Convalescent Plasma and Risk of Death From COVID-19
- Convalescent plasma with high titers of anti-SARS-CoV-2 IgG is associated with lower 30-day mortality compared to low titers.
- The effect was only seen in nonmechanically ventilated patients who received convalescent plasma and those who received it early in the course of the disease (3 days from diagnosis).
- This study helps define the use and cases for convalescent plasma and can inform future clinical trials.
Is the association of convalescent plasma and 30-day mortality in the treatment of coronavirus disease 2019 (COVID-19) dependent on its antibody levels?
In this retrospective study, the authors leveraged the expanded access program (EAP), a US national registry of hospitalized adults with COVID-19, and identified high-risk patients who received one or more units of convalescent plasma during their hospitalization according to the EAP protocol. Anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibody levels were measured in aliquots from remnant samples (n = 3,082) obtained from the various blood collection centers. IgG antibody levels were categorized as low <4.62, medium (4.62-18.45), or high (>18.45), based on the 20th and 80th percentiles of the distribution for the signal-to-cut-off ratio. The authors evaluated the association between antibody titers and mortality at 30 days after transfusion of convalescent plasma.
The cohort included 3,082 patients from 680 healthcare facilities from across the United States, of whom 61% were men, 23% were Black, 37% were Hispanics, and 69% were <70 years old. A total of 561 (18.2%) had low titers of anti-SARS-CoV-2 IgG, 2,006 (65%) had medium titers, and 515 (16.7%) had high titers. Clinical characteristics and therapies administered were similar between the three groups. Death within 30 days post-plasma transfusion occurred in 830 (26.9%) patients; 29.6% in the low titer group, 27.4% in the medium titer group, and 22.3% in the high titer group. Patients in the high titer group compared to the low titer group had a relative risk of 0.75 (95% confidence interval [CI], 0.61-0.93). The relative risk in the fully adjusted model was 0.82 (95% CI, 0.67-1.00). In subgroup analyses, the association differed according to whether the patients were mechanically ventilated; with lower risk of death among those who received convalescent plasma but were not on mechanical ventilation and those treated within 3 days of diagnosis. There was no effect in patients already mechanically ventilated. Using machine learning, the most important variables associated with risk of death at 30 days were age, receipt of mechanical ventilation, and anti-SARS-CoV-2 antibody level. Antibody levels remained inversely correlated with risk of death after adjusting for all other variables, most evidently in patients not receiving mechanical ventilation.
Convalescent plasma with high titers of anti-SARS-CoV-2 IgG administered early in the course of the disease to nonmechanically ventilated patients may be more effective in reducing 30-day mortality compared to plasma with low titers or administered in mechanically ventilated patients.
Hopes for the use convalescent plasma as a treatment for COVID-19 were dashed when randomized trials showed a lack of effectiveness in improving clinical status or mortality. This study highlights the different confounders that impact the association between convalescent plasma, notably the clinical status of the patients. Findings are consistent with other observational studies on convalescent plasma, and conclusions are similar to other therapies such as remdesivir, which effectiveness also appears to lie in its administration early in the course of the disease. Despite its limitations (selection bias, significant amount of missing data), this study helps define the use and cases for convalescent plasma and can inform future clinical trials.
Keywords: Artificial Intelligence, Blood Component Transfusion, Coronavirus, COVID-19, Delivery of Health Care, Immunoglobulin G, Receptors, IgG, Plasma, Primary Prevention, Respiration, Artificial, Risk, severe acute respiratory syndrome coronavirus 2, Ventilation
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