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High-dose intravenous immunoglobulin therapy for novel coronavirus disease 2019: A brief report of two cases

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LETTER TO THE EDITOR

Open Access

High-dose intravenous immunoglobulin

therapy for novel coronavirus disease 2019:

a brief report of two cases

Cem Erdogan

1

, Bahadir Ciftci

1*

, Deniz Kizilaslan

1

, Mursel Ekinci

1

, Gülsen

İptec

1

, Ali

İhsan Gemici

2

and

Pelin Karaaslan

1

To the Editor,

Novel coronavirus disease 2019 (2019-nCoV) is a glo-bal pandemic which threatens all over the world. The first cases were seen in Wuhan, China, in December 2019 (Guo et al. 2020; Chen et al. 2020). It has spread rapidly, and now, there are more than 2.3 million re-ported cases and 160,000 deaths worldwide. 2019-nCoV may cause multi-system infections especially respiratory infections such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) (Guo et al. 2020; Chen et al. 2020; Sanders et al.2020). In some cases, infections may be mild (only cough or fever, etc.); however, in some cases, infections may be se-vere (acute respiratory failure with diffuse pneumonia). In severe cases, there is an exaggerated immune re-sponse with low peripheral lymphocyte levels and high cytokine levels. This mechanism of pathogenesis may be responsible for the multiple organ failures (Cao et al.

2019; Lin et al. 2020). In this early stage of the 2019-nCoV, the infection may be treated successfully with immunomodulation (Cao et al. 2019). So, the immuno-modulation options like intravenous immunoglobulin should be kept in mind. The intravenous immunoglobu-lin (IVIg) has been used as a replacement therapy in

some immunodeficiency syndromes (Ballow 2008; De

Ranieri 2017). IVIg plays an immunomodulatory and

anti-inflammatory role in such cases like 2019-nCoV (Cao et al.2019; Lin et al.2020). Therefore, IVIg may be used as a supportive immunomodulatory drug as a part of the treatment of 2019-nCoV. We want to share our

high-dose IVIg treatment experiences in two 2019-nCoV patients who recovered from the infection in our tertiary university hospital intensive care unit (ICU).

Written informed consents were obtained from the pa-tients for this report. The first patient was a 35 years old man. He was diagnosed with 2019-nCoV with specific molecular test (polymerase chain reaction (PCR)) and thorax tomography. He had psoriasis as a comorbidity and received immunosuppressive treatment for 2 years. He was observed in our clinic for 3 days with a 2019-nCoV diagnosis. We admitted him to our ICU on the 4th day. He had tachypnea (respiratory rate 45/min) and dyspnea at ICU admission. His peripheral oxygen satur-ation was 75% with 10 l/min oxygen flow. He had re-ceived favipiravir and hydroxychloroquine treatment. In addition, we supported his respiration with non-invasive mechanical ventilation. However, his symptoms did not decrease and he was unstable. So, we started him high-dose IVIg (hospital day 6) at 1 g/kg for 2 days (totally 180 g for 2 days). On the second day of the IVIg treat-ment, the patient’s clinical status improved. He became afebrile, and there was no need of non-invasive mechan-ical ventilation. No adverse effect was reported. His

oxy-gen saturation level was 95–97% with no oxygen

support. Two consecutive PCR tests were negative. He was discharged from the ICU.

The second patient was a 76-year-old woman. She was diagnosed with 2019-nCoV with specific molecular test (polymerase chain reaction (PCR)) and thorax tomog-raphy. She had chronic myelocytic leukemia (CML) as a comorbidity for 2 years and received IVIG treatment routinely for CML (10 g sc for 15 days period). She was observed in our clinic for 2 days with a 2019-nCoV diag-nosis. We admitted her to our ICU on the 3rd day. She had tachypnea (respiratory rate 38/min) and dyspnea at © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visithttp://creativecommons.org/licenses/by/4.0/.

