TABLE 2.
PSM CCP studies reported to datea
| Study design | Location | No. of patients + controls | Median no. of days CCP given posthospitalization | Baseline recipient WHO score (24)b | Transfused CCP vol (mL) | Statistically significant outcomes | Reason(s) for failure | Reference |
|---|---|---|---|---|---|---|---|---|
| Retrospective | Mount Sinai, NY, USA | 39 + 156 | 4 | 5 (87%), 6 (10%) | 250 + 250 | On day 14, oxygen requirements worsened in 17.9% of plasma recipients vs 28.2% of controls (aOR, 0.86). Survival improved in plasma recipients (aHR, 0.34). | No failure | 66 |
| Providence, RI, USA | 64 + 177 | >2 (<10 from onset of symptoms, median, 7) | 4 (70%), 5 (30%) | NA (2 units) | No significant differences in incidence of in-hospital mortality (12.5% and 15.8%; aHR, 0.93) or overall rate of hospital discharge (RR, 1.28; although increased among patients of >65 yrs). | Late usage | 69 | |
| Montefiore Medical Center, NY, USA | 90 + 258 | <3 (3–7 days from onset of symptoms) | 5–6 (<24 h of mechanical ventilation) | 200 | Anti-S-IgG titer ≥ 1:2,430 (median, 1:47,385); recipients <65 yrs had 4-fold-lower mortality and 4-fold-lower deterioration in oxygenation or mortality at day 28. | No failure | 65 | |
| Washington, USA | 263 + 263 | <14 | NA | 245 (median) | Reduced 7-day (9.1 vs 19.8%) and 14-day (14.8 vs 23.6%) mortality but not 28-day mortality (P = 0.06), and longer hospital stay. | Late usage; control cohort was treated, on average, 29 days prior to the CCP cohort | 71 | |
| USA (176 HCA healthcare-affiliated community hospitals) | 3,774 + 10,687 | <3 vs 4–7 | NA | NA | Lower mortality (aHR, 0.71) and faster recovery. CCP within 3 days after admission, but not 4–7 days, was associated with a significant reduction in mortality risk (aHR, 0.53). CCP serology level was inversely associated with mortality when controlling for interaction with days to transfusion (HR, 0.998) but was not significant in a univariable analysis. | No failure | 72 | |
| China | 163 + 163 | 23 | NA | 300 | Hospital stay in CCP group was significantly longer than that of matched control group (P < 0.0001). | Very late usage; more advanced disease in the CCP group (23 vs 15 days since hospital admission). | 140 | |
| Greece | 59 + 59 | 7 | ≥4 | 200–233 (days 1, 3, and 5) | Significantly reduced risk of death (HR, 0.04; 3.4% vs 13.6%), significantly better overall survival by Kaplan-Meier analysis, and increased probability of extubation (OR, 30.3). Higher levels of antibodies (as measured with Euroimmun or pseudoVNT) in CCP recipients were independently associated with significantly reduced risk of death. | No failure | 141 | |
| New Haven, CT, USA | 132 + 2,551 | <6 vs >6 days | Moderate to severe | Early CCP recipients, of whom 31 (40%) were on mechanical ventilation, had lower 14-day (15% vs 23%) and 30-day (38% vs 49%) mortality than a matched unexposed cohort, with nearly 50% lower likelihood of in-hospital mortality (HR, 0.52). Early plasma recipients had more days alive and ventilator-free at 30 days (+3.3 days) and improved WHO scores at 7 days (−0.8) and hospital discharge (−0.9) than the matched unexposed cohort. | No failure | 70 | ||
| USA | 143 + 823 (hematological cancer) | NA | NA | NA | Improved 30-day mortality (HR, 0.52; 95% CI, 0.29–0.92) among the 338 patients admitted to the ICU, mortality was significantly lower in CCP recipients than in nonrecipients (HR, 0.40). Among the 227 patients who required mechanical ventilatory support, mortality was significantly lower in CCP recipients than in nonrecipients (HR, 0.32). | No failure | 109 | |
| Prospective | Houston, TX, USA | 136 + 251 | NA | 3 (9%), 4 (63%), 5 (18%), 6 (10%), 7 (1%)b | 300 (1–2 units) | Reduction in mortality within 28 days, specifically in patients transfused <72 h of admission with CCP with an anti-RBD titer of ≥1:1,350 (i.e., ∼80% probability of a live virus in vitro neutralization titer of ≥1:160 [142]). | No failure | 67 |
| 341 + 594 | NA | 300 (1–2 units) | Reduced 28-day (aHR, 2.09 for controls) and 60-day (5.7% vs 10.7%; aHR, 1.82 for controls) mortality in those transfused with anti-RBD titer of ≥1:1,350 within 72 h posthospitalization. Optimal window of 44 h to maximize benefit in 60-day mortality (4% vs 12.3%). 91% received CCP with an anti-RBD titer of ≥1:1,350. Median S/CO ratio of 24 using Ortho Vitros. | No failure | 68 | |||
| Poland | 102 + 102 | NA | NA | NA | Lower mortality rate (13.7% vs 34.3%; OR, 0.25) related to time of first administration (12.2% at day 5, 21.5% at day 10); no significant differences in ICU stay, ventilator time, and hospitalization time. Earlier administration resulted in a ventilator being needed for a shorter length of time (r = 0.41). | No failure | 143 | |
| Brazil | 58 + 116 (kidney transplant recipients) | 6 from onset of symptoms | Mild and moderate | 200 | No differences in need for supplementary oxygen or mechanical ventilation at day 30. | Only 48% of CCP units were high titer; compared to nonsurvivors, a trend towards a higher proportion of survivors receiving higher-titer CCP | 144 | |
| Colorado (16 hospitals) | 188 + 188 | NA | NA | 1 unit if <90 kg; 2 units if >90 kg | Increased length of hospital stay in CCP-treated patients and no change in inpatient mortality compared to controls. In subgroup analysis of CCP-treated patients within 3 or 7 days of admission, there was no difference in length of hospitalization and inpatient mortality. | Covariate matching not achieved for subgroup receiving CCP < 3 days | 145 |
a
None of these studies determined titers of NAbs in either donors or recipients using the VNT. PSM, propensity score matched; DPH, days posthospitalization. HR, hazard ratio; aHR, adjusted HR; OR, odds ratio; aOR, adjusted OR; RBD, receptor binding domain; S-IgG, secretory IgG.