Consideration for alpha-gal syndrome in two critically ill persons with group O blood who received group B plasma.

BACKGROUND: The U.S. Centers for Disease Control and Prevention (CDC) has reported increasing rates of alpha-gal syndrome, an allergic response after meat ingestion (AGS). AGS has been associated with prior exposure to tick bites or other biologics characterized by a life-threatening immunoglobulin E (IgE)-mediated hypersensitivity to galactose-alpha-1,3-galactose (alpha-gal) an oligosaccharide structurally similar to the group B antigen on red blood cells (RBC) found in most non-primate mammalian meat and products derived from these mammals. In 2023, Transfusion reported 3 group O recipients of group B plasma in the Washington, D.C. metropolitan area with no history of meat allergy who had anaphylactic transfusion reactions compatible with AGS. AIMS: We investigated allergic reactions in 2 additional patients who received ABO minor-incompatible blood products at 2 hospitals in the D.C. area during fall 2023. METHODS: For both patients, a medical chart review was performed and IgE levels to alpha-gal were measured. RESULTS: The first patient, a 64-year-old, O-positive patient status post heart transplant with no known allergies, was admitted with acute COVID-19 induced antibody-mediated transplant rejection and placed on extracorporeal membrane oxygenation (ECMO). While undergoing plasma exchange (PLEX) (50% albumin/50% fresh frozen plasma (FFP)), the patient tolerated 2 units of group O FFP and 1 unit of group A FFP before becoming hemodynamically unstable during transfusion of 1 unit of B-positive FFP. PLEX was stopped. The patient later died of sepsis from underlying causes. The second patient, a 57-year-old O-positive man with a history of melanoma and neuro fibromatosis type 1, was undergoing an abdominal resection including transfusion of 3 units of O-positive RBC when he suffered hypotension and ventricular tachycardia requiring intraoperative code after receiving 2 units of group B FFP. Hiveswere noted after resuscitation. The patient had a history of tick bites but no known allergies. He is alive 5 months after the possible allergic event. Both patients had full transfusion reaction evaluations and immunology testing results above the positive cutoff for anti-alpha-gal IgE. DISCUSSION AND CONCLUSION: Two patients with O-positive blood and no known allergies experience danaphyl axis after transfusion with group B FFP. The symptoms cannot definitively be imputed to an allergic transfusion reaction, but the presence of IgE against alpha-gal supports an association. Medicating patients with antihistamines and IV steroids pre-transfusion may prevent allergic reactions. Restricting group B plasma-containing products (plasma, platelets, cryoprecipitate) for patients who experience AGS-like symptoms may be considered.

Eficacia y seguridad de la administración de plasma de convaleciente en pacientes con COVID-19 / Efficacy and safety of convalescent plasma administration in patients with COVID-19 infection

Introducción Durante la pandemia de COVID-19 surgieron diversas estrategias para el manejo de la enfermedad, incluidos los tratamientos farmacológicos y no farmacológicos como el plasma convaleciente (PC). El uso de PC se sugirió debido a los resultados benéficos mostrados al tratar otras enfermedades virales. Objetivo Determinar la eficacia y la seguridad de la administración de PC obtenido de sangre total en pacientes con COVID-19. Métodos Ensayo clínico piloto en pacientes con COVID-19 de un hospital general. Los sujetos se separaron en 3 grupos que recibieron la transfusión de 400ml de PC (n=23) o 400ml de plasma estándar (PE) (n=19) y un grupo no transfundido (NT) (n=37). Los pacientes recibieron además, el tratamiento médico estándar disponible para COVID-19. El seguimiento de los sujetos se llevó a cabo diariamente desde el ingreso hasta el día 21. Resultados El PC no mejoró la curva de supervivencia en las variantes moderadas y graves de COVID-19, ni disminuyó el grado de severidad de la enfermedad evaluado con la escala de progresión clínica COVID-19, OMS y SOFA. Ningún paciente presentó una reacción postransfusional severa al PC. Conclusiones El tratamiento con PC no disminuye la mortalidad de los pacientes, aun cuando su administración tiene un alto grado de seguridad (AU)

