COVID-19 convalescent plasma treatment of moderate and severe cases of SARS-CoV-2 infection: A multicenter interventional study

Sondas Alsharidah 1, Mariam Ayed 2, Reem M Ameen 3, Fatma Alhuraish 4, Najat A Rouheldeen 5, Farah R Alshammari 6, Alia Embaireeg 7, Mariam Almelahi 8, Maitham Adel 9, Mohammed E Dawoud 10, Mohammad A Aljasmi 9, Nashmi Alshammari 11, Abdullah Alsaeedi 6, Wasel Al-Adsani 8, Hussan Arian 9, Husain Awad 9, Humoud A Alenezi 12, Azeez Alzafiri 6, Enas F Gouda 13, Mohammad Almehanna 9, Salem Alqahtani 14, Abdulrahman Alshammari 6, Medhat Z Askar 15

Affiliations

02 January 2021

-

doi: 10.1016/j.ijid.2020.11.198

Abstract

Objective: To study the effectiveness of COVID-19 convalescent plasma (CCP) therapy for patients with moderate and severe COVID-19 disease.

Methods: This non-randomized prospective cohort study was conducted from May 21 to June 30, 2020, at four major tertiary hospitals in Kuwait. CCP was administered to 135 patients. The control group comprised 233 patients who received standard treatment. All patients (N = 368, median age 54 [range 15-82]) had laboratory-confirmed SARS-CoV-2 infection and either moderate or severe COVID-19 disease.

Results: CCP treatment was associated with a higher rate of clinical improvement in patients with moderate or severe disease. Among those with moderate COVID-19 disease, time to clinical improvement was 7 days in the CCP group, versus 8 days in the control group (p = 0·006). For severe COVID-19 disease, time to clinical improvement was 7 days in the CCP group, versus 15.5 days in the control group (p = 0·003). In the adjusted analysis, patients with moderate disease treated with CCP had a significantly lower 30-day mortality rate. Compared to the control group, oxygen saturation improved within 3 days of CCP transfusion, and lymphocyte counts improved from day 7 in patients with moderate COVID-19 disease and day 11 in patients with severe disease. C-reactive protein levels declined throughout the first 14 days after CCP transfusion. None of the CCP patients developed a serious transfusion reaction.

Conclusions: The data show that administration of CCP is a safe treatment option for patients with COVID-19 disease with a favorable outcome in the rate of, and time to, clinical improvement.

Keywords: COVID-19; Clinical improvement; Convalescent plasma; Mortality; Pneumonia; SARS-CoV-2.

Conflict of interest statement

We declare no competing interests.

Figures

Fig. 1 Study Flow chart.

Fig. 1 Study Flow chart.

Fig. 2 Kaplan-Meier Estimate for Time to Clinical improvement according to disease severity. A) All patients; B) Moderate COVID-19 disease; C) Severe COVID-19 disease.

Fig. 2 Kaplan-Meier Estimate for Time to Clinical improvement according to disease severity. A) All patients; B) Moderate COVID-19 disease; C) Severe COVID-19 disease.

Similar articles

Reconvalescent plasma/camostat mesylate in early SARS-CoV-2 Q-PCR positive high-risk individuals (RES-Q-HR): a structured summary of a study protocol for a randomized controlled trial.

Keitel V, Jensen B, Feldt T, Fischer JC, Bode JG, Matuschek C, Bölke E, Budach W, Plettenberg C, Scheckenbach K, Kindgen-Milles D, Timm J, Müller L, Kolbe H, Stöhr A, Calles C, Hippe A, Verde P, Spinner CD, Schneider J, Wolf T, Kern WV, Nattermann J, Zoufaly A, Ohmann C, Luedde T; RES-Q-HR Trial Team.Trials. 2021 May 17;22(1):343. doi: 10.1186/s13063-021-05181-0.PMID: 34001215 Free PMC article.

Reduced Mortality among COVID-19 ICU Patients after Treatment with HemoClear Convalescent Plasma in Suriname.

Bihariesingh-Sanchit R, Bansie R, Ramdhani N, Mangroo R, Bustamente D, Diaz E, Fung A Foek C, Thakoer I, Vreden S, Choudhry Z, van 't Wout AB, Diavatopoulos DA, Nierich AP.mBio. 2023 Apr 25;14(2):e0337922. doi: 10.1128/mbio.03379-22. Epub 2023 Feb 23.PMID: 36815780 Free PMC article.

Early but not late convalescent plasma is associated with better survival in moderate-to-severe COVID-19.

