A tissue specific-infection mouse model of SARS-CoV-2.

Animal models play crucial roles in the rapid development of vaccines/drugs for the prevention and therapy of COVID-19, but current models have some deficits when studying the pathogenesis of SARS-CoV-2 on some special tissues or organs. Here, we generated a human ACE2 and SARS-CoV-2 NF/F knockin mouse line that constitutively expresses human ACE2 and specifically expresses SARS-CoV-2 N gene induced by Cre-recombinase. By crossing with Cre transgenic lines allowing for lung-specific and constitutive expression, we generated lung-specific (Sftpc-hACE2-NF/F) and constitutive SARS-CoV-2 N (EIIa-hACE2-NF/F) expressing mice. Upon intranasal infection with a SARS-CoV-2 GFP/ΔN strain which can only replicate in SARS-CoV-2 N expressed cells, we demonstrated that both the Sftpc-hACE2-NF/F and EIIa-hACE2-NF/F mice support viral replication. Consistent with our design, viral replication was limited to the lung tissues in Sftpc-hACE2-NF/F mice, while the EIIa-hACE2-NF/F mice developed infections in multiple tissues. Furthermore, our model supports different SARS-CoV-2 variants infection, and it can be successfully used to evaluate the effects of therapeutic monoclonal antibodies (Ab1F11) and antiviral drugs (Molnupiravir). Finally, to test the effect of SARS-CoV-2 infection on male reproduction, we generated Sertoli cell-specific SARS-CoV-2 N expressed mice by crossing with AMH-Cre transgenic line. We found that SARS-CoV-2 GFP/ΔN strain could infect Sertoli cells, led to spermatogenic defects due to the destruction of blood-testis barrier. Overall, combining with different tissue-specific Cre transgenic lines, the human ACE2 and SARS-CoV-2 NF/F line enables us to evaluate antivirals in vivo and study the pathogenesis of SARS-CoV-2 on some special tissues or organs.

SARS-CoV-2 ORF10 impairs cilia by enhancing CUL2ZYG11B activity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal pathogen of the ongoing global pandemic of coronavirus disease 2019 (COVID-19). Loss of smell and taste are symptoms of COVID-19, and may be related to cilia dysfunction. Here, we found that the SARS-CoV-2 ORF10 increases the overall E3 ligase activity of the CUL2ZYG11B complex by interacting with ZYG11B. Enhanced CUL2ZYG11B activity by ORF10 causes increased ubiquitination and subsequent proteasome-mediated degradation of an intraflagellar transport (IFT) complex B protein, IFT46, thereby impairing both cilia biogenesis and maintenance. Further, we show that exposure of the respiratory tract of hACE2 mice to SARS-CoV-2 or SARS-CoV-2 ORF10 alone results in cilia-dysfunction-related phenotypes, and the ORF10 expression in primary human nasal epithelial cells (HNECs) also caused a rapid loss of the ciliary layer. Our study demonstrates how SARS-CoV-2 ORF10 hijacks CUL2ZYG11B to eliminate IFT46 and leads to cilia dysfunction, thereby offering a powerful etiopathological explanation for how SARS-CoV-2 causes multiple cilia-dysfunction-related symptoms specific to COVID-19.

COVID-19 related pressure injuries in patients and personnel: A systematic review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is causing a rapid and tragic health emergency worldwide. Because of the particularity of COVID-19, people are at a high risk of pressure injuries during the prevention and treatment process of COVID-19. OBJECTIVES: This systematic review aimed to summarize the pressure injuries caused by COVID-19 and the corresponding preventive measures and treatments. METHODS: This systematic review was according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. PubMed, Web of science and CNKI (Chinese) were searched for studies on pressure injuries caused by COVID-19 published up to August 4, 2020. The quality of included studies was assessed by the Newcastle-Ottawa Quality Assessment Scale (NOS) and the CARE guidelines. RESULTS: The data were extracted from 16 studies involving 7,696 participants in 7 countries. All studies were published in 2020. There are two main types of pressure injuries caused by the COVID-19: 1) Pressure injuries that caused by protective equipment (masks, goggles and face shield, etc.) in the prevention process; 2) pressure injuries caused by prolonged prone position in the therapy process. CONCLUSIONS: In this systematic review, the included studies showed that wearing protective equipment for a long time and long-term prone positioning with mechanical ventilation will cause pressure injuries in the oppressed area. Foam dressing may need to be prioritized in the prevention of medical device related pressure injuries. The prevention of pressure injuries should be our particular attention in the course of clinical treatment and nursing.

New respirator performance monitor (RePM) for powered air-purifying respirators.

