Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients: A Randomized Clinical Trial
Importance/UNASSIGNED:There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19. Objective/UNASSIGNED:To determine the safety and efficacy of CCP compared with placebo in hospitalized patients with COVID-19 receiving noninvasive supplemental oxygen. Design, Setting, and Participants/UNASSIGNED:CONTAIN 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. Interventions/UNASSIGNED:A unit of approximately 250 mL of CCP or equivalent volume of placebo (normal saline). Main Outcomes and Measures/UNASSIGNED:The 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. Results/UNASSIGNED:Of 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]â€‰=â€‰72%); the cOR for the secondary adjusted outcome was 0.92 (95% CrI, 0.74-1.16; P[cOR<1]â€‰=â€‰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]â€‰=â€‰93%) for participants enrolled in April-June 2020 and 0.65 (95% CrI, 0.41 to 1.02; P[cOR<1]â€‰=â€‰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 (Pâ€‰=â€‰.57). Transfusion reactions occurred in 2 (0.4) placebo recipients and 8 (1.7) CCP recipients (Pâ€‰=â€‰.06). Conclusions and Relevance/UNASSIGNED:In 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 Registration/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04364737.
The Utility of Scoring Systems in Determining the Need for Echocardiography in Patients with Staphylococcus aureus Bacteremia
Impact of Streptococcus pneumoniae Urinary Antigen Testing in Patients With Community-Acquired Pneumonia Admitted Within a Large Academic Health System
Background/UNASSIGNED:Limited data support use of pneumococcal urinary antigen testing (PUAT) for patients with community-acquired pneumonia (CAP) as an antimicrobial stewardship tool. At our institution, CAP guidelines and admission order set were standardized to include universal PUAT. Methods/UNASSIGNED:This was a retrospective study of adults hospitalized in 2019 who had PUAT performed. We compared incidence and timing of de-escalation in PUAT- positive vs -negative groups and described patients' outcomes. Results/UNASSIGNED:, in-hospital mortality, or 30-day infection-related readmission. Conclusions/UNASSIGNED:We observed earlier de-escalation in the PUAT-positive group. This seems to be due to discontinuation of atypical rather than anti-MRSA or antipseudomonal coverage. Further antimicrobial stewardship interventions are warranted.
Leveraging Rapid Diagnostics and Electronic Health Records to Decrease Antimicrobial Utilization: a Step in the Right Direction
Characteristics, Comorbidities, and Outcomes in a Multicenter Registry of Patients with HIV and Coronavirus Disease-19
BACKGROUND:People with HIV (PWH) may have numerous risk factors for acquiring Coronavirus disease-19 (COVID-19) and developing severe outcomes, but current data are conflicting. METHODS:Healthcare providers enrolled consecutively by non-random sampling PWH with lab-confirmed COVID-19, diagnosed at their facilities between April 1st and July 1st, 2020. De-identified data were entered into an electronic Research Electronic Data Capture (REDCap). The primary endpoint was severe outcome, defined as a composite endpoint of intensive care unit (ICU) admission, mechanical ventilation, or death. The secondary outcome was the need for hospitalization. RESULTS:286 patients were included; the mean age was 51.4 years (SD, 14.4), 25.9% were female, and 75.4% were African-American or Hispanic. Most patients (94.3%) were on antiretroviral therapy (ART), 88.7% had HIV virologic suppression, and 80.8% had comorbidities. Within 30 days of positive SARS-CoV-2 testing, 164 (57.3%) patients were hospitalized, and 47 (16.5%) required ICU admission. Mortality rates were 9.4% (27/286) overall, 16.5% (27/164) among those hospitalized, and 51.5% (24/47) among those admitted to an ICU. The primary composite endpoint occurred in 17.5% (50/286) of all patients and 30.5% (50/164) of hospitalized patients. Older age, chronic lung disease, and hypertension were associated with severe outcomes. A lower CD4 count (<200 cells/mmÂ³) was associated with the primary and secondary endpoints. There was no association between the antiretroviral regimen or lack of viral suppression and predefined outcomes. CONCLUSION/CONCLUSIONS:Severe clinical outcomes occurred commonly in PWH and COVID-19. The risk for poor outcomes was higher in those with comorbidities and lower CD4 cell counts, despite HIV viral suppression.
SARS-CoV-2 antibodies: IgA correlates with severity of disease in early COVID-19 infection
Timing of detection of immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and their use to support the diagnosis are of increasing interest. We used the Gold Standard Diagnostics ELISA to evaluate the kinetics of SARS-CoV-2 IgG, IgA, and IgM antibodies in sera of 82 hospitalized patients with polymerase chain reaction (PCR)-confirmed coronavirus disease 2019 (COVID-19). Serum samples were collected 1-59 days post-onset of symptoms (PoS) and we examined the association of age, sex, disease severity, and symptoms' duration with antibody levels. We also tested sera of 100 ambulatory hospital employees with PCR-confirmed COVID-19 and samples collected during convalescence, 35-57 days PoS. All but four of the admitted patients (95.1%) developed antibodies to SARS-CoV-2. Antibodies were detected within 7 days PoS; IgA in 60.0%, IgM in 53.3%, and IgG in 46.7% of samples. IgG positivity increased to 100% on Day 21. We did not observe significant differences in the rate of antibody development in regard to age and sex. IgA levels were highest in patients with a severe and critical illness. In multiple regression analyses, only IgA levels were statistically significantly correlated with critical disease (pâ€‰=â€‰.05) regardless of age, sex, and duration of symptoms. Among 100 ambulatory hospital employees who had antibody testing after 4 weeks PoS only 10% had positive IgA antibodies. The most frequently isolated isotype in sera of employees after 30 days PoS was IgG (88%). IgA was the predominant immunoglobulin in early disease and correlated independently with a critical illness. IgG antibodies remained detectable in almost 90% of samples collected up to two months after infection.
Association of SARS-CoV-2 Genomic Load with COVID-19 Patient Outcomes
Recognizing Cutibacterium acnes as a cause of infectious pericarditis: A case report and review of literature [Case Report]
Cutibacterium acnes is an anaerobic bacterium commonly thought of as a culture contaminant rather than a pathogen. We present a case of Cutibacterium acnes pericarditis in a 22-year-old immunocompetent woman managed with surgical pericardial window and a 4-week course of penicillin G and review related literature on Cutibacterium acnes pericarditis.
Rate and consequences of missed Clostridioides (Clostridium) difficile infection diagnosis from nonreporting of Clostridioides difficile results of the multiplex GI PCR panel: experience from two-hospitals
INTRODUCTION/BACKGROUND:It is common among microbiology laboratories to blind the Clostridioides difficile (C. difficile) BioFire FilmArray GI Panel result in fear of overdiagnosis. METHODS:We examined the rate of missed community-onset C. difficile infection (CDI) diagnosis and associated outcomes. Adult patients with FilmArray GI Panel positive for C. difficile on hospital admission who lacked dedicated C. difficile testing were included. RESULTS:Among 144 adults with a FilmArray Panel positive for C. difficile, 18 did not have concurrent dedicated C. difficile testing. Eight patients were categorized as possible, 5 as probable and 4 as definite cases of missed CDI diagnosis. We observed associated delays in initiation of appropriate therapy, intensive care unit admissions, hospital readmissions, colorectal surgery and death/discharge to hospice. Five out of 17 lacked risk factors for CDI. CONCLUSION/CONCLUSIONS:The practice of concealing C. difficile FilmArray GI Panel results needs to be reconsidered in patients presenting with community-onset colitis.
Defining the Breakpoint Duration of Staphylococcus aureus Bacteremia Predictive of Poor Outcomes