Introduction During the COVID-19 pandemic, several strategies were suggested for the management of the disease, including pharmacological and non-pharmacological treatments such as convalescent plasma (CP). The use of CP was suggested due to the beneficial results shown in treating other viral diseases. Objective To determine the efficacy and safety of CP obtained from whole blood in patients with COVID-19. Methods Pilot clinical trial in patients with COVID-19 from a general hospital. The subjects were separated into three groups that received the transfusion of 400ml of CP (n=23) or 400ml of standard plasma (SP) (n=19) and a non-transfused group (NT) (n=37). Patients also received the standard available medical treatment for COVID-19. Subjects were followed up daily from admission to day 21. Results The CP did not improve the survival curve in moderate and severe variants of COVID-19, nor did it reduce the degree of severity of the disease evaluated with the COVID-19 WHO and SOFA clinical progression scale. No patient had a severe post-transfusion reaction to CP. Conclusions Treatment with CP does not reduce the mortality of patients even when its administration has a high degree of safety (AU)

Platelet concentrates in platelet additive solutions generate less complement activation products during storage than platelets stored in plasma.

BACKGROUND: Platelet transfusions can be associated with adverse reactions, such as febrile non-haemolytic transfusion reaction (FNHTR). It has been suggested that damage-associated molecular patterns (DAMP) and complement play a role in FNHTR. This study investigated the nature of DAMPs and complement activation products contained in platelet concentrates during storage, with a specific focus on different platelet storage solutions. MATERIALS AND METHODS: Buffy coats (BC) from healthy donors were pooled (15 BC per pool) and divided into three groups of the same volume. After addition of different storage solutions (plasma, platelet additive solutions [PAS]-C or PAS-E; n=6 for each group), BC pools were processed to platelet concentrates (PC). Leukoreduced PCs were stored on a shaking bed at 20-24°C and sampled on days 1, 2, 6 and 8 after collection for selected quality parameters: platelet activation, DAMPs (High Mobility Group Box 1 [HMGB1], nucleosomes), and complement activation products. RESULTS: During storage, equal levels of free nucleosomes and increasing concentrations of HMGB1 were present in all groups. Complement activation was observed in all PC. However, by day 8, the use of PAS had reduced C3b/c levels by approximately 90% and C4b/c levels by approximately 65%. DISCUSSION: Nucleosomes and HMGB1 were present in PCs prepared in plasma and PAS. Complement was activated during storage of platelets in plasma and in PAS. The use of PAS is associated with a lower amount of complement activation products due to the dilution of plasma by PAS . Therefore, PC in PAS have less complement activation products than platelets stored in plasma. These proinflammatory mediators in PC might induce FNHTR.

Therapeutics and COVID-19: living guideline - 16 September 2022

The WHO Therapeutics and COVID-19: living guideline contains the Organization's most up-to-date recommendations for the use of therapeutics in the treatment of COVID-19. The latest version of this living guideline is available in pdf format (via the 'Download' button) and via an online platform, and is updated regularly as new evidence emerges. This twelfth version of the WHO living guideline now contains 19 recommendations. This latest update provides updated recommendations for remdesivir, addresses the use of combination therapy with corticosteroids, interleukin-6 (IL-6) receptor blockers and Janus kinase (JAK) inhibitors in patients with severe or critical COVID-19, and modifies previous recommendations for the neutralizing monoclonal antibodies sotrovimab and casirivimab-imdevimab in patients with non-severe COVID-19.

Convalescent Plasma for Preventing Critical Illness in COVID-19: a Phase 2 Trial and Immune Profile.

