The present study aimed at exploring whether sunlight exposure might account for the relative difference in COVID-19-related morbidity and mortality between tropical and non-tropical countries. A retrospective observational study was designed and data from the World Health Organization weekly COVID-19 epidemiological update was compiled. We examined the total number of confirmed COVID-19 cases per 100 000 population, as well as the total number of COVID-19-related mortalities per 100 000 population. Solar variables data were obtained from the Global Solar Atlas website (https://globalsolaratlas.info/). These data were analyzed to determine the association of sunlight exposure to COVID-19-related morbidity and mortality in tropical and non-tropical countries. Results revealed a statistically significant decrease in the number of confirmed COVID-19 cases per 100 000 population (P<0.001), as well as the number of COVID-19-related mortalities per 100 000 population (P<0.001) between tropical and non-tropical countries. Analyses of sunlight exposure data found that specific photovoltaic power output, global horizontal irradiation, diffuse horizontal irradiation and global tilted irradiation at optimum angle were significantly inversely correlated to COVID-19-related morbidity and mortality. This suggests that stronger sunlight exposure potentially leads to lower COVID-19-related morbidity and mortality. Findings from this study suggest that the relatively low COVID-19-related morbidity and mortality in tropical countries were possibly due to better sunlight exposure that translates into adequate vitamin D status.

Dengue is a mosquito-transmitted infection endemic in tropical and subtropical locations of the world where nearly half of the world’s population resides. The disease may present as mild febrile illness to severe and can even be fatal if untreated. There are four genetically related but antigenically distinct dengue virus (DENV) serotypes. Immune responses to DENV infection are in general protective but under certain conditions, they can also aggravate the disease. The importance of the cellular immune responses and the antibody responses involving IgG and IgM has been well-studied. In contrast, not much has been described on the potential role of hypersensitivity reactions involving IgE in dengue. Several studies have shown elevated levels of IgE in patients with dengue fever, but its involvement in the immune response against the virus and disease is unknown. Activation of mast cells (MCs) and basophils mediated through dengue-specific IgE could result in the release of mediators affecting dengue virus infection. The present review explores the relationships between the induction of IgE in dengue virus infection, and the potential role of MCs and basophils, exploring both protective and pathogenic aspects, including antibody-dependent enhancement (ADE) of infection in dengue.

Nipah virus (NiV), a highly pathogenic henipavirus of the family Paramyxoviridae, which causes fatal encephalitis in 40-70% of affected patients, was first reported in Malaysia over 20 years ago. Pteropid bats are the natural hosts of henipaviruses, and ticks have been proposed as a possible link between bats and mammalian hosts. To investigate this hypothesis, infection of the tick cell line IDE8 with NiV was examined. Presence of viral RNA and antigen in the NiV-infected tick cells was confirmed. Infectious virions were recovered from NiV-infected tick cells and ultrastructural features of NiV were observed by electron microscopy. These results suggest that ticks could support NiV infection, potentially playing a role in transmission.

The Plasmodium knowlesi secreted protein with an altered thrombospondin repeat (PkSPATR) is an important protein that helps in the parasite’s invasion into the host cell. This protein has been regarded as one of the potential vaccine candidates against P. knowlesi infection. This study investigates the genetic diversity and natural selection of PkSPATR gene of P. knowlesi clinical isolates from Malaysia. PCR amplification of the full length PkSPATR gene was performed on 60 blood samples of infected P. knowlesi patients from Peninsular Malaysia and Malaysian Borneo. The amplified PCR products were cloned and sequenced. Sequence analysis of PkSPATR from Malaysia showed higher nucleotide diversity (CDS p: 0.01462) than previously reported Plasmodium vivax PvSPATR (p = 0.0003). PkSPATR from Peninsular Malaysia was observed to have slightly higher diversity (CDS p: 0.01307) than those from Malaysian Borneo (CDS p: 0.01212). Natural selection analysis on PkSPATR indicated significant purifying selection. Multiple amino acid sequence alignment revealed 69 polymorphic sites. The phylogenetic tree and haplotype network did not show any distinct clustering of PkSPATR. The low genetic diversity level, natural selection and absence of clustering implied functional constrains of the PkSPATR protein.