Briggs N, Gormally MV, Li F, Browning SL, Treggiari MM, Morrison A, Laurent-Rolle M, Deng Y, Hendrickson JE, Tormey CA, Desruisseaux MS.PLoS One. 2021 Jul 28;16(7):e0254453. doi: 10.1371/journal.pone.0254453. eCollection 2021.PMID: 34320004 Free PMC article.

COVID 19 convalescent plasma: Is there still a place for CCP?

Moog R.Transfus Apher Sci. 2023 Apr;62(2):103680. doi: 10.1016/j.transci.2023.103680. Epub 2023 Feb 24.PMID: 36870907 Free PMC article. Review.

Convalescent Plasma Therapy in Late-State, Severe COVID-19 Infection.

Kumar NR, Karanam VC, Kumar S, Kumar SD.South Med J. 2023 May;116(5):427-433. doi: 10.14423/SMJ.0000000000001546.PMID: 37137479 Free PMC article. Review.

Cited by

The effect of convalescent plasma on the treatment of COVID-19 patients in Ardabil, Iran.

Iranijam E, Ghobadi H, Matin S, Habibzadeh S, Zandian H, Mohammadshahi J, Fooladi S, Dargahi A, Safarzadeh E, Negaresh M, Hosseini J, Samadi AH, Hoseininia S, Salehzadeh H, Dezhkam S.J Educ Health Promot. 2022 Aug 25;11:266. doi: 10.4103/jehp.jehp_1439_21. eCollection 2022.PMID: 36325204 Free PMC article.

Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients-An Open-Label Phase II Clinical Trial.

Grubovic Rastvorceva RM, Useini S, Stevanovic M, Demiri I, Petkovic E, Franchini M, Focosi D.Life (Basel). 2022 Oct 9;12(10):1565. doi: 10.3390/life12101565.PMID: 36295001 Free PMC article.

Characterization of pathogen-inactivated COVID-19 convalescent plasma and responses in transfused patients.

Weisser M, Khanna N, Hedstueck A, Sutter ST, Roesch S, Stehle G, Sava M, Deigendesch N, Battegay M, Infanti L, Holbro A, Bassetti S, Pargger H, Hirsch HH, Leuzinger K, Kaiser L, Vu DL, Baur K, Massaro N, Busch MP, Simmons G, Stone M, Felgner PL, de Assis RR, Khan S, Tsai CT, Robinson PV, Seftel D, Irsch J, Bagri A, Buser AS, Corash L.Transfusion. 2022 Oct;62(10):1997-2011. doi: 10.1111/trf.17083. Epub 2022 Sep 5.PMID: 36054476 Free PMC article.

A possibilistic-robust-fuzzy programming model for designing a game theory based blood supply chain network.

Ghasemi P, Goodarzian F, Abraham A, Khanchehzarrin S.Appl Math Model. 2022 Dec;112:282-303. doi: 10.1016/j.apm.2022.08.003. Epub 2022 Aug 5.PMID: 35946032 Free PMC article.

Serial Convalescent Plasma Infusions for the Initial COVID-19 Infections in the Appalachian Region of West Virginia.

Peppers BP, Shmookler A, Stanley J, Giblin Sutton L, Perrotta PL, Kieffer T, Skoner D, Mahady S, Lewandrowski C, Damron H, Horspool A, Sakhjua A, McCarthy P, Hostoffer RW.Allergy Rhinol (Providence). 2022 Jun 30;13:21526575221110488. doi: 10.1177/21526575221110488. eCollection 2022 Jan-Dec.PMID: 35795339 Free PMC article. Clinical Trial.

