Surveillance of anti-SARS-CoV-2 antibodies in plasma pools and in immunoglobulin medicinal products manufactured since 2020 has shown high neutralizing activity against SARS-CoV-2 and current variants

Background: Patients with primary and secondary immunodeficiencies have shown an impaired humoral immune response to COVID-19 vaccination. It is therefore of paramount importance to investigate anti-SARS-CoV-2 antibody levels in plasma pools and in immunoglobulin (IgG) products used to treat these patients. AIM: To assess the evolution of anti-SARS-CoV-2 antibodies (S protein) in plasma pools and IgG products and its neutralizing activity to original-type virus (Wuhan) and the variants of concern (VOC), including Omicron. Method(s): Healthy donors plasma pools collected in the US and Europe, and the subsequent intravenous (Flebogamma DIFand Gamunex-C, Grifols) and subcutaneous (Xembify, Grifols) IgG manufactured batches were followed from March 2020. Anti-SARS-CoV-2 S protein IgG titers were determined in plasma pools and in IgG batches by ELISA. Neutralization assays analyzed the capacity of IgG products to neutralize original-type virus and VOC (Alpha, Beta, Delta, Omicron BA.1 and BA.5), using pseudo viruses expressing S protein. Results were expressed as the dilution producing 50% neutralization (ID50). Result(s): In plasma pools, anti-SARS-CoV-2 S antibodies continuously increased throughout the study period regardless of the geographic origin. In the US, the first positive plasma pools were collected at the end of 2020. Since July 2021, an exponential increase over 30-fold of anti-SARS-CoV-2 S antibodies was reported. This trend continued increasing until the end of study period. Similarly, IgG products showed a similar evolution of anti-SARS-CoV-2 S antibodies. As expected, IgG batches released at the end of 2020 presented low SARS-CoV-2 neutralization activity. However, IgG products manufactured since August 2021 showed high neutralization activity against original-type virus and the rest of VOC. Regarding Omicron BA.5, a 5 to 10-fold increase was observed over time. Conclusion(s): This study reported the onset of elevated anti-SARS-CoV-2 antibody titers in plasma pools and IgG products since mid-2021, reflecting the evolution of the pandemic and vaccine campaigns. Intravenous and subcutaneous IgG products efficiently neutralized the current circulating VOC, Omicron BA.5. Further research is warranted to assess whether a clinical protective titer against SARS-CoV-2 and passive immunization is achieved in patients with immunodeficiencies treated with IgG products.Copyright © 2023 Elsevier Inc.

Multisystemic Inflammatory Syndrome in Children and Kawasaki Disease: Parallels in Pathogenesis and Treatment.

PURPOSE OF REVIEW: Since it first appeared, multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) has been compared to Kawasaki disease (KD). Although there were early parallels between MIS-C and KD, key differences emerged over time. Here, we aim to compare the pathogenesis, clinical presentation, treatment, and outcomes of MIS-C and KD. RECENT FINDINGS: In this article, we review and compare MIS-C and KD, highlighting differentiating features. We discuss the epidemiological and immunological factors along with clinical and laboratory features which discern MIS-C from KD. We also compare treatment and our understanding of long-term outcomes. Though parallels exist between MIS-C and KD, distinguishing the two is important for clinical management of patients, counseling about natural history, and determining long-term monitoring. While both MIS-C and KD are characterized by profound inflammation and inflammatory vasculopathy, further study is needed to determine whether they are distinct immunopathogenic disorders.

Treatment of MIS-C in Children and Adolescents.

