Rates Among Hospitalized Patients With COVID-19 Treated With Convalescent Plasma: A Systematic Review and Meta-Analysis.

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.

Retained Food During Esophagogastroduodenoscopy Is a Risk Factor for Gastric-to-Pulmonary Aspiration.

BACKGROUND: Residual food (RF) during esophagogastroduodenoscopy (EGD) is thought, but not proven, to be a risk factor for gastric-to-pulmonary aspiration. AIMS: The aims of this study were to determine the prevalence of RF during EGD, to investigate whether RF was associated with an increased risk of aspiration, especially when monitored anesthesia care (MAC) or general anesthesia (GA) were administered, and to determine whether aspiration associated with RF led to a more severe clinical outcome. METHODS: Patients undergoing EGD between October 2012 and September 2018 were identified. Patient age, sex, aspiration events, RF, sedation type, structural foregut abnormalities, and diagnoses associated with impaired esophageal or gastric motility were noted. The clinical course after an aspiration event was evaluated. RESULTS: RF was identified during 4% of 81,367 EGDs. Aspiration events occurred during 41 (5/10,000) procedures. Aspiration was more likely to occur in patients with RF (odds ratio [OR] 15.1) or those receiving MAC or GA (OR 9.6 and 16.8 relative to conscious sedation, respectively). RF and MAC/GA were synergistically associated with increased odds of aspiration. In a multivariate nominal logistic regression model, older age (OR 2.6), MAC (OR 3.8), GA (OR 4.4), vagotomy (OR 5.2), achalasia (OR 3.8), and RF (OR 10.0) were risk factors for aspiration. Aspiration events in the presence or absence of RF led to similar clinical outcomes. CONCLUSIONS: While aspiration events are rare in patients undergoing EGD, RF and the use of MAC or GA were associated with substantially increased odds of aspiration.

Access to and safety of COVID-19 convalescent plasma in the United States Expanded Access Program: A national registry study.

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.

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.

Program and patient characteristics for the United States Expanded Access Program to COVID-19 convalescent plasma.

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.

Convalescent Plasma Antibody Levels and the Risk of Death from Covid-19.

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.).

Effect of Convalescent Plasma on Mortality among Hospitalized Patients with COVID-19: Initial Three-Month Experience.

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.

Safety Update: COVID-19 Convalescent Plasma in 20,000 Hospitalized Patients.

OBJECTIVE: To provide an update on key safety metrics after transfusion of convalescent plasma in hospitalized coronavirus 2019 (COVID-19) patients, having previously demonstrated safety in 5000 hospitalized patients. PATIENTS AND METHODS: From April 3 to June 2, 2020, the US Food and Drug Administration Expanded Access Program for COVID-19 convalescent plasma transfused a convenience sample of 20,000 hospitalized patients with COVID-19 convalescent plasma. RESULTS: The incidence of all serious adverse events was low; these included transfusion reactions (n=78; <1%), thromboembolic or thrombotic events (n=113; <1%), and cardiac events (n=677, ~3%). Notably, the vast majority of the thromboembolic or thrombotic events (n=75) and cardiac events (n=597) were judged to be unrelated to the plasma transfusion per se. The 7-day mortality rate was 13.0% (12.5%, 13.4%), and was higher among more critically ill patients relative to less ill counterparts, including patients admitted to the intensive care unit versus those not admitted (15.6 vs 9.3%), mechanically ventilated versus not ventilated (18.3% vs 9.9%), and with septic shock or multiple organ dysfunction/failure versus those without dysfunction/failure (21.7% vs 11.5%). CONCLUSION: These updated data provide robust evidence that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19, and support the notion that earlier administration of plasma within the clinical course of COVID-19 is more likely to reduce mortality.

YouTube as a source of medical information on the novel coronavirus 2019 disease (COVID-19) pandemic.

Media coverage on coronavirus disease 2019 (COVID-19) has been extensive, yet large gaps remain in our understanding of the role of social media platforms during worldwide health crisis. The purpose of this study was to assess the most viewed YouTube videos on COVID-19 for medical content. We coded video characteristics, source, and medical content of the 113 most-widely viewed videos about COVID-19. Seventy-nine (69.9%) videos were classified as useful, and 10 (8.8%) videos were classified as misleading. Independent users were more likely to post misleading videos than useful videos (60.0% vs 21.5%, P = 0.009). News agencies were more likely to post useful videos than misleading videos (72.2% vs 40.0%, P = 0.039). Useful videos were more likely to present any information on prevalence or incidence (79.7% vs 20.0%, P < 0.001), as well as information on outcomes or prognosis (84.8% vs 30.0%, P < 0.001) compared to misleading videos. The World Health Organization contributed one useful video (1.3%), while no videos from the Center for Disease Control were included. Although YouTube generally is a useful source of medical information on the COVID-19 pandemic, increased efforts to disseminate accurate information from reputable sources is desired to help mitigate disease spread and decrease unnecessary panic in the general population.

Post-operative functional neurological symptom disorder after anesthesia.

