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Background: Monitoring of blood pressure is an important part of management of dengue illness. Large scale studies of temporal trend of blood pressure in adult dengue are lacking. In this study, we examined the differences in time trend of systolic (SBP) and diastolic blood pressure (DBP) in patients with and without severe dengue (SD), dengue hemorrhagic fever (DHF) and pre-existing hypertension, and elderly versus non-elderly patients. Methods: We studied a retrospective cohort from 2005 to 2008 of 6,070 hospitalized adult dengue patients confirmed by polymerase chain reaction or clinical criteria plus positive dengue serology. Dengue severity was defined according to World Health Organization 1997 and 2009 guidelines. We used Bayesian hierarchical Markov models to compare the daily mean SBP and DBP between different subgroups. Analysis was conducted by day of defervescence (denoted as day 0), and day of illness onset (denoted as day 1) respectively. Results: SBP decreased to a nadir during the critical phase before defervescence and was significantly lower for patients with SD or DHF, compared with patients without SD or DHF. DBP increased marginally more for patients with SD or DHF in the critical phase before defervescence. By day of defervescence, comparison of patients with and without SD showed significant difference in SBP from day -6 to day +6, except days +1, +3 and +5, and similarly in DBP except days 0, and +4 to +6. Comparison of patients with and without DHF showed significant difference in SBP from day -6 to day -1, but for DBP, significant difference was noted from day -6 to day +6, except day -2 to day 0. By day of illness, SBP differed significantly between patients with and without SD from illness days 1 to 10, and DBP from illness days 7 to 12. Between patients with and without DHF, SBP differed significantly on illness days 1, 2, 4 to 7, while DBP from days 7 to 12. On analysis by days of defervescence or by days of illness, elderly patients and those with hypertension showed consistently higher SBP and DBP throughout their hospitalization, as compared with their younger and non-hypertensive counterparts. Conclusion: In SD or DHF, SBP decreased to a nadir around the day of defervescence, and recovered to a level exceeding that in febrile phase by days 2 or 3 post-defervescence. Elderly patients and patients with pre-existing hypertension maintained higher SBP and DBP throughout the duration of dengue infection. [ABSTRACT FROM AUTHOR]

