Public Health England and National Health Service Blood and Transplant.

Writing Committee for the REMAP-CAP Investigators IMPORTANCE The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive.OBJECTIVE To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTSThe ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. INTERVENTIONSThe immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). MAIN OUTCOMES AND MEASURESThe primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, −1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events. RESULTS Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR <1.2) was 99.4% for the convalescent plasma group compared with the no convalescent plasma group. The treatment effects were consistent across the primary outcome and the 11...

For many solid organ transplant patients dietary exposure far exceeds the risk of transfusion from unscreened donors. It is only in the immunosuppressed patient requiring extensive blood component support that transfusion risk dominates. This understanding should inform policy decisions on HEV RNA screening of blood donations.

There is evidence of probable recent HEV infections in donors with a predicted attack rate of 2.8%.

Cross-linking of EMA to DNA via photoactivation solved the previously intractable problem of reagent contamination and permitted the development of a high-sensitivity universal bacterial detection system. Trials are ongoing to assess the suitability of the system for high-throughput screening of PLT concentrates.

Dear Editor,We read with interest the letter from Baylis et al., [1] reporting on the detection of hepatitis E virus (HEV) RNA and antibody in plasma fractionation pools, which originated from several regions across the globe. The authors report that 10% of the pools were HEV RNA positive and discuss the transmission risk through the use of plasmaderived medicinal products.We recently reported evidence of current HEV infection in English and Welsh blood donors indicating a turnover of the virus in the donor panel and the potential for transfusion-associated transmission [2]. To ascertain further the risk of HEV to the English blood supply, serological and molecular investigations were undertaken in plasma minipools collected in 2007. Each mini-pool was made up of 48 individual donors and had originally been prepared for hepatitis C RNA screening. Extraction and detection of HEV RNA was carried out on 880 mini-pools (equivalent to approximately 42 000 individual donors) as previously described [2]. Six of the 880 pools (0AE7%) had detectable HEV RNA. As expected, viral loads in the HEV RNApositive pools were low (£ 2000 GEq ⁄ ml). Additional HEV antibody (anti-HEV) testing found all 6 (100%) and 1 ⁄ 6 (17%) of the HEV RNA-positive pools to be anti-HEV IgG and IgM reactive respectively. Of the 100 HEV RNA-negative pools tested, 73% and 0% were HEV IgG and IgM reactive respectively.The high incidence of asymptomatic infection with HEV gives ample opportunity for blood donors to infect recipients. Studies undertaken in the general English population indicate an anti-HEV seroprevalence of 13% and estimate that 60 000 cases occur per year [3]. It is therefore perhaps unsurprising that our study demonstrates a high anti-HEV IgG prevalence in the mini-pools tested. The detection of HEV RNA and anti-HEV IgM demonstrates current HEV infections. In contrast, Baylis et al. [1] found HEV IgG only in the pools from Asia, which is very surprising given the UK seroprevalence. They also report eightfold higher rates of HEV RNA in tested pools from Europe but do not disclose the pool size. Some of these differences may be explained by variations in the make up of the pools and in the detection assays used.Collectively, these reports provide evidence of the potential to transmit HEV from blood ⁄ blood components and products. However, the extent of HEV transmission posttransfusion and the outcome of receiving HEV-containing transfusion products remain poorly explored. The risks of transfusion-associated HEV deserves due consideration in light of emerging data on the significant harm of persistent HEV in the immunosuppressed [4,5]. It is estimated that 75% of UK blood ⁄ blood components are given as haematological support to this population. The issue of HEV and blood safety therefore warrants further studies and debate. References

Viremic donors represent primary infection in older members of the community and reflect a widespread zoonotic in the United Kingdom. The two phylogenetic groups of HEV G3 display different pathogenicity and the more common Group 2 appears less adapted to humans. There are no objective demographic criteria that can identify donors at enhanced HEV risk.

BackgroundXMRV is the most recently described retrovirus to be found in Man, firstly in patients with prostate cancer (PC) and secondly in 67% of patients with chronic fatigue syndrome (CFS) and 3.7% of controls. Both disease associations remain contentious. Indeed, a recent publication has concluded that “XMRV is unlikely to be a human pathogen”. Subsequently related but different polytropic MLV (pMLV) sequences were also reported from the blood of 86.5% of patients with CFS. and 6.8% of controls. Consequently we decided to investigate blood donors for evidence of XMRV/pMLV.Methodology/Principal FindingsTesting of cDNA prepared from the whole blood of 80 random blood donors, generated gag PCR signals from two samples (7C and 9C). These had previously tested negative for XMRV by two other PCR based techniques. To test whether the PCR mix was the source of these sequences 88 replicates of water were amplified using Invitrogen Platinum Taq (IPT) and Applied Biosystems Taq Gold LD (ABTG). Four gag sequences (2D, 3F, 7H, 12C) were generated with the IPT, a further sequence (12D) by ABTG re-amplification of an IPT first round product. Sequence comparisons revealed remarkable similarities between these sequences, endogeous MLVs and the pMLV sequences reported in patients with CFS.Conclusions/SignificanceMethodologies for the detection of viruses highly homologous to endogenous murine viruses require special caution as the very reagents used in the detection process can be a source of contamination and at a level where it is not immediately apparent. It is suggested that such contamination is likely to explain the apparent presence of pMLV in CFS.