Passive immunotherapy has been in use since the late 19th century, and in 1901, the first Nobel Prize in Physiology or Medicine was awarded for serum therapy for patients with diphtheria. During the 1918 pandemic, serum from convalescent patients was used to treat the flu, with apparently little success.1 Today, the use of immunoglobulins has been established for the prophylaxis and treatment of various diseases, including those with respiratory syncytial virus, cytomegalovirus, and hepatitis B virus or hepatitis A. Recently, passive immunotherapy has been evaluated for true severe respiratory syndrome (SARS), Middle Eastern respiratory syndrome, and Ebola virus disease. Intravenous human immunoglobulin has transformed the regulation of immunoglobulin deficiency states.
The use of convalescent plasma against SARS coronavirus 2 (SARS-CoV-2) is recommended for the treatment of patients with coronavirus disease 2019 (Covid-19). The experience with influenza A is relevant, and meta-analysis suggested that early treatment, prior to the development of a critical illness, may be an important predictor of the efficacy of passive immunotherapy for that pathogen.1 The authors of this meta-analysis identified the low quality of available evidence on early treatment. Another meta-analysis of studies on convalescent plasma and hyperimmune immunoglobulin in patients with influenza A and SARS suggested a mortality benefit “when convalescent plasma is administered early after the onset of the symptom.”2 However, in a randomized, controlled trial, high-titer convalescent plasma from patients who had recovered from H1N1 flu was ineffective against severe influenza A infection in hospitalized children and adults.3
Initial randomized trials of convalescent plasma in patients with Covid-19 targeted hospitalized patients who were already moderate to severely ill, and these trials provided weak evidence of clinical efficacy.4-6 Some were not strengthened when non-pharmacological interventions such as masks and social and physical speed reduced the frequency of Covid-19 and there was little enrollment. Also, these tests were heterogeneous in terms of the properties of the convalescent plasma used (e.g., its antibody content and stratification of the recipients according to the serologic status). Unexpected safety symptoms beyond the known risks of plasma movement (i.e., fluid overload, transfusion-associated lung injuries, and allergies) have not emerged, and there was no evidence of increased co -based antibody against Covid-19 intensity. Accordingly, it is difficult to draw conclusions about the clinical value of convalescent plasma.
Observational studies have been more promising than randomized trials; some, but not all, of these studies have quantified moderate clinical effects and virologic surrogate results.7.8 They have confirmed the safety imaging of plasma movement but have some of the same issues with randomized trials, as well as the possible biases and shortcomings of observational studies.
The Food and Drug Administration (FDA) argued that “overall evidence” suggested that the benefits of convalescent plasma outweighed its risks, and that in the absence of effective treatments, the FDA granted an Emergency Use Authorization ( EUA) and provided guidance on the manufacture and use of convalescent plasma in hospitalized patients with signs of progressive disease. In contrast, the National Institutes of Health steering panel said that “the data is not sufficient to recommend for or against” convalescent plasma use. The American Infectious Diseases Association and the AABB (formerly the American Blood Banking Association) recommend that the use of convalescent plasma be restricted to clinical trials, which are unlikely to be seriously ill and those in the intensive care unit (ICU) should benefit from convalescent plasma solutions, and convalescent plasma should be used as early as possible in the course of the disease (preferably within 3 days of diagnosis) to achieve the best results. best to achieve.9
Considering the number of SARS-CoV-2 diseases, the scarcity of treatment options, and the enthusiasm and controversy about convalescent plasma, a high-quality, multicenter, randomized, controlled trial. Libster and colleagues are now reporting in the Iris10 well-performed test results of early convalescent plasma in older adult patients in whom symptomatic SARS-CoV-2 infection was diagnosed using a polymerase-chain-reaction assay. In this double-blind trial, 250 ml of convalescent plasma with an IgG titer greater than 1: 1000 against spike protein (S) SARS-CoV-2 was compared with placebo saline in patients aged 65 to 74 years. old and prescribed. homosexual conditions and in patients aged 75 years or older with or without homogenous conditions.
Patients received convalescent plasma or placebo less than 72 hours after the onset of the symptom. In the intended treatment population, a primary termination event (progression to pre-existing severe disease) occurred in 16% (13 of 80 patients) and 31% (25 of 80 patients) of the patient. a well-matched population of convalescent and placebo plasma groups, respectively. A dose-dependent effect compared with the antibody titers after infusion was observed, and this effect was greater after the exclusion of 6 patients who had a primary termination event prior to admission. The benefits of convalescent plasma with respect to the secondary endpoints were consistent with those associated with the primary endpoint. No serious adverse events were observed. The authors conclude that “early administration of high-titer regenerative plasma reduced SARS-CoV-2 resistance in older adults with severe Covid-19 progression disease. Even before the current trial, the EUA emphasized the potential benefits of early treatment with high-density plasma. Unfortunately, a direct comparison of antibody levels in the current trial with assessments specified in the FDA EUA is not available. Antibody titers in the recipients at the time of enrollment were not provided, so the usefulness of seroreactivity in patients cannot be mentioned as a criterion for convalescent plasma use.
At this time, convalescent plasma should be maintained for patients in whom the duration, intensity, and risk of disease progression are similar to those in the patients in this trial. High-risk patients (and some immunocompromised patients) with these disease characteristics should also be considered.
Convalescent plasma supply has been largely during the sharp rise in Covid-19 cases at the time of the fall in the United States, although recent concentrations have improved. From Sept. 28 through Dec. 27, 2020, discharges of accumulated and accumulated plasma units to hospitals in the United States exceeded concentrations with 7785 units (Block W: personal communication). If clusters are limited to the high antibody titers and patient symptoms described in the article by Libster et al., Convalescent plasma supply will be stressed. In my center, high-titer concentrations (as defined by the FDA) make up only 19.5% of seroreactive convalescent plasma donations. The pool of potential recipients should be shifted away from those covered by the EUA to many outpatients who were at risk in hospital and the hospital. ultimate need for advanced care leads to the expansion of convalescent plasma transfusions to prehospital centers (although this is not yet allowed in the EUA).
Uncontrolled convalescent plasma use should not be discouraged in patients with only those with early onset disease who are prone to progress to more serious illness, even though clinicians recognize the difficulty ‘ and being “just standing there” at the bedside of an ICU patient. Restrictions on treatments for Covid-19 that are effective for limited patient numbers are a powerful argument for consistent adherence to non-pharmacological interventions and rapid use and uptake of effective vaccines.