DNA damage contributes to age-associated differences in SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is known to disproportionately affect older individuals. How aging processes affect SARS-CoV-2 infection and disease progression remains largely unknown. Here, we found that DNA damage, one of the hallmarks of aging, promoted SARS-CoV-2 infection in vitro and in vivo. SARS-CoV-2 entry was facilitated by DNA damage caused by extrinsic genotoxic stress or telomere dysfunction and hampered by inhibition of the DNA damage response (DDR). Mechanistic analysis revealed that DDR increased expression of angiotensin-converting enzyme 2 (ACE2), the primary receptor of SARS-CoV-2, by activation of transcription factor c-Jun. Importantly, in vivo experiment using a mouse-adapted viral strain also verified the significant roles of DNA damage in viral entry and severity of infection. Expression of ACE2 was elevated in the older human and mice tissues and positively correlated with γH2AX, a DNA damage biomarker, and phosphorylated c-Jun (p-c-Jun). Finally, nicotinamide mononucleotide (NMN) and MDL-800, which promote DNA repair, alleviated SARS-CoV-2 infection and disease severity in vitro and in vivo. Taken together, our data provide insights into the age-associated differences in SARS-CoV-2 infection and a novel approach for antiviral intervention.

Job satisfaction and burnout of psychiatric nurses during the COVID-19 pandemic in China-the moderation of family support.

Purpose: The study aimed at investigating the state of psychiatric nurses' job satisfaction, job burnout, and the moderating effect of family support between them in China during the COVID-19 pandemic. Materials and methods: Online self-report questionnaires were distributed and 212 psychiatric nurses participated in the research. Pearson correlation analysis, multiple stepwise regression analysis, and simple slope test were used for data analysis. Results: The results showed that the status of their job satisfaction (53.67 ± 10.72) and burnout (33.62 ± 13.84) did not reach a satisfactory level and job satisfaction had a significant negative impact on job burnout. Meanwhile, family support played a negative moderating role between the two variables. Conclusion: Psychiatric nurses suffered from job burnout in China during the COVID-19. Family support could have a counterproductive effect when the nurses were experiencing decreasing job satisfaction. It gave suggestions to the medical institutions and the government to improve the psychological well-being of the psychiatric nurses and even of all the medical staff.

An ultra-low-cost electroporator with microneedle electrodes (ePatch) for SARS-CoV-2 vaccination.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other pathogens with pandemic potential requires safe, protective, inexpensive, and easily accessible vaccines that can be developed and manufactured rapidly at a large scale. DNA vaccines can achieve these criteria, but induction of strong immune responses has often required bulky, expensive electroporation devices. Here, we report an ultra-low-cost (<1 USD), handheld (<50 g) electroporation system utilizing a microneedle electrode array ("ePatch") for DNA vaccination against SARS-CoV-2. The low cost and small size are achieved by combining a thumb-operated piezoelectric pulser derived from a common household stove lighter that emits microsecond, bipolar, oscillatory electric pulses and a microneedle electrode array that targets delivery of high electric field strength pulses to the skin's epidermis. Antibody responses against SARS-CoV-2 induced by this electroporation system in mice were strong and enabled at least 10-fold dose sparing compared to conventional intramuscular or intradermal injection of the DNA vaccine. Vaccination was well tolerated with mild, transient effects on the skin. This ePatch system is easily portable, without any battery or other power source supply, offering an attractive, inexpensive approach for rapid and accessible DNA vaccination to combat COVID-19, as well as other epidemics.

Stringent Nonpharmaceutical Interventions Are Crucial for Curbing COVID-19 Transmission in the Course of Vaccination: A Case Study of South and Southeast Asian Countries.

