Convalescent plasma in the treatment of moderate to severe COVID-19 pneumonia: a randomized controlled trial (PROTECT-Patient Trial).

There is a need for effective therapy for COVID-19 pneumonia. Convalescent plasma has antiviral activity and early observational studies suggested benefit in reducing COVID-19 severity. We investigated the safety and efficacy of convalescent plasma in hospitalized patients with COVID-19 in a population with a high HIV prevalence and where few therapeutic options were available. We performed a double-blinded, multicenter, randomized controlled trial in one private and three public sector hospitals in South Africa. Adult participants with COVID-19 pneumonia requiring non-invasive oxygen were randomized 1:1 to receive a single transfusion of 200 mL of either convalescent plasma or 0.9% saline solution. The primary outcome measure was hospital discharge and/or improvement of ≥ 2 points on the World Health Organisation Blueprint Ordinal Scale for Clinical Improvement by day 28 of enrolment. The trial was stopped early for futility by the Data and Safety Monitoring Board. 103 participants, including 21 HIV positive individuals, were randomized at the time of premature trial termination: 52 in the convalescent plasma and 51 in the placebo group. The primary outcome occurred in 31 participants in the convalescent plasma group and and 32 participants in the placebo group (relative risk 1.03 (95% CI 0.77 to 1.38). Two grade 1 transfusion-related adverse events occurred. Participants who improved clinically received convalescent plasma with a higher median anti-SARS-CoV-2 neutralizing antibody titre compared with those who did not (298 versus 205 AU/mL). Our study contributes additional evidence for recommendations against the use of convalescent plasma for COVID-19 pneumonia. Safety and feasibility in this population supports future investigation for other indications.

Characterising differences in red blood cell usage patterns between healthcare sectors in South Africa: 2014-2019.

BACKGROUND: South Africa aims to transition from a two-tiered healthcare system (public and private) to universal health coverage. Data on red blood cell (RBC) product usage reveal disparities between the sectors. Blood transfusion services further need to understand differing disease profiles and transfusion prescribing practices between the sectors to ensure blood security should the transition to a two-tiered health system come to fruition. MATERIALS AND METHODS: Operational data for public and private healthcare RBC requests between 1 January 2014 and 31 March 2019, obtained from the South African National Blood Service (SANBS), were retrospectively analysed. Sector-specific demographic and utilisation trends were compared for the dominant clinical disciplines. Pre-transfusion haemoglobin (Hb) patterns were also delineated for 2018. RESULTS: Between 2014 and 2019, 2,356,411 public and private sector RBC transfusion events resulted in the issue of 4,020,094 RBC units (1,553,159 transfusion events and 2,495,054 units within the public sector versus 803,282 transfusion events and 1,525,040 units in private). The dominant clinical disciplines within the public sector were Medical (32.9%), Gynaecology/Obstetrics (27.3%), General Surgery (13.6%), and Paediatrics (including Paediatric Surgery) (6.5%), compared to Intensive Care Units (33.2%), Medical (28.3%), General Surgery (10.4%), and Haematology/Oncology (8.3%) in the private sector. Median pre-transfusion Hb values for 2018 were lower in the public than in the private sector: 6.9 g/dL public sector versus 8 g/dL private sector. DISCUSSION: Clinical drivers of RBC usage within the public and private healthcare sectors in South Africa differ significantly. Disparate pre-transfusion Hb between the sectors are likely due to differing disease profiles and severity, as well as differences in practice in prescribing transfusions. Implementation of a nationally co-ordinated Patient Blood Management programme may help to address these disparities and help ensure a sustainable blood transfusion system.

Undisclosed HIV status and antiretroviral therapy use among South African blood donors.

BACKGROUND: Undisclosed antiretroviral drug (ARV) use among blood donors who tested HIV antibody positive, but RNA negative, was previously described by our group. Undisclosed ARV use represents a risk to blood transfusion safety. We assessed the prevalence of and associations with undisclosed ARV use among HIV-positive donors who donated during 2017. STUDY DESIGN AND METHODS: South African National Blood Service (SANBS) blood donors are screened by self-administered questionnaire, semi-structured interview, and individual donation nucleic acid amplification testing for HIV. Stored samples from HIV-positive donations were tested for ARV and characterized as recent/longstanding using lag avidity testing. RESULTS: Of the 1462 HIV-positive donations in 2017, 1250 had plasma availability for testing of which 122 (9.8%) tested positive for ARV. Undisclosed ARV use did not differ by gender (p = .205) or ethnicity (p = .505) but did differ by age category (p < .0001), donor (p < .0001), clinic type (p = .012), home province (p = .01), and recency (p < .0001). Multivariable logistic regression found older age (adjusted odds ratio [aOR] 3.73, 95% confidence interval [CI] 1.98-7.04 for donors >40 compared with those <21), first-time donation (aOR 5.24; 95% CI 2.48-11.11), and donation in a high HIV-prevalence province (aOR 9.10; 95% CI 2.70-30.72) compared with Northern Rural provinces to be independently associated with undisclosed ARV use. DISCUSSION: Almost 1 in 10 HIV-positive blood donors neglected to disclose their HIV status and ARV use. Demographic characteristics of donors with undisclosed ARV use differed from those noted in other study. Underlying motivations for nondisclosure among blood donors remain unclear and may differ from those in other populations with significant undisclosed ARV use.

