Safety and efficacy of convalescent plasma for COVID-19: the preliminary results of a clinical trial

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Abstract

Background. The lack of effective etiotropic therapy for COVID-19 has prompted researchers around the globe to seekr various methods of SARS-CoV-2 elimination, including the use of convalescent plasma.

Aim. The aim of this work was to study the safety and efficacy of the convalescence plasma treatment of severe COVID-19 using the plasma containing specific antibodies to the receptor binding domain (RBD) of SARS-CoV-2 S protein in a titer of at least 1:1000.

Methods. A single-center, randomized, prospective clinical study was performed at the FRCC FMBA of Russia with the participation of 86 patients who were stratified in two groups. The first group included 20 critically ill patients who were on mechanical ventilation the second group included 66 patients with moderate to severe COVID-19 and with spontaneous respiration. The patients in the second group were randomized into two cohorts in a ratio of 2:1. In the first cohort (46 patients), pathogen-reduced convalescent plasma was transfused (twice, 320 ml each), in the second cohort (20 patients) a similar amount of non-immune freshly frozen plasma was transfused to the patients.

Results. The use of plasma of convalescents in patients with severe COVID-19 being on mechanical ventilation does not affect the disease outcome in these patients. The mortality rate in this group was 60%, which corresponds to the average mortality of COVID patients on mechanical ventilation in our hospital. In the second group, clinical improvement was detected in 75% and 51%, for convalescent and non-immune plasma, respectively. Of the 46 people who received convalescent plasma, three patients (6.5%) were transferred to mechanical ventilation, two of them died. In the group receiving non-immune plasma, the need for mechanical ventilation also arose in three patients (15%), of which two died. The hospital mortality in the group of convalescent plasma was 4.3%, which is significantly lower than the average COVID-19 hospital mortality at our Center (6.73%) and more than two times lower than the hospital mortality in the control group (n=150), matched by age and by the disease severity.

Conclusions. Thus, we demonstrated a relative safety of convalescent plasma transfusion and the effectiveness of such therapy for COVID-19 at least in terms of the survival of hospitalized patients with severe respiratory failure without mechanical ventilation. In the absence of bioengineered neutralizing antibodies and effective etiotropic therapy, the use of hyperimmune convalescent plasma is the simplest and most effective method of specific etiopathogenetic therapy of severe forms of COVID-19.

About the authors

Vladimir P. Baklaushev

Federal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency of Russia

Author for correspondence.
Email: baklaushev.vp@fnkc-fmba.ru
ORCID iD: 0000-0003-1039-4245
SPIN-code: 3968-2971
https://fnkc-fmba.ru/about/komanda-upravleniya/

MD, PhD, Chief Scientific Officer

Russian Federation, Moscow

Alexander V. Averyanov

Federal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency of Russia; Research Institute of Pulmonology of the Federal Medical and Biological Agency of Russia

Email: averyanovav@mail.ru
ORCID iD: 0000-0003-1031-6933
SPIN-code: 2229-7100

MD, PhD, Professor

Russian Federation, Moscow

Anna G. Sotnikova

Federal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency of Russia; Research Institute of Pulmonology of the Federal Medical and Biological Agency of Russia

Email: sotnikoffaa@gmail.com
ORCID iD: 0000-0003-1237-8134

MD, PhD

Russian Federation, Moscow

Anastasia S. Perkina

Federal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency of Russia; Research Institute of Pulmonology of the Federal Medical and Biological Agency of Russia