Purpose of Review: Different treatment approaches have been described for the management of COVID-19-related multisystem inflammatory syndrome in children (MIS-C), the pathogenesis of which has not yet been fully elucidated. Here, we comprehensively review and summarize the recommendations and management strategies that have been published to date. Recent Findings: MIS-C patients are treated with different regimens, mostly revolving around the use of immunomodulatory medications, including IVIG and glucocorticoids as first-tier therapy. Refractoriness to IVIG and glucocorticoids warrants a step-up of immunomodulatory therapy to biologic agents such as anakinra, tocilizumab, and infliximab. Summary: We review the current evidence regarding the use of monotherapy versus combination therapy, as well as the current recommendations for assessing thrombotic risk and administering antiplatelet and anticoagulant therapy. We anticipate that future studies will provide evidence for management plans that maximize short- and long-term outcomes. Supplementary Information: The online version contains supplementary material available at 10.1007/s40124-021-00259-4.

Case Series Evaluating Lymphocyte Subgroups at Diagnosis and After Treatment in Multisystem Inflammatory Syndrome Associated with COVID-19 in Children

Objective: In this case series, we aimed to examine the changes in lymphocyte subgroups in children diagnosed with the multisystem inflammatory syndrome (MIS-C) during the acute phase and in the first month after treatment. Material and Methods: Ethics committee approval was received for the study from the Ethics Committee of Ondokuz Mayis University patient data were analyzed from medical records in an electronic database. Initial immunological evaluations of our first five patients diagnosed with MIS-C were made, steroid and IVIG treatments were given to the patients, and lymphocyte subgroups were evaluated for the second time in the first month for control purposes. Results: In MIS-C cases, it was observed that lymphopenia was severe in the acute period, CD3 T cells decreased, the ratio of 2:1 between cytotoxic T cells and helper T cells was impaired, B cells increased proportionally, and NK cells were normal or decreased. When we evaluated MIS-C cases with the control lymphocyte subgroup in the first month, it was observed that lymphopenia improved and CD3 T cells increased proportionally, and active T cells decreased to normal values in the first month after treatment. On the other hand, while naive B cells decreased, non-switching and switching B cells increased and NK cells decreased. Conclusion: While COVID-19 is an acute infection, MIS-C is associated with cytokine storm induced by the acute infection. Immunologic assessment of MIS-C cases is considered important since the condition causes immune dysregulation in the host immune system. Lymphopenia, increased B cell count, reversal of the CD4/CD8 ratio, and increased active T cell count may be beneficial in the early diagnosis of MIS-C. Since it is thought that the cytokine storm causes complications in MIS-C, immediate administration of IVIG treatment is considered essential. Although it was demonstrated that the disease manifests with marked cellular changes, there is still a need for further studies.

Intravenous immunoglobulins (IVIG) in severe/critical COVID-19 adult patients.

The coronavirus disease 2019 (COVID-19) pandemic has become a huge obstacle to the health system due to the high rate of contagion. It is postulated that intravenous immunoglobulins (IVIG) can lower the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related inflammation and prevent the development of acute respiratory distress syndrome (ARDS). The main advantages of IVIG treatment might be targeting cytokine storm in severe and critical COVID-19 by influences on complement, innate immune cells, effector T-cells, and Tregs. Randomized clinical trials (RCTs) and non-RCTs evaluating the safety and efficacy of IVIG in patients with severe/critical COVID-19 were performed. It seems that early administration of high-dose IVIG (in the acceleration phase of the disease) in severe or especially critical COVID-19 may be an effective therapeutic option, but there are no strong data to use it routinely. The results regarding mortality reduction are inconclusive. Additionally, IVIG treatment carries a risk of complications that should be considered when initiating treatment. However, given the COVID-19 mortality rate and limited therapeutic options, the use of IVIG is worth considering. This review summarizes the development and highlights recent advances in treatment with IVIG of severe/critically ill COVID-19 patients.

Immune Thrombocytopenia Following Booster Dose of the Moderna mRNA-1273 Vaccine.

