There have been different studies so far with different results about effect of IVIG on COVID-19 patients. But clear results have not been obtained [2, 3, 11]. Hence in this study, the therapeutic effects of IVIG on the confirmed COVID-19 cases were examined and the previous valuable results of related articles were reviewed.
Based on a randomized clinical trial on 84 patients, 52 patients received a treatment regimen including hydroxychloroquine, lopinavir / ritonavir and supportive care, plus 400 mg/kg IVIG daily for three days, but 32 patients received the same regimen without IVIG. Addition of IVIG to the standard treatment of critically ill COVID-19 patients could not decrease the duration of hospitalization, mechanical ventilation or mortality rate. In this study Tabarsi et al. found that duration of hospitalization was significantly longer in IVIG treatment group[2]. In our study we also found that the duration of hospitalization in the medium dose subgroup of IVIG was longer than control group and no positive effects were obtained on duration of mechanical ventilation and mortality of patients. Many studies have shown that IVIG administration reduces mortality in patients with COVID-19, but increases hospitalization time instead of standard COVID-19 treatment [12, 13].
In a multicenter retrospective cohort study on 325 patients (174 patients in the case group who received IVIG and 151 patients in the control group), 28-day and 60-day mortality were the primary outcomes. Subgroup analysis showed that 28-day mortality in patients with critical type was improved compared to the control group and in these critically ill patients, IVIG reduced the inflammatory response and improved some organ functions, but the length of hospital stay and overall duration of the disease was increased[11].
In another study, IVIG administration in the first 48 hours of hospitalization reduced mortality, length of stay, length of stay in the ICU, and duration of mechanical ventilation compared to IVIG administration after 48 hours of hospital admission[9]. Herth et al. retrospectively evaluated the clinical courses of 12 COVID-19 patients who received IVIG at various stages of their disease, including within the first 72 h of clinical presentation, after initiation of mechanical ventilation, and after prolonged ventilation and ICU stay. Patients in this study received 0.2 or 0.5 g/kg/d of IVIG for 1 to 4 days. Early IVIG administration in viral phase of COVID-19 infection can decrease the duration of hospitalization, ICU length of stay, duration of mechanical ventilation and even mortality rate rather than late administration [9, 14, 15].
In our retrospective matched cohort study, we examined 183 patients with severe covid-19 infection who were admitted to the ICU. Seventy-four (40/4 %) patients were included in the case group and received IVIG in addition to the standard treatment, but 109 (59/6 %) patients in the control group received only standard treatment. On admission vital signs, clinical signs, laboratory data, and risk factors did not differ significantly between the two groups. Primary outcomes in our study were, duration of hospitalization, ICU length of stay, duration of mechanical ventilation and mortality rate. The results showed that the duration of hospitalization in the IVIG group (13.74 days) was significantly longer than the standard treatment group (11.10 days) (p-value = 0.041), But there were no significant differences between the other primary outcomes (P > 0.05).
Another question that was examined in this study was the impact of the time, dose and period of IVIG prescription on its effectiveness. For this purpose, patients with IVIG treatment were divided into three subgroups of low, medium and high dose. Then the primary outcomes of mortality rate, duration of hospitalization, ICU length of stay and mechanical ventilation were compared between these subgroups, but no significant differences were obtained. Also, initial outcomes were compared separately with the standard treatment group. The results indicated that only the duration of hospitalization in the IVIG subgroup with medium dose is significantly longer than standard group, and in other cases these differences were non-significant. These findings were consistent with the results of Tabarsi et al[2]. So, in this study, it can be concluded that, the use of IVIG method in COVID-19 treatment, is not preferable to its standard treatment.
Difficulty in patient matching and the difference timing in IVIG administration were the limitations in our study which should be overcome by conducting RCT studies with a large statistical population.