Severe acute respiratory syndrome coronavirus 2 and blood safety : an updated review

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel human coronavirus first identified in late 2019 and subsequently declared a worldwide pandemic in March 2020. In this review, we provide an overview of the implications of SARS-CoV-2 for blood safety and sufficiency. Summary: Approximately one-third of SARS-CoV-2 infections are asymptomatic. The reported mean incubation period typically varies from 2 to 11 days, but longer periods up to 22 days have been reported. The blood phase of SARS-CoV-2 appears to be brief and low level, with RNAaemia detectable in only a small proportion of patients, typically associated with more severe disease and not demonstrated to be infectious virus. A small number of presymptomatic and asymptomatic blood phase cases have been reported. Transfusion-transmission (TT) of SARS-CoV-2 has not been reported. Therefore, the TT risk associated with SARS-CoV-2 is currently theoretical. To mitigate any potential TT risk, but more importantly to prevent respiratory transmission in donor centers, blood services can implement donor deferral policies based on travel, disease status, or potential risk of exposure and encourage staff vaccination. Key Messages: The TT risk of SARS-CoV-2 appears to be low. The biggest risk to blood services in the current COVID-19 pandemic is to maintain the sufficiency of the blood supply while minimizing respiratory transmission of SARS-CoV-2 to donors and staff while donating blood

Rheumatoid arthritis - treatment: 180. Utility of Body Weight Classified Low-Dose Leflunomide in Japanese Rheumatoid Arthritis

Background: In Japan, more than 20 rheumatoid arthritis (RA) patients died of interstitial pneumonia (IP) caused by leflunomide (LEF) were reported, but many of them were considered as the victims of opportunistic infection currently. In this paper, efficacy and safety of low-dose LEF classified by body weight (BW) were studied. Methods: Fifty-nine RA patients were started to administrate LEF from July 2007 to July 2009. Among them, 25 patients were excluded because of the combination with tacrolimus, and medication modification within 3 months before LEF. Remaining 34 RA patients administered 20 to 50 mg/week of LEF were followed up for 1 year and enrolled in this study. Dose of LEF was classified by BW (50 mg/week for over 50 kg, 40 mg/week for 40 to 50 kg and 20 to 30 mg/week for under 40 kg). The average age and RA duration of enrolled patients were 55.5 years old and 10.2 years. Prednisolone (PSL), methotrexate (MTX) and etanercept were used in 23, 28 and 2 patients, respectively. In case of insufficient response or adverse effect, dosage change or discontinuance of LEF were considered. Failure was defined as dosages up of PSL and MTX, or dosages down or discontinuance of LEF. Last observation carried forward method was used for the evaluation of failed patients at 1 year. Results: At 1 year after LEF start, good/ moderate/ no response assessed by the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score, including a 28-joint count (DAS28)-C reactive protein (CRP) were showed in 14/ 10/ 10 patients, respectively. The dosage changes of LEF at 1 year were dosage up: 10, same dosage: 5, dosage down: 8 and discontinuance: 11 patients. The survival rate of patients in this study was 23.5% (24 patients failed) but actual LEF continuous rate was 67.6% (11 patients discontinued) at 1 year. The major reason of failure was liver dysfunction, and pneumocystis pneumonia was occurred in 1 patient resulted in full recovery. One patient died of sepsis caused by decubitus ulcer infection. DAS28-CRP score was decreased from 3.9 to 2.7 significantly. Although CRP was decreased from 1.50 to 0.93 mg/dl, it wasn't significant. Matrix metalloproteinase (MMP)-3 was decreased from 220.0 to 174.2 ng/ml significantly. Glutamate pyruvate transaminase (GPT) was increased from 19 to 35 U/l and number of leukocyte was decreased from 7832 to 6271 significantly. DAS28-CRP, CRP, and MMP-3 were improved significantly with MTX, although they weren't without MTX. Increase of GPT and leukopenia were seen significantly with MTX, although they weren't without MTX. Conclusions: It was reported that the risks of IP caused by LEF in Japanese RA patients were past IP history, loading dose administration and low BW. Addition of low-dose LEF is a potent safe alternative for the patients showing unsatisfactory response to current medicines, but need to pay attention for liver function and infection caused by leukopenia, especially with MTX. Disclosure statement: The authors have declared no conflicts of interes

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Severe acute respiratory syndrome coronavirus‐2 : implications for blood safety and sufficiency