A rare manifestation during the post-anesthetic period may include the occurrence of functional neurological symptom disorder (FNSD). FNSD is described as neurological symptoms that are not consistently explained by neurological or medical conditions. We report a case series consisting of six patients who underwent a general anesthetic at a tertiary referral hospital and experienced FNSD in the immediate post-anesthetic period. Life-threatening causes were excluded based on benign physical exam findings and knowledge of past history. Five of six cases manifested with FNSD only in the immediate post-operative setting after exposure to anesthesia, and never otherwise experienced these symptoms during their normal daily lives. MEDLINE and Google Scholar were searched through October 2019 using a highly-sensitive search strategy and identified 38 published cases of post-anesthetic FNSD. Meta-analysis of pooled clinical data revealed that a significant proportion of patients were females (86%), reported a history of psychiatric illness (49%), reported a prior history of FNSD (53%), and underwent general anesthesia as the primary anesthetic (93%). The majority of patients were exposed to diagnostic studies (66% received radiographic tests and 52% received electroencephalogram) as well as pharmacologic therapy (57%). While no deaths occurred, many patients had unanticipated admission to the hospital (53%) or to the intensive care unit (25%). These data may help inform the anesthesia literature on presentation, risk factors, and treatment outcomes of FNSD in the context of anesthetic administration. We contemplate whether anesthetic agents may predispose a vulnerable brain to manifest with involuntary motor and sensory control seen in FNSD.

Association of Perioperative Variables and the Acute Respiratory Distress Syndrome in Liver Transplant Recipients.

BACKGROUND: The assessment of perioperative risk factors for the development of acute respiratory distress syndrome (ARDS) has been described in various surgical populations. However, there are only limited data among patients undergoing liver transplantation (LT), particularly regarding the influence of intraoperative ventilation parameters. We sought to identify the perioperative risk factors associated with the development of ARDS in LT recipients. METHODS: This is a single-center, retrospective cohort study of adult patients who underwent LT at a tertiary academic medical center between January 1, 2006, and January 31, 2016. Postoperative ARDS was identified using the Berlin definition. Multivariable logistic regression analysis was used to identify perioperative risk factors for ARDS. RESULTS: Of 817 eligible patients who underwent an LT during the study period, 20 (2.45%) developed postoperative ARDS. In the preoperative model, ongoing dialysis (odds ratio, 6.41; P < 0.01) was identified as an independent risk factor of ARDS post-LT. A higher mean peak inspiratory pressure per increase of 1 cm H2O (odds ratio, 1.31; P < 0.01) was the only independent risk factor in the intraoperative model. Patients who developed ARDS postoperatively had significantly greater intensive care unit and hospital stay compared to non-ARDS patients (P < 0.001). There were no significant differences in the 30-day (P = 0.16) and 1-year (P = 0.51) mortality between the groups. CONCLUSIONS: Dialysis at the time of transplant and elevated intraoperative mean peak inspiratory pressure were associated with the development of ARDS. ARDS post LT was associated with increased intensive care unit and hospital length of stay, but not increased mortality.

Influence of Intraoperative Transesophageal Echocardiography and Pulmonary Artery Catheter Monitoring on Outcomes in Liver Transplantation.

Anesthetic management of orthotopic liver transplantation (OLT) can be challenging. Management involves responding to sudden hemodynamic shifts, addressing instability, and performing ongoing volume assessment. To best prepare for these perturbations, various monitors are used intraoperatively. We sought to explore the impact of transesophageal echocardiography (TEE) and pulmonary artery catheter (PAC) use on outcomes of patients undergoing OLT. METHODS: We retrospectively reviewed records of patients who underwent OLT at a single institution and included all who were monitored intraoperatively with TEE alone, PAC alone, or both methods concurrently (TEE + PAC). We determined whether these groups had differences in length of hospitalization (primary outcome), 30-day mortality rate, and other outcomes. RESULTS: Three hundred eighteen liver transplant operations were included in the study. Patients in the TEE + PAC group had the shortest median length of hospitalization (TEE + PAC, 8.6 days; TEE, 10.3; PAC, 9.1; P = 0.04). The TEE + PAC group also had the lowest 30-day mortality rate (TEE + PAC, n = 1 [1.3%]; TEE, n = 5 [12.8%]; PAC, n = 7 [3.5%]; P = 0.009). However, the TEE + PAC group also had the highest rate of a new postoperative need for dialysis (TEE + PAC, n = 8 [10.3%]; TEE, n = 2 [5.1%]; PAC, n = 1 [0.5%]; P < 0.001). CONCLUSIONS: Compared with either TEE alone or PAC alone, intraoperative monitoring with TEE + PAC during OLT was associated with the shortest length of hospitalization and lowest 30-day mortality rate. Transplant anesthesiologists should be aware of the potential benefit on patient mortality and hospital length of stay with concurrent intraoperative TEE + PAC monitoring and the increased need for new postoperative dialysis.

Successful Removal of Intracardiac Thrombus With a Poole Tip Suction Device Through the Inferior Vena Cava of a Patient With Cardiovascular Collapse During Liver Transplant: A Case Report.

Intracardiac thrombus occurs in 1.2%-6.3% of patients undergoing orthotopic liver transplant and is associated with a high mortality rate. The pathophysiology and risk factors for development of this complication are not well understood. No consensus treatment guidelines exist, and specific therapies are associated with serious risks. We present the timely and successful use of a Poole tip surgical suction device advanced into the right atrium through a cavotomy created in the inferior vena cava to remove a large right atrial thrombus during liver transplant. The thrombus was identified with transesophageal echocardiography and was causing cardiovascular collapse.