Introduction: Prematurity-related respiratory disorders are an important public health concern that should be treated efficiently and effectively. Antenatal corticosteroid (ACS) therapy has been recommended to hasten fetal lung maturation in pregnancies at risk but has not been delivered adequately in low to middle-income countries. This study aimed to estimate the treatment effects associated with the use of a single-dose antenatal corticosteroid on the incidence of respiratory-associated morbidity among prematurely delivered neonates. Methods: This was a retrospective cohort study of neonates delivered at 24 to 33 weeks gestation at a tertiary hospital comparing outcomes in those given single-dose ACS with those given no ACS. Association was estimated using logistic and propensity score (PS) analyses, as well as average treatment effect (ATE) and among those treated (ATET). Results: Most neonates (78.11%) received a single dose before delivery (single-dose ACS group) and only a few (21.89%) did not receive any dose (no ACS dose group). The odds ratio of respiratory morbidity in the single-dose ACS group was 0.44 (0.23-0.84) from an adjusted logistic regression model and 0.33 (0.17-0.80) from the PS matching model. The latter model was used to estimate that the average treatment effect from a single-ACS dose on the entire sample was -0.09 (-0.03 to -0.15), while its effect among the actual recipients was -0.08 (-0.02 to -0.15). Conclusion There is a small benefit attributed to the single-dose ACS, reinforcing the need for dose administration and completion. Future studies are recommended to clarify the estimated association and improve on the methodological constraints encountered.
Morbidity ; Propensity Score

Introduction: Despite the growing popularity of utilizing observational studies for determining associations with public health implications, there is limited literature using them for examining and quantifying the effects of exposures or treatments: The study compared traditional regression with scoring approaches in estimating treatment effects considering the noted limitations in the dataset. Methods: We conducted a secondary analysis of previously collected retrospective cohort data derived from maternal-neonatal dyads delivered prematurely in a tertiary hospital. Propensity scores (PS) were estimated using logistic and boosting regression. These scores were implemented into matching, stratification, and weighting models. The estimated measures of effect from traditional regression and PS-adjusted models were compared using certain metrics (i.e., the width of CI, SE, AIC, BIC). Sensitivity analysis was also performed. Results: We included data from 562 patients (123 untreated and 439 treated). Both the estimated scores demonstrated satisfactory fit and reduction in the standardized differences between the groups. However, the logit-estimated scores had better prediction (AUC: 0.71 vs 0.66) and forecasting properties (Brier: 0.15 vs 0.17) than the boosting-estimated scores. All generated statistical models demonstrated a reduction in the occurrence of respiratory morbidity among preterm neonates exposed to a single-dose antenatal corticosteroid (ACS) (ORs ranged from 0.37 to 0.59). The estimated average treatment effects (ATE) and effect among those treated (ATET) from various models suggested a small benefit attributed to the single-dose ACS (ATEs range from -0.09 to -0.41; ATETs range from -0.07 to -0.17). Conclusion PS estimated using logistic regression performed better than those estimated using machine learning strategies. The matching model using the said scores demonstrated better fit and parsimony over conventional and propensity-adjusted models. Future studies are recommended to improve the application of these analytic techniques in real-world data.
Propensity Score ; Machine Learning ; Logistic Models

Background: The cause of end-organ damage and acute respiratory distress syndrome (ARDS) in coronavirus disease 2019 (COVID-19) patients is postulated to be connected to the uncontrolled increase of pro-inflammatory cytokines. The upregulation of many cytokines is dependent on signaling through the Janus kinase 1 (JAK-1) and JAK-2 pathways. Ruxolitinib, a JAK-1 and JAK-2 inhibitor, is documented to have potent anti-inflammatory activity by targeting several cytokines and growth factors with proposed efficacy in the cytokine storm observed in severe COVID-19 patients; therefore, this study examines the efficacy and tolerability of ruxolitinib for adult COVID-19 patients. Materials and Methods: This review was conducted using preferred reporting items for aystematic reviews and meta-analyses (PRISMA) methodology. Six reviewers analyzed 1,120 results. Seven studies were selected and validated. A quantitative meta-analysis was further performed to evaluate clinical improvement at day 28, mortality at day 28, and oxygen requirements comparing treatment and standard of care groups. Results: 168 individuals were involved in the studies selected: 122 in cohort studies, 4 in case reports, and 41 in randomized controlled studies. The ruxolitinib group had a higher likelihood of clinical improvement by the 28th day of treatment when assessed with the standard of care (SOC) group (odds ratio [OR]: 1.48; 95% confidence interval [CI]: 0.53 -4.16; P = 0.45; I2 = 0%). The SOC group was at a higher risk of experiencing serious adverse events (OR: 0.17; 95% CI: 0.03 - 1.13; P = 0.07). Notably the SOC group had a higher likelihood of death (OR: 0.51; 95% CI: 0.11-2.29; P = 0.07; I2= 0%). Conclusion Prior studies on ruxolitinib have demonstrated it is able to decrease inflammatory markers. In recent studies on COVID-19, treatment with ruxolitinib decreased the time on mechanical ventilation, hospitalization time, and the need for vasopressor support. Additionally, ruxolitinib showed decreased mortality and demonstrated improvement in lung congestion as evidenced by computerized tomography imaging. These findings warrant further clinical investigation into Ruxolitinib as a potential treatment approach for severe COVID-19.

