Convalescent plasma as an adjunctive treatment for severe and critically ill COVID-19

Damai Santosa; Muchlis Achsan Udji Sofro; Retnaningsih Retnaningsih; Eko Adhi Pangarsa; Budi Setiawan; Nur Farhanah; Fathur Nur Kholis; Thomas Handoyo; Sofyan Rahardjo; Like Rahayu Nindhita; Iva Puspitasari; Ridho M. Naibaho; Retty Kharismasari; Ika Kartiyani; Vina Yunarvika; Daniel Rizky; Suhartono Suhartono

doi:10.15562/bmj.v10i3.2590

Convalescent plasma as an adjunctive treatment for severe and critically ill COVID-19

Damai Santosa ,

Muchlis Achsan Udji Sofro ,

Retnaningsih Retnaningsih ,

Eko Adhi Pangarsa ,

Budi Setiawan ,

Nur Farhanah ,

Fathur Nur Kholis ,

Thomas Handoyo ,

Sofyan Rahardjo ,

Like Rahayu Nindhita ,

Iva Puspitasari ,

Ridho M. Naibaho ,

Retty Kharismasari ,

Ika Kartiyani ,

Vina Yunarvika ,

Daniel Rizky ,

Suhartono Suhartono ,

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DOI: https://doi.org/10.15562/bmj.v10i3.2590 |
Published: 2021-09-14

Abstract

Introduction: The historical treatment of convalescent plasma was successful against RNA viruses. However, the significance of COVID-19 convalescent plasma therapy has not been clinically proven consistently in most studies and the available data showed contradictory results so far. Our study aims to evaluate the role of convalescent plasma therapy as an adjunctive treatment for severe and critically ill COVID-19 patients.

Methods: This study was an open-label, non-randomized comparative clinical trial that was conducted at Dr. Kariadi Hospital, Semarang, Indonesia. This study sample are hospitalized severe and critically ill COVID-19 patients were assigned with a 2:1 ratio to receive convalescent plasma and local standard of care. The primary outcome was the clinical status 30 days after the intervention

Results: A total of 73 patients received convalescent plasma and 38 patients received local standards of care. Both of the groups had similar clinical ordinal scales (median was 5, p=0.65), while patients in the study groups had significantly higher SOFA scores and P/F ratio. The control group had a worse overall mortality rate (61.1% vs 18.4%) with a hazard ratio of 3.5 (95%CI, 2.1-5.9) compared to the study group. From the subgroup analysis, we found that patients in the study group without mechanical ventilation support had the best survival rate compared to other groups HR: 0.0047 (95%CI, 0.01-0.19). The clinical outcome 7 days after convalescent plasma infusion was also significantly improved in the study group (median baseline & day-7, 5 & 3, p<0.001). From the multivariate analysis of therapeutic variables, convalescent plasma was the most significant variable for survival outcome (OR=0.089, 95%CI, 0.029-0.27; p<0.001). There was one case of anaphylactic shock and was excluded.

Conclusions: The convalescent plasma administration significantly improved clinical outcomes and overall survival rates compared to those who received local standards of care.

References

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Pathak EB. Convalescent plasma is ineffective for covid-19. BMJ. 2020;371:4072.
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[2] Cucinotta D, Vanelli M. WHO Declares COVID-19 a Pandemic. Acta Biomed. 2020;91(1):157–60.

[3] Riou J, Althaus CL. Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020. Eurosurveillance. 2020;25(4).

[4] Muhyiddin, M., & Nugroho H. A Year of Covid-19: A Long Road to Recovery and Acceleration of Indonesia’s Development. J Perenc Pembang Indones J Dev Plan. 2021;5(1)(1):1–19. Available from: https://doi.org/10.36574/jpp.v5i1.181

[5] Ariawan I, Jusril H. COVID-19 in Indonesia: Where Are We? Acta Medica Indones Indones J Intern Med. 2020;52:193–4.

[6] Setiati S, Azwar MK. COVID-19 and Indonesia. Acta Med Indones. 2020;52(1):84–9.

[7] Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382(18):1708–20.

[8] Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China. JAMA. 2020;323(13):1239.

[9] Shang Y, Pan C, Yang X, Zhong M, Shang X, Wu Z, et al. Management of critically ill patients with COVID-19 in ICU: statement from front-line intensive care experts in Wuhan, China. Ann Intensive Care. 2020;10(1):73.

[10] COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. Natl Institutes Heal. 2020;

[11] Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021;384(8):693–704.

[12] Soo YOY, Cheng Y, Wong R, Hui DS, Lee CK, Tsang KKS, et al. Retrospective comparison of convalescent plasma with continuing high-dose methylprednisolone treatment in SARS patients. Clin Microbiol Infect. 2004;10(7):676–8.

[13] Yeh K-M, Chiueh T-S, Siu LK, Lin J-C, Chan PKS, Peng M-Y, et al. Experience of using convalescent plasma for severe acute respiratory syndrome among healthcare workers in a Taiwan hospital. J Antimicrob Chemother. 2005;56(5):919–22.

