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 ... -  《-》

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 ... -  《-》

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 ... -  《-》

Feasibility of a pilot program for COVID-19 convalescent plasma collection in Wuhan, China.

A novel coronavirus has caused an international outbreak. Currently, there are no specific therapeutic agents for coronavirus infections. Convalescent plasma (CP) therapy is a potentially effective treatment option. Patients who had recovered from COVID-19 and had been discharged from the hospital for more than 2 weeks were recruited. COVID-19 convalescent plasma (CCP)-specific donor screening and selection were performed based on the following criteria: 1) aged 18-55 years; 2) eligible for blood donation; 3) diagnosed with COVID-19; 4) had two consecutive negative COVID-19 nasopharyngeal swab tests based on PCR (at least 24 hr apart) prior to hospital discharge; 5) had been discharged from the hospital for more than 2 weeks; and 6) had no COVID-19 symptoms prior to convalescent plasma donation. In addition, preference was given to CCP donors who had a fever lasting more than 3 days or a body temperature exceeding 38.5°C (101.3°F), and who donated 4 weeks after the onset of symptoms. CCP collection was performed using routine plasma collection procedures via plasmapheresis. In addition to routine donor testing, the CCP donors' plasma was also tested for SARS-CoV-2 nucleic acid and S-RBD-specific IgG antibody. Of the 81 potential CCP donors, 64 (79%) plasma products were collected. There were 18 female donors and 46 male donors. There were 34 first-time blood donors and 30 repeat donors. The average time between CCP collection and initial symptom onset was 49.1 days, and the average time between CCP collection and hospital discharge was 38.7 days. The average volume of CCP collected was 327.7 mL. All Alanine transaminase (ALT) testing results met blood donation requirements. HIV Ag/Ab, anti-HCV, anti-syphilis, and HBsAg were all negative; NAT for HIV, HBV, and HCV were also negative. In addition, all of the CCP donors' plasma units were negative for SARS-CoV-2 RNA. Of the total 64 CCP donors tested, only one had an S-RBD-specific IgG titer of 1:160, all others had a titer of ≥1:320. Based on a feasibility study of a pilot CCP program in Wuhan, China, we demonstrated the success and feasibility of CCP collection. In addition, all of the CCP units collected had a titer of ≥1:160 for S-RBD-specific IgG antibody, which met the CCP quality control requirements based on the Chinese national guidelines for CCP.

Li L ，Yang R ，Wang J ，Lv Q ，Ren M ，Zhao L ，Chen H ，Xu H ，Xie S ，Xie J ，Lin H ，Li W ，Fang P ，Gong L ，Wang L ，Wu Y ，Liu Z ... -  《-》