Longitudinal analysis of SARS-CoV-2 antibodies in 8000 U.S. first-time convalescent plasma donations.

Coronavirus disease 2019 (COVID-19) convalescent individuals carry antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that, through a plasma donation, can be used as a potential therapeutic either in direct transfusion or for the manufacture of hyperimmune globulin (HIG). The success of such interventions depends on the antibody potency in such plasma donations, but little information on the collection of potent units is currently available. A total of 8749 plasma units, collected from April until September 2020 from first-time U.S. COVID-19 convalescent plasma donors, were characterized for SARS-CoV-2 immunoglobulin G (IgG) antibodies by Abbott chemiluminescent microparticle immunoassay (CMIA). The period between COVID-19 onset until donation and donor age, ethnicity, sex, and COVID-19 severity were evaluated against the obtained signal (index S/C). A marked decrease in mean index S/C was seen over the plasma collection period surveyed, which was significantly correlated to decreases in mean plasma donor age (p < .0001; R2 = .726) and percentage of donations obtained from COVID-19 convalescent patients who had been hospitalized (p = .001; R2 = .4426). The highest titer plasma units were obtained soon after convalescence from COVID-19 patients who required hospitalization, from advanced age donors, and from Black/African/Hispanic American versus White/Caucasian ethnicities, whereas there was no effect of donor sex on the values obtained with the Abbott CMIA. Since the onset of the pandemic, the average SARS-CoV-2 IgG values of first-time U.S. COVID-19 convalescent plasma donations have significantly dropped, mainly due to donations from progressively younger aged donors who tend to experience less severe COVID-19.

Karbiener M ，Farcet MR ，Ilk R ，Schreiner J ，Lenart J ，Powers N ，Stewart JM ，Tallman H ，Kreil TR ... -  《-》

Blood group O convalescent plasma donations have significantly lower levels of SARS-CoV-2 IgG antibodies compared to blood group A donations.

COVID-19 convalescent plasma (CCP) is plasma collected from individuals who have recovered from SARS-CoV-2 infection. The FDA Emergency Use Authorization restricts use of CCP to high-titer units only. The purpose of this study was to determine if donor ABO blood group was associated with SARS-CoV-2 antibody response, and subsequent qualification as high-titer CCP. All CCP donations collected from April 21, 2020 to September 1, 2020 were included. The Abbott ARCHITECT semi-quantitative chemiluminescent microparticle immunoassay was used to assess IgG antibodies to the nucleocapsid protein of SARS-CoV-2. Units with a S/C value ≥4.5 were considered high titer. A total of 232 CCP donations were evaluated. There were no significant differences in the distribution of sex, age, and interval from symptom resolution to donation by ABO blood group. The mean SARS-CoV-2 IgG antibody S/C value was significantly lower in blood group O donations (3.6), compared to blood group A (5.0) donations (p < .001). There was no difference in antibody response between the other blood group pairings. Blood group O donations resulted in a lower percentage of high-titer units (35%), compared to blood group A (60%), B (58%), and AB (65%) donations. Blood group O donations were found to have significantly lower levels of SARS-CoV-2 IgG nucleocapsid antibodies compared to blood group A donations and were less likely to produce CCP units that qualified as high titer. These findings may aid donor recruitment to promote availability of high-titer CCP to meet patient needs.

Hayes C ，Rubenstein W ，Gibb D ，Klapper E ，Tanaka J ，Pepkowitz S ... -  《-》

Production of anti-SARS-CoV-2 hyperimmune globulin from convalescent plasma.

In late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus emerged in China and quickly spread into a worldwide pandemic. Prior to the development of specific drug therapies or a vaccine, more immediately available treatments were sought including convalescent plasma. A potential improvement from convalescent plasma could be the preparation of anti-SARS-CoV-2 hyperimmune globulin (hIVIG). Convalescent plasma was collected from an existing network of plasma donation centers. A caprylate/chromatography purification process was used to manufacture hIVIG. Initial batches of hIVIG were manufactured in a versatile, small-scale facility designed and built to rapidly address emerging infectious diseases. Processing convalescent plasma into hIVIG resulted in a highly purified immunoglobulin G (IgG) product with more concentrated neutralizing antibody activity. hIVIG will allow for the administration of greater antibody activity per unit of volume with decreased potential for several adverse events associated with plasma administration. IgG concentration and IgG specific to SARS-CoV-2 were increased over 10-fold from convalescent plasma to the final product. Normalized enzyme-linked immunosorbent assay activity (per mg/ml IgG) was maintained throughout the process. Protein content in these final product batches was 100% IgG, consisting of 98% monomer and dimer forms. Potentially hazardous proteins (IgM, IgA, and anti-A, anti-B, and anti-D) were reduced to minimal levels. Multiple batches of anti-SARS-CoV-2 hIVIG that met regulatory requirements were manufactured from human convalescent plasma. The first clinical study in which the hIVIG will be evaluated will be Inpatient Treatment with Anti-Coronavirus Immunoglobulin (ITAC) [NCT04546581].

