Articles: sars-cov-2.
-
Cell host & microbe · Jun 2020
Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure.
Proper management of COVID-19 mandates better understanding of disease pathogenesis. The sudden clinical deterioration 7-8 days after initial symptom onset suggests that severe respiratory failure (SRF) in COVID-19 is driven by a unique pattern of immune dysfunction. We studied immune responses of 54 COVID-19 patients, 28 of whom had SRF. ⋯ Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production by circulating monocytes was sustained, a pattern distinct from bacterial sepsis or influenza. SARS-CoV-2 patient plasma inhibited HLA-DR expression, and this was partially restored by the IL-6 blocker Tocilizumab; off-label Tocilizumab treatment of patients was accompanied by increase in circulating lymphocytes. Thus, the unique pattern of immune dysregulation in severe COVID-19 is characterized by IL-6-mediated low HLA-DR expression and lymphopenia, associated with sustained cytokine production and hyper-inflammation.
-
Background The coronavirus disease (COVID-19) pandemic has put an excessive strain on healthcare systems across the globe, causing a shortage of personal protective equipment (PPE). PPE is a precious commodity for health personnel to protect them against infections. We investigated the availability of PPE among doctors in the United States (US) and Pakistan. ⋯ Conclusion There is a lack of different forms of PPE in the US and Pakistan. Doctors from both countries reported that they had been forced to work without PPE. Compared to the US, more doctors from Pakistan reported having faced discrimination in receiving PPE.
-
Although research on the effects of comorbidities on coronavirus disease 2019 (COVID-19) patients is increasing, the risk of cancer history has not been evaluated for the mortality of patients with COVID-19. ⋯ We evaluated prognostic factors with epidemiological analysis and highlighted a higher risk of mortality for cancer patients with COVID-19. Importantly, cancer history was the only independent risk factor for COVID-19 among common comorbidities, while other comorbidities may act through other factors. Moreover, several laboratory parameters were significantly different between cancer patients and matched noncancer patients, which may indicate specific immune and inflammatory reactions in COVID-19 patients with cancer.
-
Although infection by SARS-CoV-2, the causative agent of coronavirus pneumonia disease (COVID-19), is spreading rapidly worldwide, no drug has been shown to be sufficiently effective for treating COVID-19. We previously found that nafamostat mesylate, an existing drug used for disseminated intravascular coagulation (DIC), effectively blocked Middle East respiratory syndrome coronavirus (MERS-CoV) S protein-mediated cell fusion by targeting transmembrane serine protease 2 (TMPRSS2), and inhibited MERS-CoV infection of human lung epithelium-derived Calu-3 cells. Here we established a quantitative fusion assay dependent on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S protein, angiotensin I converting enzyme 2 (ACE2) and TMPRSS2, and found that nafamostat mesylate potently inhibited the fusion while camostat mesylate was about 10-fold less active. ⋯ On the other hand, a significantly higher dose (EC50 around 30 mM) was required for VeroE6/TMPRSS2 cells, where the TMPRSS2-independent but cathepsin-dependent endosomal infection pathway likely predominates. Together, our study shows that nafamostat mesylate potently inhibits SARS-CoV-2 S protein-mediated fusion in a cell fusion assay system and also inhibits SARS-CoV-2 infection in vitro in a cell-type-dependent manner. These findings, together with accumulated clinical data regarding nafamostat's safety, make it a likely candidate drug to treat COVID-19.
-
There has been a substantial burden of healthcare worker infection during the current coronavirus (COVID-19) pandemic, likely due to a lack of adequate preparedness, suboptimal institutional infection control measures, atypical patient presentation, poor compliance with personal protective equipment (PPE) and exposure to high-risk aerosol generating procedures, such as endotracheal intubation. There is significant concern that developing countries will face heightened levels of staff exposure during the COVID-19 pandemic. ⋯ However, in practice these boxes were found to hamper endotracheal intubation and other procedures due to the limited space and manoeuvrability they allow. To further reduce particle dispersion and to improve on the practicality and ergonomic design of the prototype "aerosol box", the Intubox was developed by staff at the Charlotte Maxeke Johannesburg Academic Hospital after instituting several changes to the prototype design.