Light-Start CRISPR-Cas12a Reaction with Caged crRNA Enables Rapid and Sensitive Nucleic Acid Detection.

The clustered regularly interspaced short palindromic repeats (CRISPR) system is a promising platform for nucleic acid detection. Regulating the CRISPR reaction would be extremely useful to improve the detection efficiency and speed of CRISPR diagnostic applications. Here, we have developed a light-start CRISPR-Cas12a reaction by employing caged CRISPR RNA (crRNA). When combined with recombinase polymerase amplification, a robust photocontrolled one-pot assay is achieved. The photocontrolled one-pot assay is simpler and is 50-fold more sensitive than the conventional assay. This improved detection efficiency also facilitates the development of a faster CRISPR diagnostic method. The detection of clinical samples demonstrated that 10-20 min is sufficient for effective detection, which is much faster than the current gold-standard technique PCR. We expect this advance in CRISPR diagnostics to promote its widespread detection applications in biomedicine, agriculture, and food safety.

COVID-19 Infection Deteriorates the Clinical Condition and Outcomes of Acute Pancreatitis: A Meta-Analysis.

Backgrounds: The novel coronavirus disease 2019 (COVID-19) has caused a global pandemic. Pancreatic injuries have been reported in COVID-19 patients. The present meta-analysis was conducted to compare the morbidity and outcomes of AP between COVID-19 positive and negative patients. Methods: Databases including Cochrane Library, PubMed, and EMBASE were systematically searched (until July 3rd 2022). Studies with English abstracts comparing the severity and outcomes of AP between COVID-19 positive and negative patients were included. Mean differences or odds ratios with a 95% confidence interval were employed for assess variables. Risk of publication bias was assessed with funnel plots. Results: Data from 7 studies with a total of 2816 AP patients were included. COVID-19 positive was associated with higher incidences of pancreatic necrosis (OR = 1.65; 95% CI: 1.13 to 2.42, P = 0.01; P = 0.82 for heterogeneity) and persistent organ failure (OR = 6.87; 95% CI: 2.37 to 19.98, P = 0.0004; P = 0.12 for heterogeneity), especially cardiovascular failure (OR = 2.92; 95% CI: 1.66 to 5.14, P = 0.0002; P = 0.58 for heterogeneity) and acute respiratory distress syndrome (ARDS) or acute lung injury (ALI) (OR = 3.03; 95% CI: 2.09 to 4.39, P < 0.00001; P = 0.20 for heterogeneity). COVID-19 infection induced a higher level of CRP (MD = 0.40; 95% CI: 0.16 to 0.64, P = 0.001; P < 0.00001 for heterogeneity) as well as coagulation disorders involving platelets, prothrombin time, activated partial thromboplastin time, and D-dimer (all P < 0.05). During hospitalization, COVID-19 positive was associated with higher ICU admission rate (OR = 2.76; 95% CI: 1.98 to 3.85 P < 0.00001; P = 0.47 for heterogeneity). COVID-19 positive AP was associated with a higher mortality rate (OR = 3.70; 95% CI: 2.60 to 5.25, P < 0.00001; P = 0.12 for heterogeneity). Discussion. The number of included studies is limited and none is RCT, thus the risks of publication and selective bias could not be ignored. COVID-19 deteriorated the severity and clinical outcomes of AP, with a high incidence of morbidity and mortality.

The Whistleblower’s Dilemma: An Evolutionary Game Analysis of the Public Health Early Warning System

Although the ability to manage public health emergencies in China has improved significantly, there are still many challenges to the existing information transmission mechanism in pandemic early warning systems. In this context, a tripartite evolutionary game model composed of the local government, the whistleblower, and the public is formulated. By using Matlab, the dynamic evolution path of the game model is stimulated under different conditions. Stable strategies for an early warning system for public health emergencies are also explored. The results indicate that the cost of whistleblowing, the cost of response, and the benefit of attention significantly influence strategic decisions among three parties. This study highlights the importance of whistleblowing in managing public health emergencies. Yet, our findings provide theoretical support for policy recommendations for promoting public health emergency preparedness.

Racial and ethnic disparity in clinical outcomes among patients with confirmed COVID-19 infection in a large US electronic health record database.

