Extending the Record of Terpenes from Soft Coral Sarcophyton mililatensis.

In the present study, a new polyoxygenated cembranoid named sarcomililatol H (1) as well as six known terpenes 2-7 with different skeletons were isolated from South China Sea soft coral Sarcophyton mililatensis. Based on the comprehensive analyses of 1D and 2D NMR spectroscopic data, the structure of the new compound 1 was established. This new cembranoid was characterized by the presence of the rarely encountered tetrahydropyran ring with the ether linkage across C-2 and C-12. By applying the time-dependent density functional theory electronic circular dichroism (TDDFT ECD) approach, the absolute configuration of sarcomililatol H (1) was determined. All of the isolates were subjected to the anti-inflammatory and anti-tumor bioassays. However, none of them was active in these evaluations. Additionally, the preliminary virtual screening of inhibitory against SARS-CoV-2 by molecular docking showed that diterpene 1 could be regarded as a SARS-CoV-2 main protease (Mpro ) inhibitor (binding energy: -7.63 kcal/mol). The discovery of these terpenes has expanded the chemical diversity and complexity of terpenes from the species S. mililatensis.

Elicitation of potent neutralizing antibodies in obese mice by ISA 51-adjuvanted SARS-CoV-2 spike RBD-Fc vaccine.

Vaccination is considered to be the most effective countermeasure to prevent and combat the global health threats of COVID-19. People with obesity are at a greater risk of hospitalization, life-threatening illness, and adverse outcomes after having COVID-19. Therefore, a safe and effective COVID-19 vaccine for obese individuals is urgently needed. In the study, the vaccine composed of the ISA 51 adjuvant and the SARS-CoV-2 spike (S) receptor-binding domain (RBD) in conjugation with the human IgG1 Fc fragment (named as ISA 51-adjuvanted RBD-Fc vaccine) was developed and inoculated in the regular chow diet (RCD) lean mice and the high-fat diet (HFD)-induced obese mice. The S protein-specific IgG titers were largely induced in an increasing manner along with three doses of ISA 51-adjuvanted RBD-Fc vaccine without causing any harmful side effect. In the HFD mice, the S protein-specific IgG titers can be quickly observed 2 weeks post the first inoculation. The antisera elicited by the ISA 51-adjuvanted RBD-Fc vaccine in the RCD and HFD mice exhibited potent SARS-CoV-2 neutralizing activities in the plaque reduction neutralization test (PRNT) assays and showed similar specificity for recognizing the key residues in the RBD which were involved in interacting with angiotensin-converting enzyme 2 (ACE2) receptor. The immune efficacy of the ISA 51-adjuvanted RBD-Fc vaccine in the HFD mice can be sustainably maintained with the PRNT50 values of 1.80-1.91×10-3 for at least 8 weeks post the third inoculation. Collectively, the RBD-Fc-based immunogen and the ISA 51-adjuvanted formulation can be developed as an effective COVID-19 vaccine for obese individuals. KEY POINTS: • The ISA 51-adjuvanted RBD-Fc vaccine can induce potent SARS-CoV-2 neutralizing antibodies in the obese mouse • The antibodies elicited by the ISA 51-adjuvanted RBD-Fc vaccine can bind to the key RBD residues involved in interacting with ACE2 • The immune efficacy of the ISA 51-adjuvanted RBD-Fc vaccine can be sustainably maintained for at least 8 weeks post the third inoculation.

Epidemiological features and risk factors for measles and rubella in Taiwan during 2011 to 2020.