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an unprecedented event requiring frequent adaptation to changing clinical circumstances. Convalescent immune plasma (CIP) is a promising treatment that can be mobilized rapidly in a pandemic setting. We tested whether administration of SARS-CoV-2 CIP at hospital admission could reduce the rate of ICU transfer or 28-day mortality or alter levels of specific antibody responses before and after CIP infusion. In a single-arm phase II study, patients >18 years-old with respiratory symptoms with confirmed COVID-19 infection who were admitted to a non-ICU bed were administered two units of CIP within 72 h of admission. Levels of SARS-CoV-2 detected by PCR in the respiratory tract and circulating anti-SARS-CoV-2 antibody titers were sequentially measured before and after CIP transfusion. Twenty-nine patients were transfused high titer CIP and 48 contemporaneous comparable controls were identified. All classes of antibodies to the three SARS-CoV-2 target proteins were significantly increased at days 7 and 14 post-transfusion compared with baseline (P < 0.01). Anti-nucleocapsid IgA levels were reduced at day 28, suggesting that the initial rise may have been due to the contribution of CIP. The groups were well-balanced, without statistically significant differences in demographics or co-morbidities or use of remdesivir or dexamethasone. In participants transfused with CIP, the rate of ICU transfer was 13.8% compared to 27.1% for controls with a hazard ratio 0.506 (95% CI 0.165-1.554), and 28-day mortality was 6.9% compared to 10.4% for controls, hazard ratio 0.640 (95% CI 0.124-3.298). IMPORTANCE Transfusion of high-titer CIP to non-critically ill patients early after admission with COVID-19 respiratory disease was associated with significantly increased anti-SARS-CoV-2 specific antibodies (compared to baseline) and a non-significant reduction in ICU transfer and death (compared to controls). This prospective phase II trial provides a suggestion that the antiviral effects of CIP from early in the COVID-19 pandemic may delay progression to critical illness and death in specific patient populations. This study informs the optimal timing and potential population of use for CIP in COVID-19, particularly in settings without access to other interventions, or in planning for future coronavirus pandemics.

Interferon-α2 Auto-antibodies in Convalescent Plasma Therapy for COVID-19.

PURPOSE: To study the effect of interferon-α2 auto-antibodies (IFN-α2 Abs) on clinical and virological outcomes in critically ill COVID-19 patients and the risk of IFN-α2 Abs transfer during convalescent plasma treatment. METHODS: Sera from healthy controls, cases of COVID-19, and other respiratory illness were tested for IFN-α2 Abs by ELISA and a pseudo virus-based neutralization assay. The effects of disease severity, sex, and age on the risk of having neutralizing IFN-α2 Abs were determined. Longitudinal analyses were performed to determine association between IFN-α2 Abs and survival and viral load and whether serum IFN-α2 Abs appeared after convalescent plasma transfusion. RESULTS: IFN-α2 neutralizing sera were found only in COVID-19 patients, with proportions increasing with disease severity and age. In the acute stage of COVID-19, all sera from patients with ELISA-detected IFN-α2 Abs (13/164, 7.9%) neutralized levels of IFN-α2 exceeding physiological concentrations found in human plasma and this was associated with delayed viral clearance. Convalescent plasma donors that were anti-IFN-α2 ELISA positive (3/118, 2.5%) did not neutralize the same levels of IFN-α2. Neutralizing serum IFN-α2 Abs were associated with delayed viral clearance from the respiratory tract. CONCLUSIONS: IFN-α2 Abs were detected by ELISA and neutralization assay in COVID-19 patients, but not in ICU patients with other respiratory illnesses. The presence of neutralizing IFN-α2 Abs in critically ill COVID-19 is associated with delayed viral clearance. IFN-α2 Abs in COVID-19 convalescent plasma donors were not neutralizing in the conditions tested.

Case Series: Convalescent Plasma Therapy for Patients with COVID-19 and Primary Antibody Deficiency.

Patients with primary antibody deficiency are at risk for severe and in many cases for prolonged COVID-19. Convalescent plasma treatment of immunocompromised individuals could be an option especially in countries with limited access to monoclonal antibody therapies. While studies in immunocompetent COVID19 patients have demonstrated only a limited benefit, evidence for the safety, timing, and effectiveness of this treatment in antibody-deficient patients is lacking. Here, we describe 16 cases with primary antibody deficiency treated with convalescent plasma in four medical centers. In our cohort, treatment was associated with a reduction in viral load and improvement of clinical symptoms, even when applied over a week after onset of infection. There were no relevant side effects besides a short-term fever reaction in one patient. Longitudinal full-genome sequencing revealed the emergence of mutations in the viral genome, potentially conferring an antibody escape in one patient with persistent viral RNA shedding upon plasma treatment. However, he resolved the infection after a second course of plasma treatment. Thus, our data suggest a therapeutic benefit of convalescent plasma treatment in patients with primary antibody deficiency even months after infection. While it appears to be safe, PCR follow-up for SARS-CoV-2 is advisable and early re-treatment might be considered in patients with persistent viral shedding.

