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Although severe coronavirus disease 2019 (COVID-19) and hospitalization associated with COVID-19 are generally preventable among healthy vaccine recipients, patients with immunosuppression have poor immunogenic responses to COVID-19 vaccines and remain at high risk of infection with SARS-CoV-2 and hospitalization. In addition, monoclonal antibody therapy is limited by the emergence of novel SARS-CoV-2 variants that have serially escaped neutralization. In this context, there is interest in understanding the clinical benefit associated with COVID-19 convalescent plasma collected from persons who have been both naturally infected with SARS-CoV-2 and vaccinated against SARS-CoV-2 ("vax-plasma"). Thus, we report the clinical outcome of 386 immunocompromised outpatients who were diagnosed with COVID-19 and who received contemporary COVID-19-specific therapeutics (standard-of-care group) and a subgroup who also received concomitant treatment with very high titer COVID-19 convalescent plasma (vax-plasma group) with a specific focus on hospitalization rates. The overall hospitalization rate was 2.2% (5 of 225 patients) in the vax-plasma group and 6.2% (10 of 161 patients) in the standard-of-care group, which corresponded to a relative risk reduction of 65% (P = 0.046). Evidence of efficacy in nonvaccinated patients cannot be inferred from these data because 94% (361 of 386 patients) of patients were vaccinated. In vaccinated patients with immunosuppression and COVID-19, the addition of vax-plasma or very high titer COVID-19 convalescent plasma to COVID-19-specific therapies reduced the risk of disease progression leading to hospitalization.IMPORTANCEAs SARS-CoV-2 evolves, new variants of concern (VOCs) have emerged that evade available anti-spike monoclonal antibodies, particularly among immunosuppressed patients. However, high-titer COVID-19 convalescent plasma continues to be effective against VOCs because of its broad-spectrum immunomodulatory properties. Thus, we report clinical outcomes of 386 immunocompromised outpatients who were treated with COVID-19-specific therapeutics and a subgroup also treated with vaccine-boosted convalescent plasma. We found that the administration of vaccine-boosted convalescent plasma was associated with a significantly decreased incidence of hospitalization among immunocompromised COVID-19 outpatients. Our data add to the contemporary data providing evidence to support the clinical utility of high-titer convalescent plasma as antibody replacement therapy in immunocompromised patients.
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Sueroterapia para COVID-19 , Vacunas contra la COVID-19 , COVID-19 , Hospitalización , Inmunización Pasiva , Huésped Inmunocomprometido , SARS-CoV-2 , Humanos , COVID-19/inmunología , COVID-19/terapia , COVID-19/prevención & control , Inmunización Pasiva/métodos , Femenino , Masculino , Persona de Mediana Edad , SARS-CoV-2/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Anciano , Hospitalización/estadística & datos numéricos , Adulto , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Terapia de Inmunosupresión , Pacientes Ambulatorios , Resultado del TratamientoRESUMEN
Consensus statements recommend the use of norepinephrine and/or vasopressin for hypotension in cardiac surgery. However, there is a paucity of data among other surgical subgroups and vasopressin analogs. Therefore, the authors conducted a systematic review of randomized controlled trials (RCTs) to compare vasopressin-receptor agonists with norepinephrine for hypotension among those undergoing surgery with general anesthesia. This review was registered prospectively (CRD42022316328). Literature searches were conducted by a medical librarian to November 28, 2023, across MEDLINE, EMBASE, CENTRAL, and Web of Science. The authors included RCTs enrolling adults (≥18 years of age) undergoing any surgery under general anesthesia who developed perioperative hypotension and comparing vasopressin receptor agonists with norepinephrine. The risk of bias was assessed by the Cochrane risk of bias tool for randomized trials (RoB-2). Thirteen (N = 719) RCTs were included, of which 8 (n = 585) enrolled patients undergoing cardiac surgery. Five trials compared norepinephrine with vasopressin, 4 trials with terlipressin, 1 trial with ornipressin, and the other 3 trials used vasopressin as adjuvant therapy. There was no significant difference in all-cause mortality. Among patients with vasoplegic shock after cardiac surgery, vasopressin was associated with significantly lower intensive care unit (N = 385; 2 trials; mean 100.8 v 175.2 hours, p < 0.005; median 120 [IQR 96-168] v 144 [96-216] hours, p = 0.007) and hospital lengths of stay, as well as fewer cases of acute kidney injury and atrial fibrillation compared with norepinephrine. One trial also found that terlipressin was associated with a significantly lower incidence of acute kidney injury versus norepinephrine overall. Vasopressin and norepinephrine restored mean arterial blood pressure with no significant differences; however, the use of vasopressin with norepinephrine was associated with significantly higher mean arterial blood pressure versus norepinephrine alone. Further high-quality trials are needed to determine pooled treatment effects, especially among noncardiac surgical patients and those treated with vasopressin analogs.