KMEL References

https://pubmed.ncbi.nlm.nih.gov/

References

  1.  
    1. American Association of Blood Banks (AABB) American Association of Blood Banks (AABB); 2020. Donor eligibility (screening and testing)
  2.  
    1. Arabi Y., Balkhy H., Hajeer A.H., Bouchama A., Hayden F.G., Al-Omari A. Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol. SpringerPlus. 2015;4:709. - PMC - PubMed
  3.  
    1. Brown B.L., McCullough J. Treatment for emerging viruses: convalescent plasma and COVID-19. Transfus Apher Sci. 2020;59(3) - PMC - PubMed
  4.  
    1. Duan K., Liu B., Li C., Zhang H., Yu T., Huang J. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci U S A. 2020;117(17):9490–9496. - PMC - PubMed
  5.  
    1. Eckhardt C.M., Cummings M.J., Rajagopalan K.N., Borden S., Bitan Z.C., Wolf A. Evaluating the efficacy and safety of human anti-SARS-CoV-2 convalescent plasma in severely ill adults with COVID-19: a structured summary of a study protocol for a randomized controlled trial. Trials. 2020;21(1):499. - PMC - PubMed
  6.  
    1. Garraud O., Heshmati F., Pozzetto B., Lefrere F., Girot R., Saillol A. Plasma therapy against infectious pathogens, as of yesterday, today and tomorrow. Transfus Clin Biol. 2016;23(1):39–44. - PMC - PubMed
  7.  
    1. Gralinski L.E., Sheahan T.P., Morrison T.E., Menachery V.D., Jensen K., Leist S.R. Complement activation contributes to severe acute respiratory syndrome coronavirus pathogenesis. mBio. 2018;9(5) - PMC - PubMed
  8.  
    1. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. - PMC - PubMed
  9.  
    1. Hung I.F., To K.K., Lee C.K., Lee K.-L., Yan W.-W., Liu R. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis. 2011;52(4):447–456. - PMC - PubMed
  10.  
    1. Integrated Management of Adolescent and Adult Illness (IMAI) District Clinician Manual: Hospital Care for Adolescents and Adults . World Health Organization; Geneva, Switzerland: 2011. Guidelines for the management of common illnesses with limited resources.
  11.  
    1. Investigational COVID-19 Convalescent Plasma Guidance for Industry . 2020. Food and drug administration center for biologics evaluation and research.
  12.  
    1. Joyner M.J., Wright R.S., Fairweather D., Senfeld J.W., Burno K.A., Klassen S.A. Early safety indicators of COVID-19 convalescent plasma in 5,000 patients. J Clin Invest. 2020;130(9):4791–4797. - PMC - PubMed
  13.  
    1. Ko J.H., Seok H., Cho S.Y., Ha Y.E., Beak J.Y., Kim S.H. Challenges of convalescent plasma infusion therapy in Middle East respiratory coronavirus infection: a single centre experience. Antivir Ther. 2018;23(7):617–622. - PubMed
  14.  
    1. Li L., Zhang W., Hu Y., Ton X., Zheng S., Yang J. Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19: a randomized clinical trial. JAMA. 2020;324(5):1–11. - PMC - PubMed
  15.  
    1. Lunemann J.D., Nimmerjahn F., Dalakas M.C. Intravenous immunoglobulin in neurology—mode of action and clinical efficacy. Nat Rev Neurol. 2015;11(2):80–89. - PubMed
  16.  
    1. Mair-Jenkins J., Saavedra-Campos M., Baillie J.K., Cleary P., Khaw F.-M., Lim W.S. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J Infect Dis. 2015;211(1):80–90. - PMC - PubMed
  17.  
    1. Perotti C., Baldanti F., Bruno R., Del Fante C., Seminari E., Casari S. Mortality reduction in 46 severe Covid-19 patients treated with hyperimmune plasma. A proof of concept single arm multicenter trial. Haematologica. 2020;105(12):2834–2840. - PMC - PubMed
  18.  
    1. Ruan Q., Yang K., Wang W., Jiang L., Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;46(5):846–848. - PMC - PubMed
  19.  
    1. Shakir E.M., Cheung D.S., Grayson M.H. Mechanisms of immunotherapy: a historical perspective. Ann Allergy Asthma Immunol. 2010;105(5):340–347. quiz 8, 68. - PubMed
  20.  
    1. Shen C., Wang Z., Zhao F., Yang Y., Li J., Yuan J. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA. 2020;323(16):1582–1589. - PMC - PubMed
  21.  
    1. Soo Y.O., Cheng Y., Wong R., Hui D.S., Lee C.K., Tsang K.K.S. Retrospective comparison of convalescent plasma with continuing high-dose methylprednisolone treatment in SARS patients. Clin Microbiol Infect. 2004;10(7):676–678. - PMC - PubMed
  22.  
    1. van Griensven J., Edwards T., de Lamballerie X., Malcom G.S., Gallian P., Baize S. Evaluation of convalescent plasma for ebola virus disease in Guinea. N Engl J Med. 2016;374(1):33–42. - PMC - PubMed
  23.  
    1. World Health Organization . World Health Organization; 2020. R&D blueprint and COVID-19.
  24.  
    1. Xia X., Li K., Wu L., Wang Z., Zhu M., Huang B. Improved clinical symptoms and mortality among patients with severe or critical COVID-19 after convalescent plasma transfusion. Blood. 2020;136(6):755–759. - PMC - PubMed
  25.  
    1. Zeng Q.L., Yu Z.J., Gou J.J., Li G., Ma S.-H., Zhang G.-F. Effect of convalescent plasma therapy on viral shedding and survival in patients with coronavirus disease 2019. J Infect Dis. 2020;222(1):38–43. - PMC - PubMed
  26.  
    1. Zhu N., Zhang D., Wang W., Li X., Yang B., Sony J. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382(8):727–733. - PMC - PubMed

Page Navigation