acids and gamma-glutamyl transferase blood levels above normal ranges. The study suggests that serum bile acid is toxic at levels ≥10.1 μmol/L, and at such levels is involved in the infl ammatory process and in progression to severe and critical clinical stages of the disease. In turn, this indicates the importance of monitoring bile acid homeostasis in hospitalized COVID-19 patients and including control of its toxicity in treatment protocols.
There is an urgent need to understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-host interactions involved in virus spread and pathogenesis, which might contribute to the identification of new therapeutic targets. In this study, we investigated the presence of SARS-CoV-2 in postmortem lung, kidney, and liver samples of patients who died with coronavirus disease (COVID-19) and its relationship with host factors involved in virus spread and pathogenesis, using microscopy-based methods. The cases analyzed showed advanced stages of diffuse acute alveolar damage and fibrosis. We identified the SARS-CoV-2 nucleocapsid (NC) in a variety of cells, colocalizing with mitochondrial proteins, lipid droplets (LDs), and key host proteins that have been implicated in inflammation, tissue repair, and the SARS-CoV-2 life cycle (vimentin, NLRP3, fibronectin, LC3B, DDX3X, and PPARγ), pointing to vimentin and LDs as platforms involved not only in the viral life cycle but also in inflammation and pathogenesis. SARS-CoV-2 isolated from a patient´s nasal swab was grown in cell culture and used to infect hamsters. Target cells identified in human tissue samples included lung epithelial and endothelial cells; lipogenic fibroblast-like cells (FLCs) showing features of lipofibroblasts such as activated PPARγ signaling and LDs; lung FLCs expressing fibronectin and vimentin and macrophages, both with evidence of NLRP3- and IL1β-induced responses; regulatory cells expressing immune-checkpoint proteins involved in lung repair responses and contributing to inflammatory responses in the lung; CD34+ liver endothelial cells and hepatocytes expressing vimentin; renal interstitial cells; and the juxtaglomerular apparatus. This suggests that SARS-CoV-2 may directly interfere with critical lung, renal, and liver functions involved in COVID-19-pathogenesis.
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