Use of convalescent plasma in COVID-19 patients with immunosuppression

In the absence of effective countermeasures, human convalescent plasma has been widely used to treat severe acute respiratory syndrome coronavirus 2, the causative agent of novel coronavirus disease 19 (COVID-19), including among patients with innate or acquired immunosuppression. However, the association between COVID-19-associated mortality in patients with immunosuppression and therapeutic use of convalescent plasma is unknown. We review 75 reports, including one large matched-control registry study of 143 COVID-19 patients with hematological malignancies, and 51 case reports and 23 case series representing 238 COVID-19 patients with immunosuppression. We review clinical features and treatment protocols of COVID-19 patients with immunosuppression after treatment with human convalescent plasma. We also discuss the time course and clinical features of recovery. The available data from case reports and case series provide evidence suggesting a mortality benefit and rapid clinical improvement in patients with several forms of immunosuppression following COVID-19 convalescent plasma transfusion. The utility of convalescent plasma or other forms of antibody therapy in immune-deficient and immune-suppressed patients with COVID-19 warrants further investigation

Effects of estrogen on blood pressure and salt and water excretion during a ten-day Angiotesin ll infusion period in ovariectomized mice

Introduction: Premenopausal women are protected from cardiovascular disease compared to age-matched men. Estrogen (E2) plays important roles in these protective mechanisms.Purpose: Our goal was to determine if E2 reduces angiotensin II (AngII)-induced elevation in blood pressure in ovariectomized (OVX) mice. We also hypothesized that E2 affects renal excretion of water and sodium.Methods: Four-week-old CD-1 OVX mice were placed in metabolic cages for a five-day baseline period followed by implantation of an Alzet osmotic pump containing either vehicle or AngII (1 µg/kg/min) and either a placebo or 0.7mg E2 pellet. Measurements of water intake (WI, ml/day), urine volume (UV, ml/day), and urine sodium excretion (UNaE, μEq/day) were recorded daily in the baseline and ten-day post-implantation periods in three groups of mice: vehicle-placebo (V-P), AngII-placebo (AngII-P), and AngII-E2 (n=4/group). Systolic blood pressure (SBP, mmHg) was determined via the tail-cuff technique.Results: Delta SBP (baseline vs AngII period) was higher in AngII-P but not significantly different from AngII-E2 mice, (33.1±3.5 vs 24.5±4.0, respectively). AngII-E2 mice compared to AngII-P mice had lower WI (4.2±0.02 vs 6.9±0.05, respectively, p<0.001), lower UV (1.3±0.02 vs 2.6±0.03, respectively, p<0.03), and lower UNaE (110.5±20.7 vs 199.7±10.8, respectively, p<0.003).Conclusion: E2 administration reduces WI, UV, and UNaE during a ten-day AngII-infusion in OVX mice. E2 did not significantly reduce SBP. Studies of longer duration are underway to investigate the important E2-induced mechanisms on blood pressure regulation

Preparation of atomically clean and flat Si(100) surfaces by low-energy ion sputtering and low-temperature annealing

Si(100) surfaces were prepared by wet-chemical etching followed by 0.3-1.5keV Ar ion sputtering, either at elevated or room temperature. After a brief anneal under ultrahigh vacuum conditions, the resulting surfaces were examined by scanning tunneling microscopy. We find that wet-chemical etching alone cannot produce a clean and flat Si(100) surface. However, subsequent 300eV Ar ion sputtering at room temperature followed by a 973K anneal yields atomically clean and flat Si(100) surfaces suitable for nanoscale device fabrication.Comment: 13 pages, 3 figures, to be published in Applied Surface Scienc

