Study of the temperature sensitivity of severe fever with thrombocytopenia syndrome virus

This study investigated the temperature sensitivity of severe fever with thrombocytopenia syndrome virus (SFTSV) to provide a basis for SFTSV disinfection and laboratory biosafety protection. We divided SFTSV cell culture supernatants into 250 L PCR vials at 100 L/tube, and placed them in a refrigerator at 4..C, and a metal bath at 25..C, 37..C, 39..C, 56..C, and 70..C. After treatment for predetermined periods of time, the viral titer was determined through indirect immunofluorescence in Vero cells. With increasing temperature, the rate of decline of the viral titer increased. After incubation at 4..C, 25..C, 37..C, and 39..C for 24 h, the titers decreased from 107.25/100 L to 107.00/100 L, 106.75/100 L, 106.50/100 L, and 105.00/100 L, respectively. At the same temperature, with prolonged storage time, the decrease in titer became more pronounced. After SFTSV was placed at 4..C, 25..C, 37..C for 72 h, the viral titer decreased from 107.25/100 L to 106.63/100 L, 106.50/100 L, and 103.38/100 L, respectively. SFTSV lost its infectivity after incubation at 39..C for 72 h. SFTSV was inactivated after exposure to 56..C for 180 min or 70..C for 5 min. We concluded that SFTSV is inactivated after incubation at 70..C for 5 min. However, after 3 days of exposure to 4..C and 25..C, the viral titer did not change significantly. Laboratories and medical staff should focus on personal protection and disinfection of items contaminated by SFTSV.

Chest radiograph-based artificial intelligence predictive model for mortality in community-acquired pneumonia.

BACKGROUND: Chest radiograph (CXR) is a basic diagnostic test in community-acquired pneumonia (CAP) with prognostic value. We developed a CXR-based artificial intelligence (AI) model (CAP AI predictive Engine: CAPE) and prospectively evaluated its discrimination for 30-day mortality. METHODS: Deep-learning model using convolutional neural network (CNN) was trained with a retrospective cohort of 2235 CXRs from 1966 unique adult patients admitted for CAP from 1 January 2019 to 31 December 2019. A single-centre prospective cohort between 11 May 2020 and 15 June 2020 was analysed for model performance. CAPE mortality risk score based on CNN analysis of the first CXR performed for CAP was used to determine the area under the receiver operating characteristic curve (AUC) for 30-day mortality. RESULTS: 315 inpatient episodes for CAP occurred, with 30-day mortality of 19.4% (n=61/315). Non-survivors were older than survivors (mean (SD)age, 80.4 (10.3) vs 69.2 (18.7)); more likely to have dementia (n=27/61 vs n=58/254) and malignancies (n=16/61 vs n=18/254); demonstrate higher serum C reactive protein (mean (SD), 109 mg/L (98.6) vs 59.3 mg/L (69.7)) and serum procalcitonin (mean (SD), 11.3 (27.8) µg/L vs 1.4 (5.9) µg/L). The AUC for CAPE mortality risk score for 30-day mortality was 0.79 (95% CI 0.73 to 0.85, p<0.001); Pneumonia Severity Index (PSI) 0.80 (95% CI 0.74 to 0.86, p<0.001); Confusion of new onset, blood Urea nitrogen, Respiratory rate, Blood pressure, 65 (CURB-65) score 0.76 (95% CI 0.70 to 0.81, p<0.001), respectively. CAPE combined with CURB-65 model has an AUC of 0.83 (95% CI 0.77 to 0.88, p<0.001). The best performing model was CAPE incorporated with PSI, with an AUC of 0.84 (95% CI 0.79 to 0.89, p<0.001). CONCLUSION: CXR-based CAPE mortality risk score was comparable to traditional pneumonia severity scores and improved its discrimination when combined.

Factors influencing social distancing to prevent the community spread of COVID-19 among Chinese adults.

