Swine acute diarrhoea syndrome coronavirus (SADS-CoV) Nsp5 antagonizes type I interferon signaling by cleaving DCP1A.

Swine acute diarrhoea syndrome coronavirus (SADS-CoV), which is a recently discovered enteric coronavirus, is the major aetiological agent that causes severe clinical diarrhoea and intestinal pathological damage in pigs, and it has caused significant economic losses to the swine industry. Nonstructural protein 5, also called 3C-like protease, cleaves viral polypeptides and host immune-related molecules to facilitate viral replication and immune evasion. Here, we demonstrated that SADS-CoV nsp5 significantly inhibits the Sendai virus (SEV)-induced production of IFN-ß and inflammatory cytokines. SADS-CoV nsp5 targets and cleaves mRNA-decapping enzyme 1a (DCP1A) via its protease activity to inhibit the IRF3 and NF-κB signaling pathways in order to decrease IFN-ß and inflammatory cytokine production. We found that the histidine 41 and cystine 144 residues of SADS-CoV nsp5 are critical for its cleavage activity. Additionally, a form of DCP1A with a mutation in the glutamine 343 residue is resistant to nsp5-mediated cleavage and has a stronger ability to inhibit SADS-CoV infection than wild-type DCP1A. In conclusion, our findings reveal that SADS-CoV nsp5 is an important interferon antagonist and enhance the understanding of immune evasion by alpha coronaviruses.

Safety and immunogenicity of heterologous boosting with orally aerosolised or intramuscular Ad5-nCoV vaccine and homologous boosting with inactivated vaccines (BBIBP-CorV or CoronaVac) in children and adolescents: a randomised, open-label, parallel-controlled, non-inferiority, single-centre study.

BACKGROUND: Heterologous booster immunisation with orally administered aerosolised Ad5-nCoV vaccine (AAd5) has been shown to be safe and highly immunogenic in adults. Here, we aimed to assess the safety and immunogenicity of heterologous booster immunisation with orally administered AAd5 in children and adolescents aged 6-17 years who had received two doses of inactivated vaccine (BBIBP-CorV or CoronaVac). METHODS: We did a randomised, open-label, parallel-controlled, non-inferiority study to assess the safety and immunogenicity of heterologous booster immunisation with AAd5 (0·1 mL) or intramuscular Ad5-nCoV vaccine (IMAd5; 0·3 mL) and homologous booster immunisation with inactivated vaccine (BBIBP-CorV or CoronaVac; 0·5 mL) in children (aged 6-12 years) and adolescents (aged 13-17 years) who had received two doses of inactivated vaccine at least 3 months earlier in Hunan, China. Children and adolescents who were previously immunised with two-dose BBIBP-CorV or CoronaVac were recruited for eligibility screening at least 3 months after the second dose. A stratified block method was used for randomisation, and participants were stratified by age and randomly assigned (3:1:1) to receive AAd5, IMAd5, or inactivated vaccine. The study staff and participants were not masked to treatment allocation. Laboratory and statistical staff were masked during the study. In this interim analysis, adverse events within 14 days and geometric mean titre (GMT) of serum neutralising antibodies on day 28 after the booster vaccination, based on the per-protocol population, were used as the primary outcomes. The analysis of non-inferiority was based on comparison using a one-sided 97·5% CI with a non-inferiority margin of 0·67. This study was registered at ClinicalTrials.gov, NCT05330871, and is ongoing. FINDINGS: Between April 17 and May 28, 2022, 436 participants were screened and 360 were enrolled: 220 received AAd5, 70 received IMAd5, and 70 received inactivated vaccine. Within 14 days after booster vaccination, vaccine-related adverse reactions were reported: 35 adverse events (in 13 [12%] of 110 children and 22 [20%] of 110 adolescents) in 220 individuals in the AAd5 group, 35 (in 18 [51%] of 35 children and 17 [49%] of 35 adolescents) in 70 individuals in the IMAd5 group, and 13 (in five [14%] of 35 children and eight [23%] of 35 adolescents) in 70 individuals in the inactivated vaccine group. Solicited adverse reactions were also reported: 34 (13 [12%] of 110 children and 21 [10%] of 110 adolescents) in 220 individuals in the AAd5 group, 34 (17 [49%] of 35 children and 17 [49%] of 35 adolescents) in 70 individuals in the IMAd5 group, and 12 (five [14%] of 35 children and seven [20%] of 35 adolescents) in 70 individuals in the inactivated vaccine group. The GMTs of neutralising antibodies against ancestral SARS-CoV-2 Wuhan-Hu-1 (Pango lineage B) in the AAd5 group were significantly higher than the GMTs in the inactivated vaccine group (adjusted GMT ratio 10·2 [95% CI 8·0-13·1]; p<0·0001). INTERPRETATION: Our study shows that a heterologous booster with AAd5 is safe and highly immunogenic against ancestral SARS-CoV-2 Wuhan-Hu-1 in children and adolescents. FUNDING: National Key R&D Program of China.

