Association of complement pathways with COVID-19 severity and outcomes.

OBJECTIVES: Complement activation has been implicated in COVID-19 pathogenesis. This study aimed to assess the levels of complement activation products and full-length proteins in hospitalized patients with COVID-19, and evaluated whether complement pathway markers are associated with outcomes. METHODS: Longitudinal measurements of complement biomarkers from 89 hospitalized adult patients, grouped by baseline disease severity, enrolled in an adaptive, phase 2/3, randomized, double-blind, placebo-controlled trial and treated with intravenous sarilumab (200 mg or 400 mg) or placebo (NCT04315298), were performed. These measurements were then correlated with clinical and laboratory parameters. RESULTS: All complement pathways were activated in hospitalized patients with COVID-19. Alternative pathway activation was predominant earlier in the disease course. Complement biomarkers correlated with multiple variables of multi-organ dysfunction and inflammatory injury. High plasma sC5b-9, C3a, factor Bb levels, and low mannan-binding lectin levels were associated with increased mortality. Sarilumab treatment showed a modest inhibitory effect on complement activation. Moreover, sera from patients spontaneously deposited C5b-9 complex on the endothelial surface ex vivo, suggesting a microvascular thrombotic potential. CONCLUSION: These results advance our understanding of COVID-19 disease pathophysiology and demonstrate the importance of specific complement pathway components as prognostic biomarkers in COVID-19.

A Tri-Channel Oxide Transistor Concept for the Rapid Detection of Biomolecules Including the SARS-CoV-2 Spike Protein.

Solid-state transistor sensors that can detect biomolecules in real time are highly attractive for emerging bioanalytical applications. However, combining upscalable manufacturing with the required performance remains challenging. Here, an alternative biosensor transistor concept is developed, which relies on a solution-processed In2 O3 /ZnO semiconducting heterojunction featuring a geometrically engineered tri-channel architecture for the rapid, real-time detection of important biomolecules. The sensor combines a high electron mobility channel, attributed to the electronic properties of the In2 O3 /ZnO heterointerface, in close proximity to a sensing surface featuring tethered analyte receptors. The unusual tri-channel design enables strong coupling between the buried electron channel and electrostatic perturbations occurring during receptor-analyte interactions allowing for robust, real-time detection of biomolecules down to attomolar (am) concentrations. The experimental findings are corroborated by extensive device simulations, highlighting the unique advantages of the heterojunction tri-channel design. By functionalizing the surface of the geometrically engineered channel with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody receptors, real-time detection of the SARS-CoV-2 spike S1 protein down to am concentrations is demonstrated in under 2 min in physiological relevant conditions.

Humanized C3 Mouse: A Novel Accelerated Model of C3 Glomerulopathy.

BACKGROUND: C3 glomerulopathy (C3G) is characterized by the alternative-pathway (AP) hyperactivation induced by nephritic factors or complement gene mutations. Mice deficient in complement factor H (CFH) are a classic C3G model, with kidney disease that requires several months to progress to renal failure. Novel C3G models can further contribute to understanding the mechanism behind this disease and developing therapeutic approaches. METHODS: A novel, rapidly progressing, severe, murine model of C3G was developed by replacing the mouse C3 gene with the human C3 homolog using VelociGene technology. Functional, histologic, molecular, and pharmacologic assays characterize the presentation of renal disease and enable useful pharmacologic interventions in the humanized C3 (C3hu/hu) mice. RESULTS: The C3hu/hu mice exhibit increased morbidity early in life and die by about 5-6 months of age. The C3hu/hu mice display elevated biomarkers of kidney dysfunction, glomerulosclerosis, C3/C5b-9 deposition, and reduced circulating C3 compared with wild-type mice. Administration of a C5-blocking mAb improved survival rate and offered functional and histopathologic benefits. Blockade of AP activation by anti-C3b or CFB mAbs also extended survival and preserved kidney function. CONCLUSIONS: The C3hu/hu mice are a useful model for C3G because they share many pathologic features consistent with the human disease. The C3G phenotype in C3hu/hu mice may originate from a dysregulated interaction of human C3 protein with multiple mouse complement proteins, leading to unregulated C3 activation via AP. The accelerated disease course in C3hu/hu mice may further enable preclinical studies to assess and validate new therapeutics for C3G.

