Primary Outcomes No difference between arms in proportion with disease progression: 30% in CCP arm vs. 32% in placebo arm (risk difference 1.9%; 95% CrI, -6.0% to 9.8%) 25 patients (19 in CCP arm and 6 in placebo arm) required hospitalization during index visit. In a post hoc analysis that excluded these patients, disease progression occurred in 24% in CCP arm vs. 30% in placebo arm (risk difference 5.8%; 95% CrI, -1.9% to 13.6%). Secondary Outcomes All-cause mortality within 30 days: 5 (1.9%) in CCP arm vs. 1 (0.4%) in placebo arm No difference between arms in illness severity or mean number of hospital-free days The CCP arm included more patients with multiple risk factors, including immunosuppression. Interpretation The use of high-titer CCP within 1 week of symptom onset did not prevent disease progression in outpatients with COVID-19 who were at high risk of severe disease. COVID-19 Treatment Guidelines Downloaded from

on 1/3/2024 219 Methods Results CoV-Early: Double-Blind RCT of CCP in Nonhospitalized, High-Risk Adults With COVID-19 in the Netherlands9 Key Inclusion Criteria Aged 70 years, aged 50 years with a comorbidity, or aged Participant Characteristics Median age 60 years; 22% women Median 5 days of symptoms Median 1 comorbidity Median SpO2 97% at baseline 7.9% SARS-CoV-2 IgG antibody negative at baseline 2.9% fully vaccinated; 5.0% received 1 vaccine Primary Outcome Odds of receiving highest score on 5-point OS by Day 28: 18 years and severely immunocompromised Positive SARS-CoV-2 RT-PCR or antigen test result COVID-19 symptoms for 7 days Key Exclusion Criteria Life expectancy <28 days History of TRALI IgA deficiency Interventions 300 mL of CCP with minimum PRNT50 titer of 1:160 (n = OR 0.86; 95% CrI, 0.591.22 in CCP arm 207) Non-SARS-CoV-2 plasma collected prior to pandemic (n = 209)

Secondary Outcomes Percentage of hospital admissions: 10 patients (4.8%) in CCP arm vs. 18 patients (8.6%) in non-SARS-CoV-2 arm (aHR 0.61; 95% CI, 0.281.34) Number of days of symptoms: 13 days in CCP arm vs. 12 days in non-CCP arm (P = 0.99) Primary Endpoint Improvement based on 5-point OS by Day 28 Secondary Endpoints Percentage of hospital admissions Number of days of symptoms Retrospective Evaluation of CCP Antibody Levels and the Risk of Death From COVID-19 in the United States10 Key Inclusion Criteria Severe or life-threatening COVID-19 Patients for whom samples of transfused CCP were available Participant Characteristics 31% aged 70 years; 61% men; 48% White, 37% Hispanic/Latinx for retrospective analysis of antibody titer Interventions High-titer CCP (n = 515), medium-titer CCP (n = 2,006), or low-titer CCP (n = 561), characterized retrospectively

Primary Endpoint Mortality by Day 30 after CCP transfusion 61% in ICU; 33% on MV 51% received corticosteroids, 31% received RDV Primary Outcomes Mortality by Day 30 after transfusion: 22% in high-titer CCP arm vs. 27% in medium-titer CCP arm vs. 30% in low-titer CCP arm COVID-19 Treatment Guidelines Downloaded from on 1/3/2024 Limitations and Interpretation Key Limitations Study was discontinued after 421 of 690 planned participants were enrolled, resulting in decreased power. The CCP used was selected based on a PRNT50 assay and may not qualify as high-titer CCP per the current FDA EUA. Interpretation This trial did not demonstrate a benefit of CCP in nonhospitalized, high-risk patients with COVID-19. Key Limitation Lack of untreated control arm Interpretation The study data are not sufficient to establish the efficacy or safety of CCP. 220 Methods Results