Dataset Information

Safety and Efficacy of Convalescent Plasma in Elderly COVID-19 Patients: The RESCUE Trial.

ABSTRACT:

Objective

To assess the safety and efficacy of convalescent plasma (CP) transfusion in elderly people with moderate to severe coronavirus disease 2019 (COVID-19) living in a long-term care facility (LTCF).

Patients and methods

Twenty-two consecutive elderly patients with COVID-19 infection living in an LTCF in Lombardy, Italy, who were given CP during May 15 to July 31, 2020, were enrolled in a prospective cohort study. Their clinical, instrumental, and laboratory parameters were assessed following the CP treatment. The overall mortality rate in this group was compared with that recorded in other LTCFs in Lombardy during the 3-month period from March to May 2020.

Results

Of the 22 patients enrolled, 68.2% (n=15) received 1 CP unit, 27.3% (n=6) received 2 units, and 4.5% (n=1) received 3 units. Of the CP units transfused, 76.7% (23/30) had a neutralizing antibody titer of 1:160 or greater. No adverse reactions were recorded during or after CP administration. Improvements in clinical, functional, radiologic, and laboratory parameters during the 14 days after CP transfusion were observed in all 19 patients who survived. Viral clearance was achieved in all patients by the end of follow-up (median, 66 days; interquartile range, 48-80 days). The overall mortality rate was 13.6% (3/22), which compared favorably with that in the control group (38.3% [281/733]; P=.02) and corresponded to a 65% reduction in mortality risk.

Conclusion

Early administration of CP with an adequate anti-severe acute respiratory syndrome coronavirus 2 antibody titer to elderly symptomatic patients with COVID-19 infection in an LTCF was safe and effective in eliminating the virus, restoring patients' immunity, and blocking the progression of COVID-19 infection, thereby improving patients' survival.

Trial registration

ClinicalTrials.gov: NCT04569188.

SUBMITTER: Franchini M

PROVIDER: S-EPMC7869678 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceThere is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19.ObjectiveTo determine the safety and efficacy of CCP compared with placebo in hospitalized patients with COVID-19 receiving noninvasive supplemental oxygen.Design, setting, and participantsCONTAIN COVID-19, a randomized, double-blind, placebo-controlled trial of CCP in hospitalized adults with COVID-19, was conducted at 21 US hospitals from April 17, 2020, to March 15, 2021. The trial enrolled 941 participants who were hospitalized for 3 or less days or presented 7 or less days after symptom onset and required noninvasive oxygen supplementation.InterventionsA unit of approximately 250 mL of CCP or equivalent volume of placebo (normal saline).Main outcomes and measuresThe primary outcome was participant scores on the 11-point World Health Organization (WHO) Ordinal Scale for Clinical Improvement on day 14 after randomization; the secondary outcome was WHO scores determined on day 28. Subgroups were analyzed with respect to age, baseline WHO score, concomitant medications, symptom duration, CCP SARS-CoV-2 titer, baseline SARS-CoV-2 serostatus, and enrollment quarter. Outcomes were analyzed using a bayesian proportional cumulative odds model. Efficacy of CCP was defined as a cumulative adjusted odds ratio (cOR) less than 1 and a clinically meaningful effect as cOR less than 0.8.ResultsOf 941 participants randomized (473 to placebo and 468 to CCP), 556 were men (59.1%); median age was 63 years (IQR, 52-73); 373 (39.6%) were Hispanic and 132 (14.0%) were non-Hispanic Black. The cOR for the primary outcome adjusted for site, baseline risk, WHO score, age, sex, and symptom duration was 0.94 (95% credible interval [CrI], 0.75-1.18) with posterior probability (P[cOR<1] = 72%); the cOR for the secondary adjusted outcome was 0.92 (95% CrI, 0.74-1.16; P[cOR<1] = 76%). Exploratory subgroup analyses suggested heterogeneity of treatment effect: at day 28, cORs were 0.72 (95% CrI, 0.46-1.13; P[cOR<1] = 93%) for participants enrolled in April-June 2020 and 0.65 (95% CrI, 0.41 to 1.02; P[cOR<1] = 97%) for those not receiving remdesivir and not receiving corticosteroids at randomization. Median CCP SARS-CoV-2 neutralizing titer used in April to June 2020 was 1:175 (IQR, 76-379). Any adverse events (excluding transfusion reactions) were reported for 39 (8.2%) placebo recipients and 44 (9.4%) CCP recipients (P = .57). Transfusion reactions occurred in 2 (0.4) placebo recipients and 8 (1.7) CCP recipients (P = .06).Conclusions and relevanceIn this trial, CCP did not meet the prespecified primary and secondary outcomes for CCP efficacy. However, high-titer CCP may have benefited participants early in the pandemic when remdesivir and corticosteroids were not in use.Trial registrationClinicalTrials.gov Identifier: NCT04364737.