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Hipotensión , Norepinefrina , Vasoconstrictores , Humanos , Norepinefrina/uso terapéutico , Hipotensión/tratamiento farmacológico , Hipotensión/epidemiología , Vasoconstrictores/uso terapéutico , Vasopresinas/uso terapéutico , Receptores de Vasopresinas/agonistas , Adulto , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Procedimientos Quirúrgicos Cardíacos/métodos , Resultado del TratamientoRESUMEN
Traditionally, patients with obesity have been deemed ineligible for extracorporeal life support (ELS) therapies such as extracorporeal membrane oxygenation (ECMO), given the association of obesity with chronic health conditions that contribute to increased morbidity and mortality. Nevertheless, a growing body of literature suggests the feasibility, efficacy, and safety of ECMO in the obese population. This review provides an in-depth analysis of the current literature assessing the effects of obesity on outcomes among patients supported with ECMO (venovenous [VV] ECMO in noncoronavirus disease 2019 and coronavirus disease 2019 acute respiratory distress syndrome, venoarterial [VA] ECMO, and combined VV and VA ECMO), offer a possible explanation of the current findings on the basis of the obesity paradox phenomenon, provides a framework for future studies addressing the use of ELS therapies in the obese patient population, and provides guidance from the literature for many of the challenges related to initiating, maintaining, and weaning ELS therapy in patients with obesity.
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Oxigenación por Membrana Extracorpórea , Síndrome de Dificultad Respiratoria , Humanos , Estudios Retrospectivos , Obesidad/complicaciones , Obesidad/terapia , Síndrome de Dificultad Respiratoria/terapiaRESUMEN
Obesity is often considered a contraindication to extracorporeal membrane oxygenation (ECMO) candidacy due to technical challenges with vascular access, higher cardiac output requirements, and known associations between obesity and overall increased morbidity and mortality due to chronic health conditions. However, a growing body of literature suggests that ECMO may be as safe and efficacious in both obese and nonobese patients. This scoping review provides a synthesis of the available literature on the outcomes of obese patients supported with (1) venovenous (VV)-ECMO in acute respiratory distress syndrome (ARDS) not due to coronavirus disease 2019 (COVID-19), (2) VV-ECMO in ARDS due to COVID-19, (3) venoarterial (VA)-ECMO for all indications, and (4) studies combining data of patients supported with VA- and VV-ECMO. A librarian-assisted search was performed using 4 primary electronic medical databases (PubMed, Web of Science, Excerpta Medica database [Embase], and Cochrane Library) from January 2003 to March 2023. Articles that reported outcomes of obese patients requiring ECMO support were included. Two reviewers independently screened titles, abstracts, and full text of articles to determine eligibility. Data extraction was performed using customized fields established a priori within a systematic review software system. A total of 354 publications were imported for screening on titles and abstracts, and 30 studies were selected for full-text review. A total of 26 publications met the inclusion criteria: 7 on VV-ECMO support in non-COVID-19 ARDS patients, 6 on ECMO in COVID-19 ARDS patients, 8 in patients supported with VA-ECMO, and 5 combining both VA- and VV-ECMO data. Although the included studies are limited to retrospective analyses and display a heterogeneity in definitions of obesity and comparison groups, the currently available literature suggests that outcomes and complications of ECMO therapy are equivalent in obese patients as compared to nonobese patients. Hence, obesity as measured by body mass index alone should not be considered an exclusion criterion in the decision to initiate ECMO.