Vaccine-mediated immune thrombocytopenia, although previously reported, is considered exceedingly rare. The probability of the incidence of profound thrombocytopenia following the COVID-19 mRNA-based vaccine has been less elucidated. We present the case of an 81-year-old female patient who became profoundly thrombocytopenic with bleeding manifestations six days after the Moderna mRNA-1273 vaccine administration. Fortunately, she exhibited platelet count recovery after treatment with intravenous immunoglobulins and steroid therapy. Furthermore, we show that the inherent risk of COVID-19 infection leading to thrombocytopenia significantly outweighs the vaccine's risk.

Efficacy of intravenous immunoglobulin (IVIg) on COVID-19-related neurological disorders over the last 2 years: an up-to-date narrative review.

Introduction: Among the clinical manifestations of SARS-CoV-2 infection, neurological features have been commonly reported and the state-of-the-art technique suggests several mechanisms of action providing a pathophysiological rationale for central and peripheral neurological system involvement. However, during the 1st months of the pandemic, clinicians were challenged to find the best therapeutic options to treat COVID-19-related neurological conditions. Methods: We explored the indexed medical literature in order to answer the question of whether IVIg could be included as a valid weapon in the therapeutic arsenal against COVID-19-induced neurological disorders. Results: Virtually, all reviewed studies were in agreement of detecting an acceptable to great efficacy upon IVIg employment in neurological diseases, with no or mild adverse effects. In the first part of this narrative review, the interaction of SARS-CoV-2 with the nervous system has been discussed and the IVIg mechanisms of action were reviewed. In the second part, we collected scientific literature data over the last 2 years to discuss the use of IVIg therapy in different neuro-COVID conditions, thus providing a summary of the treatment strategies and key findings. Discussion: Intravenous immunoglobulin (IVIg) therapy is a versatile tool with multiple molecular targets and mechanisms of action that might respond to some of the suggested effects of infection through inflammatory and autoimmune responses. As such, IVIg therapy has been used in several COVID-19-related neurological diseases, including polyneuropathies, encephalitis, and status epilepticus, and results have often shown improvement of symptoms, thus suggesting IVIg treatment to be safe and effective.

Hemolytic anemia following intravenous immunoglobulins in children with PIMS-TS: Two case reports.

This is the first case report on two children presenting with immediate and severe hemolytic anemia following the administration of high-dose intravenous immunoglobulins (IVIGs) in the context of pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). Hemolytic anemia was described as a significant decrease in hemoglobin and an increase in lactate dehydrogenase after the second administration of high-dose IVIGs was performed. Both patients were found to have AB blood group. One of our patients showed massive pallor, weakness, and inability to walk in association with hemolysis. However, in both cases, the anemia was self-limiting and transfusion of red blood cells was not required: both patients recovered without persistent impact. Nonetheless, we aim to draw attention to this widely unknown adverse effect of IVIG, especially in the context of PIMS-TS. We suggest determining the patient's blood group prior to high-dose IVIG infusion and replacing the second IVIG through high-dose steroids or anticytokine therapy. Using IVIGs containing lower titers of specifically anti-A or anti-B antibodies to avoid isoagglutinin-caused hemolytic anemia is desirable; however, the information is not routinely available.

Post-Infectious Acute Cerebellar Ataxia Treatment, a Case Report and Review of Literature.

BACKGROUND: infectious mononucleosis is very common during childhood and neurological manifestations are extremely rare. However, when they occur, an appropriate treatment must be undertaken to reduce morbidity and mortality as well as to ensure appropriate management. METHODS: we describe the clinical and neurological records of a female patient with post-EBV acute cerebellar ataxia, whose symptoms rapidly resolved with intravenous immunoglobulin therapy. Afterwards, we compared our results with published data. RESULTS: we reported the case of an adolescent female with a 5-day history of sudden asthenia, vomiting, dizziness, and dehydration, with a positive monospot test and hypertransaminasemia. In the following days, she developed acute ataxia, drowsiness, vertigo, and nystagmus with a positive EBV IgM titer, confirming acute infectious mononucleosis. The patient was clinically diagnosed with EBV-associated acute cerebellitis. A brain MRI showed no acute changes and a CT scan showed hepatosplenomegaly. She started therapy with acyclovir and dexamethasone. After a few days, because of her condition's deterioration, she received intravenous immunoglobulin and demonstrated a good clinical response. CONCLUSIONS: although there are no consensus guidelines for the treatment of post-infectious acute cerebellar ataxia, early intervention with intravenous immunoglobulin might prevent adverse outcomes, especially in cases that do not respond to high-dose steroid therapy.

