CytoSorb in patients with coronavirus disease 2019: A rapid evidence review and meta-analysis.

Background: After its approval by the European Union in 2011, CytoSorb therapy has been applied to control cytokine storm and lower the increased levels of cytokines and other inflammatory mediators in blood. However, the efficiency of this CytoSorb treatment in patients with coronavirus disease (COVID-19) still remains unclear. To elucidate the Cytosorb efficiency, we conducted a systematic review and single-arm proportion meta-analysis to combine all evidence available in the published literature to date, so that this comprehensive knowledge can guide clinical decision-making and future research. Methods: The literature published within the period 1 December 2019 to 31 December 2021 and stored in the Cochrane Library, Embase, PubMed, and International Clinical Trials Registry Platform (ICTRP) was searched for all relevant studies including the cases where COVID-19 patients were treated with CytoSorb. We performed random-effects meta-analyses by R software (3.6.1) and used the Joanna Briggs Institute checklist to assess the risk of bias. Both categorical and continuous variables were presented with 95% confidence intervals (CIs) as pooled proportions for categorical variables and pooled means for continuous outcomes. Results: We included 14 studies with 241 COVID-19 patients treated with CytoSorb hemadsorption. Our findings reveal that for COVID-19 patients receiving CytoSorb treatment, the combined in-hospital mortality was 42.1% (95% CI 29.5-54.6%, I2 = 74%). The pooled incidence of adjunctive extracorporeal membrane oxygenation (ECMO) support was 73.2%. Both the C-reactive protein (CRP) and interleukin-6 (IL-6) levels decreased after CytoSorb treatment. The pooled mean of the CRP level decreased from 147.55 (95% CI 91.14-203.96) to 92.36 mg/L (95% CI 46.74-137.98), while that of IL-6 decreased from 339.49 (95% CI 164.35-514.63) to 168.83 pg/mL (95% CI 82.22-255.45). Conclusions: The majority of the COVID-19 patients treated with CytoSorb received ECMO support. In-hospital mortality was 42.1% for the COVID-19 patients who had CytoSorb treatment. Both CRP and IL-6 levels decreased after Cytosorb treatment.

Potential of sphingosine-1-phosphate in preventing SARS-CoV-2 infection by stabilizing and protecting endothelial cells: Narrative review.

ABSTRACT: Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide, resulting in over 250 million infections and >5 million deaths. Most antiviral drugs and vaccines have shown limited efficacy against SARS-CoV-2. Clinical data revealed that except for the large number of self-healing mild cases, moderate and severe cases mostly survived after supportive treatment but not specific drug administration or vaccination. The endothelial system is the first physiological barrier, and its structural stability is of critical importance in conferring disease resistance. Membrane lipid components, particularly sphingosine-1-phosphate (S1P), play a central role in stabilizing the cell membrane.Here, we used "Boolean Operators" such as AND, OR, and NOT, to search for relevant research articles in PubMed, then reviewed the potential of S1P in inhibiting SARS-CoV-2 infection by stabilizing the endothelial system, this is the major aim of this review work.Reportedly, vasculitis and systemic inflammatory vascular diseases are caused by endothelial damage resulting from SARS-CoV-2 infection. S1P, S1P receptor (SIPR), and signaling were involved in the process of SARS-CoV-2 infection, and S1P potentially regulated the function of EC barrier, in turn, inhibited the SARS-CoV-2 to infect the endothelial cells, and ultimately has the promising therapeutic value to coronavirus disease 2019.Taken together, we conclude that maintaining or administering a high level of S1P will preserve the integrity of the EC structure and function, in turn, lowering the risk of SARS-CoV-2 infection and reducing complications and mortality.

Impact of Liver Functions by Repurposed Drugs for COVID-19 Treatment.

Liver injury is an important complication that may arise in patients suffering from coronavirus disease 2019 (COVID-19) and is accompanied by a transient increase of transaminases and/or other liver enzymes. Liver function test (LFT) abnormalities generally disappear when the COVID-19 resolves or hepatotoxic drugs are discontinued. The LFT abnormalities are associated with drug-induced liver injury (DILI), due to the overuse of antimalarials, antivirals, and antimicrobials. Studies have reported varying levels of these liver injuries in COVID-19 patients; however, most involve elevated serum aminotransferases. Hepatic dysfunction is significantly high in patients with severe illness and has poor outcome. Normally, the liver is involved in the metabolism of many drugs, including nucleoside analogs and protease inhibitors, which are currently repurposed to treat COVID-19. In addition to the manifestation of COVID-19, drugs implemented in its treatment may aggravate liver injuries. Thus, DILI should be considered especially in those COVID-19 patients with underlying liver disease. It was unclear whether the elevated liver enzymes have originated from the underlying disease or DILI in this population. Furthermore, it is difficult to establish a direct relationship between a specific drug and liver injury. Another possible effect of liver damage may due to inflammatory cytokine storm in severe COVID-19. Liver injury can change metabolism, excretion, dosing, and expected concentrations of the drugs, which may make it difficult to achieve a therapeutic dose of the drug or increase the risk of adverse effects. These repurposed drugs have shown limited efficacy against the virus and the disease itself; however, they still pose risk of adverse effects. Careful and close monitoring of LFTs in COVID-19 patients can provide early diagnosis of liver injury, and the risk of DILI could be reduced. Also, drug interactions in liver-transplanted patients should always be kept in mind for certain immunosuppressive therapies and their known signs of DILI. Altogether, abnormal LFTs should not be regarded as a contraindication to use COVID-19 experimental therapies if needed under emergent status.