Thoughts on diagnosis and treatment plan of patients infected with severe acute respiratory syndrome coronavirus 2 omicron variant in large shelter hospitals in Shanghai

The epidemic caused by the infection of severe acute respiratory syndrome coronavirus 2 omicron variant broke out in Shanghai in Mar. 2022. Omicron variant has characteristics such as strong concealment and rapid transmission, resulting in significant differences between the current round of epidemic and that in Wuhan. The number of infected patients (mainly asymptomatic infected patients) increased rapidly in a short term. Based on dynamic zero policy, shelter hospitals were set up in time in Shanghai to treat the patients. It is suggested that medical resources and patient characteristics should be taken into account in the independent cabin of a shelter hospital with more than 10 000 beds, and the clinical medical practice should be divided to 5 modes (universal education and management, community outpatient clinic, ward duty, emergency rescue, and temporary observation and transport) to optimize the allocation of medical resources, so as to further enhance the treatment capacity and efficiency of shelter hospitals.

One-quarter of COVID-19 patients developed PTSD symptoms: a one-year longitudinal study

This study investigated the longitudinal development of PTSD symptoms and respiratory sequelae among COVID-19 patients one year after hospital discharge. The cumulative occurrence of probable PTSD in COVID-19 survivors (n=329) was 26.7%, which significantly decreased over the 12-month period (23.1% to 4.3%). Non-severe patients showed marked improvement in all four clusters of PTSD symptoms at 12 months compared to 3 months, while severe patients only showed improvements in re-experiencing and numbing symptoms. Moreover, being female and having respiratory sequelae increased the risk for chronic PTSD. Psychological interventions are required for COVID-19 patients during long-term convalescence.

Parallel evolution and control method for predicting the effectiveness of non-pharmaceutical interventions in pandemics.

Aim: Nonpharmaceutical interventions (NPIs) are important strategies to utilize in reducing the negative systemic impact pandemic disasters have on human health. However, early on in the pandemic, the lack of prior knowledge and the rapidly changing nature of pandemics make it challenging to construct effective epidemiological models that can be used for anti-contagion decision-making. Subject and methods: Based on the parallel control and management theory (PCM) and epidemiological models, we developed a Parallel Evolution and Control Framework for Epidemics (PECFE), which can optimize epidemiological models according to the dynamic information during the evolution of pandemics. Results: The cross-application between PCM and epidemiological models enabled us to successfully construct an anti-contagion decision-making model for the early stages of COVID-19 in Wuhan, China. Using the model, we estimated the effects of gathering bans, intra-city traffic blockades, emergency hospitals, and disinfection, forecasted pandemic trends under different NPIs strategies, and analyzed specific strategies to prevent pandemic rebounds. Conclusion: The successful simulation and forecasting of the pandemic showed that the PECFE could be effective in constructing decision models during pandemic outbreaks, which is crucial for emergency management where every second counts. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-023-01843-2.

One-quarter of COVID-19 patients developed PTSD symptoms: A one-year longitudinal study.

This study investigated the longitudinal development of PTSD symptoms and respiratory sequelae among COVID-19 patients one year after hospital discharge. The cumulative occurrence of probable PTSD in COVID-19 survivors (n = 329) was 26.7%, which significantly decreased over the 12-month period (23.1% to 4.3%). Non-severe patients showed marked improvement in all four clusters of PTSD symptoms at 12 months compared to 3 months, while severe patients only showed improvements in re-experiencing and numbing symptoms. Moreover, being female and having respiratory sequelae increased the risk for chronic PTSD. Psychological interventions are required for COVID-19 patients during long-term convalescence.