Case Report: Serial Cases: Prolongation of High Immunoglobulin G Level in Repetitive COVID-19 Convalescence Plasma Donor in Saiful Anwar Hospital Malang, Indonesia.

Background: Convalescent plasma therapy is expected to be a promising alternative to supportive therapy during the SARS-CoV-2 pandemic outbreak. Altered immune response in repetitive convalescent plasma donors has not been widely studied. This case series was reported to analyze the patterns of immune responses and the factors that might influence them in repetitive convalescent plasma donors and increase awareness of COVID-19 survivors to donate their convalescent plasma. Cases Illustration: There were five repetitive donors who were eligible as convalescent plasma donor requirements. It was found two donors who showed increment of anti-SARS-CoV-2 IgG level after donation and two others who showed persistent anti-SARS-CoV-2 IgG level more than two months after recovered. Discussion: There was a difference in immune response in survivors who have the probability of being exposed to same antigens with survivors who did not, where the group of survivors who are at risk of exposure to antigens after recovery could trigger anamnestic immune response that can increase antiSARS-CoV-2 IgG levels. The other factor that influence the prolongation of anti-SARS-CoV-2 IgG levels are the possibility of neutralizing antibodies in plasma upregulation. Conclusion: Immunological phenomenon in SARS-CoV-2, both in survivors and convalescent plasma donors, have not been widely observed and studied. From the case series discussed above, it can be concluded that convalescent plasma donation does not yet have strong evidence of decreasing levels of specific antibodies against SARS-CoV-2 and plasmapheresis procedure is safe to be done without reducing the protective effect of donor antibody post-plasma donation.

Functional convalescent plasma antibodies and pre-infusion titers shape the early severe COVID-19 immune response.

Transfer of convalescent plasma (CP) had been proposed early during the SARS-CoV-2 pandemic as an accessible therapy, yet trial results worldwide have been mixed, potentially due to the heterogeneous nature of CP. Here we perform deep profiling of SARS-CoV-2-specific antibody titer, Fc-receptor binding, and Fc-mediated functional assays in CP units, as well as in plasma from hospitalized COVID-19 patients before and after CP administration. The profiling results show that, although all recipients exhibit expanded SARS-CoV-2-specific humoral immune responses, CP units contain more functional antibodies than recipient plasma. Meanwhile, CP functional profiles influence the evolution of recipient humoral immunity in conjuncture with the recipient's pre-existing SARS-CoV2-specific antibody titers: CP-derived SARS-CoV-2 nucleocapsid-specific antibody functions are associated with muted humoral immune evolution in patients with high titer anti-spike IgG. Our data thus provide insights into the unexpected impact of CP-derived functional anti-spike and anti-nucleocapsid antibodies on the evolution of SARS-CoV-2-specific response following severe infection.

Cross-Neutralization of Emerging SARS-CoV-2 Variants of Concern by Antibodies Targeting Distinct Epitopes on Spike.

Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have arisen that exhibit increased viral transmissibility and partial evasion of immunity induced by natural infection and vaccination. To address the specific antibody targets that were affected by recent viral variants, we generated 43 monoclonal antibodies (mAbs) from 10 convalescent donors that bound three distinct domains of the SARS-CoV-2 spike. Viral variants harboring mutations at K417, E484, and N501 could escape most of the highly potent antibodies against the receptor binding domain (RBD). Despite this, we identified 12 neutralizing mAbs against three distinct regions of the spike protein that neutralize SARS-CoV-2 and variants of concern (VOCs), including B.1.1.7 (alpha), P.1 (gamma), and B.1.617.2 (delta). Notably, antibodies targeting distinct epitopes could neutralize discrete variants, suggesting that different variants may have evolved to disrupt the binding of particular neutralizing antibody classes. These results underscore that humans exposed to the first pandemic wave of prototype SARS-CoV-2 possess neutralizing antibodies against current variants and that it is critical to induce antibodies targeting multiple distinct epitopes of the spike that can neutralize emerging variants of concern. IMPORTANCE We describe the binding and neutralization properties of a new set of human monoclonal antibodies derived from memory B cells of 10 coronavirus disease 2019 (COVID-19) convalescent donors in the first pandemic wave of prototype SARS-CoV-2. There were 12 antibodies targeting distinct epitopes on spike, including two sites on the RBD and one on the N-terminal domain (NTD), that displayed cross-neutralization of VOCs, for which distinct antibody targets could neutralize discrete variants. This work underlines that natural infection by SARS-CoV-2 induces effective cross-neutralization against only some VOCs and supports the need for COVID-19 vaccination for robust induction of neutralizing antibodies targeting multiple epitopes of the spike protein to combat the current SARS-CoV-2 VOCs and any others that might emerge in the future.

Determination of neutralising anti-SARS-CoV-2 antibody half-life in COVID-19 convalescent donors.

Despite the burgeoning field of coronavirus disease-19 (COVID-19) research, the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralising antibodies remains unclear. This study validated two high-throughput immunological methods for use as surrogate live virus neutralisation assays and employed them to examine the half-life of SARS-CoV-2 neutralising antibodies in convalescent plasma donations made by 42 repeat donors between April and September 2020. SARS-CoV-2 neutralising antibody titres decreased over time but typically remained above the methods' diagnostic cut-offs. Using this longitudinal data, the average half-life of SARS-CoV-2 neutralising antibodies was determined to be 20.4 days. SARS-CoV-2 neutralising antibody titres appear to persist in the majority of donors for several months. Whether these titres confer protection against re-infection requires further study and is of particular relevance as COVID-19 vaccines become widely available.

Cross-neutralization of SARS-CoV-2 by HIV-1 specific broadly neutralizing antibodies and polyclonal plasma.

Cross-reactive epitopes (CREs) are similar epitopes on viruses that are recognized or neutralized by same antibodies. The S protein of SARS-CoV-2, similar to type I fusion proteins of viruses such as HIV-1 envelope (Env) and influenza hemagglutinin, is heavily glycosylated. Viral Env glycans, though host derived, are distinctly processed and thereby recognized or accommodated during antibody responses. In recent years, highly potent and/or broadly neutralizing human monoclonal antibodies (bnAbs) that are generated in chronic HIV-1 infections have been defined. These bnAbs exhibit atypical features such as extensive somatic hypermutations, long complementary determining region (CDR) lengths, tyrosine sulfation and presence of insertions/deletions, enabling them to effectively neutralize diverse HIV-1 viruses despite extensive variations within the core epitopes they recognize. As some of the HIV-1 bnAbs have evolved to recognize the dense viral glycans and cross-reactive epitopes (CREs), we assessed if these bnAbs cross-react with SARS-CoV-2. Several HIV-1 bnAbs showed cross-reactivity with SARS-CoV-2 while one HIV-1 CD4 binding site bnAb, N6, neutralized SARS-CoV-2. Furthermore, neutralizing plasma antibodies of chronically HIV-1 infected children showed cross neutralizing activity against SARS-CoV-2 pseudoviruses. Collectively, our observations suggest that human monoclonal antibodies tolerating extensive epitope variability can be leveraged to neutralize pathogens with related antigenic profile.

Mortality in individuals treated with COVID-19 convalescent plasma varies with the geographic provenance of donors.