BACKGROUND: Racial and ethnic minority groups have been disproportionately affected by the US coronavirus disease 2019 (COVID-19) pandemic; however, nationwide data on COVID-19 outcomes stratified by race/ethnicity and adjusted for clinical characteristics are sparse. This study analyzed the impacts of race/ethnicity on outcomes among US patients with COVID-19. METHODS: This was a retrospective observational study of patients with a confirmed COVID-19 diagnosis in the electronic health record from 01 February 2020 through 14 September 2020. Index encounter site, hospitalization, and mortality were assessed by race/ethnicity (Hispanic, non-Hispanic Black [Black], non-Hispanic White [White], non-Hispanic Asian [Asian], or Other/unknown). Associations between racial/ethnic categories and study outcomes adjusted for patient characteristics were evaluated using logistic regression. FINDINGS: Among 202,908 patients with confirmed COVID-19, patients from racial/ethnic minority groups were more likely than White patients to be hospitalized on initial presentation (Hispanic: adjusted odds ratio 1·690, 95% CI 1·620-1·763; Black: 1·810, 1·743-1·880; Asian: 1·503, 1·381-1·636) and during follow-up (Hispanic: 1·700, 1·638-1·764; Black: 1·578, 1·526-1·633; Asian: 1·391, 1·288-1·501). Among hospitalized patients, adjusted mortality risk was lower for Black patients (0·881, 0·809-0·959) but higher for Asian patients (1·205, 1·000-1·452). INTERPRETATION: Racial/ethnic minority patients with COVID-19 had more severe disease on initial presentation than White patients. Increased mortality risk was attenuated by hospitalization among Black patients but not Asian patients, indicating that outcome disparities may be mediated by distinct factors for different groups. In addition to enacting policies to facilitate equitable access to COVID-19-related care, further analyses of disaggregated population-level COVID-19 data are needed.

Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan. A Retrospective Observational Study.

Rationale: The global death toll from coronavirus disease (COVID-19) virus as of May 12, 2020, exceeds 286,000. The risk factors for death were attributed to advanced age and comorbidities but have not been accurately defined.Objectives: To report the clinical features of 85 fatal cases of COVID-19 in two hospitals in Wuhan.Methods: Medical records were collected of 85 fatal cases of COVID-19 between January 9, 2020, and February 15, 2020. Information recorded included medical history, exposure history, comorbidities, symptoms, signs, laboratory findings, computed tomographic scans, and clinical management.Measurements and Main Results: The median age of the patients was 65.8 years, and 72.9% were male. Common symptoms were fever (78 [91.8%]), shortness of breath (50 [58.8%]), fatigue (50 [58.8%]), and dyspnea (60 [70.6%]). Hypertension, diabetes, and coronary heart disease were the most common comorbidities. Notably, 81.2% of patients had very low eosinophil counts on admission. Complications included respiratory failure (80 [94.1%]), shock (69 [81.2%]), acute respiratory distress syndrome (63 [74.1%]), and arrhythmia (51 [60%]), among others. Most patients received antibiotic (77 [90.6%]), antiviral (78 [91.8%]), and glucocorticoid (65 [76.5%]) treatments. A total of 38 (44.7%) and 33 (38.8%) patients received intravenous immunoglobulin and IFN-α2b, respectively.Conclusions: In this depictive study of 85 fatal cases of COVID-19, most cases were males aged over 50 years with noncommunicable chronic diseases. The majority of the patients died of multiple organ failure. Early onset of shortness of breath may be used as an observational symptom for COVID-19 exacerbations. Eosinophilopenia may indicate a poor prognosis. A combination of antimicrobial drugs did not offer considerable benefit to the outcome of this group of patients.

Management and Treatment of COVID-19: The Chinese Experience.

With more than 1,800,000 cases and 110,000 deaths globally, COVID-19 is one of worst infectious disease outbreaks in history. This paper provides a critical review of the available evidence regarding the lessons learned from the Chinese experience with COVID-19 prevention and management. The steps that have led to a near disappearance of new cases in China included rapid sequencing of the virus to establish testing kits, which allowed tracking of infected persons in and out of Wuhan. In addition, aggressive quarantine measures included the complete isolation of Wuhan and then later Hubei Province and the rest of the country, as well as closure of all schools and nonessential businesses. Other measures included the rapid construction of two new hospitals and the establishment of "Fangcang" shelter hospitals. In the absence of a vaccine, the management of COVID-19 included antivirals, high-flow oxygen, mechanical ventilation, corticosteroids, hydroxychloroquine, tocilizumab, interferons, intravenous immunoglobulin, and convalescent plasma infusions. These measures appeared to provide only moderate success. Although some measures have been supported by weak descriptive data, their effectiveness is still unclear pending well controlled clinical trials. In the end, it was the enforcement of drastic quarantine measures that stopped SARS-CoV-2 from spreading. The earlier the implementation, the less likely resources will be depleted. The most critical factors in stopping a pandemic are early recognition of infected individuals, carriers, and contacts and early implementation of quarantine measures with an organised, proactive, and unified strategy at a national level. Delays result in significantly higher death tolls.