[14] Wong SSY, Yuen K-Y. The management of coronavirus infections with particular reference to SARS. J Antimicrob Chemother. 2008;62(3):437–41.

[15] Shankar-Hari M, Estcourt L, Harvala H, Roberts D, Menon DK. Convalescent plasma to treat critically ill patients with COVID-19: framing the need for randomised clinical trials. Crit Care. 2020;24(1):449.

[16] Lagunas-Rangel FA, Chávez-Valencia V. What do we know about the antibody responses to SARS-CoV-2? Immunobiology. 2021;226(2):152054.

[17] Acosta-Ampudia Y, Monsalve DM, Rojas M, Rodríguez Y, Gallo JE, Salazar-Uribe JC, et al. COVID-19 convalescent plasma composition and immunological effects in severe patients. J Autoimmun. 2021;118:102598.

[18] Rojas M, Rodríguez Y, Monsalve DM, Acosta-Ampudia Y, Camacho B, Gallo JE, et al. Convalescent plasma in Covid-19: Possible mechanisms of action. Autoimmun Rev. 2020;19(7):102554.

[19] Joyner MJ, Bruno KA, Klassen SA, Kunze KL, Johnson PW, Lesser ER, et al. Safety Update. Mayo Clin Proc. 2020;95(9):1888–97.

[20] Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, et al. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. 2020;(29):1–8.

[21] Duan K, Liu B, Li C, Zhang H, Yu T, Qu J, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci. 2020;117(17):9490–6.

[22] Cunningham AC, Goh HP, Koh D. Treatment of COVID-19: old tricks for new challenges. Crit Care. 2020;24(1):91.

[23] Salazar E, Perez KK, Ashraf M, Chen J, Castillo B, Christensen PA, et al. Treatment of Coronavirus Disease 2019 (COVID-19) Patients with Convalescent Plasma. Am J Pathol. 2020;190(8):1680–90.

[24] Xia X, Li K, Wu L, Wang Z, Zhu M, Huang B, et al. Improved clinical symptoms and mortality among patients with severe or critical COVID-19 after convalescent plasma transfusion. Blood. 2020;136(6):755–9.

[25] Li L, Zhang W, Hu Y, Tong X, Zheng S, Yang J, et al. Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients with Severe and Life-threatening COVID-19: A Randomized Clinical Trial. JAMA - J Am Med Assoc. 2020;324(5):460–70.

[26] Simonovich VA, Burgos Pratx LD, Scibona P, Beruto M V., Vallone MG, Vázquez C, et al. A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia. N Engl J Med. 2020;1–11.

[27] Agarwal A, Mukherjee A, Kumar G, Chatterjee P, Bhatnagar T, Malhotra P. Convalescent plasma in the management of moderate covid-19 in adults in India: Open label phase II multicentre randomised controlled trial (PLACID Trial). BMJ. 2020;371:10–1.

[28] Tanne JH. Covid-19: FDA approves use of convalescent plasma to treat critically ill patients. BMJ. 2020;368(August):m1256.

[29] Pathak EB. Convalescent plasma is ineffective for covid-19. BMJ. 2020;371:4072.

[30] Sj V, Piechotta V, Kl C, Doree C, Monsef I, Em W, et al. with COVID-19 : a rapid review ( Review ). 2020;

[31] Gharbharan A, Jordans CCE, GeurtsvanKessel C, Hollander JG den, Karim F, Mollema FPN, et al. Convalescent Plasma for COVID-19. A randomized clinical trial. medRxiv. 2020;2020.07.01.20139857.

[32] Joyner MJ, Senefeld JW, Klassen SA, Mills JR, Johnson PW, Theel ES, et al. Effect of Convalescent Plasma on Mortality among Hospitalized Patients with COVID-19: Initial Three-Month Experience. medRxiv Prepr Serv Heal Sci. 2020;1–31.

[33] Wang L. C-reactive protein levels in the early stage of COVID-19. Med Mal Infect. 2020;50(4):332–4.

[34] Liu S, Yao N, Qiu Y, He C. Predictive performance of SOFA and qSOFA for in-hospital mortality in severe novel coronavirus disease. Am J Emerg Med. 2020;38(10):2074–80.

[35] ECDC. Rapid increase of a SARS-CoV-2 variant with multiple spike protein mutations observed in the United Kingdom. Eur Cent Dis Prev Control. 2020;1–13.

[36] Nidom R V., Indrasari S, Normalina I, Kusala MKJ, Ansori ANM, Nidom CA. Investigation of the D614G mutation and antibody-dependent enhancement sequences in indonesian SARS-CoV-2 isolates and comparison to southeast Asian isolates. Syst Rev Pharm. 2020;11(8):203–13.

Convalescent plasma as an adjunctive treatment for severe and critically ill COVID-19

Abstract

References

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