Dataset Information

Convalescent Plasma Use in the United States was inversely correlated with COVID-19 Mortality: Did Plasma Hesitancy cost lives?

ABSTRACT:

Background

The US Food and Drug Administration authorized Convalescent Plasma (CCP) therapy for hospitalized COVID-19 patients via the Expanded Access Program (EAP) and the Emergency Use Authorization (EUA), leading to use in about 500,000 patients during the first year of the pandemic for the US.

Methods

We tracked the number of CCP units dispensed to hospitals by blood banking organizations and correlated that usage with hospital admission and mortality data.

Results

CCP usage per admission peaked in Fall 2020, with more than 40% of inpatients estimated to have received CCP between late September and early November 2020. However, after randomized controlled trials failed to show a reduction in mortality, CCP usage per admission declined steadily to a nadir of less than 10% in March 2021. We found a strong inverse correlation (r = -0.52, P = 0.002) between CCP usage per hospital admission and deaths occurring two weeks after admission, and this finding was robust to examination of deaths taking place one, two or three weeks after admission. Changes in the number of hospital admissions, SARS-CoV-2 variants, and age of patients could not explain these findings. The retreat from CCP usage might have resulted in as many as 29,000 excess deaths from mid-November 2020 to February 2021.

Conclusions

A strong inverse correlation between CCP use and mortality per admission in the USA provides population level evidence consistent with the notion that CCP reduces mortality in COVID-19 and suggests that the recent decline in usage could have resulted in excess deaths.

SUBMITTER: Casadevall A

PROVIDER: S-EPMC8043483 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe US Food and Drug Administration authorized COVID-19 convalescent plasma (CCP) therapy for hospitalized COVID-19 patients via the Expanded Access Program (EAP) and the Emergency Use Authorization (EUA), leading to use in about 500,000 patients during the first year of the pandemic for the USA.MethodsWe tracked the number of CCP units dispensed to hospitals by blood banking organizations and correlated that usage with hospital admission and mortality data.ResultsCCP usage per admission peaked in Fall 2020, with more than 40% of inpatients estimated to have received CCP between late September and early November 2020. However, after randomized controlled trials failed to show a reduction in mortality, CCP usage per admission declined steadily to a nadir of less than 10% in March 2021. We found a strong inverse correlation (r = -0.52, p=0.002) between CCP usage per hospital admission and deaths occurring 2 weeks after admission, and this finding was robust to examination of deaths taking place 1, 2, or 3 weeks after admission. Changes in the number of hospital admissions, SARS-CoV-2 variants, and age of patients could not explain these findings. The retreat from CCP usage might have resulted in as many as 29,000 excess deaths from mid-November 2020 to February 2021.ConclusionsA strong inverse correlation between CCP use and mortality per admission in the USA provides population-level evidence consistent with the notion that CCP reduces mortality in COVID-19 and suggests that the recent decline in usage could have resulted in excess deaths.FundingThere was no specific funding for this study. AC was supported in part by RO1 HL059842 and R01 AI1520789; MJJ was supported in part by 5R35HL139854. This project has been funded in whole or in part with Federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority under Contract No. 75A50120C00096.

Project description:Routine childhood vaccination is declining in some regions of the United States due to vaccine hesitancy, which risks the resurgence of many infectious diseases with public health and economic consequences. There are ongoing policy debates on the state and national level, including legislation around nonmedical (personal-belief) exemptions for childhood vaccination and possibly a special government commission on vaccine safety, which may affect vaccine coverage.To estimate the number of measles cases in US children and the associated economic costs under scenarios of different levels of vaccine hesitancy, using the case example of measles, mumps, and rubella (MMR) vaccination and measles.Publicly available data from the US Centers for Disease Control and Prevention were used to simulate county-level MMR vaccination coverage in children (age 2-11 years) in the United States. A stochastic mathematical model was adapted for infectious disease transmission that estimated a distribution for outbreak size as it relates to vaccine coverage. Economic costs per measles case were obtained from the literature. The predicted effects of increasing the prevalence of vaccine hesitancy as well as the removal of nonmedical exemptions were estimated. The model was calibrated to annual measles cases in US children over recent years, and the model prediction was validated using an independent data set from England and Wales.Annual measles cases in the United States and the associated public sector costs.A 5% decline in MMR vaccine coverage in the United States would result in an estimated 3-fold increase in measles cases for children aged 2 to 11 years nationally every year, with an additional $2.1 million in public sector costs. The numbers would be substantially higher if unvaccinated infants, adolescents, and adult populations were also considered. There was variation around these estimates due to the stochastic elements of measles importation and sensitivity of some model inputs, although the trend was robust.This analysis predicts that even minor reductions in childhood vaccination, driven by vaccine hesitancy (nonmedical and personal belief exemptions), will have substantial public health and economic consequences. The results support an urgent need to address vaccine hesitancy in policy dialogues at the state and national level, with consideration of removing personal belief exemptions of childhood vaccination.

Project description:BackgroundThe 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 findingsMayo 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.ConclusionsThese 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 registrationClinicalTrials.gov NCT#: NCT04338360.