The risk of geographic transmission of infectious diseases due to air travel varies greatly. Our aim is to survey empirical data that provide a retrospective historical perspective on measles and rubella. This study used the open data website provided by the Taiwan Centers for Disease Control (TCDC) to extract the reported numbers of measles and rubella case between 2011 and 2020. There were 306 cases of measles and 135 cases of rubella. The incidence of measles and rubella per million population were 0 to 6.0 and 0 to 2.6, respectively. There was a gradual increase in the numbers of cases in those aged 20-39 years, and distinct duration patterns. It indicated that the risk of contracting rubella has significantly decreased in the last 5 years. Measles cases aged 20 to 39 years accounted for 72.5% of all cases. Rubella cases aged 20 to 39 years accounted for 59.3% of all cases. The male and residency in the Taipei metropolitan area or northern area were identified as potential risk factors for measles and rubella. Coverage with the first dose of the measles, mumps and rubella (MMR) vaccine in Taiwan increased from 97.31% to 98.86%, and the uptake rate of the second dose of the MMR vaccine increased from 95.73% to 98.39% between 2010 and 2020. Furthermore, the numbers of imported cases of measles (n = 0) and rubella (n = 0) reported during the coronavirus disease 2019 (COVID-19) pandemic were lower than those from 2011 to 2019. Measles and rubella cases were imported most frequently from Cambodia and Vietnam. This study represents the first report of confirmed cases of acquired measles and rubella from surveillance data of the TCDC between 2011 and 2020, also demonstrates that the numbers of cases of measles and rubella significantly decreased in Taiwan during the COVID-19 pandemic.

Efficiency and input congestion of major marine transport companies in the world

The marine transport companies have been experiencing intense competition with the supply increasing faster than the demand, making most of them face input congestion. This paper applies the input congestion data envelopment analysis (DEA) model proposed by Tone and Sahoo (2004) to compute efficiency scores and input congestions of 159 major marine transport companies in the world during 2010–2019. The inputs include employees, total assets, and capital whereas the output is net sales. The base year for monetary values is 2010. It is found that the annual ratios of input-congested marine companies are between 20.9% and 65.7%, indicating that input congestion is not an unusual phenomenon among these companies. This paper also applies a BCG-like analysis to consider inefficiency and input congestion at the same time. The Mann-Whitney U test shows that most of the marine transport companies in Asia, Europe, and the Americas face both inefficiency and input congestion problems during the data period. This analysis is able to provide the implications for shipping companies to conduct more precise and efficient resource allocation and coordination in the post Covid-19 era.

Epidemic Source Detection in Contact Tracing Networks: Epidemic Centrality in Graphs and Message-Passing Algorithms (preprint)

We study the epidemic source detection problem in contact tracing networks modeled as a graph-constrained maximum likelihood estimation problem using the susceptible-infected model in epidemiology. Based on a snapshot observation of the infection subgraph, we first study finite degree regular graphs and regular graphs with cycles separately, thereby establishing a mathematical equivalence in maximal likelihood ratio between the case of finite acyclic graphs and that of cyclic graphs. In particular, we show that the optimal solution of the maximum likelihood estimator can be refined to distances on graphs based on a novel statistical distance centrality that captures the optimality of the nonconvex problem. An efficient contact tracing algorithm is then proposed to solve the general case of finite degree-regular graphs with multiple cycles. Our performance evaluation on a variety of graphs shows that our algorithms outperform the existing state-of-the-art heuristics using contact tracing data from the SARS-CoV 2003 and COVID-19 pandemics by correctly identifying the superspreaders on some of the largest superspreading infection clusters in Singapore and Taiwan.

Epidemiological features of domestic and imported cases with COVID-19 between January 2020 and March 2021 in Taiwan.