Powered air-purifying respirators (PAPRs) that offer protection from particulates are deployed in different workplace environments. Usage of PAPRs by healthcare workers is rapidly increasing; these respirators are often considered the best option in healthcare settings, particularly during public health emergency situations, such as outbreaks of pandemic diseases. At the same time, lack of user training and certain vigorous work activities may lead to a decrease in a respirator's performance. There is a critical need for real-time performance monitoring of respiratory protective devices, including PAPRs. In this effort, a new robust and low-cost real-time performance monitor (RePM) capable of evaluating the protection offered by a PAPR against aerosol particles at a workplace was developed. The new device was evaluated on a manikin and on human subjects against a pair of condensation nuclei counters (P-Trak) used as the reference protection measurement system. The outcome was expressed as a manikin-based protection factor (mPF) and a Simulated Workplace Protection Factor (SWPF) determined while testing on subjects. For the manikin-based testing, the data points collected by the two methods were plotted against each other; a near-perfect correlation was observed with a correlation coefficient of 0.997. This high correlation is particularly remarkable since RePM and condensation particle counter (CPC) measure in different particle size ranges. The data variability increased with increasing mPF. The evaluation on human subjects demonstrated that RePM prototype provided an excellent Sensitivity (96.3% measured on human subjects at a response time of 60 sec) and a Specificity of 100%. The device is believed to be the first of its kind to quantitatively monitor PAPR performance while the wearer is working; it is small, lightweight, and does not interfere with job functions.

Cardio-Cerebrovascular Disease is Associated With Severity and Mortality of COVID-19: A Systematic Review and Meta-Analysis.

At present, COVID-19 is raging all over the world. Many comorbidities, such as diabetes mellitus (OR = 2.67, 95% CI = 1.91-3.74) and hypertension (OR = 2.3, 95% CI = 1.76-3.00), have been shown to worsen the patient's condition. However, whether cardio-cerebrovascular disease will affect COVID-19 remains unclear. In this meta-analysis, we collected studies from PubMed, Wed of Science and CNKI (Chinese) to July 25, which reported COVID-19 patients with and without cardio-cerebrovascular disease as well as their severity and mortality. The random-effect model meta-analysis was used to analyze them and get overall odds ratios (OR) with 95% CIs. Funnel plots and the Begg's and Egger's test were used to assess publication bias. Thirty-one studies with 23,632 patients were finally included in the meta-analysis. The results showed an OR of 3.004 (95% CI = 2.097-4.303) for COVID-19 severity and an OR of 5.587 (95% CI = 2.810-11.112) for COVID-19 mortality. Compared with cardiovascular disease, the subgroup analysis indicated that cerebrovascular disease was more likely to increase the severity (OR = 3.400, 95% CI = 1.569-7.368) and mortality (OR = 23.477, 95% CI = 3.050-180.735) of COVID-19. Therefore, it can be inferred that cardio-cerebrovascular disease is associated with an increase in the risk of severe illness and death among COVID-19 patients. This meta-analysis showed that cardio-cerebrovascular disease has a significant relation with severe and death outcomes of COVID-19. Nurses should pay special attention to COVID-19 patients with the cardio-cerebrovascular disease.

Association between ABO blood groups and COVID-19 infection, severity and demise: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The COVID-19 spreads rapidly around the world which has brought a global health crisis. The pathogen of COVID-19 is SARS-COV-2, and previous studies have proposed the relationship between ABO blood group and coronavirus. Here, we aim to delve into the association between ABO blood group and COVID-19 infection, severity and demise. METHODS: The relevant studies were retrieved from five databases: PubMed, MedRxiv, BioRxiv,Web of Science and CNKI. Members of cases(symptomatic cases, severe cases, died cases) and controls(asymptomatic controls, non-severe controls, alive controls) were extracted from collected studies. Odds ratios (OR) and 95% confidence intervals (CI) were calculated and interpreted from extracted data. Publication bias and sensitivity analysis were also applied to confirm our discovery. RESULTS: Overall 31,100 samples were included in the analysis. Compared to other ABO blood type, an increased odds of infecting COVID-19 among individuals with A blood group (OR: 1.249, 95%CI: 1.114-1.440, P < 0.001) and a decreased odds of infecting COVID-19 among individuals with blood group O (OR: 0.699, 95%CI: 0.635-0.770, P < 0.001) were found. Besides, individuals with blood group AB seems to link a higher risk to COVID-19 severity (OR: 2.424, 95%CI: 0.934-6.294) and demise (OR: 1.348, 95%CI: 0.507-3.583). Meantime, individuals with O blood group might had lower risk to COVID-19 severity (OR: 0.748, 95%CI: 0.556-1.007), and individuals with B blood group were likely to relate a lower risk to COVID-19 demise. CONCLUSIONS: The current meta-analysis suggest that blood type A might be more susceptible to infect COVID-19 while blood type O might be less susceptible to infect COVID-19; there were no correlation between ABO blood group and severity or demise of COVID-19. However, more investigation and research are warranted to clarify the relationship between COVID-19 and ABO blood type.