Anti COVID-19 Convalescent Plasma Therapy
Study Details
Study Description
Brief Summary
Why is the research needed? The pandemic known as COVID-19 is now spreading across the world with currently (April 10, 2020) more than 1 115 530 active cases and 96 791 deaths. In most affected countries the current goal is to 'flatten the curve' of the epidemic since there is no health care system that is able to treat an extremely high volume of patients all at once. There is a need for immediately applicable treatments for the patients at highest risk, which gains time until targeted therapies become available. A key feature in the pathomechanism of the disease is that the virus elicits an immunological over-reaction in the human body termed 'cytokine storm'. In susceptible patients this hyper-inflammation itself is a significant burden and may even inhibit the body to generate antibodies against the virus in adequate quantities. Therefore, identifying the subset of patients with excess cytokine response and supplementing them with convalescent plasma from recovered donors may be a life-saving treatment option.
What is our study about? In light of recent promising data on plasma therapy in the treatment of COVID-19 and other viral epidemics, there is a need for better understanding the cytokine response to the virus in order to better characterize the target population for convalescent plasma therapy.
Our hypothesis is that convalescent plasma transfusion from healthy donors who recovered from SARS CoV-2 is able to reduce the cytokine storm in addition to replenish the patient's own antibodies in the acutely infected phase of the disease.
A plasmapheresis donation of 400ml will be performed in subjects who recovered from COVID-19 and who are otherwise eligible for plasma donation. The sample will be tested for anti-SARS CoV-2 neutralizing antibody titers and those that reach the level of 1:320 will be processed for transfusion at the Hungarian National Transfusion Service.
Recipients will be COVID-19 patients requiring hospitalization regardless of the severity of the disease or other co-morbidities. A blood-type matched transfusion of 200 ml convalescent plasma will be infused in a single sitting through an iv. infusion of 4 hours.
Recipients will be followed up at days 1, 3,7,12, 17, 28 for clinical symptoms, antibody levels and cytokine response.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Hospitalized patients with SARS CoV-2 infection
|
Biological: anti-SARS-CoV-2 convalescent plasma
Infusion of one unit of anti-SARS-CoV-2 convalescent plasma ~200 mL over 4 hours
|
Outcome Measures
Primary Outcome Measures
- Changing of viral load of SARS-CoV2 [Day 1,3, 7, 12]
Copies of COVID-19 per ml
Secondary Outcome Measures
- Changes in immunglobulin G COVID-19 antibody titer [12 days]
Immunoglobulin G COVID-19 antibodies Immunglobulin G antibody titer
- Changes at the cytokine pattern [12 days]
- Intensive Care Unit Admission [Day 7,12,28]
Proportion of patients with Intensive Care Unit Admission requirement
- Length of hospital stay [Day 7, 12, 28]
Days of Hospitalization
- Duration of mechanical ventilation [Day 7, 12, 28]
Days with mechanical ventilation
- Clinical Status [Day 7, 12, 28]
Clinical status assessed according to the World Health Organization guideline
- Mortality [Day 7, 12, 28]
Proportion of death patients at days
Eligibility Criteria
Criteria
Inclusion criteria for blood donors :
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age : >18 and <60 years
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body weight : >50 kg
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confirmed previous SARS CoV-2 infection
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2 negative SARS CoV-2 test result
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written informed consent
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neutralizing antibody titer min. 1 : 120
Exclusion criteria for blood donors :
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age : <18 or >60 years
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female subjects who are pregnant
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HIV1,2 hepatitis B,C or syphilis infection
to minimize the transfusional side effects our aim is to include mostly male donors.
Inclusion criteria for patients/recipients :
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age : >18 years
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admitted to hospital due to SARS CoV-2 infection
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written informed consent
Exclusion criteria for patients/recipients :
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age : <18 years
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female subjects who are pregnant or breastfeeding
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patients with prior allergic reaction to transfusion
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patients who received in the past 30 days immunoglobulin therapy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Semmelweis University's Department of Pulmonology | Budapest | Hungary | 1083 |
Sponsors and Collaborators
- Orthosera Kft.
- Semmelweis University
- University of Pecs
- Hungarian National Blood Service
- Humán Bioplazma Kft - Kedrion
Investigators
- Principal Investigator: Veronika Müller, MD, PhD, Semmelweis University
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Arabi Y, Balkhy H, Hajeer AH, Bouchama A, Hayden FG, Al-Omari A, Al-Hameed FM, Taha Y, Shindo N, Whitehead J, Merson L, AlJohani S, Al-Khairy K, Carson G, Luke TC, Hensley L, Al-Dawood A, Al-Qahtani S, Modjarrad K, Sadat M, Rohde G, Leport C, Fowler R. Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol. Springerplus. 2015 Nov 19;4:709. doi: 10.1186/s40064-015-1490-9. eCollection 2015.
- Belyakov IM, Hel Z, Kelsall B, Kuznetsov VA, Ahlers JD, Nacsa J, Watkins DI, Allen TM, Sette A, Altman J, Woodward R, Markham PD, Clements JD, Franchini G, Strober W, Berzofsky JA. Mucosal AIDS vaccine reduces disease and viral load in gut reservoir and blood after mucosal infection of macaques. Nat Med. 2001 Dec;7(12):1320-6.
- Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum in: Lancet. 2020 Jan 30;:.
- Kardos D, Marschall B, Simon M, Hornyák I, Hinsenkamp A, Kuten O, Gyevnár Z, Erdélyi G, Bárdos T, Paukovits TM, Magos K, Béres G, Szenthe K, Bánáti F, Szathmary S, Nehrer S, Lacza Z. Investigation of Cytokine Changes in Osteoarthritic Knee Joint Tissues in Response to Hyperacute Serum Treatment. Cells. 2019 Aug 3;8(8). pii: E824. doi: 10.3390/cells8080824.
- Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034. doi: 10.1016/S0140-6736(20)30628-0. Epub 2020 Mar 16.
- Nacsa J, Edghill-Smith Y, Tsai WP, Venzon D, Tryniszewska E, Hryniewicz A, Moniuszko M, Kinter A, Smith KA, Franchini G. Contrasting effects of low-dose IL-2 on vaccine-boosted simian immunodeficiency virus (SIV)-specific CD4+ and CD8+ T cells in macaques chronically infected with SIVmac251. J Immunol. 2005 Feb 15;174(4):1913-21.
- Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, Wang F, Li D, Yang M, Xing L, Wei J, Xiao H, Yang Y, Qu J, Qing L, Chen L, Xu Z, Peng L, Li Y, Zheng H, Chen F, Huang K, Jiang Y, Liu D, Zhang Z, Liu Y, Liu L. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. 2020 Apr 28;323(16):1582-1589. doi: 10.1001/jama.2020.4783.
- AntiCOVID19ORT