ABSTRACT: Coronavirus disease-2019 (COVID-19) is a global pandemic affecting numerous countries around the world. This study elaborates Taiwan's epidemiological characteristics from the 2020 to 2021 COVID-19 pandemic from human, temporal, and geographical dimensions. Big data for cases were obtained from a public database from the Taiwan Centers for Disease Control (CDC) in April 2021. The data were analyzed and used to compare differences, correlations, and trends for human, temporal, and geographical characteristics for imported and domestic COVID-19 cases. During the study period, 1030 cases were confirmed and the mortality rate of 1.0%. The epidemiological features indicated that most cases (953/1030, 92.5%) were imported. A comparison of the domestic confirmed and imported cases revealed the following findings: No significant difference of COVID-19 between males and females for sex was observed; For age, the risk of domestic transmission was significantly lower for 20 to 29 years old, higher for 50 to 59 years old, and >60 years old with odds ratios (ORs) (P value < .05) of 0.36, 3.37, and 2.50, respectively; For the month of infection, the ORs (P value < .05) of domestic confirmed cases during January and February 2020 were 22.428; and in terms of area of residence, the ORs (P value < .05) for domestic confirmed cases in northern and southern Taiwan were 4.473 and 0.033, respectively. Thus, the increase in domestic cases may have been caused by international travelers transmitting the virus in March 2020 and December 2020, respectively. Taiwan has been implementing effective screening and quarantine measures at airports. Moreover, Taiwan has implemented and maintained stringent interventions such as large-scale epidemiological investigation, rapid diagnosis, wearing masks, washing hands frequently, safe social distancing, and prompt clinical classifications for severe patients who were given appropriate medical measures. This is the first report comparing imported and domestic cases of COVID-19 from surveillance data from the Taiwan Centers for Disease Control during January 2020 and March 2021. It illustrates that individuals infected during overseas travel are the main risk factors for the spread of COVID-19 in Taiwan. The study also highlights the importance of longitudinal and geographically extended studies in understanding the implications of COVID-19 transmission for Taiwan's population.

Incidence and Risk Factors for Notifiable Typhoid and Paratyphoid in Taiwan during the Period 2011-2020.

The risk of the geographic transmission of emerging infectious diseases through air travel varies greatly. In this study, we collected data on cases of food-borne diseases between the years 2011 and 2020 in Taiwan to access the epidemiological features, differences, and trends in domestic and imported cases of typhoid and paratyphoid in terms of patient sex, age, month of confirmation, and area of residence. In this study, we made use of the open data website provided by Taiwan's Centers for Disease Control (TCDC) to extract the reported numbers of cases of typhoid and paratyphoid between January and December from 2011 to 2020 for comparison. Univariate analysis was performed using the Chi-square test for categorical variables. Fisher's exact test was performed if an expected frequency was less than 5. A total of 226 typhoid cases and 61 paratyphoid cases were analyzed from the database. The incidences of typhoid and paratyphoid per million of the population were 0.42-2.11 and 0-0.39, respectively. There was a significant difference in the incidence of the diseases between the age groups (p = 0.019), with a gradual increase in the 20-40 years group. A distinct seasonal (between fall and spring) variation was also observed (p = 0.012). There were 34 cases of children with typhoid in the period 2011-2015 and 12 cases of children with typhoid in the period 2016-2020. During these periods, there were two cases of paratyphoid. This study indicated that the risk of children suffering from typhoid has been significantly reduced in the last five years. Furthermore, we found that more women have acquired typhoid and paratyphoid than men, and that living in the Taipei metropolitan area and the northern area was a potential risk factor. Furthermore, the number of imported cases of typhoid (n = 3) and paratyphoid (n = 0) reported during the COVID-19 pandemic was lower than that reported for the same disease from 2011 to 2020. More typhoid and paratyphoid cases were imported from Indonesia, India, Myanmar, and Cambodia. This study represents the first report on confirmed cases of acquired typhoid and paratyphoid from surveillance data from Taiwan's CDC for the period 2011-2020. This study also demonstrates that the cases of typhoid and paratyphoid decreased in Taiwan during the COVID pandemic. Big data were used in this study, which may inform future surveillance and research efforts in Taiwan.

Incidence and Characteristics of Co-infection and Secondary Infection in Patients with COVID-19 (preprint)