An Update on Reports of Atypical Presentations of Kawasaki Disease and the Recognition of IVIG Non-Responder Children.

Kawasaki disease (KD) is an acute vasculitis with an intrinsic risk of severe involvement of coronary arteries. The worldwide spread of KD and the importance of early diagnosis for preventing cardiovascular complications have ascertained the need for updating guidelines for prompt disease recognition and treatment efficacy assessment. All KD patients who comply with the definition of classic or atypical disease should be treated with intravenous immunoglobulin (IVIG) soon after diagnosis. The objective of our narrative review was to analyze the medical literature about case reports with atypical KD in relation to diagnosis and potential identification of predictors of non-responsiveness to IVIG. Our analysis has shown that the seminal challenge in KD management is the timeliness of diagnosis, although both extreme variability and transience of clinical manifestations make this goal difficult. A non-negligible percentage of patients, especially in the first 6 months of life, might have atypical manifestations of KD, whose painstaking differential diagnosis may be tricky. Many attempts to develop universal scoring systems and detect children at higher risk of IVIG resistance have been rather unsuccessful. Additionally, KD may show different evolutions according to unraveled demographic, genetic, or epigenetic factors. Further research is needed to elucidate all open questions about KD and clarify the long-term outcome of its potential complications.

Preclinical Evaluation of a New Anti-COVID-19 Intravenous Immunoglobulin

Introduction. Using of immunoglobulins containing SARS-CoV-2 neutralizing antibodies may be an effective and safe tool for COVID-19 treatment. An intravenous immunoglobulin COVID-globulin from donor blood plasma containing SARS-CoV-2 neutralizing antibodies was developed at Joint-Stock Company Nacimbio. Aim. A pilot study of the safety of the "COVID-globulin". Materials and methods. When studying the safety of the preparation in animals the following parameters were evaluated: general toxicity, thrombogenic potential, influence on hematological and biochemical parameters, blood clotting and hemolytic activity, determination of local irritant action, pyrogenic properties, bacterial endotoxins, allergic effect of the drug preparation and its physicochemical characteristics. Results and discussion. Safety studies of "COVID-globulin" in animals showed no signs of intoxication, local irritant action and thrombogenic properties. Macroscopic and histological examination of the organs of rats treated with COVID-globulin showed no signs of necrosis, inflammation, atypia, or any significant pathological changes. Hematological and biochemical parameters of the blood of laboratory animals after the administration of "COVID-globulin" corresponded to the reference values. Administration of COVID-globulin to rabbits did not activate blood clot formation. The IgG subclasses distribution in the preparation corresponded to that in human plasma. The activity of the Fc-function of the immunoglobulin molecule was more than 130 % compared to the reference standard preparation, the concentration of the prekallikrein activator in the COVID-globulin ranged from 4.2 to 4.8 IU/ml, anticomplementary activity was less than 1 unit complement per 1 mg of protein. Conclusion. The results of all studies have demonstrated a high level of safety of the developed COVID-globulin preparation, which meets the safety requirements for human immunoglobulins for intravenous administration by national regulatory documents and the European Pharmacopoeia. © Nikolaeva A. M., Ivanov A. V., Smolyanova T. I., Razumikhin M. V., Belyakova O. V., Shilova E. G., Selezneva N. R., Vyaznikova T. V., Semicheva A. I., Sakanyan E. I., 2023.

