Adjunctive treatment with high-titre convalescent plasma in severely and critically ill COVID-19 patients – a safe but futile intervention. A comparative cohort study

Abstract

Background Convalescent plasma (CP) containing antibodies derived from coronavirus disease 2019 (COVID-19) survivors has been proposed as a promising therapeutic option for severe COVID-19. Methods In our intensive care unit (ICU), 55 patients (46 male, median age 61 years) with PCR-confirmed COVID-19 (35 = 63.6% on mechanical ventilation, 7 = 14.5% on high-flow nasal oxygen, 12 = 20% on non-invasive ventilation, 1 = 1.8% without respiratory support) were treated with high-titre CP (200 mL per dose, range 1–6 doses, median 3 doses per patient, minimum titre > 1:100, Wantai test). 139 COVID-19 patients treated in the same ICU who did not receive CP served as control group. In 27 patients, the effect of CP on the individual levels of SARS-CoV-2 IgG antibodies was assessed by ELISA in serum sample pairs collected before and after CP transfusion. Results The first CP dose was administered at a median of 8 days after symptom onset. 13 patients in the plasma cohort died (28-day mortality 24.1%), compared to 42 (30.2%) in the cohort who did not receive CP ( p = 0.5, Pearson Chi-squared test). Out of the 27 individuals investigated for the presence of IgG antibodies, 8 did not have detectable IgG levels before the first CP transfusion. In this subpopulation, 3 patients (37.5%) died. Not a single confirmed adverse reaction to CP was noted. Conclusions While adjunctive treatment with CP for severe and life-threatening COVID-19 was a very safe intervention, we did not observe any effect on mortality.

CONVALESCENT plasma for COVID‐19: A meta‐analysis of clinical trials and real‐world evidence

“…A total of 4728 records were identified from databases, websites and citation searching. There were 47 studies 16‐62 fulfilled the inclusion criteria and were used for the systematic review and meta‐analysis (Figure 1). Of 47 included studies, 21 were clinical trials 16‐33,60‐62 and 26 were observational studies 34‐59 .…”

“…Of 47 included studies, 21 were clinical trials 16‐33,60‐62 and 26 were observational studies 34‐59 . Among clinical trials, there were 18 studies published in peer‐reviewed journals 16‐33 while the other three were preprints 60‐62 . Among clinical trials, there were 14 studies used the randomization process 17‐20,23,25,26,28,30,31,33,60‐62 .…”

“…There were 47 studies fulfilled the inclusion criteria and were used for the systematic review and meta-analysis (Figure 1). Of 47 included studies, 21 were clinical trials [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][60][61][62] and 26 were observational studies. Among clinical trials, there were 18 studies published in peer-reviewed journals [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] while the other three were preprints.…”

Diagnostik und Therapie von COVID-19 auf der Intensivstation

“…Einen interessanten Ansatz stellt die Behandlung von kritisch kranken COVID-19 Patientinnen und Patienten mit Rekonvaleszentenplasma dar. Die Autoren haben ihn bei 55 Patientinnen und Patienten auf ihrer Intensivstation angewendet, jedoch trotz eines hervorragenden Sicherheitsprofils (keine einzige nachgewiesene „adverse reaction“) keinen positiven Effekt auf das Überleben gesehen [ 23 ]. Dies deckt sich mit internationalen Publikationen: In einer indischen Studie mit über 230 plasmabehandelten, moderat (Horowitz-Index 200–300 mmHg) an COVID-19 erkrankten Patientinnen und Patienten konnte im Vergleich zum Placebo kein Effekt auf den Progress zu einer schwereren Erkrankung oder auf das Überleben gezeigt werden [ 24 ].…”

Generation and characterization of humanized synergistic neutralizing antibodies against SARS‐CoV‐2

“…It has been well‐established that antibody‐based passive immunotherapy is an effective approach to combat virus infection. 1 Recent reports have demonstrated that the administration of convalescent plasma containing neutralizing antibodies can improve the clinical status of some critically ill patients 2 , 3 , 4 , 5 ; however, the outcomes of passive plasma therapy are unpredictable, and the wide‐spread clinical use of plasma therapy is unrealistic. Therefore, it is important to develop neutralizing antibodies that can be administered to enhance the prevention and treatment of COVID‐19.…”