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Objective: To examine the association of COVID-19 convalescent plasma transfusion with mortality and the differences between subgroups in hospitalized patients with COVID-19. Patients and Methods: On October 26, 2022, a systematic search was performed for clinical studies of COVID-19 convalescent plasma in the literature from January 1, 2020, to October 26, 2022. Randomized clinical trials and matched cohort studies investigating COVID-19 convalescent plasma transfusion compared with standard of care treatment or placebo among hospitalized patients with confirmed COVID-19 were included. The electronic search yielded 3841 unique records, of which 744 were considered for full-text screening. The selection process was performed independently by a panel of 5 reviewers. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were extracted by 5 independent reviewers in duplicate and pooled using an inverse-variance random effects model. The prespecified end point was all-cause mortality during hospitalization. Results: Thirty-nine randomized clinical trials enrolling 21,529 participants and 70 matched cohort studies enrolling 50,160 participants were included in the systematic review. Separate meta-analyses reported that transfusion of COVID-19 convalescent plasma was associated with a decrease in mortality compared with the control cohort for both randomized clinical trials (odds ratio [OR], 0.87; 95% CI, 0.76-1.00) and matched cohort studies (OR, 0.76; 95% CI, 0.66-0.88). The meta-analysis of subgroups revealed 2 important findings. First, treatment with convalescent plasma containing high antibody levels was associated with a decrease in mortality compared with convalescent plasma containing low antibody levels (OR, 0.85; 95% CI, 0.73 to 0.99). Second, earlier treatment with COVID-19 convalescent plasma was associated with a decrease in mortality compared with the later treatment cohort (OR, 0.63; 95% CI, 0.48 to 0.82). Conclusion: During COVID-19 convalescent plasma use was associated with a 13% reduced risk of mortality, implying a mortality benefit for hospitalized patients with COVID-19, particularly those treated with convalescent plasma containing high antibody levels treated earlier in the disease course.
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OBJECTIVE: No recent prospective studies have analyzed the accuracy of standard coagulation tests and thromboelastography (TEG) to identify patients with excessive microvascular bleeding following cardiopulmonary bypass (CPB). The aim of this study was to assess the value of coagulation profile tests, as well as TEG, for the classification of microvascular bleeding after CPB. DESIGN: A prospective observational study. SETTING: At a single-center academic hospital. PARTICIPANTS: Patients ≥18 years of age undergoing elective cardiac surgery. INTERVENTIONS: Qualitative assessment of microvascular bleeding post-CPB (surgeon and anesthesiologist consensus) and the association with coagulation profile tests and TEG values. MEASUREMENTS AND MAIN RESULTS: A total of 816 patients were included in the study-358 (44%) bleeders and 458 (56%) nonbleeders. Accuracy, sensitivity, and specificity for the coagulation profile tests and TEG values ranged from 45% to 72%. The predictive utility was similar across tests, with prothrombin time (PT) (62% accuracy, 51% sensitivity, 70% specificity), international normalized ratio (INR) (62% accuracy, 48% sensitivity, 72% specificity), and platelet count (62% accuracy, 62% sensitivity, 61% specificity) displaying the highest performance. Secondary outcomes were worse in bleeders versus nonbleeders, including higher chest tube drainage, total blood loss, transfusion of red blood cells, reoperation rates (p < 0.001, respectively), readmission within 30 days (p = 0.007), and hospital mortality (p = 0.021). CONCLUSIONS: Standard coagulation tests and individual components of TEG in isolation agree poorly with the visual classification of microvascular bleeding after CPB. The PT-INR and platelet count performed best but had low accuracy. Further work is warranted to identify better testing strategies to guide perioperative transfusion decisions in cardiac surgical patients.
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Puente Cardiopulmonar , Hemorragia , Humanos , Estudios Prospectivos , Puente Cardiopulmonar/efectos adversos , Pruebas de Coagulación Sanguínea , Tiempo de Protrombina , TromboelastografíaRESUMEN
Direct oral anticoagulants (DOACs) have rapidly emerged as popular alternatives to warfarin in the setting of nonvalvular atrial fibrillation, prevention and treatment of venous thromboembolism, and secondary prevention of arterial thrombosis. It is now estimated that more patients in the United States take DOACs than warfarin for approved indications. Studies to date have shown that these drugs are similarly efficacious with perhaps a lower bleeding risk than warfarin. The purpose of this review is to provide insight into the currently available DOACs and discuss the management and reversal strategies for patients in the perioperative period.