The ongoing spread of coronavirus disease 2019 (COVID-19) in most South and Southeast Asian countries has led to severe health and economic impacts. Evaluating the performance of nonpharmaceutical interventions in reducing the number of daily new cases is essential for policy designs. Analysis of the growth rate of daily new cases indicates that the value (5.47%) decreased significantly after nonpharmaceutical interventions were adopted (1.85%). Vaccinations failed to significantly reduce the growth rates, which were 0.67% before vaccination and 2.44% and 2.05% after 14 and 28 d of vaccination, respectively. Stringent nonpharmaceutical interventions have been loosened after vaccination drives in most countries. To predict the spread of COVID-19 and clarify the implications to adjust nonpharmaceutical interventions, we build a susceptible-infected-recovered-vaccinated (SIRV) model with a nonpharmaceutical intervention module and Metropolis-Hastings sampling in three scenarios (optimistic, neutral, and pessimistic). The daily new cases are expected to decrease rapidly or increase with a flatter curve with stronger nonpharmaceutical interventions, and the peak date is expected to occur earlier (5-20 d) with minimum infections. These findings demonstrate that adopting stringent nonpharmaceutical interventions is the key to alleviating the spread of COVID-19 before attaining worldwide herd immunity.

Clinical characteristics of COVID-19 patients with complications: implications for management.

BACKGROUND: A novel coronavirus disease 2019 (COVID-19) has caused outbreaks worldwide, and the number of cases is rapidly increasing through human-to-human transmission. Because of the greater transmission capacity and possible subsequent multi-organ damage caused by the virus, it is crucial to understand precisely and manage COVID-19 patients. However, the underlying differences in the clinical features of COVID-19 with and without comorbidities are not fully understood. AIM: The objective of this study was to identify the clinical features of COVID-19 patients with and without complications to guide treatment and predict the prognosis. METHOD: We collected the clinical characteristics of COVID-19 patients with and without different complications, including hypertension, cardiovascular disease and diabetes. Next, we performed a baseline comparison of each index and traced the dynamic changes in these factors during hospitalization to explore the potential associations. RESULT: A clinical index of differential expression was used for the regression to select top-ranking factors. The top-ranking clinical characteristics varied in each subgroup, such as indices of liver function, renal function and inflammatory markers. Among them, the indices of renal function were highly ranked in all subgroups and displayed significant differences during hospitalization. CONCLUSION: Organ functions of COVID-19 patients, particularly renal function, should be cautiously taken care of during management and might be a crucial factor for a poor prognosis of these patients with complications.

A rapid screening classifier for diagnosing COVID-19.

Rationale: Coronavirus disease 2019 (COVID-19) has caused a global pandemic. A classifier combining chest X-ray (CXR) with clinical features may serve as a rapid screening approach. Methods: The study included 512 patients with COVID-19 and 106 with influenza A/B pneumonia. A deep neural network (DNN) was applied, and deep features derived from CXR and clinical findings formed fused features for diagnosis prediction. Results: The clinical features of COVID-19 and influenza showed different patterns. Patients with COVID-19 experienced less fever, more diarrhea, and more salient hypercoagulability. Classifiers constructed using the clinical features or CXR had an area under the receiver operating curve (AUC) of 0.909 and 0.919, respectively. The diagnostic efficacy of the classifier combining the clinical features and CXR was dramatically improved and the AUC was 0.952 with 91.5% sensitivity and 81.2% specificity. Moreover, combined classifier was functional in both severe and non-serve COVID-19, with an AUC of 0.971 with 96.9% sensitivity in non-severe cases, which was on par with the computed tomography (CT)-based classifier, but had relatively inferior efficacy in severe cases compared to CT. In extension, we performed a reader study involving three experienced pulmonary physicians, artificial intelligence (AI) system demonstrated superiority in turn-around time and diagnostic accuracy compared with experienced pulmonary physicians. Conclusions: The classifier constructed using clinical and CXR features is efficient, economical, and radiation safe for distinguishing COVID-19 from influenza A/B pneumonia, serving as an ideal rapid screening tool during the COVID-19 pandemic.