Various methods have been developed for rapid and high throughput full genome sequencing of SARS-CoV-2. Here, we described a protocol for targeted multiplex full genome sequencing of SARS-CoV-2 genomic RNA directly extracted from human nasopharyngeal swabs using the Ion Personal Genome Machine (PGM). This protocol involves concomitant amplification of 237 gene fragments encompassing the SARS-CoV-2 genome to increase the abundance and yield of viral specific sequencing reads. Five complete and one near-complete genome sequences of SARS-CoV-2 were generated with a single Ion PGM sequencing run. The sequence coverage analysis revealed two amplicons (positions 13 751-13 965 and 23 941-24 106), which consistently gave low sequencing read coverage in all isolates except 4Apr20-64Hu. We analyzed the potential primer binding sites within these low covered regions and noted that the 4Apr20-64-Hu possess C at positions 13 730 and 23 929, whereas the other isolates possess T at these positions. The genome nucleotide variations observed suggest that the naturally occurring variations present in the actively circulating SARS-CoV-2 strains affected the performance of the target enrichment panel of the Ion AmpliSeq™ SARS CoV 2 Research Panel. The possible impact of other genome nucleotide variations warrants further investigation, and an improved version of the Ion AmpliSeq™ SARS CoV 2 Research Panel, hence, should be considered.

Background: The cause of end-organ damage and acute respiratory distress syndrome (ARDS) in coronavirus disease 2019 (COVID-19) patients is postulated to be connected to the uncontrolled increase of pro-inflammatory cytokines. The upregulation of many cytokines is dependent on signaling through the Janus kinase 1 (JAK-1) and JAK-2 pathways. Ruxolitinib, a JAK-1 and JAK-2 inhibitor, is documented to have potent anti-inflammatory activity by targeting several cytokines and growth factors with proposed efficacy in the cytokine storm observed in severe COVID-19 patients; therefore, this study examines the efficacy and tolerability of ruxolitinib for adult COVID-19 patients. Materials and Methods: This review was conducted using preferred reporting items for aystematic reviews and meta-analyses (PRISMA) methodology. Six reviewers analyzed 1,120 results. Seven studies were selected and validated. A quantitative meta-analysis was further performed to evaluate clinical improvement at day 28, mortality at day 28, and oxygen requirements comparing treatment and standard of care groups. Results: 168 individuals were involved in the studies selected: 122 in cohort studies, 4 in case reports, and 41 in randomized controlled studies. The ruxolitinib group had a higher likelihood of clinical improvement by the 28th day of treatment when assessed with the standard of care (SOC) group (odds ratio [OR]: 1.48; 95% confidence interval [CI]: 0.53 -4.16; P = 0.45; I2 = 0%). The SOC group was at a higher risk of experiencing serious adverse events (OR: 0.17; 95% CI: 0.03 - 1.13; P = 0.07). Notably the SOC group had a higher likelihood of death (OR: 0.51; 95% CI: 0.11-2.29; P = 0.07; I2= 0%). Conclusion Prior studies on ruxolitinib have demonstrated it is able to decrease inflammatory markers. In recent studies on COVID-19, treatment with ruxolitinib decreased the time on mechanical ventilation, hospitalization time, and the need for vasopressor support. Additionally, ruxolitinib showed decreased mortality and demonstrated improvement in lung congestion as evidenced by computerized tomography imaging. These findings warrant further clinical investigation into Ruxolitinib as a potential treatment approach for severe COVID-19.

The recommended test guidelines for Zika virus (ZIKV) include using both molecular and serological tools. While the molecular tools are useful for detecting acute infection, the serological tools are useful for the detection of previous infections. Nevertheless, detection of ZIKV-specific antibodies remains a challenge due to the high cross-reactivity between ZIKV and other flaviviruses such as dengue virus (DENV) and Japanese encephalitis virus (JEV). The objective of this study is to evaluate the commercially available enzyme-linked immunosorbent assay (ELISA) for the detection of ZIKV IgG. In this study, we evaluated 6 commercially available anti-ZIKV IgG ELISA kits. Pre-characterized serum panels consisting of 70 sera were selected for the evaluation. The diagnostic accuracy of each ELISA kits was determined and compared to the gold standard, Foci Reduction Neutralization Test (FRNT). The present study established that the performance of the NS1-based anti-ZIKV IgG ELISA kit was superior to that which uses of the E protein as antigen. Overall, commercial ZIKV IgG ELISA showed varying test performances, with some achieving moderate to high test sensitivities and specificities. When compared against the FRNT, the test sensitivities ranged from 7.1% to 78.6%, whereas, the test specificities ranged from 40.0% to 100%. Limitation to the study includes the cross reactivity between flavivirus and specificity of the kit in addressing the cross reactivity.