ObjectiveThe etiology and epidemiology of co-infection and secondary infection in COVID-19 patients remain unknown. The study aims to investigate the occurrence and characteristics of co-infection and secondary infection in COVID-19 patients, mainly focusing on Streptococcus pneumoniae co-infections. MethodsThis study was a prospective, observational cohort study of the inpatients diagnosed with COVID-19 in two designated hospitals in south China enrolled between Jan 11 and Feb 22, 2020. The urine specimen was collected on admission and applied for pneumococcal urinary antigen tests (PUATs). Demographic, clinical and microbiological data of patients were recorded simultaneously. ResultA total of 146 patients with a confirm diagnosis of COVID-19 at the median age of 50.0 years (IQR 36.0-61.0) were enrolled, in which, 16 (11.0%) were classified as severe cases and 130 (89.0%) as non-severe cases. Of the enrolled patients, only 3 (2.1%) were considered to present the co-infection, in which 1 was co-infected with S.pneumoniae, 1 with B. Ovatus infection and the other one with Influenza A virus infection. Secondary infection occurred in 16 patients, with S. maltophilia as the most commonly isolated pathogen (43.8%), followed by P. aeruginosa (25.0%), E. aerogenes (25.0%), C. parapsilosis (25.0%) and A. fumigates (18.8%). ConclusionPatients with confirmed COVID-19 were rarely co-infected with Streptococcus pneumoniae or other pathogens, indicating that the application of antibiotics against CAP on admission may not be necessary in the treatment of COVID-19 cases.

Renal dysfunction and prognosis of COVID-19 patients: a hospital-based retrospective cohort study (preprint)

Introduction: Increasing evidence indicate that coronavirus disease 2019 (COVID-19) is companied by renal dysfunction. However, the association of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)-induced renal dysfunction with prognosis remains unclear.Materials and methods: This prospective case-cohort study analyzed 154 COVID-19 patients from the Second People’s Hospital of Fuyang City in Anhui Province. Clinical and demographic information were collected. Renal function was evaluated and its prognosis was followed up. Results: Of 154 hospitalized patients with COVID-19, 125 were common and 29 were severe patients. On admission, 16 (10.4%) patients were with renal dysfunction. Serum creatinine and cystatin C were increased, eGFR was decreased in severe patients compared with those in common patients. Renal dysfunction was more common in severe patients. By multivariate logistic regression, male, higher age and hypertension were three importantly independent risk factors of renal dysfunction in COVID-19 patients. Follow-up study found that at least one renal function marker of 3.33% patients remained abnormal in two weeks after discharge. Conclusion: Male elderly COVID-19 patients with hypertension elevates the risk of renal dysfunction. SARS-CoV-2-induced renal dysfunction are not fully recovered in two weeks after discharge.

Myocardial Injury at Early Stage and Its Association with Death Risk of Patients with COVID-19: A Hospital-Based Prospective Case-Cohort Study (preprint)

Background: There are growing evidence demonstrating that coronavirus disease 2019 (COVID-19) is companied by acute myocardial injury. However, the association of SARS-CoV-2-induced myocardial injury with death risk of COVID-19 is unclear.Methods: This prospective case-cohort study analyzed 355 COVID-19 patients from two hospitals in different regions. Clinical and demographic information were collected. Myocardial injury was evaluated and its prognosis was followed up. Results: Of 355 hospitalized patients with COVID-19, 213 were mild, 90 severe and 52 critically ill patients. On admission, 220 (62.0%) patients were with myocardial injury. Myocardial injury was more popular in critically ill patients. Using multivariate logistic regression, male, older age and comorbidity with hypertension were three crucial independent risk factors predicting myocardial injury of COVID-19 patients. Among 220 COVID-19 patients with myocardial injury, 33 (15.0%) died on mean 10.9 day after hospitalization. Mortality was increased among COVID-19 patients with myocardial injury (15.0% vs 1.74%, RR=8.625, P<0.001). Follow-up study observed that at least one myocardial index of 21.3% patients remained abnormal 14 days after discharge. Conclusion: Myocardial injury at early stage elevates mortality of COVID-19 patients. Male elderly patients with hypertension are more vulnerable to myocardial injury. SARS-CoV-2-induced myocardial injury has not completely recovered 14 days after discharge.

