Clinical predictors of donor antibody titre and correlation with recipient antibody response in a COVID-19 convalescent plasma clinical trial.

BACKGROUND: Convalescent plasma therapy for COVID-19 relies on transfer of anti-viral antibody from donors to recipients via plasma transfusion. The relationship between clinical characteristics and antibody response to COVID-19 is not well defined. We investigated predictors of convalescent antibody production and quantified recipient antibody response in a convalescent plasma therapy clinical trial. METHODS: Multivariable analysis of clinical and serological parameters in 103 confirmed COVID-19 convalescent plasma donors 28 days or more following symptom resolution was performed. Mixed-effects regression models with piecewise linear trends were used to characterize serial antibody responses in 10 convalescent plasma recipients with severe COVID-19. RESULTS: Donor antibody titres ranged from 0 to 1 : 3892 (anti-receptor binding domain (RBD)) and 0 to 1 : 3289 (anti-spike). Higher anti-RBD and anti-spike titres were associated with increased age, hospitalization for COVID-19, fever and absence of myalgia (all P < 0.05). Fatigue was significantly associated with anti-RBD (P = 0.03). In pairwise comparison amongst ABO blood types, AB donors had higher anti-RBD and anti-spike than O donors (P < 0.05). No toxicity was associated with plasma transfusion. Non-ECMO recipient anti-RBD antibody titre increased on average 31% per day during the first three days post-transfusion (P = 0.01) and anti-spike antibody titre by 40.3% (P = 0.02). CONCLUSION: Advanced age, fever, absence of myalgia, fatigue, blood type and hospitalization were associated with higher convalescent antibody titre to COVID-19. Despite variability in donor titre, 80% of convalescent plasma recipients showed significant increase in antibody levels post-transfusion. A more complete understanding of the dose-response effect of plasma transfusion amongst COVID-19-infected patients is needed.

Multicenter clinical evaluation of a continuous monitoring blood culture system using fluorescent-sensor technology (BACTEC 9240).

The BACTEC 9240 (Becton Dickinson Diagnostic Instrument Systems, Sparks, Md.) is a new continuous-monitoring blood culture system that uses internal, fluorescent-CO2 sensors. In a multicenter clinical trial, organism yield and times to detection with the prototype BACTEC 9240 system were compared with those of the BACTEC NR 660 system. Equal volumes of blood were inoculated into the bottles included in the study blood culture sets (aerobic and anaerobic 9240 and NR6A and NR7A bottles). A total of 9,391 aerobic and 8,951 anaerobic bottle pairs were inoculated with 9,801 blood specimens. A total of 587 clinically significant positive blood cultures and 415 cases of sepsis were studied. The standard 9240 aerobic bottle detected significantly more Staphylococcus aureus (P < 0.05), coagulase-negative staphylococci (P < 0.01), and total microorganisms (P < 0.001) than the NR6A bottle. The standard 9240 anaerobic bottle detected significantly more coagulase-negative staphylococci (P < 0.001), members of the family Enterobacteriaceae (P < 0.01), and total microorganisms (P < 0.001) than the NR7A bottle. A total of 420 positive cultures were detected in both systems; for 284, the time to detection was equivalent with both systems (within 12 h); for 123, the 9240 system was faster; and for 13, the NR 660 system was faster (P < 0.001). The average times to detection for the 9240 and the NR 660 systems were 20.2 and 27.5 h, respectively. Ninety-nine cultures were positive only in the 9240 system, and 68 cultures were positive only in the NR 660 system (P < 0.02). The 9240 system also detected significantly more episodes of bacteremia (P < 0.001). The false-positive rates for the 9240 and NR 660 systems were 2.2 and 2.3%, respectively. The false-negative rates for the two systems after 5 days of incubation did not differ significantly. The contamination rates for the 9240 and NR 660 systems were 1.9 and 1.5%, respectively (P < 0.05). In conclusion, the prototype 9240 system detected more clinically significant positive blood cultures and did so sooner than the NR 660 system, with the additional advantages of full automation, continuous monitoring, and noninvasive sampling.

Performance of a BACTEC nonradiometric medium for pediatric blood cultures.

A BACTEC aerobic nonradiometric medium, PEDS Plus, designed for diagnosis of pediatric bacteremia was evaluated in three hospital centers. Equivalent blood volumes (up to 5 ml) were inoculated into and incubated in BACTEC NR-6A (6A) and PEDS Plus broths. Among 4,581 compliant sets, 289 clinically significant organisms, representing more than 20 bacterial and two Candida species, were isolated. One hundred eighty-one isolates were recovered in both bottles, 75 in PEDS Plus only, and 33 in 6A only (P less than 0.001). Time to detection when both bottles were positive was the same for 129 isolates, detection with PEDS Plus was earlier for 39, and detection with 6A was earlier for 13 (P less than 0.005). Staphylococcus aureus was recovered significantly more often in PEDS Plus than in 6A (P less than 0.01), and more coagulase-negative staphylococci and pediatric pathogens (pneumococci, Haemophilus influenzae, and Streptococcus agalactiae) were recovered in PEDS Plus than in 6A. Coagulase-negative staphylococci and H. influenzae were detected significantly earlier in PEDS Plus (P less than 0.05 and less than 0.01, respectively). When the eight species of the family Enterobacteriaceae isolated were considered together, recovery in PEDS Plus was better than in 6A (P less than 0.05). For 66 of the 143 isolates from patients known to be on antimicrobial therapy at the time blood was drawn, PEDS Plus was superior to 6A. In 45 cases, organisms were isolated from PEDS Plus only (P less than 0.001) and in 21 cases they were isolated from PEDS Plus before 6A (P less than 0.01). PEDS Plus broth aids diagnosis of pediatric bacteremia by increasing recovery of etiologic agents and decreasing the time required for detection.