Background While persistence of chronic symptoms following dengue infection has been documented in small prospective cohorts, population-based studies are limited. The post-acute risk of new-incident multi-systemic complications following dengue infection was contrasted against that following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a multi-ethnic adult Asian population. Methods National testing and healthcare claims that databases in Singapore were utilized to build a retrospective population-based adult cohort with laboratory-confirmed infection during overlapping waves of SARS-CoV-2 and dengue transmission (1 July 2021 to 31 October 2022). Risks of new-incident cardiovascular/neuropsychiatric/autoimmune complications 31–300 days of post-dengue infection, contrasted with SARS-CoV-2 infection, were estimated using Cox regression with overlap weights. Risks were reported in terms of adjusted hazard ratio (aHR) and excess burden per 1000 persons. Results 11 707 dengue-infected individuals and 1 248 326 contemporaneous coronavirus disease 2019 (COVID-19) cases were included; the majority had mild initial infection not requiring hospitalization. Amongst dengue-infected individuals, there was 21% [aHR = 1.21 (1.06–1.38)] increased risk of any sequelae, with 55% [aHR = 1.55 (1.27–1.89)] increased risk of cardiovascular sequelae. Specifically, increased risk of dysrhythmias [aHR = 1.79(1.35–2.37)], ischemic heart disease [aHR = 1.45(1.12–1.89)], other cardiac disorders [aHR = 2.21(1.54–3.16)] and thrombotic disorders [aHR = 2.55(1.50–4.35)] was noted. Elevated risk of individual neuropsychiatric sequelae, including cerebrovascular disorders [aHR = 1.49(1.09–2.13)], cognition/memory disorders [aHR = 2.13(1.55–2.93)], extrapyramidal/movement disorders [aHR = 1.98(1.33–2.94)] and anxiety disorders [aHR = 1.61(1.01–2.56)], was observed in dengue-infected individuals compared to COVID-19 cases. Elevated risks of post-acute sequelae in dengue survivors were observed when contrasted against COVID-19 survivors infected during Delta/Omicron predominance, as well as across vaccination strata. Conclusion Increased risk of post-acute cardiovascular/neuropsychiatric complications was observed in dengue survivors, when contrasted against COVID-19 survivors infected during Delta/Omicron predominance. Research in context Evidence before this study Post-acute sequelae following SARS-CoV-2 infection has been extensively reported; however, long-term sequelae may also occur after other acute infections, such as dengue. While chronic symptom persistence has been reported in small cohorts of dengue survivors, population-based cohort studies are lacking, given dengue's disproportionate burden in tropical low-and-middle-income countries (LMICs) where access to diagnostic testing and follow-up is limited. We searched PubMed for studies published until 1 March 2024, using search terms 'dengue', 'chronic', 'long term', "with search terms found in abstract, title or MESH headings. Current research on post-acute sequelae following dengue is limited to small prospectively recruited cohorts, impairing generalizability to the population at-large. We only found four population-based retrospective cohort studies from a single country, Taiwan, which examined long-term risk of a limited set of autoimmune and cognitive sequelae following dengue infection. Evidence for post-acute sequelae was mixed, particularly when milder non-hospitalized cases were included. There are no reports on the risk of post-acute sequelae across multiple organ systems following dengue infection, and no reports contrasting the risk of post-acute sequelae in dengue versus SARS-CoV-2 infection. Added value of this study National testing and healthcare claims that databases in Singapore were utilized to build a retrospective population-based adult cohort of laboratory-confirmed dengue and SARS-CoV-2 infections during overlapping waves of COVID-19/dengue transmission. Increased overall risk of any post-acute sequelae and individual cardiovascular/neurological sequelae in dengue-infected adults was observed up to 300 days postinfection, compared against COVID-19 cases infected during Delta/Omicron predominance. While other studies have compared the risk of post-acute sequelae across different respiratory viral infections, such as influenza and SARS-CoV-2, to the best of our knowledge no prior studies have contrasted the potential risks of post-acute sequelae following dengue with that arising after SARS-CoV-2 infection. Implication of all the available evidence Risk of chronic multi-systemic sequelae arising post-dengue infection was significantly elevated when contrasted against post-acute sequelae following COVID-19. Post-acute sequelae may increase the burden of disease attributable to dengue in tropical countries where seasonal outbreaks occur; this is increasingly relevant, given that climate change has broadened the list of countries at risk of dengue endemicity. [ABSTRACT FROM AUTHOR]

This article discusses a case study of a previously healthy young male who developed large vessel vasculopathy and recurrent thrombosis after recovering from COVID-19. The patient presented with acute limb pain and was found to have hypercoagulability and evidence of chronic endothelial dysfunction. Radiological and histopathological evidence showed damage to the arterial walls and thrombosis. The study suggests that persistent endothelial dysfunction and hypercoagulability may contribute to post-COVID-19 thrombosis, and further research is needed to understand the mechanisms and identify effective treatments. [Extracted from the article]

Studies have reported increased rates of long-term neuropsychiatric sequelae after SARS-CoV-2 infection using electronic health-record (EHR) data; however, the majority were conducted before Omicron and booster rollout. We estimated the long-term risks and excess burdens of pre–specified new-incident neuropsychiatric diagnoses after Delta versus Omicron BA.1/2 infection in a highly-vaccinated and boosted cohort of adult Singaporeans. The national SARS-CoV-2 testing registry was used to construct cohorts of Singaporean adults infected during periods of Delta and Omicron BA.1/2 predominance and a contemporaneous test-negative control group. New-incident neuropsychiatric diagnoses recorded in the national health care claims database were identified up to 300 days postinfection. Risks and excess burden were estimated using a doubly robust competing-risks survival analysis. 104 179 and 375 903 infected cases were assigned to Delta and Omicron cohorts and compared against test-negative controls (Delta: N = 666 575 and Omicron: N = 619 379). Elevated risk of cognition or memory disorders was consistently reported across Omicron (Adjusted hazards ratio [aHR], 1.24; 95% CI, 1.12–1.38) and Delta cohorts (aHR, 1.63; 95% CI, 1.39–1.92). Delta-variant infection was associated with an increased risk of anosmia or dysgeusia (aHR, 4.53; 95% CI, 2.78–7.41) and psychosis (aHR, 1.65; 95% CI, 1.22–2.22). By contrast, Omicron-variant infection was associated with a risk of abnormal involuntary movements (aHR, 1.93; 95% CI, 1.32–2.83). Risks of neuropsychiatric sequelae predominantly accrued in hospitalized individuals. A modestly increased risk of cognition and memory disorders at 300 days after SARS-CoV-2 infection was observed among adult Singaporeans infected during the Delta/Omicron BA.1/2 transmission. There was no overall increased risk of neuropsychiatric sequelae observed across other domains. Variant-specific differences were also observed in individual neuropsychiatric sequelae, including an elevated risk of anosmia or dysgeusia after Delta-variant infection. [ABSTRACT FROM AUTHOR]

