Methods
Setting and Treatment
All patients in this study were hospitalized at a single site located in San Diego, California. Treatment patients in both cohorts received IVIG 0.5 g/kg adjusted for body weight daily for 3 consecutive days.
Patient Cohort #1: Retrospective Case-Control Trial
Intravenous immunoglobulin (Privigen 10%, CSL Behring) was utilized off-label to treat moderately to severely ill non-intensive care unit (ICU) patients with COVID-19 requiring ≥3 L of oxygen by nasal cannula who were not mechanically ventilated but were considered at high risk for respiratory failure. Preset exclusion criteria for off-label use of IVIG in the treatment of COVID-19 were age >70 years, active malignancy, organ transplant recipient, renal failure, heart failure, or dementia. Controls were obtained from a list of all admitted patients with COVID-19, matched to cases 2:1 on the basis of age (±10 years), body mass index (±1), gender, comorbidities present at admission (eg, hypertension, diabetes mellitus, lung disease, or history of tobacco use), and maximum oxygen requirements within the first 48 hours of admission. In situations where more than 2 potential matched controls were identified for a patient, the 2 controls closest in age to the treatment patient were selected. One IVIG patient was excluded because only 1 matched-age control could be found. Pregnant patients who otherwise fulfilled the criteria for IVIG administration were also excluded from this analysis.
Patient Cohort #2: Prospective, Randomized, Open-Label Trial
Use of IVIG (Octagam 10%, Octapharma) in COVID-19 was studied in a previously published, prospective, open-label randomized trial.10 This pilot trial included 16 IVIG-treated patients and 17 control patients, of which 13 and 14 patients, respectively, had hospital cost data available for analysis.10 Most notably, COVID-19 patients in this study were required to have ≥4 L of oxygen via nasal cannula to maintain arterial oxygen saturationof ≤96%.
Outcomes
Cost data were independently obtained from our finance team, which provided us with the total direct cost and the total pharmaceutical cost associated with each admission. We also compared total length of stay (LOS) and ICU LOS between treatment arms, as these were presumed to be the major drivers of cost difference.
Statistics
Nonparametric comparisons of medians were performed with the Mann-Whitney U test. Comparison of means was done by Student t test. Categorical data were analyzed by Fisher exact test.
This analysis was initiated as an internal quality assessment. It received approval from the Sharp Healthcare Institutional Review Board (research@sharp.com), and was granted a waiver of subject authorization and consent given the retrospective nature of the study.