ABSTRACT
BACKGROUND: Hyperimmune anti-COVID-19 Intravenous Immunoglobulin (C-IVIG) is an unexplored therapy amidst the rapidly evolving spectrum of medical therapies for COVID-19 and is expected to counter the three most life-threatening consequences of COVID-19 including lung injury by the virus, cytokine storm and sepsis. METHODS: A single center, phase I/II, randomized controlled, single-blinded trial was conducted at Dow University of Health Sciences, Karachi, Pakistan. Participants were COVID-19 infected individuals, classified as either severely or critically ill with Acute Respiratory Distress Syndrome (ARDS). Participants were randomized through parallel-group design with sequential assignment in a 4:1 allocation to either intervention group with four C-IVIG dosage arms (0.15, 0.20, 0.25, 0.30 g/kg), or control group receiving standard of care only (n = 10). Primary outcomes were 28-day mortality, patient's clinical status on ordinal scale and Horowitz index (HI), and were analysed in all randomized participants that completed the follow-up period (intention-to-treat population). The trial was registered at clinicaltrials.gov (NCT04521309). FINDINGS: Fifty participants were enrolled in the study from June 19, 2020 to February 3, 2021 with a mean age of 56.54±13.2 years of which 22 patients (44%) had severe and 28 patients (56%) had critical COVID-19. Mortality occurred in ten of 40 participants (25%) in intervention group compared to six of ten (60%) in control group, with relative risk reduction in intervention arm I (RR, 0.333; 95% CI, 0.087-1.272), arm II (RR, 0.5; 95% CI, 0.171-1.463), arm III (RR, 0.167; 95% CI, 0.024-1.145), and arm IV (RR, 0.667; 95% CI, 0.268-1.660). In intervention group, median HI significantly improved to 359 mmHg [interquartile range (IQR) 127-400, P = 0.009)] by outcome day, while the clinical status of intervention group also improved as compared to control group, with around 15 patients (37.5%) being discharged by 7th day with complete recovery. Additionally, resolution of chest X-rays and restoration of biomarkers to normal levels were also seen in intervention groups. No drug-related adverse events were reported during the study. INTERPRETATION: Administration of C-IVIG in severe and critical COVID-19 patients was safe, increased the chance of survival and reduced the risk of disease progression. FUNDING: Higher Education Commission (HEC), Pakistan (Ref no. 20-RRG-134/RGM/R&D/HEC/2020).
ABSTRACT
BACKGROUND: Research surrounding COVID-19 (coronavirus disease 2019) is rapidly increasing, including the study of biomarkers for predicting outcomes. There is little data examining the correlation between serum albumin levels and COVID-19 disease severity. The purpose of this study is to evaluate whether admission albumin levels reliably predict outcomes in COVID-19 patients. METHODS: We retrospectively reviewed 181 patients from two hospitals who had COVID-19 pneumonia confirmed by polymerase chain reaction (PCR) testing and radiologic imaging, who were hospitalized between March and July 2020. We recorded demographics, COVID-19 testing techniques, and day of admission labs. The outcomes recorded included the following: venous thromboembolism (VTE), acute respiratory distress syndrome (ARDS), intensive care unit (ICU) admission, discharge with new or higher home oxygen supplementation, readmission within 90 days, in-hospital mortality, and total adverse events. A multivariate modified Poisson regression analysis was then performed to determine significant predictors for increased adverse events in patients with COVID-19 pneumonia. RESULTS: A total of 109 patients (60.2%) had hypoalbuminemia (albumin level < 3.3 g/dL). Patients with higher albumin levels on admission had a 72% decreased risk of developing venous thromboembolism (adjusted relative risk [RR]:0.28, 95% confidence interval [CI]:0.14-0.53, p<0.001) for every 1 g/dL increase of albumin. Moreover, higher albumin levels on admission were associated with a lower risk of developing ARDS (adjusted RR:0.73, 95% CI:0.55-0.98, p = 0.033), admission to the ICU (adjusted RR:0.64, 95% CI:0.45-0.93, p = 0.019), and were less likely to be readmitted within 90 days (adjusted RR:0.37, 95% CI:0.17-0.81, p = 0.012). Furthermore, higher albumin levels were associated with fewer total adverse events (adjusted RR:0.65, 95% CI:0.52-0.80, p<0.001). CONCLUSIONS: Admission serum albumin levels appear to be a predictive biomarker for outcomes in COVID-19 patients. We found that higher albumin levels on admission were associated with significantly fewer adverse outcomes, including less VTE events, ARDS development, ICU admissions, and readmissions within 90 days. Screening patients may lead to early identification of patients at risk for developing in-hospital complications and improve optimization and preventative efforts in this cohort.