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-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. 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.

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.

Predictors of mortality among inpatients with COVID-19 infection in a tertiary referral center in the Philippines.

Objectives: The aim of this study was to determine the predictors of mortality and describe laboratory trends among adults with confirmed COVID-19. Methods: The medical records of adult patients admitted to a referral hospital with COVID-19 were retrospectively reviewed. Demographic and clinical characteristics, and laboratory parameters, were compared between survivors and non-survivors. Predictors of mortality were determined by multivariate analysis. Mean laboratory values were plotted across illness duration. Results: Of 1215 patients, 203 (16.7%) had mild, 488 (40.2%) moderate, 183 (15.1%) severe, and 341 (28.1%) critical COVID-19 on admission. In-hospital mortality was 18.2% (0% mild, 6.1% moderate, 15.8% severe, 47.5% critical). Predictors of mortality were age ≥ 60 years, COPD, qSOFA score ≥ 2, WBC > 10 × 109/L, absolute lymphocyte count < 1000, neutrophil ≥ 70%, PaO2/FiO2 ratio ≤ 200, eGFR < 90 mL/min/1.73 m2, LDH > 600 U/L, and CRP > 12 mg/L. Non-survivors exhibited an increase in LDH and decreases in PaO2/FiO2 ratio and eGFR during the 2nd-3rd week of illness. Conclusion: The overall mortality rate was high. Predictors of mortality were similar to those of other reports globally. Marked inflammation and worsening pulmonary and renal function were evident among non-survivors by the 2nd-3rd week of illness.

Clinical characteristics of patients with asymptomatic and symptomatic COVID-19 admitted to a tertiary referral centre in the Philippines.

Objectives: To describe the clinical profile and outcomes of hospitalized patients with coronavirus disease 2019 (COVID-19) across the spectrum of disease severity. Methods: This retrospective study included adult patients with confirmed COVID-19 infection admitted to a referral hospital. Descriptive statistics, tests for trend, Kaplan-Meier curve and log-rank test were used to compare characteristics and outcomes across disease severity categories. Results: Of 1500 patients with COVID-19, 14.8% were asymptomatic, 13.5% had mild disease, 36.6% had moderate disease, 12.3% had severe disease and 22.7% had critical disease. Asymptomatic patients were admitted for a concurrent condition or for isolation. Patients aged >60 years, male gender and with co-morbidities had more severe disease. Fever, cough, shortness of breath, malaise, gastrointestinal symptoms and decreased sensorium were more common in patients with severe disease. Bilateral pulmonary infiltrates were common (51.1%), with sicker patients having more abnormal findings. The overall mortality rate was 15.1%. Adopting a symptom-based strategy reduced the length of hospitalization from a median of 13 [interquartile range (IQR) 7-21] days to 9 (IQR 5-14) days. Conclusion: The clinical profile and outcomes for this cohort of patients with COVID-19 was consistent with published reports. Asymptomatic infection was common, and universal testing may be a valuable strategy in the correct context, given the implications for infection control. A symptom-based strategy was found to reduce the length of hospitalization considerably.