Background Growing evidence suggests that some coronavirus disease 2019 (COVID-19) survivors experience a wide range of long-term postacute sequelae. We examined the postacute risk and burden of new-incident cardiovascular, cerebrovascular, and other thrombotic complications after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a highly vaccinated multiethnic Southeast Asian population, during Delta predominance. Methods This cohort study used national testing and healthcare claims databases in Singapore to build a cohort of individuals who had a positive SARS-CoV-2 test between 1 September and 30 November 2021 when Delta predominated community transmission. Concurrently, we constructed a test-negative control group by enrolling individuals between 13 April 2020 and 31 December 2022 with no evidence of SARS-CoV-2 infection. Participants in both groups were followed up for a median of 300 days. We estimated risks of new-incident cardiovascular, cerebrovascular, and other thrombotic complications using doubly robust competing-risks survival analysis. Risks were reported using 2 measures: hazard ratio (HR) and excess burden (EB) with 95% confidence intervals. Results We included 106 012 infected cases and 1 684 085 test-negative controls. Compared with the control group, individuals with COVID-19 exhibited increased risk (HR, 1.157 [1.069–1.252]) and excess burden (EB, 0.70 [.53–.88]) of new-incident cardiovascular and cerebrovascular complications. Risks decreased in a graded fashion for fully vaccinated (HR, 1.11 [1.02–1.22]) and boosted (HR, 1.10 [.92–1.32]) individuals. Conversely, risks and burdens of subsequent cardiovascular/cerebrovascular complications increased for hospitalized and severe COVID-19 cases (compared to nonhospitalized cases). Conclusions Increased risks and excess burdens of new-incident cardiovascular/cerebrovascular complications were reported among infected individuals; risks can be attenuated with vaccination and boosting. [ABSTRACT FROM AUTHOR]

The novel coronavirus disease 2019 (COVID-19) presents with non-specific clinical features. This may result in misdiagnosis or delayed diagnosis, and lead to further transmission in the community. We aimed to derive early predictors to differentiate COVID-19 from influenza and dengue. The study comprised 126 patients with COVID-19, 171 with influenza and 180 with dengue, who presented within 5 days of symptom onset. All cases were confirmed by reverse transcriptase polymerase chain reaction tests. We used logistic regression models to identify demographics, clinical characteristics and laboratory markers in classifying COVID-19 versus influenza, and COVID-19 versus dengue. The performance of each model was evaluated using receiver operating characteristic (ROC) curves. Shortness of breath was the strongest predictor in the models for differentiating between COVID-19 and influenza, followed by diarrhoea. Higher lymphocyte count was predictive of COVID-19 versus influenza and versus dengue. In the model for differentiating between COVID-19 and dengue, patients with cough and higher platelet count were at increased odds of COVID-19, while headache, joint pain, skin rash and vomiting/nausea were indicative of dengue. The cross-validated area under the ROC curve for all four models was above 0.85. Clinical features and simple laboratory markers for differentiating COVID-19 from influenza and dengue are identified in this study which can be used by primary care physicians in resource limited settings to determine if further investigations or referrals would be required. [ABSTRACT FROM AUTHOR]

