4. Discussion
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.