Characterization and pathogenicity of the porcine epidemic diarrhea virus isolated in China.

Piglet diarrhea caused by the porcine epidemic diarrhea virus (PEDV) is a common problem on pig farms in China associated with high morbidity and mortality rates. In this study, three PEDV isolates were successfully detected after the fourth blind passage in Vero cells. The samples were obtained from infected piglet farms in Jilin (Changchun), and Shandong (Qingdao) Provinces of China and were designated as CH/CC-1/2018, CH/CC-2/2018, and CH/QD/2018. According to the analysis of the complete S protein gene sequence, the CH/CC-1/2018 and CH/CC-2/2018 were allocated to the G2b branch, while CH/QD/2018 was located in the G1a interval and was closer to the vaccine strain CV777. Successful detection and identification of the isolated strains were carried out using electron microscopy and indirect immunofluorescence. Meanwhile, animal challenge experiments and viral RNA copies determination were used to compare the pathogenicity. The results showed that CH/CC-1/2018 in Changchun was more pathogenic than CH/QD/2018 in Qingdao. In conclusion, the discovery of these new strains is conducive to the development of vaccines to prevent the pandemic of PEDV, especially that the CH/CC-1/2018, and CH/CC-2/2018 were not related to the classical vaccine strain CV777.

A novel heterologous receptor-binding domain dodecamer universal mRNA vaccine against SARS-CoV-2 variants.

There are currently approximately 4,000 mutations in the SARS-CoV-2 S protein gene and emerging SARS-CoV-2 variants continue to spread rapidly worldwide. Universal vaccines with high efficacy and safety urgently need to be developed to prevent SARS-CoV-2 variants pandemic. Here, we described a novel self-assembling universal mRNA vaccine containing a heterologous receptor-binding domain (HRBD)-based dodecamer (HRBDdodecamer) against SARS-CoV-2 variants, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (B.1.1.28.1), Delta (B.1.617.2) and Omicron (B.1.1.529). HRBD containing four heterologous RBD (Delta, Beta, Gamma, and Wild-type) can form a stable dodecameric conformation under T4 trimerization tag (Flodon, FD). The HRBDdodecamer -encoding mRNA was then encapsulated into the newly-constructed LNPs consisting of a novel ionizable lipid (4N4T). The obtained universal mRNA vaccine (4N4T-HRBDdodecamer) presented higher efficiency in mRNA transfection and expression than the approved ALC-0315 LNPs, initiating potent immune protection against the immune escape of SARS-CoV-2 caused by evolutionary mutation. These findings demonstrated the first evidence that structure-based antigen design and mRNA delivery carrier optimization may facilitate the development of effective universal mRNA vaccines to tackle SARS-CoV-2 variants pandemic.

Manganese-coordinated mRNA vaccines with enhanced mRNA expression and immunogenicity induce robust immune responses against SARS-CoV-2 variants.

It is urgent to develop more effective mRNA vaccines against the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants owing to the immune escape. Here, we constructed a novel mRNA delivery system [IC8/Mn lipid nanoparticles (IC8/Mn LNPs)]with high immunogenicity, via introducing a stimulator of interferon genes (STING) agonist [manganese (Mn)] based on a newly synthesized ionizable lipid (IC8). It was found that Mn can not only promote maturation of antigen-presenting cells via activating STING pathway but also improve mRNA expression by facilitating lysosomal escape for the first time. Subsequently, IC8/Mn LNPs loaded with mRNA encoding the Spike protein of SARS-CoV-2 Delta or Omicron variant (IC8/Mn@D or IC8/Mn@O) were prepared. Both mRNA vaccines induced substantial specific immunoglobulin G responses against Delta or Omicron. IC8/Mn@D displayed strong pseudovirus neutralization ability, T helper 1-biased immune responses, and good safety. It can be concluded that IC8/Mn LNPs have great potential for developing Mn-coordinated mRNA vaccines with robust immunogenicity and good safety.

The relationship between oxygen therapy, drug therapy, and COVID-19 mortality.

Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19). We conducted a retrospective study of COVID-19 inpatients in Wuhan Pulmonary Hospital (Wuhan, China) from January 1 to February 29, 2020. The subjects were divided into four groups due to different treatment regimes. We used the Kaplan-Meier method to determine the cumulative rates of in-hospital death and the Cox proportional hazard model to calculate the risk factors and corresponding hazard ratios. A total of 185 patients were included in this study. The median age of the patients was 62 years, including 94 men and 91 women. Kaplan-Meier analysis demonstrated that mortality was higher in older patients, higher in men, and lower in the low-flow oxygen therapy group. Body mass index (BMI) had no influence on mortality, as well as high flow oxygen therapy, Lopinavir-ritonavir (LPV/r) therapy, and the interferon-alpha add LPV/r therapy. Cox proportional hazard regression confirmed that the low flow oxygen therapy was independent protective factor for in-hospital death after adjusting for age, gender, and BMI. In conclusion, the mortality was higher in older patients, higher in men, and lower in the low-flow oxygen therapy group. BMI had no influence on mortality, as well as high flow oxygen therapy, LPV/r therapy, and interferon-alpha add LPV/r therapy.

Batch-to-batch consistency trial of an adenovirus type-5 vector-based COVID-19 vaccine in adults aged 18 years and above.

BACKGROUND: The demonstration of batch-to-batch consistency is indispensable for quality control of vaccines. METHODS: We conducted a randomized, double-blind, parallel-controlled trial to evaluate the immunogenicity consistency of a single shot of Ad5-nCoV in healthy adults who had not previously received any COVID-19 vaccine. All eligible participants were randomly assigned equally to receive one of the three consecutive batches of Ad5-nCoV (5 × 1010 viral particles/vial, 0.5 mL). The primary endpoint was geometric mean titers (GMTs) of serum SARS-CoV-2 receptor-binding domain (RBD)-specific IgG on day 28 post-vaccination. RESULTS: One thousand fifty participants were enrolled, with 350 (33%) participants per group. On day 28 post-vaccination, GMTs in three groups were 78.3 binding antibody units (BAU)/mL (95% CI 70.3-87.3), 82.9 BAU/mL (73.9-92.9), and 78.8 BAU/mL (70.2-88.4), respectively. The two-sided 95% CIs for the GMT ratios between each pair of batches were all between 0.67 and 1.5. The highest incidence of solicited adverse reactions within 7 days post-vaccination was reported by batch 3 recipients (23.1% versus 15.1% in batch 1 recipients and 14.6% in bath 2 recipients; p = 0.0039). None of the serious adverse events were related to vaccination. CONCLUSIONS: Immunogenicity consistency between consecutive batches of Ad5-nCoV was well established in adults. CLINICAL TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT05313646).

mRNA Vaccines Against SARS‐CoV‐2 Variants Delivered by Lipid Nanoparticles Based on Novel Ionizable Lipids

SARS‐CoV‐2 variants are now still challenging all the approved vaccines, including mRNA vaccines. There is an urgent need to develop new generation mRNA vaccines with more powerful efficacy and better safety against SARS‐CoV‐2 variants. In this study, a new set of ionizable lipids named 4N4T are constructed and applied to form novel lipid nanoparticles called 4N4T‐LNPs. Leading 4N4T‐LNPs exhibit much higher mRNA translation efficiency than the approved SM‐102‐LNPs. To test the effectiveness of the novel delivery system, the DS mRNA encoding the full‐length S protein of the SARS‐CoV‐2 variant is synthesized and loaded in 4N4T‐LNPs. The obtained 4N4T‐DS mRNA vaccines successfully trigger robust and durable humoral immune responses against SARS‐CoV‐2 and its variants including Delta and Omicron. Importantly, the novel vaccines have higher RBD‐specific IgG titers and neutralizing antibody titers than SM‐102‐based DS mRNA vaccine. Besides, for the first time, the types of mRNA vaccine‐induced neutralizing antibodies are found to be influenced by the chemical structure of ionizable lipids. 4N4T‐DS mRNA vaccines also induce strong Th1‐skewed T cell responses and have good safety. This work provides a novel vehicle for mRNA delivery that is more effective than the approved LNPs and shows its application in vaccines against SARS‐CoV‐2 variants. In this study, mRNA vaccines against SARS‐CoV‐2 variants delivered by lipid nanoparticles based on 4N4T lipids are constructed, and successfully trigger robust and durable humoral immune responses against SARS‐CoV‐2 and its variants including Delta and Omicron. In addition, head‐to‐head comparison studies find that the novel 4N4T lipids have a higher mRNA delivery efficiency than SM‐102.