Influence factors of death risk among COVID-19 patients in Wuhan, China: a hospital-based case-cohort study (preprint)

Background Coronavirus disease 2019 (COVID-19) triggered by infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been widely pandemic all over the world. The aim of this study was to analyze the influence factors of death risk among 200 COVID-19 patients.Methods Two hundred patients with confirmed SARS-CoV-2 infection were recruited. Demographic data and clinical characteristics were collected from electronic medical records. Biochemical indexes on admission were measured and patient's prognosis was tracked. The association of demographic data, clinical characteristics and biochemical indexes with death risk was analyzed.Results Of 200 COVID-19 patients, 163 (81.5%) had at least one of comorbidities. Among all patients, critical cases accounted for 26.2%. Severe cases were 29.7%. Besides, common cases accounted for 44.1%. At the end of follow-up, 34 (17%) were died on mean 10.9 day after hospitalization. Stratified analysis revealed that older ages, lower oxygenation index and comorbidities elevated death risk of COVID-19 patients. On admission, 85.5% COVID-19 patients were with at least one of extrapulmonary organ injuries. Univariable logistic regression showed that ALT, TBIL, AST, myoglobin and LDH, AST/ALT ratio, creatinine, urea nitrogen and uric acid were positively associated with death risk of COVID-19 patients. Multivariable logistic regression revealed that AST/ALT ratio, urea nitrogen, TBIL and LDH on admission were positively correlated with death risk of COVID-19 patients.Conclusion Older age, lower oxygenation index and comorbidities on admission elevate death risk of COVID-19 patients. AST/ALT ratio, urea nitrogen, TBIL and LDH on admission may be potential prognostic indicators.

Acute liver injury and its association with death risk of patients with COVID-19: a hospital-based prospective case-cohort study (preprint)

Background: Coronavirus disease 2019 (COVID-19) is a newly respiratory infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with multiple organ injuries. The aim of this study was to analyze SARS-CoV-2-induced acute liver injury (ALI), its association with death risk and prognosis after discharge. Methods: Three-hundred and fifty-five COVID-19 patients were recruited. Clinical data were collected from electronic medical records. ALI was evaluated and its prognosis was tracked. The association between ALI and death risk was analyzed. Results: Of 355 COVID-19 patients, 211 were common, 88 severe, and 51 critical ill cases, respectively. On admission, 223 (62.8%) patients were with hypoproteinemia, 151(42.5%) with cholestasis, and 101 (28.5%) with hepatocellular injury. As expected, ALI was more common in critical ill patients. By multivariate logistic regression, male, older age and lymphocyte reduction were three important independent risk factors predicting ALI among COVID-19 patients. Death risk analysis shows that fatality rate was higher among patients with hypoproteinemia than those without hypoproteinemia (RR=9.471, P<0.001). Moreover, fatality rate was higher among patients with cholestasis than those without cholestasis (RR=2.182, P<0.05). Follow-up observation found that more than one hepatic functional indexes of two-third patients remained abnormal 14 days after discharge. Conclusions: ALI at early stage elevates death risk of COVID-19 patients. SARS-CoV-2-induced ALI has not recovered completely 14 days after discharge.

Reduction of lymphocyte at early stage elevates severity and death risk of COVID-19 patients: a hospital-based case-cohort study (preprint)

Background and objective: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced coronavirus disease 2019 (COVID-19) has been pandemic worldwide. Several reports observed a reduction of lymphocytes among COVID-19 patients. However, clinical significance of lymphocyte reduction in COVID-19 patients remains unclear. The objective of this study was to analyze the association between lymphocyte reduction at early stage and the prognosis of COVID-19 patients. Methods: All 192 hospitalized patients with COVID-19 were enrolled. Electronic medical records, including demographic data, clinical characteristics, comorbidities and exposure history, were collected. Biochemical indexes on admission and chest computed tomography (CT) were detected. Patient's prognosis was followed up. Results: On admission, 84 (43.8%) patients suffered from lymphocyte reduction among COVID-19 patients. The count and percentage of lymphocytes on admission were lower among more than seventy-year-old patients than those of younger patients. Multivariate logistic regression revealed that older age was a risk factor of lymphocyte reduction. Of interest, chest CT score, a key marker of lung injury, was increased among COVID-19 patients with lymphocyte reduction. By contrast, PaCO2, SpO2 and oxygenation index, several respiratory function markers, were decreased in COVID-19 patients with lymphocyte reduction. Moreover, TBIL and DBIL, two markers of hepatic injury, creatinine and urea nitrogen, two indices of renal function, and creatine kinase, AST and LDH, three myocardial enzymes, were elevated in COVID-19 patients with lymphocyte reduction. Among 84 COVID-19 patients with lymphocyte reduction, 32.1% died. Fatality rate was obviously higher in COVID-19 patients with lymphocyte reduction than those with normal lymphocyte (RR=5.789, P<0.001). Conclusion: Older COVID-19 patients are more susceptible to lymphocyte reduction. Lymphocyte reduction at early stage aggravates the severity of multiple organ injuries and elevates death risk of COVID-19 patients.

