Predictors of high SARS-CoV-2 immunoglobulin G titers in COVID-19 convalescent whole-blood donors: a cross-sectional study in China.

Demographic information has been shown to help predict high antibody titers of COVID-19 convalescent plasma (CCP) in CCP donors. However, there is no research on the Chinese population and little evidence on whole-blood donors. Therefore, we aimed to investigate these associations among Chinese blood donors after SARS-CoV-2 infection. In this cross-sectional study, 5,064 qualified blood donors with confirmed or suspected SARS-CoV-2 infection completed a self-reported questionnaire and underwent tests of SARS-CoV-2 Immunoglobulin G (IgG) antibody and ABO blood type. Logistic regression models were used to calculate odds ratios (ORs) for high SARS-CoV-2 IgG titers according to each factor. Totally, 1,799 participants (with SARS-CoV-2 IgG titers≥1:160) had high-titer CCPs. Multivariable analysis showed that a 10-year increment in age and earlier donation were associated with higher odds of high-titer CCP, while medical personnel was associated with lower odds. The ORs (95% CIs) of high-titer CCP were 1.17 (1.10-1.23, p< 0.001) and 1.41 (1.25-1.58, p< 0.001) for each 10-year increment in age and earlier donation, respectively. The OR of high-titer CCP was 0.75 (0.60-0.95, p = 0.02) for medical personnel. Female early donors were associated with increased odds of high-titer CCP, but this association was insignificant for later donors. Donating after 8 weeks from the onset was associated with decreased odds of having high-titer CCP compared to donating within 8 weeks from the onset, and the HR was 0.38 (95% CI: 0.22-0.64, p <0.001). There was no significant association between ABO blood type or race and the odds of high-titer CCP. Older age, earlier donation, female early donors, and non-medical-related occupations are promising predictors of high-titer CCP in Chinese blood donors. Our findings highlight the importance of CCP screening at the early stage of the pandemic.

Tang J ，Liu H ，Wang Q ，Gu X ，Wang J ，Li W ，Luo Y ，Li Y ，Deng L ，Luo Y ，Du X ，Tan D ，Fu X ，Chen X ... -  《Frontiers in Immunology》

Association between clinical symptoms during the COVID-19 infection and SARS-CoV-2 immunoglobulin G titers in COVID-19 convalescent whole-blood donors in China.

Limited studies have explored the association between clinical symptoms and titers of SARS-CoV-2 antibodies. In this cross-sectional study, whole-blood donors who had experienced a confirmed or suspected COVID-19 infection completed questionnaires at the time of blood donation. Plasma SARS-CoV-2 immunoglobulin G (IgG) titers were measured using an enzyme-linked immunosorbent assay. Logistic regression models were used to calculate odds ratios (ORs) for high-titer COVID-19 convalescent plasma (CCP) for each variable. Among the total 386 donors, 120 (31%) donors with IgG titers ≥1:160 were classified as high-titer donors. The multivariable ORs (95% confidence intervals [CIs]) for high titers were 2.33 (1.45-3.75), 2.11 (1.29-3.43), 1.10 (1.01-1.21), 1.19 (1.00-1.43), and 1.97 (1.05-3.71) for sore throat, cough, symptom count, fever duration, and low fever (compared with non-fever), respectively. No significant association was observed between other symptoms and medical visits and the odds of high-titer CCP. The association between high-titer CCP and fever duration was restricted to confirmed COVID-19-infected donors, while associations with sore throat and cough remained significant in suspected infected donors. In addition, medical visit was positively associated with high-titer CCP in suspected donors, but not in confirmed donors. In bootstrapped logistic regression models, the associations remained significant and reproducible for medical visit in suspected donors and for sore throat and cough in both suspected donors and total donors. Experiencing a sore throat and cough were associated with high-titer CCP in overall donors. We also identified sore throat, cough, and medical visits as potential predictors of high-titer CCP for suspected donors during the pandemic.

Chen X ，Liu H ，Li M ，Kang J ，Li Y ，Luo Y ，Du X ，Tan D ，Wang Q ，Gu X ，Zhao Z ，Fu X ，Tang J ... -  《-》

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 ... -  《-》

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 ... -  《-》

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》