Successful therapeutics and vaccines for coronavirus disease 2019 (COVID-19) have harnessed the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence that SARS-CoV-2 exists as locally evolving variants suggests that immunological differences may impact the effectiveness of antibody-based treatments such as convalescent plasma and vaccines. Considering that near-sourced convalescent plasma likely reflects the antigenic composition of local viral strains, we hypothesize that convalescent plasma has a higher efficacy, as defined by death within 30 days of transfusion, when the convalescent plasma donor and treated patient were in close geographic proximity. Results of a series of modeling techniques applied to approximately 28,000 patients from the Expanded Access to Convalescent Plasma program (ClinicalTrials.gov number: NCT04338360) support this hypothesis. This work has implications for the interpretation of clinical studies, the ability to develop effective COVID-19 treatments, and, potentially, for the effectiveness of COVID-19 vaccines as additional locally-evolving variants continue to emerge.

SARS-CoV-2 Variants: A Synopsis of In Vitro Efficacy Data of Convalescent Plasma, Currently Marketed Vaccines, and Monoclonal Antibodies.

We summarize here in vitro evidences of efficacy for convalescent plasma, currently approved vaccines and monoclonal antibodies against SARS-CoV-2 variants of concern (VOC: B.1.1.7, B.1.351, P.1, and B.1.617.2), variants of interest (VOI: B.1.427/B.1.429, P.2, B.1.525, P.3, B.1.526, and B.1.671.1), and other strains (B.1.1.298 and B.1.258delta). While waiting from real world clinical efficacy, these data provide guidance for the treating physician.

Ex vivo hemostatic and immuno-inflammatory profiles of freeze-dried plasma.

BACKGROUND: Hemorrhage is a leading cause of preventable death in civilian and military trauma. Freeze-dried plasma is promising for hemostatic resuscitation in remote prehospital settings, given its potential benefits in reducing blood loss and mortality, long storage at ambient temperatures, high portability, and rapid reconstitution for transfusion in austere environments. Here we assess the ex vivo characteristics of a novel Terumo's freeze-dried plasma product (TFDP). STUDY DESIGN AND METHODS: Rotational thromboelastometry (ROTEM) tests (INTEM, EXTEM, and FIBTEM) were conducted on plasma samples at 37°C with a ROTEM delta-machine using standard reagents and procedures. The following samples were analyzed: pooled plasma to produce TFDP, TFDP reconstituted, and stored immediately at -80°C, reconstituted TFDP stored at 4°C for 24 h and room temperature (RT) for 4 h before freezing at -80°C. Analysis of plasma concentrations of selected cytokines, chemokines, and vascular molecules was performed using a multiplex immunoassay system. One-way ANOVA with post hoc tests assessed differences in hemostatic and inflammatory properties. RESULTS: No significant differences in ROTEM variables (coagulation time [CT], clot formation time, α-angle, maximum clot firmness, and lysis index 30) between the TFDP-producing plasma and reconstituted TFDP samples were observed. Compared to control plasma, reconstituted TFDP stored at 4°C for 24 h or RT for 4 h showed a longer INTEM CT. Levels of immuno-inflammatory mediators were similar between frozen plasma and TFDP. CONCLUSIONS: TFDP is equivalent to frozen plasma with respect to global hemostatic and immuno-inflammatory mediator profiles. Further investigations of TFDP in trauma-induced coagulopathy models and bleeding patients are warranted.

When O Bites Back: Unrecognized Acute Hemolytic Reaction from Out-of-Group HLA-Compatible Platelet Transfusion.

Managing a platelet blood product inventory in a hospital-based transfusion service (TS) is challenging. Thus, to optimize platelet inventory availability and to prevent excess outdating, most tertiary care center-based TSs do not require ABO-identical platelet (PLT) transfusions. To mitigate the risk of hemolysis associated with the transfusion of high titer ABO antibody-containing PLT, our institutional policy allows the transfusion of PLT containing ABO-incompatible plasma only if PLT is re-suspended in platelet additive solution (PAS). Despite the steps taken to reduce the risk of hemolytic transfusion reactions to PLT transfusions at our institution, our center has observed hemolytic reactions to PLT in PAS. The current case study highlights the importance of recognizing a hemolytic reaction (HTR) from ABO-incompatible PLT transfusions and discusses the current strategies and recommendations to mitigate this risk.

A novel nano therapeutic using convalescent plasma derived exosomal (CPExo) for COVID-19: A combined hyperactive immune modulation and diagnostics.