Phenotypic and lifestyle determinants of HbA1c in the general population-The Hoorn Study.

AIM: To investigate the relative contribution of phenotypic and lifestyle factors to HbA1c, independent of fasting plasma glucose (FPG) and 2h post-load glucose (2hPG), in the general population. METHODS: The study populations included 2309 participants without known diabetes from the first wave of the Hoorn Study (1989) and 2619 from the second wave (2006). Multivariate linear regression models were used to analyze the relationship between potential determinants and HbA1c in addition to FPG and 2hPG. The multivariate model was derived in the first wave of the Hoorn Study, and replicated in the second wave. RESULTS: In both cohorts, independent of FPG and 2hPG, higher age, female sex, larger waist circumference, and smoking were associated with a higher HbA1c level. Larger hip circumference, higher BMI, higher alcohol consumption and vitamin C intake were associated with a lower HbA1c level. FPG and 2hPG together explained 41.0% (first wave) and 53.0% (second wave) of the total variance in HbA1c. The combination of phenotypic and lifestyle determinants additionally explained 5.7% (first wave) and 3.9% (second wave). CONCLUSIONS: This study suggests that, independent of glucose, phenotypic and lifestyle factors are associated with HbA1c, but the contribution is relatively small. These findings contribute to a better understanding of the low correlation between glucose levels and HbA1c in the general population.

Trends in platelet distributions from 2008 to 2017: a survey of twelve national and regional blood collectors.

BACKGROUND: This multi-national study evaluated changes in platelet (PLT) unit distributions at 12 national or regional blood collectors over a 10-year period. METHODS: Data on the total number of PLT distributions, the collection method, that is apheresis vs whole blood-derived (WBD), the PLT unit characteristics and post-collection modifications were obtained from 12 national or regional blood collectors from 2008 through 2017. Individual WBD PLT units were converted to apheresis equivalent units (i.e. a dose of PLTs) by dividing by 4, the typical pool size; WBD units that were pooled before distribution were counted as a single dose. RESULTS: Overall at these 12 blood collectors, the total number of PLTs distributed in 2008 was 1 373 200, which rose by 10·2% to 1 513 803 in 2017. The Japanese Red Cross, which distributes only apheresis PLTs, had a 13·4% increase in the number of distributions between the years 2008 and 2017, while the other 11 blood collectors combined demonstrated a 6·8% increase in distributions between these two years. Between the years 2008 and 2017, the changes in the proportion of apheresis, platelet-rich plasma and buffy coat PLT distributions were -29·9%, -70·7% and 80·0%, respectively. CONCLUSION: The number of PLT distributions increased during the 10-year study period despite prophylactic PLT transfusion thresholds having remained fairly consistent over the last decade. Perhaps this increase is in part driven by increased administration of platelets to patients with massive haemorrhage or an increase in stem cell transplantation. The use of buffy coat PLTs is increasing at these collectors.

Urinary Excretion of N1-methyl-2-pyridone-5-carboxamide and N1-methylnicotinamide in Renal Transplant Recipients and Donors.

N1-methylnicotinamide (N1-MN) and N1-methyl-2-pyridone-5-carboxamide (2Py) are successive end products of NAD+ catabolism. N1-MN excretion in 24-h urine is the established biomarker of niacin nutritional status, and recently shown to be reduced in renal transplant recipients (RTR). However, it is unclear whether 2Py excretion is increased in this population, and, if so, whether a shift in excretion of N1-MN to 2Py can be attributed to kidney function. Hence, we assessed the 24-h urinary excretion of 2Py and N1-MN in RTR and kidney donors before and after kidney donation, and investigated associations of the urinary ratio of 2Py to N1-MN (2Py/N1-MN) with kidney function, and independent determinants of urinary 2Py/N1-MN in RTR. The urinary excretion of 2Py and N1-MN was measured in a cross-sectional cohort of 660 RTR and 275 healthy kidney donors with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Linear regression analyses were used to investigate associations and determinants of urinary 2Py/N1-MN. Median 2Py excretion was 178.1 (130.3-242.8) µmol/day in RTR, compared to 155.6 (119.6-217.6) µmol/day in kidney donors (p < 0.001). In kidney donors, urinary 2Py/N1-MN increased significantly after kidney donation (4.0 ± 1.4 to 5.2 ± 1.5, respectively; p < 0.001). Smoking, alcohol consumption, diabetes, high-density lipoprotein (HDL), high-sensitivity C-reactive protein (hs-CRP) and estimated glomerular filtration rate (eGFR) were identified as independent determinants of urinary 2Py/N1-MN in RTR. In conclusion, the 24-h urinary excretion of 2Py is higher in RTR than in kidney donors, and urinary 2Py/N1-MN increases after kidney donation. As our data furthermore reveal strong associations of urinary 2Py/N1-MN with kidney function, interpretation of both N1-MN and 2Py excretion may be recommended for assessment of niacin nutritional status in conditions of impaired kidney function.