Markedly prolonged compound muscle action potential duration in a patient with coronavirus disease 2019 related critical illness myopathy

A 56-year-old man admitted with coronavirus disease 2019 (COVID-19) became severely ill, required ventilator support and intensive care unit management. After ventilator weaning, he was found to have quadriparesis. Guillain-Barre syndrome (GBS) was suspected and administration of high-dose intravenous immunoglobulin (IVIg) was considered. However, markedly prolonged compound muscle action potential (CMAP) duration was observed, leading to a diagnosis of critical illness myopathy (CIM). Therefore, IVIg was not given at all, and supportive care was continued. A good functional recovery was obtained. Prolonged CMAP duration is a characteristic finding to CIM. CIM following severe COVID-19 infection is probably common, although the diagnostic value of prolonged CMAP duration is not widely recognized. This characteristic finding deserves more attention because it contributes to early differentiation between CIM and GBS and the use of IVIg in patients with COVID-19 may cause thrombotic complications and worsen the prognosis.Copyright © 2023 The Authors. Neurology and Clinical Neuroscience published by Japanese Society of Neurology and John Wiley & Sons Australia, Ltd.

Intravenous immunoglobulin and convalescent plasma treatment in the COVID-19 patient

The severe acute respiratory coronavirus 2 (SARS-CoV-2), responsible for COVID-19 disease, proved to cause the activation of the innate and adaptive immune system in a small percentage of patients, which resulted in immune dysregulation with massive inflammatory responses and cytokines release. At the same time, complex interactions between SARS-CoV-2 and immune system led to a higher evidence of COVID-19 related autoimmune diseases. In this chapter, we analyze the probable mechanisms of action of high dose intravenous immunoglobulin (IVIg) in the treatment of SARS-CoV-2 infection. We reported evidence in which IVIg proved to be useful in severe COVID-19 disease and in the management of immune dysregulation. Similarly, the use of IVIg was important in the treatment of autoimmune diseases related to COVID-19 and SARS-CoV-2 vaccination. We also discuss the use of convalescent plasma in COVID-19 disease. © 2023 Elsevier Inc. All rights reserved.

Clinical Course Associated with Aseptic Meningitis Induced by Intravenous Immunoglobulin for the Treatment of Multisystem Inflammatory Syndrome in Children.

Aseptic meningitis is a rare but potentially serious complication of intravenous immunoglobulin treatment. In this case series, meningitic symptoms following intravenous immunoglobulin initiation in patients with multisystem inflammatory syndrome were rare (7/2,086 [0.3%]). However, they required the need for additional therapy and/or readmission.

Post-COVID-19 Encephalitis With Claustrum Sign Responsive to Immunomodulation.

We describe a case of encephalitis following coronavirus disease 2019 (COVID-19) in a six-and-a-half-year-old girl who presented with acute onset confusion and jerky movements of the limbs. The patient was unvaccinated for COVID-19. Subsequent magnetic resonance imaging revealed a bilateral "claustrum sign" on T2 and fluid-attenuated inversion recovery (FLAIR) images and electroencephalogram reported moderate diffuse encephalopathy. The patient tested negative for COVID-19 by polymerase chain reaction, had positive serology for COVID-19 indicating past infection, and had a negative autoimmune panel and infectious workup. She was treated on the lines of post-infectious encephalitis with immunomodulatory therapies such as high-dose intravenous steroids and intravenous immunoglobulins. She responded significantly and had complete resolution of her symptoms; therefore, further supporting the suspicion of an immune-mediated etiology. Cases of post-COVID-19 encephalitis have been reported all over the world; however, most cases are based on speculation and temporal associations and therefore more research is required to optimize treatment guidelines.

Exploring the Potential of Broadly Neutralizing Antibodies for Treating SARS-CoV-2 Variants of Global Concern in 2023: A Comprehensive Clinical Review.