15-Month Health Outcomes and the Related Risk Factors of Hospitalized COVID-19 Patients From Onset: A Cohort Study.

Objective: The long-term impact of COVID-19 on patient health has been a recent focus. This study aims to determine the persistent symptoms and psychological conditions of patients hospitalized with COVID-19 15 months after onset, that patients first developed symptoms. The potential risk factors were also explored. Methods: A cohort of COVID-19 patients discharged from February 20, 2020 to March 31, 2020 was recruited. Follow-ups were conducted using validated questionnaires and psychological screening scales at 15 months after onset to evaluate the patients' health status. The risk factors for long-term health impacts and their associations with disease severity was analyzed. Findings: 534 COVID-19 patients were enrolled. The median age of the patients was 62.0 years old (IQR 52.0-70.0) and 295 were female (55.2%). The median time from onset to follow-up was 460.0 (451.0-467.0) days. Sleep disturbance (18.5%, 99/534) and fatigue (17.2%, 92/534) were the most common persistent symptoms. 6.4% (34/534) of the patients had depression, 9.2% (49/534) were anxious, 13.0% (70/534) had insomnia and 4.7% (25/534) suffered from post-traumatic stress disorder (PTSD). Multivariate adjusted logistic regression analysis showed that glucocorticoid use during hospitalization (OR 3.58, 95% CI 1.12-11.44) was significantly associated with an increased risk of fatigue. The OR values for anxiety and sleep disorders were 2.36 (95% CI 1.07-5.20) and 2.16 (95% CI 1.13-4.14) in females to males. The OR value of PTSD was 25.6 (95% CI 3.3-198.4) in patients with persistent symptoms to those without persistent symptoms. No significant associations were observed between fatigue syndrome or adverse mental outcomes and disease severity. Conclusions: 15-month follow-up in this study demonstrated the need of extended rehabilitation intervention for complete recovery in COVID-19 patients.

Electronic health literacy among older adults in the context of the COVID-19 pandemic: A mixed-methods study.

AIM: This study aimed to investigate eHealth literacy about coronavirus disease 2019 (COVID-19) among older adults during the pandemic. BACKGROUND: The COVID-19 pandemic promoted the development of online health care. Higher demand for accessing information from the Internet was seen. METHODS: This was a sequential explanatory mixed-method study, involving a survey of older adults to explore the status and influencing factors of eHealth literacy regarding COVID-19. Semi-structured interviews were used to understand experiences and challenges regarding information retrieval, judgment and utilization. RESULTS: A total of 337 older adults participated in the online questionnaire survey. Overall, older adults had slightly higher scores on eHealth literacy during the COVID-19 pandemic. Participants' location in the past month and current health issues were associated with eHealth literacy. Qualitative data were collected from nine older adults and included that some older adults retrieved health-related information during the pandemic. However, those who used non-smartphones described difficulties in information retrieval. A glut of misinformation has resulted in an 'infodemic', which has not only increased the difficulty of judging information but also posed challenges in information utilization for older adults. CONCLUSION: Improving older adults' eHealth literacy is essential in promoting an improved response to major public health events and in providing better health care for this group in the future. It is essential that government health agencies and health care providers provide evidence-based health information via social media platforms. Further efforts are needed to combine aspects of traditional and online health care services and provide reliable and updated online information and resources for older adults. IMPLICATIONS FOR NURSING MANAGEMENT: Providing evidence to eHealth literacy improvement and health management of older adults in the context of public health events.

How Flow Experience and Self-Efficacy Define Students' Online Learning Intentions: View From Task Technology Fit (Framework).

The ongoing pandemic has transformed communication modes globally. Especially in the case of higher education, where countermeasures against coronavirus disease 2019 (COVID-19) have affected students' learning experience. This study emphasized the case of business simulation games, where critical factors were underlined to define learners' intention to use an online learning environment through the lens of task technology fit (TTF) as a theoretical stance. This study considered the statistical analysis of 523 students who attended the business simulation module online at the tertiary level of education. Findings conclude that flow experience is the most critical factor to define learners' perceived TTF in the case of an online learning experience. However, the learners' self-efficacy is significant enough to map learners' intentions to use an online environment for learning. The study discussed several theoretical and practical implications for learners' educators and policymakers.