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Fibrilación Atrial , Tromboembolia Venosa , Humanos , Warfarina/uso terapéutico , Administración Oral , Anticoagulantes/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/complicacionesRESUMEN
Respiratory epithelium in the conducting airways of the human body is one of the primary targets of SARS-CoV-2 infection, however, there is a paucity of studies describing the association between COVID-19 and physical characteristics of the conducting airways. To better understand the pathophysiology of COVID-19 on the size of larger conducting airways, we determined the luminal area of the central airways in patients with a history of COVID-19 compared to a height-matched cohort of controls using a case-control study design. Using three-dimensional reconstruction from low-dose high-resolution computed tomography, we retrospectively assessed airway luminal cross-sectional area in 114 patients with COVID-19 (66 females, 48 males) and 114 healthy, sex- and height-matched controls (66 females, 48 males). People with a history of smoking, cardiopulmonary disease, or a body mass index greater than 40 kg·m-2 were excluded. Luminal areas of seven conducting airways were analyzed, including trachea, left and right main bronchus, intermediate bronchus, left and right upper lobe, and left lower lobe. For the central conducting airways, luminal area was ~ 15% greater patients with COVID-19 compared to matched controls (p < 0.05). Among patients with COVID-19, there were generally no differences in the luminal areas of the conducting airways between hospitalized patients compared to patients who did not require COVID-19-related hospitalization. Our findings suggest that males and females with COVID-19 have pathologically larger conducting airway luminal areas than healthy, sex- and height-matched controls.
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COVID-19 , Masculino , Femenino , Humanos , Estudios de Casos y Controles , Estudios Retrospectivos , SARS-CoV-2 , Pulmón/diagnóstico por imagenAsunto(s)
COVID-19 , Vacunas , Humanos , COVID-19/terapia , Inmunización Pasiva , Terapia de Inmunosupresión , Sueroterapia para COVID-19RESUMEN
McConnell's sign is a well-established, specific echocardiographic sign for acute pulmonary embolism. Multiple theories have been proposed regarding the mechanism of McConnell's sign in the context of acute pulmonary embolism. Here, we present 2 patient cases in which McConnell's sign was seen with right ventricular ischemia without pulmonary embolism. (Level of Difficulty: Beginner.).
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BACKGROUND: The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma. METHODS AND FINDINGS: Mayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician-principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had-or were at risk of progression to-severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate at the state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions, as well as assessing enrollment in metropolitan areas and less populated areas that did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low (<1%), and the overall crude 30-day mortality rate was 25.2% (95% CI, 25.0% to 25.5%). This registry study was limited by the observational and pragmatic study design that did not include a control or comparator group; thus, the data should not be used to infer definitive treatment effects. CONCLUSIONS: These results suggest that the EAP provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The study design of the EAP may serve as a model for future efforts when broad access to a treatment is needed in response to an emerging infectious disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT#: NCT04338360.
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COVID-19/terapia , Ensayos de Uso Compasivo/métodos , Necesidades y Demandas de Servicios de Salud/estadística & datos numéricos , Sistemas de Distribución en Hospital/organización & administración , Sistema de Registros , Reacción a la Transfusión/complicaciones , Reacción a la Transfusión/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/epidemiología , Minorías Étnicas y Raciales , Femenino , Humanos , Inmunización Pasiva/efectos adversos , Inmunización Pasiva/métodos , Pacientes Internos , Masculino , Área sin Atención Médica , Persona de Mediana Edad , Pandemias , Seguridad del Paciente , SARS-CoV-2 , Resultado del Tratamiento , Estados Unidos , Sueroterapia para COVID-19RESUMEN
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.