Acute kidney injury at early stage as a negative prognostic indicator of patients with COVID-19: a hospital-based retrospective analysis (preprint)

Coronavirus disease 2019 (COVID-19) is a newly emerged infection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has been pandemic all over the world. This study described acute kidney injury (AKI) at early stage of COVID-19 and its clinical significance. Three-hundred and fifty-five COVID-19 patients with were recruited and clinical data were collected from electronic medical records. Patient's prognosis was tracked and risk factors of AKI was analyzed. Of 355 COVID-19 patients, common, severe and critical ill cases accounted for 63.1%, 16.9% and 20.0%, respectively. On admission, 56 (15.8%) patients were with AKI. Although AKI was more common in critical ill patients with COVID-19, there was no significant association between oxygenation index and renal functional indices among COVID-19 patients with AKI. By multivariate logistic regression, male, older age and comorbidity with diabetes were three important independent risk factors predicting AKI among COVID-19 patients. Among 56 COVID-19 patients with AKI, 33.9% were died on mean 10.9 day after hospitalization. Fatality rate was obviously higher among COVID-+19 patients with AKI than those without AKI (RR=7.08, P<0.001). In conclusion, male elderly COVID-19 patients with diabetes are more susceptible to AKI. AKI at early stage may be a negative prognostic indicator for COVID-19.

Influence factors of death risk among COVID-19 patients in Wuhan, China: a hospital-based case-cohort study (preprint)

Background. Coronavirus disease 2019 (COVID-19) triggered by infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been widely pandemic all over the world. The aim of this study was to analyze the influence factors of death risk among 200 COVID-19 patients. Methods. Two hundred patients with confirmed SARS-CoV-2 infection were recruited. Demographic data and clinical characteristics were collected from electronic medical records. Biochemical indexes on admission were measured and patient's prognosis was tracked. The association of demographic data, clinical characteristics and biochemical indexes with death risk was analyzed. Results. Of 200 COVID-19 patients, 163 (81.5%) had at least one of comorbidities, including diabetes, hypertension, hepatic disease, cardiac disease, chronic pulmonary disease and others. Among all patients, critical cases, defined as oxygenation index lower than 200, accounted for 26.2%. Severe cases, oxygenation index from 200 to 300, were 29.7%. Besides, common cases, oxygenation index higher than 300, accounted for 44.1%. At the end of follow-up, 34 (17%) were died on mean 10.9 day after hospitalization. Stratified analysis revealed that older ages, lower oxygenation index and comorbidities elevated death risk of COVID-19 patients. On admission, 85.5% COVID-19 patients were with at least one of extrapulmonary organ injuries. Univariable logistic regression showed that ALT and TBIL, two indexes of hepatic injury, AST, myoglobin and LDH, AST/ALT ratio, several markers of myocardial injury, creatinine, urea nitrogen and uric acid, three indexes of renal injury, were positively associated with death risk of COVID-19 patients. Multivariable logistic regression revealed that AST/ALT ratio, urea nitrogen, TBIL and LDH on admission were positively correlated with death risk of COVID-19 patients. Conclusion. Older age, lower oxygenation index and comorbidities on admission elevate death risk of COVID-19 patients. AST/ALT ratio, urea nitrogen, TBIL and LDH on admission may be potential prognostic indicators. Early hospitalization is of great significance to prevent multiple organ damage and improve the survival of COVID-19 patients.