Systematic optimization of host-directed therapeutic targets and preclinical validation of repositioned antiviral drugs.

Inhibition of host protein functions using established drugs produces a promising antiviral effect with excellent safety profiles, decreased incidence of resistant variants and favorable balance of costs and risks. Genomic methods have produced a large number of robust host factors, providing candidates for identification of antiviral drug targets. However, there is a lack of global perspectives and systematic prioritization of known virus-targeted host proteins (VTHPs) and drug targets. There is also a need for host-directed repositioned antivirals. Here, we integrated 6140 VTHPs and grouped viral infection modes from a new perspective of enriched pathways of VTHPs. Clarifying the superiority of nonessential membrane and hub VTHPs as potential ideal targets for repositioned antivirals, we proposed 543 candidate VTHPs. We then presented a large-scale drug-virus network (DVN) based on matching these VTHPs and drug targets. We predicted possible indications for 703 approved drugs against 35 viruses and explored their potential as broad-spectrum antivirals. In vitro and in vivo tests validated the efficacy of bosutinib, maraviroc and dextromethorphan against human herpesvirus 1 (HHV-1), hepatitis B virus (HBV) and influenza A virus (IAV). Their drug synergy with clinically used antivirals was evaluated and confirmed. The results proved that low-dose dextromethorphan is better than high-dose in both single and combined treatments. This study provides a comprehensive landscape and optimization strategy for druggable VTHPs, constructing an innovative and potent pipeline to discover novel antiviral host proteins and repositioned drugs, which may facilitate their delivery to clinical application in translational medicine to combat fatal and spreading viral infections.

Establishing and evaluating physician-pharmacist collaborative clinics to manage patients with type 2 diabetes in primary hospitals in Hunan province: study protocol of a multi-site randomized controlled trial in the era of COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has exerted an unprecedented and universal impact on global health system, resulting in noticeable challenges in traditional chronic disease care, of which diabetes was reported to be most influenced by the reduction in healthcare resources in the pandemic. China has the world's largest diabetes population, and current diabetes management in China is unsatisfactory, particularly in rural areas. Studies in developed countries have demonstrated that physician-pharmacist collaborative clinics are efficient and cost-effective for diabetes management, but little is known if this mode could be adapted in primary hospitals in China. The aim of this proposed study is to develop and evaluate physician-pharmacist collaborative clinics to manage type 2 diabetes mellitus (T2DM) in primary hospitals in Hunan province. METHODS: A multi-site randomized controlled trial will be conducted to evaluate the effectiveness and cost-effectiveness of the physician-pharmacist collaborative clinics compared with usual care for Chinese patients with T2DM. Six primary hospitals will participate in the study, which will recruit 600 eligible patients. Patients in the intervention group will receive services from both physicians and pharmacists in the collaborative clinics, while the control group will receive usual care from physicians. Patients will be followed up at the 3rd, 6th, 9th and 12th month. Comparison between the two groups will be conducted by assessing the clinical parameters, process indicators and costs on diabetes. A satisfaction survey will also be carried out at the end of the study. DISCUSSION: If effective, the physician-pharmacist collaborative clinics can be adapted and used in primary hospitals of China to improve glycemic control, enhance medication adherence, decrease incidence of complications and reduce patients' dependence on physicians. Findings from the present study are meaningful for developing evidence-based diabetes care policy in rural China, especially in the COVID-19 pandemic era. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000031839 , Registered 12 April 2020.