Health economic implications of testing blood donors in South Africa for HTLV 1 & 2 infection.

BACKGROUND AND OBJECTIVES: Currently, HTLV screening is not performed in South Africa (SA). This report describes an economic assessment (budget impact and cost-effectiveness) of implementing different HTLV screening strategies. METHODS: A modified version of the Alliance of Blood Operators risk-based decision-making framework was used to assess the risk and consequences of HTLV in the blood supply in SA. We developed a deterministic model of the cost and consequences of four screening strategies: none, universal, all donors once and first time donors only assuming a transfusion-transmission (TT) efficiency of 10% and a manifestation of clinical disease of 6%. RESULTS: Unscreened blood results in 3·55 symptomatic TT-HTLV cases and a total healthcare cost of Rand (R)3 446 950 (US Dollars (USD)229 800) annually. Universal screening would cost R24 000 000 (USD1 600 000) per annum and prevent 3·54 (99·8%) symptomatic TT-HTLV cases in the first year and 0·55 (98·4%) symptomatic TT-HTLV cases in the second year at a cost per TT-HTLV prevented of R6 780 000 (USD450 000) in year one and R43 254 000 (USD2 890 000) in year two. Screening all donors once would cost R16,200,000 (USD1 080 000) or R4 600 000 (USD306 000) per symptomatic TT-HTLV infection prevented in year one. Total costs decrease to R5 100 000 (USD340 000) in year 2 but the cost per TT-HTLV prevented increases to R10 700 000 (USD713 333). CONCLUSION: This analysis contributed to the decision not to implement HTLV screening as the healthcare budget and particularly the budget for blood transfusion in SA is insufficient to provide appropriate treatment. Arguably, available resources can be more efficiently utilized in other healthcare programs.

Discovery of False Elite Controllers: HIV Antibody-Positive RNA-Negative Blood Donors Found To Be on Antiretroviral Therapy.

BACKGROUND: An increase in potential HIV elite controllers (EC) and anecdotal reports of antiretroviral therapy (ART) use among South African blood donors led us to verify EC status. METHODS: Stored plasma samples from potential EC were tested for ART drugs. Demographic and temporal associations were examined using multivariable logistic regression. RESULTS: Of 226 potential EC, 150 (66.4%) had detectable ART with increasing prevalence by year (OR = 7.57 for 2016 vs 2010, 95% confidence interval, 1.96-32.17). DISCUSSION: False presumptive EC status due to undisclosed ART represents a growing proportion of potential EC donors in South Africa coincident with the country's ART rollout.

The iron status of South African blood donors: balancing donor safety and blood demand.

BACKGROUND: Several studies in developed countries have demonstrated high levels of iron deficiency (ID) among blood donors. There is a paucity of data for developing countries where blood shortages remain a major concern. STUDY DESIGN AND METHODS: A total of 4412 donors were enrolled in the study. Specimens were collected for full blood count, iron, transferrin saturation, and ferritin assessment. Donor demographics were recorded. ID was indicated by a ferritin level of less than 20 ng/mL for men and less than 12 ng/mL for women. Anemia was defined as hemoglobin levels less than 12.5 g/dL. Regression models for predictors of ID were developed. RESULTS: A total of 17.5% of all donors had ID, with 16.3% prevalence in women and 18.6% in men. Low hemoglobin had the highest association with ID (adjusted odds ratio [AOR], 11.078; 95% confidence interval [CI], 7.915-15.505); male donors had twice the odds of ID compared to female donors (AOR, 2.501; 95% CI, 1.964-3.185), while increasing age was associated with lower odds (AOD, 0.965; 95% CI, 0.956-0.975). Among male donors, an interdonation interval of less than 3 months (AOR, 2.679; 95% CI, 1.929-3.720) was associated with ID. Compared to other females combined, colored female donors (AOR, 2.335; 95% CI, 1.310-4.160) had higher odds and black female donors (AOR, 0.559; 95% CI, 0.369-0.845) lower odds of ID. CONCLUSION: ID is common among South African donors; low hemoglobin, gender, ethnicity, and past donation history is independently associated with ID. Recommendations aimed at protecting donor health may increase blood shortages in South Africa.