Study Cohort
Of 856 immunosuppressed or high-volume blood recipients who received at least one transfusion at NIH or JHSH during the ZIKV epidemic period, 260 (30%) met the TRIPS study inclusion and/or exclusion criteria and were enrolled. Among the remaining 596 cases, 278 (47%) were excluded for a history of transfusion within 6 weeks, 201 (34%) for residing outside of the U.S. during the six month follow-up period, 68 (11%) for having a poor prognosis and life expectancy less than three months, and 49 (8%) for being younger than 18 years old.
Sixty-four (25%) of the two hundred sixty enrolled TRIPS study participants had samples available for ZIKV, DENV and CHIKV testing, and 46 (18%) agreed to participate in this survey-based sub-study.
Characteristics and Responses from Surveyed Blood Recipients
Characteristics of surveyed blood recipients are given in Table 1. The average age at transfusion was 63 ± 12 years, 16 (35%) were female and 29 (63%) were Caucasian. Among all recipients, the mean hemoglobin was 10.7 g/dL (normal range 11.2-15.7), mean hematocrit was 31.7% (34.1-44.9) and mean platelet count was 179 K/uL (173-369). On average, recipients received 5.9 units of blood products. Four (9%) recipients had non-surgical indications for blood transfusion, primarily for cancer-related cytopenias, and 42 (91%) recipients had a surgical indication, primarily cardiac. Cardiac surgeries included 23 coronary artery bypass graft cases, 3 aortic valve repairs, 1 abdominal aortic aneurysm repair, 1 mitral valve repair, 14 partial nephrectomies and 1 radical cystectomy. Five cardiac patients had more than 1 procedure during the same surgery; none had more than 2 procedures. Compared to non-immunosuppressed recipients, immunosuppressed recipients had significantly lower mean white blood cell counts 3.5 vs. 8.5 K/uL; P=0.003) and absolute neutrophil counts (3.0 vs. 6.8 K/uL; P=0.021).
Forty-six (72%) of 64 enrolled recipients were successfully contacted by telephone and agreed to complete the survey. Eleven (17%) had died, 6 (9%) were lost to follow-up and 1 (2%) declined to participate. The mean age of survey respondents was 63 ± 12 years, 16 (35%) were female, and 29 (63%) were Caucasian. The demographics of survey respondents were similar to all enrolled blood recipients (data not shown).
Among females, the average age was 65 ± 12 years (range, 36-80); only one female recipient was less than 50 years old. None of the female respondents reported having sexual intercourse within the first month following transfusion and none became pregnant within 6 months post-transfusion. After answering the survey questions, 14 (88%) of female respondents offered an elaboration of their survey answers: 7 (50%) of the woman said they had not been sexually active for many years; 4 (29%) said they felt too ill to have sexual relations for months after transfusion; and 3 (21%) of the women noted that they were still in the hospital 1 month after transfusion.
Among males, the average age was 62 ± 12 years (range, 31-81). Six (20%) of the total 30 male respondents reported having sexual intercourse with a female partner during the 3 months following transfusion. Sexually active males reported that no pregnancies resulted from any sexual encounter during this time period. Eleven of twenty-four (46%) male respondents who did not have sex after transfusion volunteered additional information: 4 (36%) said they were no longer sexually active; 3 (27%) said they suffered from impotence; 3 (27%) felt too ill to have sexual relations 3 months following transfusion; 1 man (9%) was still in the hospital 3 months after transfusion.
Serologic, FRNT and Molecular Testing
Serum specimens from 46 surveyed transfusion recipients and 19 linked donors were tested for the presence of IgM and IgG antibodies to ZIKV, DENV and CHIKV by ELISA. None of the recipients or their donors had detectable ZIKV or DENV IgM. CHIKV IgM was detectable in one blood recipient, however the sample was focus reduction neutralization test (FRNT) and CHIKV RNA-negative, and the donor-linked samples were CHIKV IgM, IgG and RNA-negative, supporting a false-positive test result. Virus-specific IgG antibodies were detectable for ZIKV in 3 recipients, for DENV in 6 recipients and for CHIKV in 2 recipients; all were male. These IgG-positive recipient specimens were all RNA negative. However, in five of these cases, both donors and a linked-recipient were positive for IgG, suggesting passive antibody transfer through transfusion: two recipients and a linked donor were both ZIKV and DENV IgG positive; and an additional three recipients and a linked donor were both DENV IgG positive.