In the aftermath of the coronavirus disease 2019 (COVID-19) pandemic, the world is still seeing outbreaks of COVID-19 infections as of 2023, especially in populations that have been adequately vaccinated. This situation across the globe gives rise to important questions regarding the efficacy of current treatments and the real rate of mutations in the COVID-19 virus itself which can make the currently available treatments and vaccines obsolete. We have tried to answer a few of those questions and put forth some new questions of our own. Our efforts in this paper were directed towards understanding the utilization of broadly neutralizing antibodies as a treatment for COVID-19 infection with a particular focus on the Omicron variant and other newer variants. We gathered our data from three major databases: PubMed, Google Scholar, and Cochrane Central Register of Controlled Trials (CENTRAL). We have screened 7070 studies from inception till March 5, 2023, and gathered 63 articles that were relevant to the topic of interest. Based on the existing medical literature regarding the topic of interest and also based on our own personal and clinical experience treating COVID-19 patients across the multiple waves in the United States and India since the beginning of the pandemic, we have concluded that broad neutralizing antibodies could be an effective option for treatment and prophylaxis for current and future outbreaks of COVID-19 including the Omicron variant and newer variants. Further research, including clinical trials, is required to tailor optimal dosages, prevent adverse reactions/side effects, and develop treatment strategies.

Use of immunoglobulin replacement therapy in patients with secondary antibody deficiency in daily practice: a European expert Q&A-based review.

INTRODUCTION: Secondary antibody deficiencies (SAD) are often a side effect of specific therapies that target B cells directly or affect the antibody response indirectly. Treatment of immunodeficiency by immunoglobulin replacement therapy (IgRT) is well established in primary antibody deficiencies, although the evidence for its use in SAD is less well established. To fill the gap and provide opinion and advice for daily practice, a group of experts met to discuss current issues and share best practical experience. AREAS COVERED: A total of 16 questions were considered that covered use of a tailored approach, definition of severe infections, measurement of IgG levels and specific antibodies, indications for IgRT, dosage, monitoring, discontinuation of IgRT, and Covid-19. EXPERT OPINION: Key points for better management SID should include characterization of the immunological deficiency, determination of the severity and degree of impairment of antibody production, distinguish between primary and secondary deficiency, and design a tailored treatment protocol that should include dose, route, and frequency of Ig replacement. There remains the need to carry out well-designed clinical studies to develop clear guidelines for the use of IgRT in patients with SAD.

Ten-month follow-up of patients with covid-19 temporally related multi-system inflammatory syndrome in children: the experience of the children hospital of Palermo.

BACKGROUND: In Sicily, the first wave of COVID-19 showed a low epidemic impact in paediatric population, while the second and the third waves had a higher impact on clinical presentation of COVID-19 in children and a significantly higher severe outcome in patients with multisystem inflammatory syndrome in children (MIS-C), with a frequent life-threatening progression. METHODS: We describe a cohort of 22 Sicilian children (11 M; 11 F; age: 1.4-14 years), presenting with clinical features compatible with MIS-C. Patients with negative swab had a history of recent personal or parental infection. RESULTS: The following diagnostic criteria were detected: fever (100%); cheilitis and/or pharyngeal hyperaemia (86%); latero-cervical lymphadenitis (82%); rash (73%); abdominal pain and/or vomiting and/or diarrhoea (64%); conjunctivitis (64%); hands and feet oedema (18%). 59% showed cardiac involvement (6 pericardial effusion; 8 mitral valve insufficiency; 4 insufficiency of two valves; 3 coronary artery lesions (CAL)). In all the patients, treatment was started within 72 h after the admission, with intravenous immunoglobulins (IVIG) (2 g/Kg/dose), methylprednisolone (2 mg/Kg/day in 73% of patients; 30 mg/Kg/day for 3 days, followed by 2 mg/Kg/day in 27% of patients). Two patients were treated with enoxaparin. Two patients with shock, were additionally treated with vasoactive drugs, albumin, diuretics. Cardiac involvement evolved into the complete resolution of lesions in most of the patients. All the patients were included in a follow-up, to investigate on clinical outcome and resolution of organ involvement. Cardiac valve insufficiency persisted only in 18% of children, CAL persisted only in 33% of children with coronary involvement, however without the evolution into aneurisms. CONCLUSIONS: The preferred treatment strategy was more aggressive at the diagnosis of MIS-C, to block the cytokine cascade. Most of our patients, in fact, received a first-line treatment with IVIG and steroids. This approach could explain the favourable prognosis, the rapid restoring of cardiac function also in patients with MAS or shock, and the good outcome during the 10 months follow-up in all the patients.

