Utility of laboratory and immune biomarkers in predicting disease progression and mortality among patients with moderate to severe COVID-19 disease at a Philippine tertiary hospital.

Purpose: This 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 methods: Clinical 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-1ß, 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. Results: We 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). Conclusion: Elevated 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.

Rheumatoid arthritis and the risk of preterm birth.

During pregnancy, many diseases are correlated with different adverse outcomes. In turn, pregnancy affects the body, leading to increased disease susceptibility. This interplay between diseased states and pregnancy outcomes is illustrated in the effect of the chronic autoimmune disorder, rheumatoid arthritis (RA), and the adverse outcome, preterm birth (PTB). RA is a systemic disorder characterized by inflammation of the joints and other body organs. Joint pain and swelling are the most prominent manifestations of RA during pregnancy. However, the exact role of RA on PTB among pregnant women has yet to be established. This review highlighted the immunologic mechanisms involved in PTB in pregnant patients with RA. The immune cell population in pregnant women with RA exhibited higher activity of macrophages, dendritic cells, neutrophils, helper T (Th) 1 cells, and Vδ1 cells, but lower activity of CD4 + CD25high T regulatory (CD24 + CD25high Treg ), Th2, and Vδ2 cells. Increased pro-inflammatory cytokines IL-6, TNF-α, and IFN-γ and decreased anti-inflammatory cytokines IL-12 and IL-10 are also exhibited by pregnant patients with RA. This review also discussed factors that may predict the risk of PTB in RA. These include disease activity and severity of RA, laboratory parameters (cytokines and immune cell population), and sociodemographic factors such as ethnicity, smoking, alcohol intake, and the level of education. Current findings on the underlying immunological mechanisms of RA can help identify possible strategies to prevent PTB.

Current Perspectives and Unmet Needs of Primary Immunodeficiency Care in Asia Pacific.

Background: The Asia Pacific Society for Immunodeficiencies (APSID) conducted nine primary immunodeficiency (PID) Schools in 5 years since inauguration to provide PID care training for early career physicians in Asia Pacific, a region with divergent needs in PID resources and training. Objective: To identify differences in PID patient care resource and training needs across Asia Pacific and propose a corresponding action plan. Methods: The Human Development Index (HDI) indicates the degree of socio-economic development in each country/region. Information related to investigations and learning issues were extracted from the abstracts and personal statements from all Schools and mapped onto resource and training needs. Correlations between HDI and country/region-specific parameters were tested by two-tailed Pearson correlation. Results: A total of 427 abstracts were received in nine Schools between 2015 and 2020, predominantly on immunodeficiencies affecting cellular and humoral immunity. Genetic confirmation was described in 61.8% of abstracts, and its absence negatively correlated with HDI (r = -0.696, p = 0.004). Essential immunologic and genetic tests were not available in 25.4 and 29.5% of abstracts, respectively, and their absence negatively correlated with HDI (r = -0.788, p < 0.001; r = -0.739, p = 0.002). HDI positively correlated with average testing level (r = 0.742, p = 0.002). Cases from medium-HDI countries/regions focused on learning how to investigate a patient for PIDs in cases of severe or atypical infections, whereas those from very-high-HDI countries/regions, from which most faculty members originated, listed hematopoietic stem cell transplantation and gene therapy, newborn screening, and research as learning issues more frequently. Conclusion: There are unique HDI-related PID resource and training needs in each country/region. APSID proposes HDI group-specific strategies to improve PID care and education in her member countries/regions. Further quantitative analysis of needs in PID care in Asia Pacific is needed for lobbying governments to increase their support for PID care and research.