Vandeberg P ，Cruz M ，Diez JM ，Merritt WK ，Santos B ，Trukawinski S ，Wellhouse A ，Jose M ，Willis T ... -  《-》

A trend of dropping anti-SARS-CoV-2 plaque reduction neutralization test titers over time in Canadian convalescent plasma donors.

Convalescent plasma products are a potential passive immunotherapy for Coronavirus disease 2019 (COVID-19) disease. Various approaches have been utilized to determine the concentration of Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-neutralizing antibodies in plasma products. The Canadian Blood Services used Plaque Reduction Neutralization Test 50 (PRNT50) -generated values to qualify convalescent plasma donations supporting clinical trials in Canada. This manuscript describes changes in PRNT50 titers of repeat male plasma donations collected approximately 1-4 months after onset of COVID-19 signs and symptoms in donors. Men were eligible to donate if they: met standard criteria, were < 67 years of age, reported a previous SARS-CoV-2-positive nucleic acid test, and recovered and were symptom free for at least 28 days prior to donation. Repeat donation analysis required at least one original and one repeat donation where a PRNT50 was performed. From April 29, 2020 to July 25, 2020, 156 donors donated once, with 78 (50%) of the donated plasma having PRNT50 titers of ≥1:160. Thirty-seven (23.7%) of the donated plasma had a titer of 1:40 or 1:80 (individuals donating this plasma were asked to donate a second time only). A total of 30 donors (19.2%) had repeat donations. Of the repeat donors, 15 (50%) had at least an eightfold change from peak to trough PRNT50 titers within greater than 90 days after onset of COVID-19 symptoms. Blood operators cannot infer that SARS-CoV-2 PRNT50 will remain high in repeat plasma donors 3-4 months after onset of COVID-19 symptoms.

Drews SJ ，Devine DV ，McManus J ，Mendoza E ，Manguiat K ，Wood H ，Girardin R ，Dupuis A ，McDonough K ，Drebot M ... -  《-》

Characteristics and serological patterns of COVID-19 convalescent plasma donors: optimal donors and timing of donation.

The lack of effective treatments against the 2019 coronavirus disease (COVID-19) has led to the exploratory use of convalescent plasma for treating COVID-19. Case reports and case series have shown encouraging results. This study investigated SARS-CoV-2 antibodies and epidemiological characteristics in convalescent plasma donors, to identify criteria for donor selection. Recovered COVID-19 patients, aged 18-55 years, who had experienced no symptoms for more than 2 weeks, were recruited. Donor characteristics such as disease presentations were collected and SARS-CoV-2 N-specific IgM, IgG, and S-RBD-specific IgG levels were measured by enzyme-linked immunosorbent assay (ELISA). Whereas levels of N-specific IgM antibody declined after recovery, S-RBD-specific and N-specific IgG antibodies increased after 4 weeks from the onset of symptoms, with no significant correlation to age, sex, or ABO blood type. Donors with the disease presentation of fever exceeding 38.5°C or lasting longer than 3 days exhibited higher levels of S-RBD-specific IgG antibodies at the time of donation. Of the 49 convalescent plasma donors, 90% had an S-RBD-specific IgG titer of ≥1:160 and 78% had a titer of ≥1:640 at the time of plasma donation. Of the 30 convalescent plasma donors, who had donated plasma later than 28 days after the onset of symptoms and had a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5°C, 100% had an S-RBD-specific IgG titer of ≥1:160 and 93% had a titer of ≥1:640. This study indicates that the S-RBD-specific IgG antibody reaches higher levels after 4 weeks from the onset of COVID-19 symptoms. We recommend the following selection criteria for optimal donation of COVID-19 convalescent plasma: 28 days after the onset of symptoms and with a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5°C. Selection based on these criteria can ensure a high likelihood of achieving sufficiently high S-RBD-specific IgG titers.

Li L ，Tong X ，Chen H ，He R ，Lv Q ，Yang R ，Zhao L ，Wang J ，Xu H ，Liu C ，Chen G ，Chen S ，Li C ，Qiao J ，Yang J ，Wu Y ，Liu Z ... -  《-》