Objective: The use of coronavirus disease 2019 (COVID‐19) serological testing to diagnose acute infection or determine population seroprevalence relies on understanding assay accuracy during early infection. We aimed to evaluate the diagnostic performance of serological testing in COVID‐19 by providing summary sensitivity and specificity estimates with time from symptom onset. Methods: A systematic search of Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and PubMed was performed up to May 13, 2020. All English language, original peer‐reviewed publications reporting the diagnostic performance of serological testing vis‐à‐vis virologically confirmed SARS‐CoV‐2 infection were included. Results: Our search yielded 599 unique publications. A total of 39 publications reporting 11 516 samples from 8872 human participants met eligibility criteria for inclusion in our study. Pooled percentages of IgM and IgG seroconversion by Day 7, 14, 21, 28 and after Day 28 were 37.5%, 73.3%, 81.3%, 72.3% and 73.3%, and 35.4%, 80.6%, 93.3%, 84.4% and 98.9%, respectively. By Day 21, summary estimate of IgM sensitivity was 0.872 (95% CI: 0.784‐0.928) and specificity 0.973 (95% CI: 0.938‐0.988), while IgG sensitivity was 0.913 (95% CI: 0.823‐0.959) and specificity 0.960 (95% CI: 0.919‐0.980). On meta‐regression, IgM and IgG test accuracy was significantly higher at Day 14 using enzyme‐linked immunosorbent assay (ELISA) compared to other methods. Conclusions: Serological assays offer imperfect sensitivity for the diagnosis of acute SARS‐CoV‐2 infection. Estimates of population seroprevalence during or shortly after an outbreak will need to adjust for the delay between infection, symptom onset and seroconversion. [ABSTRACT FROM AUTHOR]

Background: The anti-retroviral combination of abacavir/lamivudine plus rilpivirine (ABC/3TC/RPV) is not recommended by international guidelines as the first-line regimen. However, it is potent, well-tolerated, and affordable, especially in resource-limited settings. This study evaluates the efficacy and safety of ABC/3TC/RPV as an initial regimen for treatment-naïve HIV-1 infected patients. Methods: A retrospective study was conducted in the largest HIV care centre in Singapore, with data collected June 2011 to September 2017. All treatment-naïve HIV-1 infected adults prescribed ABC/3TC as part of their initial anti-retroviral therapy regimen were included. The third drug was a non-nucleoside reverse-transcriptase inhibitor (NNRTI) such as RPV or efavirenz (EFV), or boosted protease-inhibitor (PI). Patients were followed up for 48 weeks. The primary end-point was the percentage of patients achieving virologic suppression, analysed using on-treatment analysis. Secondary outcomes included CD4-count change, treatment discontinuation and treatment-related adverse events. Results: 170 patients were included in the study, 66 patients in the RPV group, 104 patients in the comparator group (EFV or boosted PI). 96% (n = 24) in the RPV group and 87% (n = 26) in the comparator group achieved viral suppression at 48 weeks (p = 0.28). Median (interquartile range) time to viral suppression was similar: 17 (14–24) weeks in the RPV group, and 21 (13–26) weeks in the comparator group. There were no statistically significant differences in the CD4 count between the two groups. 14% (n = 9) of patients on RPV discontinued treatment before 48 weeks, compared to 30% (n = 31) from the comparator group (p = 0.053). Of these, 23 discontinuations were due to drug adverse effects, and only 1 attributed to RPV (p < 0.01). One patient in each group had virologic failure. Conclusion: RPV is effective, safe and considerably more tolerable than compared to NNRTI or boosted PI in ABC/3TC-containing regimens for treatment-naïve patients. It offers an affordable and attractive option, especially in resource-limited settings. [ABSTRACT FROM AUTHOR]

Dengue is endemic in Singapore but not China. We compared clinical features and disease severity of dengue between local and migrant Chinese, most of whom were construction workers, in Singapore. A retrospective study with all hospitalized dengue patients from 2005 to 2008 were performed, including 2609 local and 1195 migrant Chinese. Compared with local Chinese, migrant Chinese were younger. There were more males, but fewer had comorbidities. Migrant Chinese had more headache, eye pain, nausea and myalgia. They had significantly lower median leukocyte count, ALT and AST, and higher platelet count nadir. Among warning signs, migrant Chinese had significantly less persistent vomiting, clinical fluid accumulation, hepatomegaly, hematocrit rise with rapid platelet drop, and more mucosal bleeding. Adjusted for age, gender and comorbidities, migrant Chinese were significantly at higher risk of dengue hemorrhagic fever (DHF) (adjusted odds ratio [aOR]: 1.20, 95% confidence interval [CI]: 1.03–1.41) and dengue shock syndrome (aOR: 1.49, 95% CI: 1.06–2.10), and had longer hospitalization (β coefficient value: 0.27, 95%CI: 0.09–0.44, p = 0.003). There was 1 death among migrant Chinese and 2 deaths among local Chinese. We documented differences in clinical and laboratory features, and dengue severity between local and migrant Chinese in Singapore. Migrant Chinese may need more medical attention given higher risk of DHF. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