Extracellular vesicles like exosomes are important therapeutic tactics for treating COVID -19. By utilizing convalescent plasma derived exosomes (CPExo) from COVID-19 recovered persistence could accelerate the treatment strategies in the current state of affairs. Adequate literature has shown that administering the exosome to the in vivo system could be beneficial and could target the pathogens in an effective and precise manner. In this hypothesis we highlight the CPExo instead of convalescent plasma (CP), perhaps to dispense of exosomes are gratified and it's more effectively acquired immune response conferral through antibodies. COVID-19 convalescent plasma has billions of exosomes and it has aptitudes to carry molecular constituents like proteins, lipids, RNA and DNA, etc. Moreover, exosomes are capable of recognizing antigens with adequate sensitivity and specificity. Many of these derivatives could trigger an immune modulation into the cells and act as an epigenetic inheritor response to target pathogens through RNAs. COIVID-19 resistance activated plasma-derived exosomes are either responsible for the effects of plasma beyond the contained immune antibodies or could be inhibitory. The proposed hypothesis suggests that preselecting the plasma-derived antibodies and RNAs merged exosomes would be an optimized therapeutic tactic for COVID-19 patients. We suggest that, the CPExo has a multi-potential effect for treatment efficacy by acting as immunotherapeutic, drug carrier, and diagnostic target with noncoding genetic materials as a biomarker.

Evaluation of safety of using incompatible plasma for therapeutic plasma exchange during shortage of AB plasma.

BACKGROUND: Criteria for selection of FFP blood type has not been clearly established and use of group AB plasma is preferred by numerous transplantation protocols. AIMS: This study assesses the safety and efficacy of alternative group A or B plasma in ABO incompatible solid organ transplantation. MATERIALS & METHODS: Alternative use of group A or B plasma (incompatible plasma) was inevitable during the shortage of group AB plasma. Experience from select number of patients during the period of extreme group AB plasma shortage is described. RESULTS: The result of alternative use of group A or B plasma was within expectation, showing effective reduction of isoagglutinin titers for pre-operative desensitization and efficacy for treatment of post-operative patients. No immediate hemolytic transfusion reaction was reported. DISCUSSION: While validation in a larger cohort of patients is necessary, our limited experience have shown satisfactory clinical outcomes without adverse events. CONCLUSIONS: Use of incompatible group A or B plasma is a viable option when group AB plasma is limited.

Guía para el cuidado de pacientes adultos críticos con COVID-19 en las Américas - versión 3 / Guide for the care of critical adult patients with COVID-19 in the Americas - version 3

Esta guía de práctica clínica, en cuya elaboración se siguió el método GRADE, tiene por objeto proveer recomendaciones para el manejo de pacientes adultos críticos con COVID-19 atendidos en las unidades de cuidados intensivos. Ofrece recomendaciones basadas en evidencia para la identificación de marcadores y factores de riesgo de mortalidad de los pacientes críticos, el control de la infección, la recogida de muestras, el cuidado de los pacientes (ventilatorio y hemodinámico), el tratamiento farmacológico, la rehabilitación temprana, el uso de imágenes diagnósticas, la prevención de complicaciones y los criterios de egreso. En esta tercera versión se actualizan cinco preguntas incluidas en la primera versión y se añaden tres preguntas formuladas en formato PICO. Las recomendaciones están dirigidas a todo el personal de salud que atiende a pacientes en los servicios de urgencias y de emergencias y las unidades de cuidados intensivos. Asimismo, tienen por objetivo brindar apoyo a los responsables de la toma de decisiones y miembros de entidades gubernamentales relacionados con el manejo de pacientes con COVID-19 en las unidades de cuidados intensivos de la Región de las Américas. Esta guía se encuentra en proceso continuo de actualización de la evidencia con el fin de proporcionar las recomendaciones más actualizadas para el manejo de los pacientes críticos con COVID-19, en especial sobre las intervenciones de tratamiento farmacológico como el uso de antivirales, inmunomoduladores, plasma de convalecientes y antibióticos.