Plasma therapy: a passive resistance against the deadliest

Figures & data

Figure 1. Schematic representation of the mechanism of action of Convalescent plasma (CP).

Convalescent plasma can act in several ways to neutralize pathogens 1. Apart from the broadly reactive natural IgM antibodies (Abs), specific neutralizing Abs present in CP can bind to viral landing proteins (S protein in case of SARS-CoV2) and prevent its interaction with the cell surface receptors (ACE-2). 2. Abs can also bind to bacterial membrane protein and opsonize the pathogen. 3. Opsonized pathogens are recognized and engulfed by macrophages. 4. Other components of CP like anti-inflammatory cytokines (IL-4, IL-10) can help in suppressing effector T cell function/inflammatory response and the complement proteins help in opsonization of pathogens that eventually leads to destruction of the pathogen.

Table 1. Outcomes of CP therapy in various viral diseases

Sl. No.	Diseases	Outcomes on CP therapy	References
01.	Spanish Flu	Reduction in fatality rate, improvement in clinical symptoms on early transfusion	^Citation18
02.	Avian Influenza	Lower mortality rate	^Citation18
03.	Swine Flu	Reduction in the viral load and relative mortality risk	^Citation19
04.	Severe Acute Respiratory Syndrome (SARS)	Overall reduction in mortality rate	^Citation22
05.	Middle East Respiratory Syndrome (MERS)	Seroconversion on therapy in case of donor plasma PRNT titer ≥1:80	^Citation23
06.	Coronavirus Disease (COVID 19)	Conflicting reports about success of CP therapy has been documented	^Citation36–46
07.	Lassa fever	Decrease in mortality on early administration	^Citation27
08.	Argentine hemorrhagic fever	Lower case fatality rate on early administration	^Citation4,Citation28–32
09.	Ebola	Lower viral load, improvement of clinical symptoms	^Citation26
10.	Hantavirus Pulmonary Syndrome	Decrease in case fatality rate in treated cases	^Citation33

Table 2. FDA approved IVIG products in primary immunodeficiencies and non-communicable inflammatory diseases

Product name	Manufacturer name	Diseases	Source
Flebogamma DIF 5% & 10%	Instituto Grifols, SA	Primary immunodeficiency X-linked gammaglobulinemia Severe combined immunodeficiency Wiskott-Aldrich syndrome	https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/flebogamma-dif-5-10
Gammagard Liquid	Baxter HealthCare Corp	Primary immunodeficiency Multifocal Motor Neuropathy	https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/gammagard-liquid
Octagam	OCTAPHARMA Pharmazeutika Produktionsges.m.b.H.	Chronic immune thrombocytopenic purpura Dermatomyositis	https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/octagam
Vigam-S	Bio Products Laboratory Limited	Primary immune thrombocytopenia Guillain Barré Syndrome Kawasaki disease Chronic inflammatory demyelinating polyradiculoneuropathy Multifocal motor neuropathy	https://www.medicines.org.uk/emc/product/5556/smpc#gref
Gamunex-C	Grifols Therapeutics Inc	Primary immunodeficiency Idiopathic thrombocytopenia purpura Chronic inflammatory demyelinating polyneuropathy	https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/gamunex-c
Carrimune NF	CSL Behring AG	Primary immunodeficiency Immune thrombocytopenic Purpura	https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/carimune-nf-nanofiltered
Privigen	CSL Behring AG	Primary immunodeficiency Immune thrombocytopenic Purpura Chronic inflammatory demyelinating polyneuropathy	https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/privigen
Asceniv	ADMA Biologics, Inc.	Primary immunodeficiency	https://www.fda.gov/vaccines-blood-biologics/asceniv
Bivigam	Biotest Pharmaceuticals Corporation	Primary immunodeficiency	https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/bivigam
PANZYGA	Octapharma Pharmazeutika Produktionsges.m.b.HIndication	Chronic inflammatory demyelinating polyneuropathy Primary immunodeficiency Chronic immune thrombocytopenia	https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/panzyga
Gammaked	Kedrion Biopharma	Chronic inflammatory demyelinating polyneuropathy Primary immunodeficiency Idiopathic thrombocytopenic purpura	http://www.gammaked.com/ https://primaryimmune.org/kedrion-biopharma-inc-launches-gammaked-in-the-u-s-market#:~:text=Kedrion%2C%20a%20biopharmaceutical%20company%20that,for%20the%20next%20seven%20years
Gammaplex 5% & 10%	Bio Products Laboratory	Primary immunodeficiency Chronic immune thrombocytopenic purpura	https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/gammaplex-5-10

Table 3. List of FDA approvedimmunoglobulin products in infectious diseases

Product Name/ Manufacturer	Disease	Product formulation	Condition/s of disease therapy	Reference
Anthrasil (Cangene Corporation)	Anthrax	Sterile solution of purified human IgG, stabilized with 10% maltose and 0.03% polysorbate 80	Adult and pediatric patient of inhalational anthrax in combination with appropriate antimicrobial agent	https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/anthrasil
BabyBiG (California Department of Public Health)	Botulism	Sterile, lyophilized powder of IgG, stabilized with 5% sucrose and 1% human albumin	Infant botulism infected with type A and type B toxin	https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/babybig
CytoGam (Saol Therapeutics Inc)	Cytomegalovirus (CMV)	Liquid solution of IgG against CMV, stabilized by 5% sucrose and 1% Human Albumin	As a prophylactic measure to organs (kidney, lung, liver, pancreas and heart) transplant associated CMV infected patients.	https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/cytogam
HepaGam B (Cangene Corp) And Nabi-HB (Nabi Biopharmaceuticals)	Hepatitis B	Prepared from plasma donors with high-titers of anti-HBs and formulated as 5% protein solution with 10% maltose and 0.03% polysorbate 80	As apreventive agent of Hepatitis B recurrence post liver transplantation in HBsAg-positive patients.Also, as post-exposure treatment to acute HBV Infected, HepB contaminated blood exposed, infants born to HepB positive mothers	https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/hepagam-b
KEDRAB (Kamada Ltd.)	Rabies	Liquid solution of anti-rabies purified IgG immunoglobulin, stabilized with 0.3 M glycine	Post-exposure prophylaxis of rabies infected patient, given promptly after contact with rabid animal and in combination with rabies vaccine.	https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/kedrab
VariZIG (Cangene Corporation)	Varicella-zoster virus	Lyophilized preparation of purified IgG, formulated as 0.04 M sodium 197 chloride, 0.1 M glycine and 0.01% polysorbate 80	As a post-exposure prophylaxis in high risk individuals such as immunocompromised children and adults, newborns of mothers with varicella, infants below one-year age and pregnant women	https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/varizig
GamaSTAN S/D (Grifols Therapeutics Inc)	Hepatitis A Measels Rubella	Sterile solution of immunoglobulin, formulated as 15–18% protein and contains 0.21–0.32 M glycine as buffer	Used as a prophylactic measure in Hepatitis A, Measels and Rubella virus exposed person	https://www.fda.gov/media/86789/download
RespiGam (MedImmune Inc)	Respiratory Syncytial Virus (RSV)	Pooled hyperimmune polyclonal immunoglobulins from donors with high titer anti-RSV antibodies	Discontinued since 2003 due to long intravenous infusion, high dosage volume and high risk to blood borne pathogens	https://www.sec.gov/Archives/edgar/data/873591/0000873591-96-000038.txt https://www.intechopen.com/chapters/65931

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