Email: anastasyaperkina@gmail.com
ORCID iD: 0000-0003-0351-1802

MD

Russian Federation, Moscow

Alexander V. Ivanov

Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences

Email: aivanov@yandex.ru
ORCID iD: 0000-0002-5659-9679

PhD

Russian Federation, Moscow

Gaukhar M. Yusubalieva

Federal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency of Russia

Email: gaukhar@gaukhar.org
ORCID iD: 0000-0003-3056-4889
SPIN-code: 1559-5866

MD, PhD

Russian Federation, Moscow

Oksana N. Novikova

Federal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency of Russia

Email: Novikova_oksana_@mail.ru
ORCID iD: 0000-0003-2779-0383

MD, PhD

Russian Federation, Moscow

Valentina E. Shikina

Federal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency of Russia

Email: shik-val@mail.ru
ORCID iD: 0000-0002-6672-4269

MD, PhD

Russian Federation, Moscow

Nikolay V. Dupik

Federal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency of Russia

Email: dnv-74@yandex.ru
ORCID iD: 0000-0002-6672-4269

MD

Russian Federation, Moscow

Anna G. Kedrova

Federal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency of Russia

Email: kedrova.anna@gmail.com
ORCID iD: 0000-0003-1031-9376
SPIN-code: 3184-9760

MD, PhD

Russian Federation, Moscow

Andrey E. Sanzharov

Federal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency of Russia

Email: sanzh@mail.ru
ORCID iD: 0000-0003-1056-3053
SPIN-code: 5713-5791

MD

Russian Federation, Moscow

Elena V. Shirshova

Federal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency of Russia

Email: shirshova60@rambler.ru
ORCID iD: 0000-0001-9193-0534

MD, PhD

Russian Federation, Moscow

Olga I. Balionis

Federal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency of Russia

Email: balionis.oi@gmail.com
ORCID iD: 0000-0002-8251-4050
SPIN-code: 7208-4442

MD

Russian Federation, Moscow

Vladimir T. Valuev-Elliston

Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences

Email: gansfaust@mail.ru
ORCID iD: 0000-0003-0365-570X
SPIN-code: 3492-4501
Russian Federation, Moscow

Natalia F. Zakirova

Federal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency of Russia; Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences

Email: nat_zakirova@mail.ru
ORCID iD: 0000-0001-9704-6977
SPIN-code: 8050-2592

PhD

Russian Federation, Moscow

Yaroslav N. Glazov

Blood Center of the Federal Medical and Biological Agency of Russia

Email: yglazov@bloodfmba.ru
ORCID iD: 0000-0001-7761-8093

MD

Russian Federation, Moscow

Irina A. Panukhina

Federal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency of Russia

Email: panyuirina@yandex.ru
ORCID iD: 0000-0002-8662-3457

MD

Russian Federation, Moscow

Nikolay A. Soloviev

Federal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency of Russia

Email: my_docs@mail.ru
ORCID iD: 0000-0001-9760-289X
SPIN-code: 8024-7220

MD, PhD

Russian Federation, Moscow

Alexei G. Vinokurov

Federal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency of Russia

Email: avinok@yandex.ru
ORCID iD: 0000-0002-6672-4269

MD, PhD

Russian Federation, Moscow

Yu. V. Ivanov

Federal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency of Russia

Email: ivanovkb83@yandex.ru
ORCID iD: 0000-0001-6209-4194
SPIN-code: 3240-4335

MD, PhD

Russian Federation, Moscow

Valentin N. Vasilev

Federal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency of Russia

Email: vasilievvn@list.ru
ORCID iD: 0000-0002-2853-4528

MD

Russian Federation, Moscow

Tatyana V. Klypa

Federal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency of Russia

Email: tvklypa@gmail.com
ORCID iD: 0000-0002-2732-967X

MD, PhD

Russian Federation, Moscow

Alexander V. Troitsky

Federal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency of Russia

Email: drtroitskiy@gmail.com
ORCID iD: 0000-0003-2411-6043

MD, PhD, Professor

Russian Federation, Moscow

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Supplementary files

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2. Fig. 1. Determination of the titer of virus-neutralizing antibodies to RBD S-protein SARS-CoV-2 in a patient after transfusion of two doses of plasma.

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3. Fig. 2. Cumulative survival curves of patients receiving immune and non-immune plasma

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4. Fig. 3. Dynamics of body temperature in patients after plasma transfusion, ° С

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5. Fig. 4. Dynamics of the concentration of C-reactive protein in blood serum in patients after plasma transfusion, mg / l

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Copyright (c) 2020 Baklaushev V.P., Averyanov A.V., Sotnikova A.G., Perkina A.S., Ivanov A.V., Yusubalieva G.M., Novikova O.N., Shikina V.E., Dupik N.V., Kedrova A.G., Sanzharov A.E., Shirshova E.V., Balionis O.I., Valuev-Elliston V.T., Zakirova N.F., Glazov Y.N., Panukhina I.A., Soloviev N.A., Vinokurov A.G., Ivanov Y.V., Vasilev V.N., Klypa T.V., Troitsky A.V.

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