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Authors: Sean T. H. Liu et al.

Link to paper: https://doi.org/10.1101/2020.05.20.20102236

Journal/ Pre-Print: MedRXiv

Tags: Clinical, Immunology/Immunity, Therapeutics

Research Highlights

1. The administration of convalescent plasma is a strategy which has previously been used for a number of other viral diseases

2. This study assessed the use of plasma transfusions from convalescent COVID-19 patients

3. Transfusion was significantly associated with improved survival in non-intubated patients although there are some significant confounders that reduce confidence in the results of the study

Summary

In this study, 39 patients received convalescent plasma transfusions from donors screened for SARS-COV-2 antibodies (with anti-spike titres of 1:320 dilution or more) and matched against a historical control cohort from the same period. Patients were compared for their survival and oxygen status at 1,7 and 14 days post-transfusion. Deterioration (defined as increasing ventilation assistance compared to day 0) and mortality were better in treated (18.0% and 12.8%) than control patients (24.3% and 12.8%). Survival of patients who were intubated was no better than non-intubated patients. The study highlights a promising treatment strategy. However, there are several significant confounding issues, which temper the translatability.

Impact for SARS-CoV2/COVID19 research efforts

Clinical symptoms and pathogenesis of SARS-Cov2/COVID19

Treat of SARS-CoV2/COVID19 positive individuals – Convalescent therapeutics.

Study Type

· Clinical Cohort study (e.g. drug trials)

· Patient Case study

Strengths and limitations of the paper

Novelty: COVID-19 patients who are given plasma from convalescent COVID-19 patients may have better outcomes

Standing in the field: This paper agrees with previous work in that an immunomodulatory approach shows benefit in the management of the study. Although the use of anti-coagulants confounded the results, the use of these agents may have promise.

Appropriate statistics: Yes

Viral model used: SARS-Cov-2, SARS-Cov-2 Spike

Translatability: This highlights the principle of treatment using plasma donors. Due to the limitations of the study, it would not be prudent to use this as an evidence base for practice.

Main limitations:

1. This is not a randomised controlled trial and the control group is historical. Antibody itself regardless of specificity may be beneficial in patients with dyregulated immune systems and therefore an appropriate control would be infusion of control plasma/IVIG/FFP.

2. Patients in the group receiving convalescent plasma had a higher proportion of anticoagulation. Coagulopathy is now known to be critical in the pathogenesis of severe COVID-19 disease, therefore this is major confounder.

3. As knowledge of COVID-19 advances so do treatment strategies therefore historical matching is not appropriate.

4. The follow up period is not clear given that the control group had a follow up range of 0-31 days. What does 0 mean – were they discharged at the point at which the authors decided to include them or are some of the matched control patients in fact already dead?

5. Small number of patients in a single centre