The global outbreak of the coronavirus disease 2019 (COVID-19) in 2020 has been an international public health threat. Early strong social distancing efforts is needed to stop transmission of the virus. The purpose of the present study is to identify individual and environmental factors related to individuals' compliance with the recommended social distancing, as well as the moderating role of social media in influencing individuals' implementation of social distancing. A total of 2130 Chinese adults were surveyed in March 2020 during the COVID-19 pandemic. Logistic regression analyses were performed to ascertain the predictors of social distancing. Overall, the majority of respondents (95.6%) reported compliance with social distancing. Women were more likely to practice social distancing compared to men (odds ratio [OR] = 3.12, 95% confidence interval [CI] = 1.93-5.02). Psychological distress, depressive symptoms, and social media were significant predictors of social distancing after controlling for other individual and environmental factors. Social media moderated the effects of psychological distress on social distancing (OR = 0.96, 95% CI = 0.94-0.99). Findings from the study indicates that mental health status and social media are influential factors of social distancing, which have significant implications in enhancing the effectiveness of prevention strategies to contain the spread of COVID-19.

Small molecule therapeutics for COVID-19: repurposing of inhaled furosemide.

The novel coronavirus SARS-CoV-2 has become a global health concern. The morbidity and mortality of the potentially lethal infection caused by this virus arise from the initial viral infection and the subsequent host inflammatory response. The latter may lead to excessive release of pro-inflammatory cytokines, IL-6 and IL-8, as well as TNF-α ultimately culminating in hypercytokinemia ("cytokine storm"). To address this immuno-inflammatory pathogenesis, multiple clinical trials have been proposed to evaluate anti-inflammatory biologic therapies targeting specific cytokines. However, despite the obvious clinical utility of such biologics, their specific applicability to COVID-19 has multiple drawbacks, including they target only one of the multiple cytokines involved in COVID-19's immunopathy. Therefore, we set out to identify a small molecule with broad-spectrum anti-inflammatory mechanism of action targeting multiple cytokines of innate immunity. In this study, a library of small molecules endogenous to the human body was assembled, subjected to in silico molecular docking simulations and a focused in vitro screen to identify anti-pro-inflammatory activity via interleukin inhibition. This has enabled us to identify the loop diuretic furosemide as a candidate molecule. To pre-clinically evaluate furosemide as a putative COVID-19 therapeutic, we studied its anti-inflammatory activity on RAW264.7, THP-1 and SIM-A9 cell lines stimulated by lipopolysaccharide (LPS). Upon treatment with furosemide, LPS-induced production of pro-inflammatory cytokines was reduced, indicating that furosemide suppresses the M1 polarization, including IL-6 and TNF-α release. In addition, we found that furosemide promotes the production of anti-inflammatory cytokine products (IL-1RA, arginase), indicating M2 polarization. Accordingly, we conclude that furosemide is a reasonably potent inhibitor of IL-6 and TNF-α that is also safe, inexpensive and well-studied. Our pre-clinical data suggest that it may be a candidate for repurposing as an inhaled therapy against COVID-19.

Is Inhaled Furosemide a Potential Therapeutic for COVID-19?

The potentially lethal infection caused by the novel Severe Acute Respiratory Disease Coronavirus-2 (SARS-CoV-2) has evolved into a global crisis. Following the initial viral infection is the host inflammatory response that frequently results in excessive secretion of inflammatory cytokines (e.g., IL-6 and TNFα), developing into a self-targeting, toxic "cytokine storm" causing critical pulmonary tissue damage. The need for a therapeutic that is available immediately is growing daily but the de novo development of a vaccine may take years. Therefore, repurposing of approved drugs offers a promising approach to address this urgent need. Inhaled furosemide, a small molecule capable of inhibiting IL-6 and TNFα, may be an agent capable of treating the Coronavirus Disease 2019 cytokine storm in both resource-rich and developing countries. Furosemide is a "repurpose-able" small molecule therapeutics, that is safe, easily synthesized, handled, and stored, and is available in reasonable quantities worldwide.