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COVID-19/terapia , Plasma/inmunología , Adolescente , Adulto , Anciano , Anticuerpos Antivirales/inmunología , Especificidad de Anticuerpos , Variación Antigénica , Donantes de Sangre , COVID-19/mortalidad , Femenino , Humanos , Inmunización Pasiva/mortalidad , Masculino , Persona de Mediana Edad , SARS-CoV-2/genética , SARS-CoV-2/inmunología , Resultado del Tratamiento , Estados Unidos/epidemiología , Adulto Joven , Sueroterapia para COVID-19RESUMEN
BACKGROUND: Social media remains a growing platform for physicians to facilitate learning, network, and disseminate information. The Coronavirus Disease 2019 (COVID-19) pandemic has challenged traditional medical student recruitment and outreach. Instagram is a platform that can be used by residency programs to increase engagement and as a potential recruitment tool. The authors present social media failed and successful strategies used to increase engagement and gain new followers. METHODS: In June 2020, an initiative began to use Instagram on a more frequent and intentional basis. Three different strategies were implemented during the pandemic: mirroring Twitter posts, increasing multimedia, and leveraging Instagram Stories. The outcomes of interest included number of followers and engagement on posts. Data were collected October 2020. RESULTS: After June 1, 2020, the @mayoanesthesia account gained 1000 followers through 127 days, an average of 4.26 new followers each day. Before June 1, there were 24 total posts over 3.3 years with a total of 458 followers. Three different strategies were implemented at different times during the pandemic. During the mirroring Twitter posts period, the mean number of interactions per post was 14.5. During the second phase after separating the Twitter and Instagram strategy, the mean number of interactions per post increased to 57.8. CONCLUSION: Residency programs can creatively, yet methodically, use Instagram posts to increase social media engagement during resident recruitment season during the COVID-19 pandemic and likely beyond.
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BACKGROUND: The United States (US) Expanded Access Program (EAP) to COVID-19 convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease-2019 (COVID-19). While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents particularly for vulnerable racial and ethnic minority populations who were disproportionately affected by the pandemic. The objective of this study is to report on the demographic, geographic, and chronological access to COVID-19 convalescent plasma in the US via the EAP. METHODS AND FINDINGS: Mayo Clinic served as the central IRB for all participating facilities and any US physician could participate as local physician-principal investigator. Registration occurred through the EAP central website. Blood banks rapidly developed logistics to provide convalescent plasma to hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal trends in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate on a state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions as well as assessing enrollment in metropolitan and less populated areas which did not have access to COVID-19 clinical trials.From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. A majority of patients were older than 60 years of age (57.8%), male (58.4%), and overweight or obese (83.8%). There was substantial inclusion of minorities and underserved populations, including 46.4% of patients with a race other than White, and 37.2% of patients were of Hispanic ethnicity. Severe or life-threatening COVID-19 was present in 61.8% of patients and 18.9% of patients were mechanically ventilated at time of convalescent plasma infusion. Chronologically and geographically, increases in enrollment in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled patients in the EAP, including both in metropolitan and less populated areas. CONCLUSIONS: The EAP successfully provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The efficient study design of the EAP may serve as an example framework for future efforts when broad access to a treatment is needed in response to a dynamic disease affecting demographic groups and areas historically underrepresented in clinical studies.
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BACKGROUND: Convalescent plasma has been widely used to treat coronavirus disease 2019 (Covid-19) under the presumption that such plasma contains potentially therapeutic antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be passively transferred to the plasma recipient. Whether convalescent plasma with high antibody levels rather than low antibody levels is associated with a lower risk of death is unknown. METHODS: In a retrospective study based on a U.S. national registry, we determined the anti-SARS-CoV-2 IgG antibody levels in convalescent plasma used to treat hospitalized adults with Covid-19. The primary outcome was death within 30 days after plasma transfusion. Patients who were enrolled through July 4, 2020, and for whom data on anti-SARS-CoV-2 antibody levels in plasma transfusions and on 30-day mortality were available were included in the analysis. RESULTS: Of the 3082 patients included in this analysis, death within 30 days after plasma transfusion occurred in 115 of 515 patients (22.3%) in the high-titer group, 549 of 2006 patients (27.4%) in the medium-titer group, and 166 of 561 patients (29.6%) in the low-titer group. The association of anti-SARS-CoV-2 antibody levels with the risk of death from Covid-19 was moderated by mechanical ventilation status. A lower risk of death within 30 days in the high-titer group than in the low-titer group was observed among patients who had not received mechanical ventilation before transfusion (relative risk, 0.66; 95% confidence interval [CI], 0.48 to 0.91), and no effect on the risk of death was observed among patients who had received mechanical ventilation (relative risk, 1.02; 95% CI, 0.78 to 1.32). CONCLUSIONS: Among patients hospitalized with Covid-19 who were not receiving mechanical ventilation, transfusion of plasma with higher anti-SARS-CoV-2 IgG antibody levels was associated with a lower risk of death than transfusion of plasma with lower antibody levels. (Funded by the Department of Health and Human Services and others; ClinicalTrials.gov number, NCT04338360.).