• In hospitalized older adults with COVID-19, geriatric syndromes are not uncommon. • Frailty and initial acuity are important predictors of COVID-19 disease severity. • CFS and FI are complementary in predicting disease progression in COVID-19. Older adults with COVID-19 have disproportionately higher rates of severe disease and mortality. It is unclear whether this is attributable to age or attendant age-associated risk factors. This retrospective cohort study aims to characterize hospitalized older adults and examine if comorbidities, frailty and acuity of clinical presentation exert an age-independent effect on COVID-19 severity. We studied 275 patients admitted to the National Centre of Infectious Disease, Singapore. We measured: 1)Charlson Comorbidity Index(CCI) as burden of comorbidities; 2)Clinical Frailty Scale(CFS) and Frailty Index(FI); and 3)initial acuity. We studied characteristics and outcomes of critical illness, stratified by age groups (50–59,60–69 and ≥70). We conducted hierarchical logistic regression in primary model(N = 262, excluding direct admissions to intensive care unit) and sensitivity analysis(N = 275): age and gender in base model, entering CCI, frailty (CFS or FI) and initial acuity sequentially. The ≥70 age group had highest CCI(p <.001), FI(p <.001) and CFS(p <.001), and prevalence of geriatric syndromes (polypharmacy,53.5%; urinary symptoms,37.5%; chronic pain,23.3% and malnutrition,23.3%). Thirty-two (11.6%) developed critical illness. In the primary regression model, age was not predictive for critical illness when a frailty predictor was added. Significant predictors in the final model (AUC 0.809) included male gender (p =.012), CFS (p =.038), and high initial acuity (p =.021) but not CCI or FI. In sensitivity analysis, FI (p =.028) but not CFS was significant. In hospitalized older adults with COVID-19, geriatric syndromes are not uncommon. Acuity of clinical presentation and frailty are important age-independent predictors of disease severity. CFS and FI provide complimentary information in predicting interval disease progression and rapid disease progression respectively. [ABSTRACT FROM AUTHOR]

Multiple in vitro and mice model studies suggest statins may attenuate dengue severity. However, little is known about statin use and dengue severity in adult dengue patients with hyperlipidemia. We conducted a retrospective cohort study from 2004-2008 and 2012-2013 in Tan Tock Seng Hospital, Singapore on adult dengue patients with hyperlipidemia, comparing those with and without statin usage at hospitalization in terms of primary outcome of dengue hemorrhagic fever (DHF) or shock syndrome (DSS), and severe dengue (SD). Of 13,975 subjects screened, 257 dengue patients were included; 191 (74.3%) were statin users and 66 (25.7%) were non-users. Compared with non-users, statin use was not associated with decreased risk of DHF/DSS (adjusted risk ratio [aRR] = 0.66, 95%confidence interval [CI]: 0.41-1.08, P = 0.10) and SD (aRR = 1.43, 95%CI: 0.84-2.43, P = 0.19). Therefore, statin usage had minimal effect on dengue severity in our study population in Singapore. [ABSTRACT FROM AUTHOR]

Plasma leakage is a major pathogenic mechanism of severe dengue, but the etiology remains unclear. The association between endothelial glycocalyx integrity and vascular permeability in older adults with dengue has not been evaluated. A prospective cohort study of adults with undifferentiated fever screened for dengue by RT-PCR or NS1 antigen testing was performed. Patients were assessed daily while symptomatic and at convalescence. Serum hyaluronic acid (HA), heparan sulfate (HS) and selected cytokines (TNF-α, IL-6, IL-10) were measured on enrollment and convalescence. Patients were diagnosed as dengue fever (DF, n = 30), dengue hemorrhagic fever (DHF, n = 20) and non-dengue (ND) febrile illness (n = 11). Acute HA and HS levels were significantly higher in all dengue patients compared to ND (p = 0.0033 and p = 0.0441 respectively), but not different between DF and DHF (p = 0.3426 and p = 0.9180 respectively). Enrolment HA inversely correlated with serum albumin, protein and platelets in all dengue and DHF (p < 0.05). HA and HS in all dengue patients decreased significantly at convalescence. Serum IL-10 was significantly associated with HA in all dengue patients (p = 0.002). Serum HA and HS levels were increased in adult dengue and HA was associated with markers of disease severity. Endothelial glycocalyx damage may have a role in vascular leakage in dengue. [ABSTRACT FROM AUTHOR]