Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients: A Randomized Clinical Trial.

Importance: There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19. Objective: 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: 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: A unit of approximately 250 mL of CCP or equivalent volume of placebo (normal saline). Main Outcomes and Measures: 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: 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] = 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 Relevance: 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: ClinicalTrials.gov Identifier: NCT04364737.

Journalists' views on media coverage of medical tests and overdiagnosis: a qualitative study.

OBJECTIVE: Promotional media coverage of early detection tests is an important driver of overdiagnosis. Following research evidence that global media coverage presents the benefits of testing healthy people far more frequently than harms, and gives little coverage to overdiagnosis, we sought to examine journalists' views on media reporting of tests, overdiagnosis, and strategies to improve critical reporting on tests. DESIGN: Qualitative study using semistructured telephone interviews. Interviews were conducted between February and March 2020 and were audiorecorded and transcribed verbatim. Framework thematic analysis was used to analyse the data. PARTICIPANTS AND SETTING: Twenty-two journalists (mainly specialising in health reporting, average 14.5 years' experience) based in Australia. RESULTS: This sample of journalists acknowledged the potential harms of medical tests but felt that knowledge of harms was low among journalists and the public at large. Most were aware of the term overdiagnosis, but commonly felt that it is challenging to both understand and communicate in light of strong beliefs in the benefits of early detection. Journalists felt that newsworthiness in the form of major public health impact was the key ingredient for stories about medical tests. The journalists acknowledged that factors, like the press release and 'click bait culture' in particular, can influence the framing of coverage about tests. Lack of knowledge and training, as well as time pressures, were perceived to be the main barriers to critical reporting on tests. Journalists felt that training and better access to information about potential harms would enable more critical reporting. CONCLUSIONS: Effectively communicating overdiagnosis is a challenge in light of common beliefs about the benefits of testing and the culture of current journalism practices. Providing journalists with training, support and better access to information about potential harms of tests could aid critical reporting of tests.