Treating Pediatric Myocarditis with High Dose Steroids and Immunoglobulin.

There is considerable variability in practice among pediatric centers for treatment of myocarditis. We report outcomes using high dose steroids in conjunction with IVIG. This is a single center retrospective study of children < 21 years of age diagnosed with myocarditis and treated with high dose steroids and IVIG from January 2004-April 2021. Diagnostic criteria for myocarditis included positive endomyocardial biopsy, cardiac magnetic resonance (CMR) imaging meeting Lake Louise criteria, or strictly defined clinical diagnosis. Forty patients met inclusion criteria. Median age at diagnosis was 11.6 years (0.7-14.6). Diagnosis was made clinically in 70% of cases (N = 28), by CMR in 12.5% (N = 5) and by biopsy in 17.5% (N = 7). Median ejection fraction (EF) at diagnosis was 35% (IQR 24-48). Median duration of IV steroids was 7 days (IQR 4-12) followed by an oral taper. Median cumulative dose of IV immunoglobulin (IVIG) was 2 g/kg. There were no serious secondary bacterial infections after steroid initiation. Ten patients (25%) required mechanical circulatory support. Overall transplant free survival was 92.5% with median follow-up of 1 year (IQR 0-6 years). Six patients required re-admission for cardiovascular reasons. By 3 months from diagnosis, 70% of patients regained normal left ventricular function. High dose steroids in conjunction with IVIG to treat acute myocarditis can be safe without significant infections or long-term side effects. Our cohort had excellent recovery of ventricular function and survival without transplant. Prospective comparison of a combination of high dose steroids with IVIG versus other therapies is needed.

Injection of intravenous immunoglobulin (IVIg) for the treatment of Coronavirus induced cytokine storm

Background. COVID-19 disease is the cause of daily morbidity and mortality worldwide due to its high transmissibility and pathogenicity. To date, intravenous immunoglobulin (IVIg) injection has been used as one of the various treatments for this disease. This study aimed to determine the effect of IVIg injection on the treatment of patients with Coronavirus-induced cytokine storm. Methods. A total of 174 patients with COVID-19 were included in this study based on their clinical characteristics and laboratory findings and were divided into two groups of IVIg recipients and non-recipients according to the treatment they received. Statistical analysis was performed using SPSS version 22.0. A p-value less than 0.05 was considered statistically significant. Results. IVIg was used to treat merely 20 patients and Kaletra and hemoperfusion drugs were used more among IVIg recipient patients (P=0.003 and P=0.001, respectively). COVID-19-positive PCR tests were significantly more frequent among IVIg recipients (P=0.026). The polymorphonuclear neutrophil (PMN) count (P=0.007) and sodium level (P=0.007) were significantly higher in the IVIg recipient group on the first admission day. Moreover, INR levels in the IVIg recipient group were significantly lower on the seventh admission day (P=0.020). The median of total intensive care unit (ICU) duration of hospitalization among IVIg recipients was significantly higher (P=0.001). Conclusion. It seems that the use of IVIg in COVID-19 patients should be further investigated. Practical Implications. IVIg injection could decrease mortality and slightly increase the survival rate among COVID-19 patients. © 2022 The Authors.