Dengue is a viral disease transmitted by mosquitoes that in recent years has spread rapidly across all continents. The dengue virus is transmitted by female mosquitoes, mainly of the Aedes aegypti species and, to a lesser extent, of the Aedes albopictus species. There are four distinct but closely related serotypes of the virus that causes dengue (DENV-1, DENV-2, DENV-3 and DENV-4). The present study evaluated and reviewd the temporal spreading and molecular evolution of dengue virus serotypes worldwide. A total of 1,581 dengue virus whole-genome sequences (WGSs) with available information from the country and sampling date (Jan/1944 – Jul/2022), were obtained. Bayesian coalescent analyses with dengue virus WGS were performed to study viral phylodynamic and phylogeography. The time of the Most Recent Common Ancestor (tMRCA) and 95% highest posterior density (HPD 95%) were estimated for each serotype. Bayes factor (BF) was determined to infer phylogeographic data. The results demonstrated that the tMRCA of DENV-1 was 1884-11-15 (HPD95%: 1882-01-28; 1890-08-27) in Southeast Asia, DENV-2 was 1723-01-29 (HPD95%: 1714-05-22; 1728-10-09) in Europe, DENV-3 was 1921-04-12 (HPD95%: 1918-05-25; 1924-03-13) in Southeast Asia, and DENV-4 was 1876-03-28 (HPD95%: 1865-08-02; 1899-08-27) in Southeast Asia. The molecular origin of the dengue virus was in Spain in 1682 (BF=38), later it was disseminated in Asia (Indonesia; BF=15) and Oceania (Papua New Guinea, BF=13) in 1847. After this period, the virus presented dissemination in Asia (Malaysia, BF=13; India, BF=28; and China BF=30) and in North America (USA; BF=35) in 1890. In South America, it was first disseminated to Ecuador in 1897 (BF=15) and then to Brazil in 1910 (BF=38). During this same period there were disseminations to countries such as Puerto Rico (BF=18) and to the African continent (Senegal; BF=14). After this period, the virus was widely disseminated, especially in the American and Asian continents. The dengue disease has had a significant impact on global health worldwide and the present study provides an overview of the molecular evolution of dengue virus serotypes (from 1944 to 2022).

Aims of the study: To investigate the effect of clinical predictors on admission and the set of therapeutic interventions on length of stay, ICU admission, need for MV and mortality. Methods used to conduct the study: Retrospective cohort of inpatients with RT-PCR positive for COVID-19 from March to July 2020. Multivariate models were used to assess risk for ICU admission, need for MV and hospital mortality. Logistic regression analysis was conducted to examine factors associated with the results. Results of the study: 459 patients were enrolled (median age 60.0 years old). For patients treated with AZM-Corticosteroid (46.8%) the risk for ICU admission was 0.17 (OR; 95%CI 0.05-0.57), for MV 0.16 (OR; 95%CI 0.04-0.74) and for mortality 0.16 (OR; 95%CI 0.03-0.91). AZM-Corticosteroid also decreased the length of stay in 1.5 day. AZM-Corticosteroid and anticoagulation when indicated (17.2%), also reduced the ICU stay in 1.5 and MV in 4 days. When included HCQ, the benefits were lost and the times increased. Age >65 years, presence of up one comorbidity, pulmonary involvement more than or equal to 50%, saturation <93%, lymphocytes <900 mm3, D-dimers >1,250 ng/mL and CRP >8.0 mg/dL at admission were clinical predictors for death. HFNC was able to prevent intubation by 38.1%. Conclusion drawn from the study and clinical implications: AZM-Corticosteroids and anticoagulation represented a favorable combination for inpatients with COVID-19, reducing length of hospitalization, risk of MV and mortality. HCQ did not yield benefits to combination therapy and we do not support its use for inpatients. HFNC was able to prevent intubation in one third of patients. Already on admission some clinical predictors may help to estimate a higher risk of poor evolution.