Project description:BACKGROUNDConvalescent plasma is the only antibody-based therapy currently available for patients with coronavirus disease 2019 (COVID-19). It has robust historical precedence and sound biological plausibility. Although promising, convalescent plasma has not yet been shown to be safe as a treatment for COVID-19.METHODSThus, we analyzed key safety metrics after transfusion of ABO-compatible human COVID-19 convalescent plasma in 5000 hospitalized adults with severe or life-threatening COVID-19, with 66% in the intensive care unit, as part of the US FDA expanded access program for COVID-19 convalescent plasma.RESULTSThe incidence of all serious adverse events (SAEs), including mortality rate (0.3%), in the first 4 hours after transfusion was <1%. Of the 36 reported SAEs, there were 25 reported incidences of related SAEs, including mortality (n = 4), transfusion-associated circulatory overload (n = 7), transfusion-related acute lung injury (n = 11), and severe allergic transfusion reactions (n = 3). However, only 2 of 36 SAEs were judged as definitely related to the convalescent plasma transfusion by the treating physician. The 7-day mortality rate was 14.9%.CONCLUSIONGiven the deadly nature of COVID-19 and the large population of critically ill patients included in these analyses, the mortality rate does not appear excessive. These early indicators suggest that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19.TRIAL REGISTRATIONClinicalTrials.gov NCT04338360.FUNDINGMayo Clinic, Biomedical Advanced Research and Development Authority (75A50120C00096), National Center for Advancing Translational Sciences (UL1TR002377), National Heart, Lung, and Blood Institute (5R35HL139854 and R01 HL059842), National Institute of Diabetes and Digestive and Kidney Diseases (5T32DK07352), Natural Sciences and Engineering Research Council of Canada (PDF-532926-2019), National Institute of Allergy and Infectious Disease (R21 AI145356, R21 AI152318, and AI152078), Schwab Charitable Fund, United Health Group, National Basketball Association, Millennium Pharmaceuticals, and Octapharma USA Inc.

Project description:Convalescent plasma is currently being used in the treatment of COVID-19. Recommendations regarding use convalescent plasma in COVID-19 requires systematic summaries of available evidence. We searched the databases Medline, Embase, Cochrane CENTRAL, Epistomonikos, Medrxiv and Biorxiv. Title/abstract screening, full text screening and data abstraction were carried out in duplicate by two reviewers. Pooled effect sizes and 95% confidence intervals were calculated using random effects meta-analysis. GRADE tool was used to rate the certainty of evidence. Twenty two studies were found eligible for inclusion: nine randomized controlled trials and thirteen cohort studies. Low certainty evidence from eight RCTs showed inconclusive effects of convalescent plasma on mortality at 28 days (OR 0.85, 95% CI 0.61 to 1.18). Low certainty evidence from thirteen cohort studies showed a reduction in mortality at 28 days (OR 0.66, 95% CI 0.53 to 0.82). The pooled OR for clinical improvement was 1.07 (95% CI 0.86 to 1.34) representing low certainty evidence. Evidence from three RCTs showed inconclusive effect of CP on the need for mechanical ventilation (OR 1.20, 95% CI 0.72 to 1.98). Four cohort studies reporting unadjusted estimates suggested a reduction in the need for mechanical ventilation with convalescent plasma (OR 0.80 95% CI 0.71 to 0.91, low certainty). Pooled estimates from 2 RCTs showed inconclusive effects of convalescent plasma on the proportion of patients with nondetectable levels of virus in nasopharyngeal specimens on day 3 (OR 3.62, 95% CI 0.43, 30.49, very low-quality evidence). The present review reports uncertain estimates on the efficacy of convalescent plasma in the treatment of COVID-19. There is low certainty evidence of a possible reduction in mortality and mechanical ventilation, a faster viral clearance and the absence of any serious adverse events. However, its efficacy for these outcomes requires evidence from good quality and adequately powered randomized controlled trials.Supplementary informationThe online version contains supplementary material available at 10.1007/s12288-021-01417-w.