* Correspondence:[email protected];[email protected]

1Department of Anesthesiology and Reanimation, Mega Medipol University

Hospital, Istanbul Medipol University, School of Medicine, Bagcilar, 34040 Istanbul, Turkey

Full list of author information is available at the end of the article

Ain-Shams Journal

of Anesthesiology

Erdogan et al. Ain-Shams Journal of Anesthesiology (2020) 12:39 https://doi.org/10.1186/s42077-020-00089-4

(2)

ICU admission. Her peripheral oxygen saturation was 65% with 10 l/min oxygen flow. She had received favipir-avir and hydroxychloroquine treatment. We supported her respiration with non-invasive mechanical ventilation. However, her symptoms did not decrease, she was un-stable, and we intubated her. So, we started high-dose IVIg (hospital day 5) at 1 g/kg for 2 days (in total, 180 g for 2 days). On the first day of the IVIg treatment, the patient’s clinical status improved. She became afebrile. After 6 days of IVIg treatment, she was extubated. There was no adverse event. Her oxygen saturation level was 96–98% with no oxygen support. Two consecutive PCR tests were negative. She was discharged from the ICU.

Discussion

The aim of IVIg therapy is to provide antibodies against in-fections. IgG preparations are derived from a plasma pool of approximately 10,000 donors. These preparations contain mainly IgG (95–99%). It contains a large number of bioactive molecules. IVIg may be indicated for several conditions such as replacement therapy, anti-inflammatory treatment, and immunomodulatory therapy in different situations (Cao et al.

2019; Ballow2008; De Ranieri2017). High-dose IVIg may be used as an effective and safe immune modulator in 2019-nCoV infection.

In conclusion, IVIg may be performed in 2019-nCoV infection as a part of the main treatment for immuno-modulation. However, further studies are needed to understand the efficacy of this strategy.

Abbreviations

2019-nCoV:Novel coronavirus disease 2019; SARS: Severe acute respiratory syndrome; MERS: Middle East respiratory syndrome; IVIg: Intravenous immunoglobulin; ICU: Intensive care unit; PCR: Polymerase chain reaction; CML: Chronic myelocytic leukemia

Acknowledgements Not applicable Authors’ contributions

Cem Erdogan: writing, literature scanning, study design, and data. Bahadir Ciftci: writing, literature scanning, study design, and data. Deniz Kizilaslan: study design and data. Mürsel Ekinci: study design and data. Aliİhsan Gemici: writing, literature scanning and data. Pelin Karaaslan: Writing and reviewing. The authors read and approved the final manuscript. Funding

The authors have not declared a specific grant for this research and from any funding agency in the public, commercial, or not-for-profit sectors. Availability of data and materials

Not applicable

Ethics approval and consent to participate Not applicable

Consent for publication Not applicable Competing interests None declared.

Author details

1Department of Anesthesiology and Reanimation, Mega Medipol University

Hospital, Istanbul Medipol University, School of Medicine, Bagcilar, 34040 Istanbul, Turkey.2Department of Hematology, Istanbul Medipol University, School of Medicine, Istanbul, Turkey.

Received: 25 May 2020 Accepted: 26 August 2020

References

Ballow M (2008) Immunoglobulin therapy: methods of delivery. J Allergy Clin Immunol. 122(5):1038–1039.https://doi.org/10.1016/j.jaci.2008.08.012

Cao W, Liu X, Bai T, et al. High-dose intravenous immunoglobulin as a therapeutic option for deteriorating patients with coronavirus disease 2019. Open Forum Infect Dis. 2020;7(3):ofaa102. Published 2020 Mar 21. doi:https:// doi.org/10.1093/ofid/ofaa102

Chen N, Zhou M, Dong X et al (2020) Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 395(10223):507–513. https://doi.org/10.1016/S0140-6736(20)30211-7

De Ranieri D (2017) Intravenous immunoglobulin and its clinical applications. Pediatr Ann. 46(1):e6–e7.https://doi.org/10.3928/19382359-20161213-04

Guo YR, Cao QD, Hong ZS, et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. Mil Med Res. 2020;7(1):11. Published 2020 Mar 13. doi:10.1186/s40779-020-00240-0

Lin L, Lu L, Cao W, Li T (2020) Hypothesis for potential pathogenesis of SARS-CoV-2 infection-a review of immune changes in patients with viral pneumonia. Emerg Microbes Infect. 9(1):727–732.https://doi.org/10.1080/ 22221751.2020.1746199

Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a review [published online ahead of print, 2020 Apr 13]. JAMA. 2020;10.1001/jama.2020.6019. doi:10.1001/jama. 2020.6019

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