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Anticuerpos Antivirales/sangre , COVID-19/terapia , SARS-CoV-2/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/inmunología , COVID-19/mortalidad , Femenino , Hospitalización , Humanos , Inmunización Pasiva , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Sistema de Registros , Respiración Artificial , Estudios Retrospectivos , Factores de Riesgo , Tiempo de Tratamiento , Estados Unidos/epidemiología , Adulto Joven , Sueroterapia para COVID-19RESUMEN
Convalescent plasma has emerged as a promising therapeutic agent for patients with coronavirus disease 2019 (COVID-19), has received emergency use authorization, and is being widely used during the COVID-19 pandemic. Passive antibody therapy via plasma or serum has been successfully used to treat infectious diseases for more than a century. Passive antibody administration is based on the presumption that convalescent plasma or serum contains therapeutic antibodies that can be passively transferred to the plasma recipient. There are numerous examples in which convalescent plasma has been used successfully as post-exposure prophylaxis and treatment of infectious diseases, including previous coronavirus outbreaks. In the context of the COVID-19 pandemic, convalescent plasma was demonstrated to be safe and potentially effective among patients infected with COVID-19. This review provides an overview of the historical uses of convalescent plasma therapy, summarizes current evidence for convalescent plasma use for COVID-19, and highlights future antibody therapies.
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BACKGROUND: Preoperative anemia is common in cardiac surgery, yet there were limited data describing the role of sex in the associations between anemia and clinical outcomes. Understanding these relationships may guide preoperative optimization efforts. METHODS: This is an observational cohort study of adults undergoing isolated coronary artery bypass grafting or single- or double-valve surgery from 2008 to 2018 at a large tertiary medical center. Multivariable regression assessed the associations between preoperative hemoglobin concentrations and a primary outcome of postoperative acute kidney injury (AKI) and secondary outcomes of perioperative red blood cell (RBC) transfusion, reoperation, vascular complications (ie, stroke, pulmonary embolism, and myocardial infarction), and hospital length of stay (LOS). Each outcome was a single regression model, using interaction terms to assess sex-specific associations between hemoglobin and outcome. RESULTS: A total of 4117 patients were included (57% men). Linear splines with sex-specific knots (13 g/dL in women and 14 g/dL in men) provided the best overall fit for preoperative hemoglobin and outcome relationships. In women, each 1 g/dL decrease in hemoglobin <13 g/dL was associated with increased odds of AKI (odds ratio = 1.49; 95% confidence interval [CI], [1.23-1.81]; P < .001), and there was no significant association between hemoglobin per 1 g/dL >13 g/dL and AKI (0.90 [0.56-1.45]; P = .67). The association between hemoglobin and AKI in men did not meet statistical significance (1.10 [0.99-1.22]; P = .076, per 1 g/dL decrease <14 g/dL; 1.00 [0.79-1.26]; P = .98 for hemoglobin per 1 g/dL >14 g/dL). In women, lower preoperative hemoglobin (per 1 g/dL decrease <13 g/dL) was associated with increased odds of RBC transfusion (2.90 [2.33-3.60]; P < .001), reoperation (1.27 [1.11-1.45]; P < .001) and a longer hospital LOS (multiplicative increase in geometric mean 1.05 [1.03-1.07]; P < .001). In men, preoperative hemoglobin (per 1 g/dL decrease <14 g/dL) was associated with increased odds of perioperative RBCs (2.56 [2.27-2.88]; P < .001) and longer hospital LOS (multiplicative increase in geometric mean 1.02 [1.01-1.04] days; P < .001) but not reoperation (0.94 [0.85-1.04]; P = .256). Preoperative hemoglobin per 1 g/dL >13 g/dL in women and 14 g/dL in men were associated with lower odds of RBCs transfusion (0.57 [0.47-0.69]; P < .001 and 0.74 [0.60-0.91]; P = .005, respectively). CONCLUSIONS: Preoperative anemia was associated with inferior clinical outcomes after cardiac surgery. The associations between hemoglobin and outcomes were distinct for women and men, with different spline knot points identified (13 and 14 g/dL, respectively). Clinicians should consider data-driven approaches to determine preoperative hemoglobin values associated with increasing risk for adverse perioperative outcomes across sexes.
