While much work has been done in associating differentially methylated positions (DMPs) to type 2 diabetes (T2D) across different populations, not much attention has been placed on identifying its possible functional consequences. We explored methylation changes in the peripheral blood of Filipinos with T2D and identified 177 associated DMPs. Most of these DMPs were associated with genes involved in metabolism, inflammation and the cell cycle. Three of these DMPs map to the TXNIP gene body, replicating previous findings from epigenome-wide association studies (EWAS) of T2D. The TXNIP downmethylation coincided with increased transcription at the 3’-UTR, H3K36me3 histone markings, and Sp1 binding, suggesting spurious transcription initiation at the TXNIP 3’-UTR as a functional consequence of T2D methylation changes. We also explored potential epigenetic determinants to increased incidence of T2D in Filipino immigrants in the United States and found 3 DMPs associated with the interaction of T2D and immigration. Two of these DMPs were located near MAP 2 K7 and PRMT1, which may point towards dysregulated stress response and inflammation as a contributing factor to T2D among Filipino immigrants.
Objectives We aimed to describe the clinical profile and outcomes of hospitalized patients with COVID-19 across the spectrum of disease activity. Methods This was a retrospective study of adult patients with confirmed COVID-19 infection admitted in a referral hospital. Descriptive statistics, tests for trend, Kaplan-Meier curve and log-rank test were used to compare characteristics and outcomes across disease activity. Results Of 1500 patients, 14.8% had asymptomatic, while 85.2% had mild (13.5%), moderate (36.6%), severe (12.3%), and critical (22.7%) COVID-19. Asymptomatics were admitted for concurrent condition or for isolation. Age >60 years, male gender, and patients with comorbidities had more severe disease. Fever, cough, shortness of breath, malaise, gastro-intestinal symptoms, and decreased sensorium were more frequent with severe disease. Bilateral pulmonary infiltrates were common (51.1%), with sicker patients having more abnormal findings. Overall mortality rate was 15.1%. Adopting a symptom-based strategy shortened hospitalization from a median of 13 days (IQR 7,21) to 9 days (IQR 5,14). Conclusion The clinical profile and outcomes of our COVID-19 cohort is consistent with published reports. Asymptomatic infection is common, and universal testing may be a valuable strategy in the right context, given infection control implications. Symptom-based strategy considerably shortens the duration of hospitalization.
PurposeThis study was performed to determine the clinical biomarkers and cytokines that may be associated with disease progression and in-hospital mortality in a cohort of hospitalized patients with RT-PCR confirmed moderate to severe COVID-19 infection from October 2020 to September 2021, during the first wave of COVID-19 pandemic before the advent of vaccination.Patients and methodsClinical profile was obtained from the medical records. Laboratory parameters (complete blood count [CBC], albumin, LDH, CRP, ferritin, D-dimer, and procalcitonin) and serum concentrations of cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, IFN-γ, IP-10, TNF-α) were measured on Days 0-3, 4-10, 11-14 and beyond Day 14 from the onset of illness. Regression analysis was done to determine the association of the clinical laboratory biomarkers and cytokines with the primary outcomes of disease progression and mortality. ROC curves were generated to determine the predictive performance of the cytokines.ResultsWe included 400 hospitalized patients with COVID-19 infection, 69% had severe to critical COVID-19 on admission. Disease progression occurred in 139 (35%) patients, while 18% of the total cohort died (73 out of 400). High D-dimer >1 µg/mL (RR 3.5 95%CI 1.83–6.69), elevated LDH >359.5 U/L (RR 1.85 95%CI 1.05–3.25), lymphopenia (RR 1.91 95%CI 1.14–3.19), and hypoalbuminemia (RR 2.67, 95%CI 1.05–6.78) were significantly associated with disease progression. High D-dimer (RR 3.95, 95%CI 1.62–9.61) and high LDH (RR 5.43, 95%CI 2.39–12.37) were also significantly associated with increased risk of in-hospital mortality. Nonsurvivors had significantly higher IP-10 levels at 0 to 3, 4 to 10, and 11 to 14 days from illness onset (p<0.01), IL-6 levels at 0 to 3 days of illness (p=0.03) and IL-18 levels at days 11-14 of illness (p<0.001) compared to survivors. IP-10 had the best predictive performance for disease progression at days 0-3 (AUC 0.81, 95%CI: 0.68–0.95), followed by IL-6 at 11-14 days of illness (AUC 0.67, 95%CI: 0.61–0.73). IP-10 predicted mortality at 11-14 days of illness (AUC 0.77, 95%CI: 0.70–0.84), and IL-6 beyond 14 days of illness (AUC 0.75, 95%CI: 0.68–0.82).ConclusionElevated D-dimer, elevated LDH, lymphopenia and hypoalbuminemia are prognostic markers of disease progression. High IP-10 and IL-6 within the 14 days of illness herald disease progression. Additionally, elevated D-dimer and LDH, high IP-10, IL-6 and IL-18 were also associated with mortality. Timely utilization of these biomarkers can guide clinical monitoring and management decisions for COVID-19 patients in the Philippines.
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