A pangolin-origin SARS-CoV-2-related coronavirus: infectivity, pathogenicity, and cross-protection by preexisting immunity.

Virus spillover remains a major challenge to public health. A panel of SARS-CoV-2-related coronaviruses have been identified in pangolins, while the infectivity and pathogenicity of these pangolin-origin coronaviruses (pCoV) in humans remain largely unknown. Herein, we comprehensively characterized the infectivity and pathogenicity of a recent pCoV isolate (pCoV-GD01) in human cells and human tracheal epithelium organoids and established animal models in comparison with SARS-CoV-2. pCoV-GD01 showed similar infectivity to SARS-CoV-2 in human cells and organoids. Remarkably, intranasal inoculation of pCoV-GD01 caused severe lung pathological damage in hACE2 mice and could transmit among cocaged hamsters. Interestingly, in vitro neutralization assays and animal heterologous challenge experiments demonstrated that preexisting immunity induced by SARS-CoV-2 infection or vaccination was sufficient to provide at least partial cross-protection against pCoV-GD01 challenge. Our results provide direct evidence supporting pCoV-GD01 as a potential human pathogen and highlight the potential spillover risk.

Hemoperfusion with CytoSorb® in Critically Ill COVID-19 Patients.

INTRODUCTION: Systematic inflammatory response occurred in some critically ill patients with COVID-19. Cytokine reduction by hemadsorption is a mechanism of treatment. However, whether CytoSorb hemoperfusion works for critically ill COVID-19 patients remains unknown. MATERIALS AND METHODS: We observed case series of critically ill COVID-19 patients receiving CytoSorb hemoperfusion as rescue therapy from 3 hospitals in Hubei, China from February 28, 2020, to April 7, 2020. Their demographic, laboratory, and clinical data were collected. The parameters for organ function and IL-6 levels were compared before and after treatments. RESULTS: A total of 10 cases were included. The median age of the patients was 67.7 years (range = 50-85) with APACHE II (23.5) and SOFA (11.4). Patients received a median of 3 attempts of hemoperfusion (range = 1-6). The median CytoSorb perfusion time was 47 h (12-92 h). The level of IL-6 significantly decreased after treatments (712.6 [145-5,000] vs. 136.7 [46.3-1,054] pg/mL, p = 0.005). Significant improvement was found in PaO2/FiO2 (118 [81-220] vs. 163 [41-340] mm Hg, p = 0.04) and lactate levels (2.5 [1-18] vs. 1.7 [1.1-10] mmol/L, p = 0.009). The hemodynamics measured by norepinephrine/MAP slightly improved after treatment (17 [0-68] vs. 8 [0-39], p = 0.09). Albumin mildly decreased after CytoSorb. No significant changes were found in red blood cell counts, white cell counts, and platelets. CONCLUSION: Treatment with CytoSorb in critically ill COVID-19 patients was associated with decreased IL-6 improvement in oxygenation. However, these effects cannot be confirmed as the direct effects of CytoSorb owing to lack of controls. Establishing causality requires large-scale randomized clinical trials.

Blood purification in sepsis and systemic inflammation.

PURPOSE OF REVIEW: Sepsis and septic shock are life-threatening diseases with high mortality. Although efforts have made to improve the survivals, the outcomes are still frustrating. Blood purification was thought to be a promising adjunctive therapy to regulate the excessive cytokine storm or to reduce the endotoxin activity caused by sepsis. Critically ill COVID-19 characterized with the similar disease to sepsis may also benefit from blood purification. RECENT FINDINGS: The recent studies mainly focused on hemadsorption materials. The results of the clinical trials showed a tendency in decrease of cytokine levels and endotoxin activity and improvement in haemodynamics. However, the results were controversial. More evidence about blood purification in sepsis and COVID-19 are needed from currently ongoing trials and future well designed trials. SUMMARY: The blood purification therapy demonstrated the tendency in decrease of cytokines and endotoxin activity in different degree according to the current studies. However, the effect on mortality and haemodynamics is still in controversy. Further well designed, large sample sized studies should focus on the timing of initiating blood purification, the appropriate indications and the optimal type of blood purification membrane or cartridge to provide more evidence for clinical practice.