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Anemia/complicaciones , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Hemoglobinas/análisis , Complicaciones Posoperatorias/etiología , Anciano , Anemia/sangre , Anemia/diagnóstico , Biomarcadores/sangre , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Donantes de Sangre , Infecciones por Coronavirus/terapia , Neumonía Viral/terapia , Obtención de Tejidos y Órganos/métodos , Betacoronavirus , COVID-19 , Humanos , Inmunización Pasiva , Minnesota , Pandemias , SARS-CoV-2 , Obtención de Tejidos y Órganos/organización & administración , Sueroterapia para COVID-19RESUMEN
IMPORTANCE: Passive antibody transfer is a longstanding treatment strategy for infectious diseases that involve the respiratory system. In this context, human convalescent plasma has been used to treat coronavirus disease 2019 (COVID-19), but the efficacy remains uncertain. OBJECTIVE: To explore potential signals of efficacy of COVID-19 convalescent plasma. DESIGN: Open-label, Expanded Access Program (EAP) for the treatment of COVID-19 patients with human convalescent plasma. SETTING: Multicenter, including 2,807 acute care facilities in the US and territories. PARTICIPANTS: Adult participants enrolled and transfused under the purview of the US Convalescent Plasma EAP program between April 4 and July 4, 2020 who were hospitalized with (or at risk of) severe or life threatening acute COVID-19 respiratory syndrome. INTERVENTION: Transfusion of at least one unit of human COVID-19 convalescent plasma using standard transfusion guidelines at any time during hospitalization. Convalescent plasma was donated by recently-recovered COVID-19 survivors, and the antibody levels in the units collected were unknown at the time of transfusion. Main Outcomes and Measures: Seven and thirty-day mortality. RESULTS: The 35,322 transfused patients had heterogeneous demographic and clinical characteristics. This cohort included a high proportion of critically-ill patients, with 52.3% in the intensive care unit (ICU) and 27.5% receiving mechanical ventilation at the time of plasma transfusion. The seven-day mortality rate was 8.7% [95% CI 8.3%-9.2%] in patients transfused within 3 days of COVID-19 diagnosis but 11.9% [11.4%-12.2%] in patients transfused 4 or more days after diagnosis (p<0.001). Similar findings were observed in 30-day mortality (21.6% vs. 26.7%, p<0.0001). Importantly, a gradient of mortality was seen in relation to IgG antibody levels in the transfused plasma. For patients who received high IgG plasma (>18.45 S/Co), seven-day mortality was 8.9% (6.8%, 11.7%); for recipients of medium IgG plasma (4.62 to 18.45 S/Co) mortality was 11.6% (10.3%, 13.1%); and for recipients of low IgG plasma (<4.62 S/Co) mortality was 13.7% (11.1%, 16.8%) (p=0.048). This unadjusted dose-response relationship with IgG was also observed in thirty-day mortality (p=0.021). The pooled relative risk of mortality among patients transfused with high antibody level plasma units was 0.65 [0.47-0.92] for 7 days and 0.77 [0.63-0.94] for 30 days compared to low antibody level plasma units. CONCLUSIONS AND RELEVANCE: The relationships between reduced mortality and both earlier time to transfusion and higher antibody levels provide signatures of efficacy for convalescent plasma in the treatment of hospitalized COVID-19 patients. This information may be informative for the treatment of COVID-19 and design of randomized clinical trials involving convalescent plasma. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04338360.