Characteristics of US Blood Donors Testing Reactive for Antibodies to SARS-CoV-2 Prior to the Availability of Authorized Vaccines

Abstract

In the United States, many blood collection organizations initiated programs to test all blood donors for antibodies to SARS-CoV-2, as a measure to increase donations and to assist in the identification of potential donors of COVID-19 convalescent plasma (CCP). As a result, it was possible to investigate the characteristics of healthy blood donors who had previously been infected with SARS-CoV-2. We report the findings from all blood donations collected by the American Red Cross, representing 40% of the national blood supply covering 44 States, in order to characterize the seroepidemiology of SARS-CoV-2 infection among blood donors in the United States, prior to authorized vaccine availability. We performed an observational cohort study from June 15th to November 30th, 2020 on a population of 1.531 million blood donors tested for antibodies to the S1 spike antigen of SARS-CoV-2 by person, place, time, ABO group and dynamics of test reactivity, with additional information from a survey of a subset of those with reactive test results. The overall seroreactivity was 4.22% increasing from 1.18 to 9.67% (June 2020 - November 2020); estimated incidence was 11.6 per hundred person-years, 1.86-times higher than that based upon reported cases in the general population over the same period. In multivariable analyses, seroreactivity was highest in the Midwest (5.21%), followed by the South (4.43%), West (3.43%) and Northeast (2.90%). Seroreactivity was highest among donors aged 18-24 (Odds Ratio 3.02 [95% Confidence Interval 2.80-3.26] vs age >55), African-Americans and Hispanics (1.50 [1.24-1.80] and 2.12 [1.89-2.36], respectively, vs Caucasian). Group O frequency was 51.5% among nonreactive, but 46.1% among seroreactive donors (P< .0001). Of surveyed donors, 45% reported no COVID-19-related symptoms, but 73% among those unaware of testing. Signal levels of antibody tests were stable over 120 days or more and there was little evidence of reinfection. Evaluation of a large population of healthy, voluntary blood donors provided evidence of widespread and increasing SARS-CoV-2 seroprevalence and demonstrated that at least 45% of those previously infected were asymptomatic. Epidemiologic findings were similar to those among clinically reported cases.

Keywords: Antibodies; Blood Group O; Blood donors; COVID-19; Demographics; Incidence; SARS-CoV-2; Symptoms.

Fig. 1.

Frequency of Ortho anti-SARS-CoV-2 test-seroreactive donations among total donations by week and in 4 US Census Regions from June 15 to November 30, 2020. The X-axis gives the calendar week number for year 2020. Weeks are Monday to Sunday and week 49 is 1 day. At a 5% significance level, there were significant associations between weeks of testing and seroreactive rates for all Census Regions and overall (P< .0001). The dashed line shows the total seroreactivity of 3.51% (75,988 of 2,191,731), with 95% confidence intervals. Each point is the percentage of seroreactive donors/total number of donations for each week. Solid lines represent the percentage of new infections by four US Census Regions. They are 4.26% (33,094 of 776,865) in the Midwest, 2.56% (11,178 of 437,185) in the Northeast, 3.72% (21,054 of 565,931) in the South and 2.83% (11,662 of 411,750) in the West. Note that the overall percentages expressed here for the total seroreactivity and each US Census Region are based on reactive donations/all donations; an individual donor may have given more than once within the study period whereas data in the text and Table 1 are based on individual donors only.

Fig. 2.

Mean log₁₀ Ortho S/CO levels among donations from 11,392 donors with incident seroreactivity, by time from first donation in the study period. Data represent all donors with 2 or more donations who acquired and maintained a seroreactive test result (S/CO ≥ log₁₀ = 0). The 11,392 donors gave a total of 27,533 donations, or 2.42 per donor. The boxplots show the mean (red solid line), median (red dashed line), the first and third quartiles (boxes), while the whiskers show 1.5X the interquartile range (IQR) above and below the box. Outliers are depicted as circles. Numbers of donors (N) for each time interval are shown below the X-axis. The Spearman rank correlation coefficient (r) is 0.75098 (P< .0001), indicating there is strong positive correlation between the time intervals (days) and the Ortho signal levels.

Fig. 3

(A) Distribution of the log₁₀ Ortho S/CO levels by time interval between multiple seroreactive donations. There were 469,605 repeat donors and the data represent those among 8,583 donors with 19,449 total donations, all of which were reactive at each donation within the study. There were an additional 11,392 donors that had a prior nonreactive donation and 205 donors that became nonreactive; neither group is represented in the Figure. The boxplots show the mean (red solid line), median (red dashed line), the first and third quartiles (boxes), while the whiskers show 1.5X the interquartile range (IQR) above and below the box. Outliers are depicted as circles. Numbers of donors (N) for each time interval are shown below the X-axis. Spearman rank correlation coefficient (r) is 0.25244 (P< .0001), indicating a weak correlation between time (days) and Ortho increasing signal levels. By the Kruskal-Wallis test, the median of log₁₀-transformed Ortho S/COs of the 6 groups are significantly different (P<.0001). (B, C and D) Examples of changes in log₁₀ Ortho S/CO signal levels by time interval plotted for individual seroreactive donors randomly selected (partial data shown for clarity). Fig. 3B shows donors with donation decreases of > 0.1 log₁₀, Fig. 3C shows donors with donation changes within the range of ± 0.1 log₁₀ and Fig. 3D shows donors with donation increases of > 0.1 log₁₀. The red line is the fitted ordinary least square individual growth trajectory for the three groups representing the total 8,583 donors with persistent seroreactivity demonstrating the average change in trajectory for each group. Overall, there were 590 donors with 1,425 donations who showed a decline, 1,721 donors with 3963 donations who were stable and 6,272 donors with 14,061 donations who showed an increase. The grey lines are the fitted regression lines of the changes in trajectories for each individual donor.

Fig. 4.

Proportion of surveyed seroreactive donors reporting COVID-19 related symptoms 14 or more days prior to donation. Of 13,343 seroreactive donors completing the survey, 95% or greater responded to each symptom question; 45% of responding donors reported no symptoms. Specific data for each symptom for donors reporting symptoms are: fatigue, 5,215 of 12,902; headache, 4,297 of 12,838; myalgia, 4,074 of 12,845; loss of smell, 3,545 of 12,827; cough, 3,518 of 12,820; loss of taste, 3,338 of 12,814; runny nose, 2,739 of 12,705; fever, 2,493 of 13,335; sore throat, 2,145 of 12,696; shortness of breath, 1,821 of 12,709; nausea/vomiting, 1,752 of 12,685; and, congestion, 1,716 of 12,651.