Convalescent Plasma in COVID-19. Mortality-Safety First Results of the Prospective Multicenter FALP 001-2020 Trial

Abstract

Background

The use of convalescent plasma (CP) to treat COVID-19 has shown promising results; however, its effectiveness remains uncertain. The purpose of this study was to determine the safety and mortality of CP among patients hospitalized with COVID-19.

Study Design and Methods

This multicenter, open-label, uncontrolled clinical trial is currently being conducted at nine hospitals in Chile. Patients hospitalized due to COVID-19 who were still within 14 days since symptom onset were classified into four groups: Patients with cancer and severe COVID-19. Patients with cancer and non-severe COVID-19. Patients with severe COVID-19 and patients with non-severe COVID-19 only. The intervention involved two 200-cc. CP transfusions with anti-SARS-CoV-2 IgG titers ≥ 1:320 collected from COVID-19-recovered donors.

Results

192 patients hospitalized for COVID-19 received CP transfusions. At the first transfusion, 90.6% fulfilled the criteria for severity, and 41.1% required mechanical ventilation. 11.5% of the patients had cancer. Overall 7-day and 30-day mortality since the first CP transfusion was 5.7% and 16.1% respectively. There were no differences at either time point in mortality between the four groups. Patients on mechanical ventilation when receiving CP had higher mortality rates than those who were not (22.8% vs. 11.5%; p = 0.037). Overall 30-day mortality was higher in patients over 65 than in younger patients (p = 0.019). Severe adverse events were reported in four patients (2.1%) with an overall transfusion-related lung injury rate of 1.56%. No CP-related deaths occurred.

Discussion

CP is safe when used in patients with COVID-19 even when also presenting severity criteria or risk factors. Our mortality rate is comparable to reports from larger studies. Controlled clinical trials are required to determine efficacy.

Registration

NCT04384588

SciScore for 10.1101/2020.11.30.20218560: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Institutional Review Board Statement	Consent: This project was developed and executed in accordance with Chilean Law No. 20,120 (“On scientific research in the human being, its genome, and prohibitis human clonation” : All scientific research on a human being must have his prior, express, free and informed consent, or, failing that, that of the person who must supply his will in accordance with the law.”); Law No. 20,584 (“Regulates the rights and duties that people have in relation to actions related to their health care”); Law No. 19.628 (“On protection of prívate life”); CIOMS Guidelines, Declaration of Helsinki, Nuremberg code, The Universal Declaration of Human Rights and The International Covenant on Civil and Political Rights This protocol was approved by our local ethics committee: Comité Ético Científico Fundación Arturo López Pérez, on April 7th, 2020.
Randomization	not detected.
Blinding	not detected.
Power Analysis	not detected.
Sex as a biological variable	not detected.

Table 2: Resources

Antibodies
Sentences	Resources
All women, with or without a history of pregnancy, were tested for anti-HLA antibodies.	anti-HLA suggested: None
Anti-SARS-CoV2 antibodies were measured, and only donors with IgG ≥ 1:320 (ELISA Euroimmun®) were selected.	Anti-SARS-CoV2 suggested: None
Software and Algorithms
Sentences	Resources
Statistical analyses were performed with STATA and R program v 3.6.0.	STATA suggested: (Stata, RRID:SCR_012763)

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

The present study has some limitations. Since we aimed to assess mortality rates and safety, the absence of a control group prevents drawing conclusions on the benefits of CP treatment. The lack of a control group was grounded on ethical concerns raised at the beginning of the outbreak when the study was designed. Nevertheless, the observed mortality rates are encouraging and additional studies with matched control cases are planned. While donor anti-SARS-CoV-2 spike protein antibody titers were elevated (≥ 1:320), we have not yet investigated their neutralizing activity. Ongoing experiments aim to characterize the neutralizing antibody and cytokine content of CP and identify the factors potentially responsible for its therapeutic benefits in patients with COVID-19 using multivariate analysis. Such studies will generate new hypotheses on CP efficacy in regards to specific types and amounts of neutralizing antibodies and cytokines. Although CP transfusion has shown promising results against COVID-19 in case series (18,19) and case-control studies (38), its real benefit remains unclear. The first published randomized trial with CP in COVID-19 did not show significant improvement in the clinical condition of patients with severe, life-threatening COVID-19 but the interpretation is limited by the study’s early endpoint. Nevertheless, patients with severe, non-life-threatening COVID-19 improved significantly compared with the control group (91.3% vs. 68.2% (HR, 2.15 [95% CI, 1.07-...

Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

Identifier	Status	Title
NCT04384588	Recruiting	COVID19-Convalescent Plasma for Treating Patients With Activ…
NCT04375098	Completed	Efficacy and Safety of Early COVID-19 Convalescent Plasma in…

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

Results from rtransparent:

Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
No protocol registration statement was detected.

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