COVID-19 therapies for inpatients: a review and quality assessment of clinical guidelines.

Owing to condensed development processes, expanding evidence and differences in healthcare system characteristics, many COVID-19 guidelines differ in their quality and treatment recommendations, which has consequences for clinical practice. This review aimed to identify COVID-19 treatment guidelines, assess their quality and summarise their recommendations. Guidelines were identified for five therapies most commonly used among inpatients with COVID-19 (remdesivir, dexamethasone, tocilizumab, baricitinib and casirivimab/imdevimab) from 11 countries. Guideline quality was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE-II) tool. Full details of recommendations and supporting evidence were analysed for high-quality guidelines, defined as those scoring ≥50% in Domain 3 (Rigour of Development) of AGREE-II. Overall, guidelines differed substantially in their quality and, even among high-quality guidelines using the same evidence, recommendations regarding specific therapeutics varied. Potential reasons for this heterogeneity, including the availability and consistency of clinical data, visibility of trial end-points and context-specific factors, are discussed.

Comparison of prediction accuracies between two mathematical models for the assessment of COVID-19 damage at the early stage and throughout 2020.

BACKGROUND: The negative impacts of COVID-19 (ImpactCOVID) on public health are commonly assessed using the cumulative numbers of confirmed cases (CNCCs). However, whether different mathematical models yield disparate results based on varying time frames remains unclear. This study aimed to compare the differences in prediction accuracy between 2 proposed COVID-19 models, develop an angle index that can be objectively used to evaluate ImpactCOVID, compare the differences in angle indexes across countries/regions worldwide, and examine the difference in determining the inflection point (IP) on the CNCCs between the 2 models. METHODS: Data were downloaded from the GitHub website. Two mathematical models were examined in 2 time-frame scenarios during the COVID-19 pandemic (the early 20-day stage and the entire year of 2020). Angle index was determined by the ratio (=CNCCs at IP÷IP days). The R2 model and mean absolute percentage error (MAPE) were used to evaluate the model's prediction accuracy in the 2 time-frame scenarios. Comparisons were made using 3 visualizations: line-chart plots, choropleth maps, and forest plots. RESULTS: Exponential growth (EXPO) and item response theory (IRT) models had identical prediction power at the earlier outbreak stage. The IRT model had a higher model R2 and smaller MAPE than the EXPO model in 2020. Hubei Province in China had the highest angle index at the early stage, and India, California (US), and the United Kingdom had the highest angle indexes in 2020. The IRT model was superior to the EXPO model in determining the IP on an Ogive curve. CONCLUSION: Both proposed models can be used to measure ImpactCOVID. However, the IRT model (superior to EXPO in the long-term and Ogive-type data) is recommended for epidemiologists and policymakers to measure ImpactCOVID in the future.

Coagulation Disorders and Thrombosis in COVID-19 Patients and a Possible Mechanism Involving Endothelial Cells: A Review.

Coronavirus disease 2019 (COVID-19) is still an ongoing pandemic worldwide. COVID-19 is an age-related disease with a higher risk of organ dysfunction and mortality in older adults. Coagulation disorders and thrombosis are important pathophysiological changes in COVID-19 infection. Up to 95% of COVID-19 patients have coagulation disorders characterized by an elevated D-dimer, a prolonged prothrombin time, a low platelet count and other laboratory abnormalities. Thrombosis is found in critical cases with an increased risk of death. Endothelial cells are prone to be affected by the novel SARS-CoV-2 and express angiotensin-converting enzyme 2. The evidence, such as the presence of the virus, has been identified, leading to the inflammation and dysfunction. Endothelial cell activation and dysfunction play a pivotal role in the hypercoagulation status in COVID-19 patients. In addition to the direct exposure of subendothelial tissue to blood, Weibel-Palade bodies within the endothelium containing coagulants can be released into the circulation. Endothelial nitric oxide synthase may be impaired, thus facilitating platelet adhesion. Moreover, anti-ß2-glycoprotein I antibodies may also contribute to the coagulopathy in COVID-19 by inducing the upregulation of proinflammatory mediators and adhesion molecules. To conclude, coagulation disorders and thrombosis are vital and predict a poor outcome in COVID-19 patients, especially in severe cases. Endothelial cell activation and dysfunction may play an important role in causing clot formation. More basic and clinical research is warranted to further our understanding of the role of coagulopathy and their possible mechanism in COVID-19 patients.

Histone demethylase LSD1 promotes RIG-I poly-ubiquitination and anti-viral gene expression.

Under RNA virus infection, retinoic acid-inducible gene I (RIG-I) in host cells recognizes viral RNA and activates the expression of type I IFN. To investigate the roles of protein methyltransferases and demethylases in RIG-I antiviral signaling pathway, we screened all the known related enzymes with a siRNA library and identified LSD1 as a positive regulator for RIG-I signaling. Exogenous expression of LSD1 enhances RIG-I signaling activated by virus stimulation, whereas its deficiency restricts it. LSD1 interacts with RIG-I, promotes its K63-linked polyubiquitination and interaction with VISA/MAVS. Interestingly, LSD1 exerts its function in antiviral response not dependent on its demethylase activity but through enhancing the interaction between RIG-I with E3 ligases, especially TRIM25. Furthermore, we provide in vivo evidence that LSD1 increases antiviral gene expression and inhibits viral replication. Taken together, our findings demonstrate that LSD1 is a positive regulator of signaling pathway triggered by RNA-virus through mediating RIG-I polyubiquitination.

Clinical considerations for the management of cancer patients in the mitigation stage of the COVID-19 pandemic.

The ongoing outbreak of the coronavirus disease 2019 (COVID-19) has become an unprecedented threat to public health around the world. The crisis has also brought great challenges to the routine diagnosis and treatment of cancer patients, especially given the urgency and continuity of cancer care. Cancer patients need to be more prudently and individually managed to combat COVID-19. At present, the COVID-19 epidemic in some countries has moved from the outbreak phase to the remission phase. How to preserve high-quality anti-tumor therapy for cancer patients while maintaining strict prevention and control of COVID-19 is a matter of concern. Here, we summarized essential data about COVID-19 and cancer and provided the clinical recommendations for the management of cancer patients during the COVID-19 pandemic based on our practical experience and relevant literatures.