COVID-19 convalescent plasma cohort study: Evaluation of the association between both donor and recipient neutralizing antibody titers and patient outcomes.

Current evidence regarding COVID-19 convalescent plasma (CCP) transfusion practices is limited and heterogeneous. We aimed to determine the impact of the use of CCP transfusion in patients with previous circulating neutralizing antibodies (nAbs) in COVID-19. Prospective cohort including 102 patients with COVID-19 transfused with ABO compatible CCP on days 0-2 after enrollment. Clinical status of patients was assessed using the adapted World Health Organization (WHO) ordinal scale on days 0, 5, and 14. The nAbs titration was performed using the cytopathic effect-based virus neutralization test with SARS-CoV-2 (GenBank MT126808.1). The primary outcome was clinical improvement on day 14, defined as a reduction of at least two points on the adapted WHO ordinal scale. Secondary outcomes were the number of intensive care unit (ICU)-free days and the number of invasive mechanical ventilation-free days. Both nAbs of CCP units transfused (p < 0.001) and nAbs of patients before CCP transfusions (p = 0.028) were associated with clinical improvements by day 14. No significant associations between nAbs of patients or CCP units transfused were observed in the number of ICU or mechanical ventilation-free days. Administration of CCP units after 10 days of symptom onset resulted in a decrease in ICU-free days (p < 0.001) and mechanical ventilation-free days (p < 0.001). Transfusion of high titer nAbs CCP units may be a determinant in clinical strategies against COVID-19. We consider these data as useful parameters to guide future CCP transfusion practices.

Yokoyama APH ，Wendel S ，Bonet-Bub C ，Fachini RM ，Dametto APF ，Blumm F ，Dutra VF ，Candelaria GTP ，Sakashita AM ，Machado RRG ，Fontão-Wendel R ，Hamerschlak N ，Achkar R ，Assunção MSC ，Scuracchio P ，Nudelman V ，Pastore L ，Pinho JRR ，Ben MD ，Filho RK ，Marra AR ，Amano MT ，Kallás EG ，Helito AS ，de Carvalho CRR ，Araujo DB ，Durigon EL ，Camargo AA ，Rizzo LV ，Reis LFL ，Kutner JM ... -  《-》

Use of Outpatient-Derived COVID-19 Convalescent Plasma in COVID-19 Patients Before Seroconversion.

Transfusion of COVID-19 convalescent plasma (CCP) containing high titers of anti-SARS-CoV-2 antibodies serves as therapy for COVID-19 patients. Transfusions early during disease course was found to be beneficial. Lessons from the SARS-CoV-2 pandemic could inform early responses to future pandemics and may continue to be relevant in lower resource settings. We sought to identify factors correlating to high antibody titers in convalescent plasma donors and understand the magnitude and pharmacokinetic time course of both transfused antibody titers and the endogenous antibody titers in transfused recipients. Plasma samples were collected up to 174 days after convalescence from 93 CCP donors with mild disease, and from 16 COVID-19 patients before and after transfusion. Using ELISA, anti-SARS-CoV-2 Spike RBD, S1, and N-protein antibodies, as well as capacity of antibodies to block ACE2 from binding to RBD was measured in an in vitro assay. As an estimate for viral load, viral RNA and N-protein plasma levels were assessed in COVID-19 patients. Anti-SARS-CoV-2 antibody levels and RBD-ACE2 blocking capacity were highest within the first 60 days after symptom resolution and markedly decreased after 120 days. Highest antibody titers were found in CCP donors that experienced fever. Effect of transfused CCP was detectable in COVID-19 patients who received high-titer CCP and had not seroconverted at the time of transfusion. Decrease in viral RNA was seen in two of these patients. Our results suggest that high titer CCP should be collected within 60 days after recovery from donors with past fever. The much lower titers conferred by transfused antibodies compared to endogenous production in the patient underscore the importance of providing CCP prior to endogenous seroconversion.

Wirz OF ，Röltgen K ，Stevens BA ，Pandey S ，Sahoo MK ，Tolentino L ，Verghese M ，Nguyen K ，Hunter M ，Snow TT ，Singh AR ，Blish CA ，Cochran JR ，Zehnder JL ，Nadeau KC ，Pinsky BA ，Pham TD ，Boyd SD ... -  《Frontiers in Immunology》

Screening for SARS-CoV-2 antibodies in convalescent plasma in Brazil: Preliminary lessons from a voluntary convalescent donor program.

Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) collection began in two Brazilian hospitals for treatment of severe/critical patients. Mild/moderate COVID-19 convalescents were selected as CCP donors after reverse transcription polymerase chain reaction (RT-PCR) confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and absence of symptoms for ≥14 days plus (a) age (18-60 years), body weight greater than 55 kg; (b) immunohematological studies; (c) no infectious markers of hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human T-lymphotropic virus-1/2, Chagas and syphilis infection; (d) no HLA antibodies (multiparous); (e) second RT-PCR (nasopharyngeal swab and/or blood) negativity; (f) virus neutralization test (cytopathic effect-based virus neutralization test neutralizing antibody) and anti-nucleocapsid protein SARS-CoV-2 IgM, IgG, and IgA enzyme-linked immunosorbent assays. Among 271 donors (41 females, 230 males), 250 presented with neutralizing antibodies. Final RT-PCR was negative on swab (77.0%) or blood (88.4%; P = .46). Final definition of RT-PCR was only defined at more than 28 days after full recovery in 59 of 174 (33.9%) RT-PCR -ve, and 25/69 RT-PCR +ve (36.2%; 13 between 35 and 48 days). Neutralizing antibody titers of 160 or greater were found in 63.6%. Correlation between IgG signal/cutoff of 5.0 or greater and neutralizing antibody of 160 or greater was 82.4%. Combination of final RT-PCR -ve with neutralizing antibody ≥160 was 41.3% (112/271). Serial plasma collection showed decline in neutralizing antibody titers and IgA levels (P < .05), probably denoting a "golden period" for CCP collection (≤28 days after joining the program); IgA might have an important role as neutralizing antibody. Donor's weight, days between disease onset and serial plasma collection, and IgG and IgM levels are important predictors for neutralizing antibody titer. RT-PCR +ve cases are still detected in 36.2% within 28 to 48 days after recovery. High anti-nucleocapsid protein IgG levels may be used as a surrogate marker to neutralizing antibody.

Wendel S ，Kutner JM ，Machado R ，Fontão-Wendel R ，Bub C ，Fachini R ，Yokoyama A ，Candelaria G ，Sakashita A ，Achkar R ，Hamerschlak N ，Scuracchio P ，Amaral M ，Dal Ben M ，Araujo D ，Soares C ，Camargo A ，Kallás E ，Durigon E ，Reis LF ，Rizzo LV ... -  《-》

Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.

Park HS ，Yin A ，Barranta C ，Lee JS ，Caputo CA ，Sachithanandham J ，Li M ，Yoon S ，Sitaras I ，Jedlicka A ，Eby Y ，Ram M ，Fernandez RE ，Baker OR ，Shenoy AG ，Mosnaim GS ，Fukuta Y ，Patel B ，Heath SL ，Levine AC ，Meisenberg BR ，Spivak ES ，Anjan S ，Huaman MA ，Blair JE ，Currier JS ，Paxton JH ，Gerber JM ，Petrini JR ，Broderick PB ，Rausch W ，Cordisco ME ，Hammel J ，Greenblatt B ，Cluzet VC ，Cruser D ，Oei K ，Abinante M ，Hammitt LL ，Sutcliffe CG ，Forthal DN ，Zand MS ，Cachay ER ，Raval JS ，Kassaye SG ，Marshall CE ，Yarava A ，Lane K ，McBee NA ，Gawad AL ，Karlen N ，Singh A ，Ford DE ，Jabs DA ，Appel LJ ，Shade DM ，Lau B ，Ehrhardt S ，Baksh SN ，Shapiro JR ，Ou J ，Na YB ，Knoll MD ，Ornelas-Gatdula E ，Arroyo-Curras N ，Gniadek TJ ，Caturegli P ，Wu J ，Ndahiro N ，Betenbaugh MJ ，Ziman A ，Hanley DF ，Casadevall A ，Shoham S ，Bloch EM ，Gebo KA ，Tobian AA ，Laeyendecker O ，Pekosz A ，Klein SL ，Sullivan DJ ... -  《JCI Insight》

Simple prediction of COVID-19 convalescent plasma units with high levels of neutralization antibodies.

Hyperimmune convalescent COVID-19 plasma (CCP) containing anti-SARS-CoV-2 neutralizing antibodies (NAbs) was proposed as a therapeutic option for patients early in the new coronavirus disease pandemic. The efficacy of this therapy depends on the quantity of neutralizing antibodies (NAbs) in the CCP units, with titers ≥ 1:160 being recommended. The standard neutralizing tests (NTs) used for determining appropriate CCP donors are technically demanding and expensive and take several days. We explored whether they could be replaced by high-throughput serology tests and a set of available clinical data. Our study included 1302 CCP donors after PCR-confirmed COVID-19 infection. To predict donors with high NAb titers, we built four (4) multiple logistic regression models evaluating the relationships of demographic data, COVID-19 symptoms, results of various serological testing, the period between disease and donation, and COVID-19 vaccination status. The analysis of the four models showed that the chemiluminescent microparticle assay (CMIA) for the quantitative determination of IgG Abs to the RBD of the S1 subunit of the SARS-CoV-2 spike protein was enough to predict the CCP units with a high NAb titer. CCP donors with respective results > 850 BAU/ml SARS-CoV-2 IgG had a high probability of attaining sufficient NAb titers. Including additional variables such as donor demographics, clinical symptoms, or time of donation into a particular predictive model did not significantly increase its sensitivity and specificity. A simple quantitative serological determination of anti-SARS-CoV-2 antibodies alone is satisfactory for recruiting CCP donors with high titer NAbs.

Jazbec K ，Jež M ，Žiberna K ，Mali P ，Ramšak Ž ，Potokar UR ，Kvrzić Z ，Černilec M ，Gracar M ，Šprohar M ，Jovanovič P ，Vuletić S ，Rožman P ... -  《Virology Journal》