Impact of the COVID-19 pandemic on emergency medical service response to out-of-hospital cardiac arrests in Taiwan: a retrospective observational study.

BACKGROUND: Emergency medical service (EMS) personnel have high COVID-19 risk during resuscitation. The resuscitation protocol for patients with out-of-hospital cardiac arrest (OHCA) was modified in response to the COVID-19 pandemic. However, how the adjustments in the EMS system affected patients with OHCA remains unclear. METHODS: We analysed data from the Taichung OHCA registry system. We compared OHCA outcomes and rescue records for 622 cases during the COVID-19 outbreak period (1 February to 30 April 2020) with those recorded for 570 cases during the same period in 2019. RESULTS: The two periods did not differ significantly with respect to patient age, patient sex, the presence of witnesses or OHCA location. Bystander cardiopulmonary resuscitation and defibrillation with automated external defibrillators were more common in 2020 (52.81% vs 65.76%, p<0.001%, and 23.51% vs 31.67%, p=0.001, respectively). The EMS response time was longer during the COVID-19 pandemic (445.8±210.2 s in 2020 vs 389.7±201.8 s in 2019, p<0.001). The rate of prehospital return of spontaneous circulation was lower in 2020 (6.49% vs 2.57%, p=0.001); 2019 and 2020 had similar rates of survival discharge (5.96% vs 4.98%). However, significantly fewer cases had favourable neurological function in 2020 (4.21% vs 2.09%, p=0.035). CONCLUSION: EMS response time for patients with OHCA was prolonged during the COVID-19 pandemic. Early advanced life support by EMS personnel remains crucial for patients with OHCA.

Factors Related to Care Competence, Workplace Stress, and Intention to Stay among Novice Nurses during the Coronavirus Disease (COVID-19) Pandemic.

The outbreak of coronavirus (COVID-19), a public health emergency of international concern, has made healthcare staff preparation and the nurturing of high-quality and adequate nursing professionals critical issues. This study aimed to explore registered nurses' competence in nursing care and their intention to stay in their current workplace. In this study, participants who had graduated from different nursing education systems were recruited. The results indicated that nurses' level of commitment to the workplace and clinical stress were positively correlated with the experience of working with patients. Stepwise regression analysis revealed the following significant predictors for intention to stay: clinical stress, frequency of caring for people with infections, and taking a course on infectious nursing. The novice nurses' competencies in the areas of pandemic disease care and care for infectious adults depended on the experience of nursing care and nursing competence in their professional careers, which may have impact on the nurses' intention to stay. Therefore, clinical stress, frequency of caring for patients, and taking nursing courses were correlated with novice nurses' intention to stay in their professional careers.

The First 100 Days: Establishment and Effectiveness of Campus Protection Measures at a College during the COVID-19 Pandemic.

To prevent transmission of the coronavirus, we established the campus protection measures for coronavirus disease 2019 (COVID-19) (CPMCV-19) and analyzed the effectiveness and cost in practice. This project was set in Taiwan. We organized an anti-epidemic task force team from multidisciplinary co-workers to establish the CPMCV-19. The essential components were as follows: no close contact communication, sterilization, temperature control, social distancing, activity restrictions, personal hygiene control, and situational awareness. During 100 days of operation, the mean time spent for frontal temperature measuring was 2.7 ± 0.3 s per person. The mean on-duty time for individual personnel to control the gate and measure temperature was 3.5 h per day. In total, 31 persons with loss of taste/smell or fever were detected on campus and sent to hospital for screening within 1 h. A total of 6 persons were instructed to observe self-health management due to possible contact or travel history, and none were diagnosed with COVID-19 infection. A total budget of USD 27,100 was used for CMPCV-19 in this period. The established campus protection measures for COVID-19 were practical and might be effective. They can be used as reference for schools in a pandemic, such as COVID-19.