ABSTRACT
INTRODUCTIONCOVID-19 convalescent plasma (CCP) transfusion has emerged in the past months as an alternative approach to treat pneumonia cases of SARS-CoV-2. Current evidence regarding characteristics of the plasma product, the titer of neutralizing antibodies (nAbs) in the transfused units, time to onset of intervention, and impact of nAbs produced by the patient are limited and heterogeneous. MATERIAL AND METHODSWe describe the preliminary results of 104 patients with severe pneumonia due to SARS-CoV-2 transfused with CCP at three medical centers in Brazil. All enrolled patients were transfused with doses between 200 mL through 600mL of ABO compatible CCP on days 0-2 after enrolment. Clinical parameters were monitored and nAbs titration was performed using the cytopathic effect-based virus neutralization test with SARS-CoV-2 (GenBank MT126808.1). RESULTSForty-one patients achieved clinical improvement on day 14, and multivariable logistic regression showed that nAbs T (from CCP units transfused) (p= 0.001), nAbs P0 (on day of enrolment) (p=0.009) and use of other supportive therapies (p<0.001) were associated with higher odds for this clinical improvement. Considering ICU length of stay (LOS) and length of mechanical ventilation, in our analysis, nAbs P0 were associated with a significant reduction in ICU LOS (p=0.018) and duration of mechanical ventilation (p<0.001). Administration of CCP after 10 days of symptom onset was associated with increases in ICU length of stay (p<0.001). DISCUSSION/CONCLUSIONDespite the study limitations, our data have shown an association between patients previously acquired nAbs and clinical outcomes. The potential value of timely administration of CCP transfusion before day 10 of disease onset was demonstrated and nAbsP0, but not nAbsT, were associated with ICU LOS, and duration of mechanical ventilation on the improvement of clinical outcomes was also demonstrated. In conclusion, we consider these data are useful parameters to guide future CPP transfusion strategies to COVID-19.
ABSTRACT
IntroductionA cohort of COVID-19 convalescent volunteers allowed the study of neutralizing (nAb) and ligand antibodies kinetics by providing sequential samples during a median of 100 days after onset of disease. Material and MethodsA cohort of previously RT-PCR+ve (detected by nasopharyngeal swab during the acute phase), male convalescent patients, all with mild symptoms, were enrolled on serial blood sample collection for evaluation of longitudinal nAb titers and anti-nucleocapsid (NP) antibodies (IgM, IgG and IgA). Nabs were detected by a cytopathic effect-based virus neutralization test (CPE-based VNT), carried out with SARS-CoV-2 (GenBank: MT350282) ResultsA total of 78 male volunteers provided 316 samples, spanning a total of 4820 days of study. Although only 25% of donors kept nAb titers [≥]160, after a median of 100 days after the onset of disease, there was a high probability of sustaining nAB titers [≥]160 in volunteers whose initial nAb titer was [≥]1280, weight [≥] 90kg or BMI classified as overweight or obese, evidenced by Kaplan-Meier estimates and Cox hazard regression. There was no correlation between ABO group, ABO antibody titers and persistent high nAb titers. High IgG anti-NP (S/CO [≥]5.0) is a good surrogate for detecting nAB [≥]160, defined by ROC curve (sensitivity = 90.5%; CI95% 84.5-94.7%) ConclusionSelection of CCP donors for multiple collections based on initial high nAb titers ([≥]1280) or overweight/obese (BMI) provides a simple strategy to achieve higher quality in CCP programs. High IgG anti-NP levels can also be used as surrogate markers for high nAb screening.