Background and Objective: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus, first identified in China at the end of 2019 and has now caused a worldwide pandemic. In this review, we provide an overview of the implications of SARS-CoV-2 for blood safety and sufficiency. Material and Method: We searched the PubMed database, the preprint sites bioRxiv and medRxiv, the websites of the World Health Organization, European Centre for Disease Prevention and Control, the US Communicable Diseases Center and monitored ProMed updates. Results: An estimated 15%–46% of SARS-CoV-2 infections are asymptomatic. The reported mean incubation period is 3 to 7 days with a range of 1–14 days. The blood phase of SARS-CoV-2 appears to be brief and low level, with RNAaemia detectable in only a small proportion of patients, typically associated with more severe disease and not demonstrated to be infectious virus. An asymptomatic blood phase has not been demonstrated. Given these characteristics of SARS-CoV-2 infection and the absence of reported transfusion transmission (TT), the TT risk is currently theoretical. To mitigate any potential TT risk, but more importantly to prevent respiratory transmission in donor centres, blood centres can implement donor deferral policies based on travel, disease status or potential risk of exposure. Conclusion: The TT risk of SARS-CoV-2 appears to be low. The biggest risk to blood services in the current COVID-19 pandemic is to maintain the sufficiency of the blood supply while minimizing respiratory transmission of SARS-CoV-19 to donors and staff while donating blood

An Outbreak of Japanese Encephalitis Virus in Australia; What Is the Risk to Blood Safety?

A widespread outbreak of Japanese encephalitis virus (JEV) was detected in mainland Australia in 2022 in a previous non-endemic area. Given JEV is known to be transfusion-transmissible, a rapid blood-safety risk assessment was performed using a simple deterministic model to estimate the risk to blood safety over a 3-month outbreak period during which 234,212 donors attended. The cumulative estimated incidence in donors was 82 infections with an estimated 4.26 viraemic components issued, 1.58 resulting in transfusion-transmission and an estimated risk of encephalitis of 1 in 4.3 million per component transfused over the risk period. Australia has initiated a robust public health response, including vector control, animal control and movement, and surveillance. Unlike West Nile virus, there is an effective vaccine that is being rolled-out to those at higher risk. Risk evaluation considered options such as restricting those potentially at risk to plasma for fractionation, which incorporates additional pathogen reduction, introducing a screening test, physicochemical pathogen reduction, quarantine, post donation illness policy changes and a new donor deferral. However, except for introducing a new deferral to potentially cover rare flavivirus risks, no option resulted in a clear risk reduction benefit but all posed threats to blood sufficiency or cost. Therefore, the blood safety risk was concluded to be tolerable without specific mitigations.</p

Endoscopies, blood-borne viruses and blood donors : time to move on from precaution

Background and objectives: Based on the Council of Europe directive which dictates regulatory requirements in Australia, blood donors are currently deferred from donating for 4 months after an endoscopic procedure if either polyps were removed or a biopsy sample was taken. We aimed to assess the incidence of blood-borne viruses (BBVs) (HIV, hepatitis B and C) in blood donors who donated after an endoscopic procedure and evaluate the risk to blood safety through risk modelling. Materials and methods: Donors from 1/1/2013 to 31/12/2017 with an endoscopy deferral on their blood donor file with pre- and post-BBV testing were analysed to determine an incidence of BBVs using standard methods. The standard blood donor cohort was used as a comparator group. Using the incidence of endoscopies and BBV risk, the total residual risk estimate of allowing donors to return postendoscopy without restriction was calculated. Results: The incidence of a BBV postendoscopy in this large cohort of 16,283 where testing has been confirmed postendoscopy was zero (95% CI 0–0·000105). The upper confidence interval of the zero events is 10·5 per 100 000 donations. Total positive donations from 2017 repeat donors were 1·87 per 100 000 (95% CI 0·0000117–0·0000277). Sensitivity analysis demonstrated that the residual risk remained negligible under realistic worst-case scenarios. Conclusion: A BBV endoscopy deferral is not required for blood safety in Australia. The presented data has enabled us to submit a request for an exemption to our regulator, which has been approved and the policy change subsequently implemented by Lifeblood on 4/4/2020

Blood safety assessment of hepatitis A outbreak linked to frozen pomegranate arils: are foodborne outbreaks an emerging blood safety risk?

BACKGROUND: Foodborne hepatitis A virus (HAV) outbreaks are becoming more common in high-income countries with low HAV incidence, and the associated blood safety risk may not be adequately mitigated by routine HAV risk mitigation strategies. This study describes the rapid risk modeling undertaken in response to a 2018 HAV outbreak in Australia associated with imported frozen pomegranate arils. STUDY DESIGN AND METHODS: The input parameters used in the modeling were the outbreak-associated HAV incidence, duration of viremia, population seroprevalence, and rate of symptomatic infection in adults. The number and risk of viremic components issued, cases of transfusion transmission, and symptomatic infections among recipients were estimated. RESULTS: The incidence of pomegranate-associated HAV infection among donors was very low, with fewer than 0.1 viremic fresh components estimated to have been released during the risk period. The risk of this event was less than one in 500,000, and the risks of transfusion transmission and symptomatic illness in recipients were less than one in one million. When considering only donors who had consumed the pomegranate product, the risk was much higher, with approximately one in 1000 components estimated to be viremic. CONCLUSION: Rapid risk assessment indicated that the overall risk to blood safety associated with a small foodborne outbreak of HAV was negligible. Because fresh components collected from donors known to have consumed the affected product were at high risk, these donors were identified via signage in donor centers and deferred. The contribution of factors other than outbreak size to risk management decisions is discussed