Treatment of patients with Covid-19 with a high dose of ulinastatin

Currently, there are no specific therapeutic agents available for the treatment of coronavirus disease 2019 (Covid-19). The present study aimed to assess the efficacy of high-dose ulinastatin for the treatment of patients with Covid-19. A total of 12 patients hospitalized with confirmed severe acute respiratory syndrome coronavirus 2 infection were treated with a high dose of ulinastatin alongside standard care. Changes in clinical manifestations, laboratory examinations and chest images were retrospectively analyzed. A total of 10 patients with severe Covid-19 and two patients with moderate Covid-19 received ulinastatin treatment. The average age of the patients was 68.0±11.9 years (age range, 48-87 years). In total, nine of the 12 patients (75.0%) had one or more comorbidities. The most common symptoms on admission were fever (8/12, 66.7%), cough (5/12, 41.7%) and dyspnea (5/12, 41.7%). The percentage of lymphocytes was decreased in 41.7% of patients (5/12) and 58.3% of patients (7/12) had elevated hypersensitive C-reactive protein (CRP) levels (mean, 49.70±77.70 mg/l). The white blood cell levels and the percentage of lymphocytes returned to normal in all of the patients, and CRP was significantly decreased and returned to normal in 83.3% of patients (10/12;mean, 6.87±6.63 mg/l) on day 7 after ulinastatin treatment. Clinical symptoms were relieved synchronously. The peripheral oxygen saturation improved and 66.7% of the patients (8/12) did not require further oxygen therapy 7 days after ulinastatin treatment. No patients required intensive care unit admission or mechanical ventilation. All patients revealed different degrees of absorption of pulmonary lesions after treatment. Compared with the standard care group, ulinastatin treatment significantly prevented illness deterioration. In conclusion, these preliminary data revealed that high-dose ulinastatin treatment was safe and exhibited a potential beneficial effect for patients with Covid-19. [ FROM AUTHOR] Copyright of Experimental & Therapeutic Medicine is the property of Spandidos Publications UK Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Treatment of patients with Covid-19 with a high dose of ulinastatin.

Currently, there are no specific therapeutic agents available for the treatment of coronavirus disease 2019 (Covid-19). The present study aimed to assess the efficacy of high-dose ulinastatin for the treatment of patients with Covid-19. A total of 12 patients hospitalized with confirmed severe acute respiratory syndrome coronavirus 2 infection were treated with a high dose of ulinastatin alongside standard care. Changes in clinical manifestations, laboratory examinations and chest images were retrospectively analyzed. A total of 10 patients with severe Covid-19 and two patients with moderate Covid-19 received ulinastatin treatment. The average age of the patients was 68.0±11.9 years (age range, 48-87 years). In total, nine of the 12 patients (75.0%) had one or more comorbidities. The most common symptoms on admission were fever (8/12, 66.7%), cough (5/12, 41.7%) and dyspnea (5/12, 41.7%). The percentage of lymphocytes was decreased in 41.7% of patients (5/12) and 58.3% of patients (7/12) had elevated hypersensitive C-reactive protein (CRP) levels (mean, 49.70±77.70 mg/l). The white blood cell levels and the percentage of lymphocytes returned to normal in all of the patients, and CRP was significantly decreased and returned to normal in 83.3% of patients (10/12; mean, 6.87±6.63 mg/l) on day 7 after ulinastatin treatment. Clinical symptoms were relieved synchronously. The peripheral oxygen saturation improved and 66.7% of the patients (8/12) did not require further oxygen therapy 7 days after ulinastatin treatment. No patients required intensive care unit admission or mechanical ventilation. All patients revealed different degrees of absorption of pulmonary lesions after treatment. Compared with the standard care group, ulinastatin treatment significantly prevented illness deterioration. In conclusion, these preliminary data revealed that high-dose ulinastatin treatment was safe and exhibited a potential beneficial effect for patients with Covid-19.

Multicenter analysis and a rapid screening model to predict early novel coronavirus pneumonia using a random forest algorithm.

ABSTRACT: Early determination of coronavirus disease 2019 (COVID-19) pneumonia from numerous suspected cases is critical for the early isolation and treatment of patients.The purpose of the study was to develop and validate a rapid screening model to predict early COVID-19 pneumonia from suspected cases using a random forest algorithm in China.A total of 914 initially suspected COVID-19 pneumonia in multiple centers were prospectively included. The computer-assisted embedding method was used to screen the variables. The random forest algorithm was adopted to build a rapid screening model based on the training set. The screening model was evaluated by the confusion matrix and receiver operating characteristic (ROC) analysis in the validation.The rapid screening model was set up based on 4 epidemiological features, 3 clinical manifestations, decreased white blood cell count and lymphocytes, and imaging changes on chest X-ray or computed tomography. The area under the ROC curve was 0.956, and the model had a sensitivity of 83.82% and a specificity of 89.57%. The confusion matrix revealed that the prospective screening model had an accuracy of 87.0% for predicting early COVID-19 pneumonia.Here, we developed and validated a rapid screening model that could predict early COVID-19 pneumonia with high sensitivity and specificity. The use of this model to screen for COVID-19 pneumonia have epidemiological and clinical significance.