Deployment of convalescent plasma for the prevention and treatment of COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has spurred a global health crisis. To date, there are no proven options for prophylaxis for those who have been exposed to SARS-CoV-2, nor therapy for those who develop COVID-19. Immune (i.e., convalescent ) plasma refers to plasma that is collected from individuals following resolution of infection and development of antibodies. Passive antibody administration through transfusion of convalescent plasma may offer the only short-term strategy for conferring immediate immunity to susceptible individuals. There are numerous examples in which convalescent plasma has been used successfully as postexposure prophylaxis and/or treatment of infectious diseases, including other outbreaks of coronaviruses (e.g., SARS-1, Middle East respiratory syndrome [MERS]). Convalescent plasma has also been used in the COVID-19 pandemic; limited data from China suggest clinical benefit, including radiological resolution, reduction in viral loads, and improved survival. Globally, blood centers have robust infrastructure for undertaking collections and constructing inventories of convalescent plasma to meet the growing demand. Nonetheless, there are nuanced challenges, both regulatory and logistical, spanning donor eligibility, donor recruitment, collections, and transfusion itself. Data from rigorously controlled clinical trials of convalescent plasma are also few, underscoring the need to evaluate its use objectively for a range of indications (e.g., prevention vs. treatment) and patient populations (e.g., age, comorbid disease). We provide an overview of convalescent plasma, including evidence of benefit, regulatory considerations, logistical work flow, and proposed clinical trials, as scale-up is brought underway to mobilize this critical resource

The effect of convalescent plasma therapy on mortality among patients with COVID-19: Systematic review and meta-analysis

To determine the effect of COVID-19 convalescent plasma on mortality, we aggregated patient outcome data from 10 randomized clinical trials, 20 matched control studies, 2 dose-response studies, and 96 case reports or case series. Studies published between January 1, 2020, and January 16, 2021, were identified through a systematic search of online PubMed and MEDLINE databases. Random effects analyses of randomized clinical trials and matched control data demonstrated that patients with COVID-19 transfused with convalescent plasma exhibited a lower mortality rate compared with patients receiving standard treatments. Additional analyses showed that early transfusion (within 3 days of hospital admission) of higher titer plasma is associated with lower patient mortality. These data provide evidence favoring the efficacy of human convalescent plasma as a therapeutic agent in hospitalized patients with COVID-19

Convalescent plasma therapy for COVID-19: A graphical mosaic of the worldwide evidence

Convalescent plasma has been used worldwide to treat patients hospitalized with coronavirus disease 2019 (COVID-19) and prevent disease progression. Despite global usage, uncertainty remains regarding plasma efficacy, as randomized controlled trials (RCTs) have provided divergent evidence regarding the survival benefit of convalescent plasma. Here, we argue that during a global health emergency, the mosaic of evidence originating from multiple levels of the epistemic hierarchy should inform contemporary policy and healthcare decisions. Indeed, worldwide matched-control studies have generally found convalescent plasma to improve COVID-19 patient survival, and RCTs have demonstrated a survival benefit when transfused early in the disease course but limited or no benefit later in the disease course when patients required greater supportive therapies. RCTs have also revealed that convalescent plasma transfusion contributes to improved symptomatology and viral clearance. To further investigate the effect of convalescent plasma on patient mortality, we performed a meta-analytical approach to pool daily survival data from all controlled studies that reported Kaplan-Meier survival plots. Qualitative inspection of all available Kaplan-Meier survival data and an aggregate Kaplan-Meier survival plot revealed a directionally consistent pattern among studies arising from multiple levels of the epistemic hierarchy, whereby convalescent plasma transfusion was generally associated with greater patient survival. Given that convalescent plasma has a similar safety profile as standard plasma, convalescent plasma should be implemented within weeks of the onset of future infectious disease outbreaks

Guidance on the use of convalescent plasma to treat immunocompromised patients with coronavirus disease 2019

Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) is a safe and effective treatment for COVID-19 in immunocompromised (IC) patients. IC patients have a higher risk of persistent infection, severe disease, and death from COVID-19. Despite the continued clinical use of CCP to treat IC patients, the optimal dose, frequency/schedule, and duration of CCP treatment has yet to be determined, and related best practices guidelines are lacking. A group of individuals with expertise spanning infectious diseases, virology and transfusion medicine was assembled to render an expert opinion statement pertaining to the use of CCP for IC patients. For optimal effect, CCP should be recently and locally collected to match circulating variant. CCP should be considered for the treatment of IC patients with acute and protracted COVID-19; dosage depends on clinical setting (acute vs protracted COVID-19). CCP containing high-titer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies, retains activity against circulating SARS-CoV-2 variants, which have otherwise rendered monoclonal antibodies ineffective