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

Staphylococcus aureus bacteremia, Australia

Staphylococcus aureus bacteremia (SAB) is common and increasing worldwide. A retrospective review wyas undertaken to quantify the number of cases, their place of acquisition, and the proportions caused by methicillin-resistant S. aureus (MRSA) in 17 hospitals in Australia. Of 3,192 episodes, 1,571 (49%) were community onset. MRSA caused 40% of hospital-onset episodes and 12% of community-onset episodes. The median rate of SAB was 1.48/1,000 admissions (range 0.61-3.24; median rate for hospital-onset SAB was 0.7/1,000 and for community onset 0.8/1,000 admissions). Using these rates, we estimate that ≈6,900 episodes of SAB occur annually in Australia (35/100,000 population). SAB is common, and a substantial proportion of cases may be preventable. The epidemiology is evolving, with >10% of community-onset SAB now caused by MRSA. This is an emerging infectious disease concern and is likely to impact on empiric antimicrobial drug prescribing in suspected cases of SAB

Staphylococcus aureus Bacteremia, Australia

S. aureus bacteremia in Australia is increasingly caused by MRSA, which is likely to affect empiric prescribing of antimicrobial drugs in suspected cases

Association between VTE and antibiotic prophylaxis guideline compliance and patient-reported outcomes after total hip and knee arthroplasty : an observational study

Background: Surgical site infection (SSI) and venous thromboembolism (VTE) are associated with high burden and cost and are considered largely preventable following total knee or hip arthroplasty (TKA, THA). The risk of developing VTE and SSI is reduced when prophylaxis is compliant with evidence-based clinical guidelines. However, the association between VTE and antibiotic prophylaxis clinical guideline compliance and patient-reported outcome measures (PROMs) after THA/TKA is unknown. This study aims to explore whether care that is non-compliant with VTE and antibiotic guideline recommendations is associated with PROMs (Oxford Hip/Knee Score and EQ-5D Index scores) at 90- and 365-days after surgery. Methods: This prospective observational study included high-volume arthroplasty public and private sites and consenting eligible participants undergoing elective primary THA/TKA. We conducted multiple linear regression and linear mixed-effects modelling to explore the associations between non-compliance with VTE and antibiotic guidelines, and PROMs. Results: The sample included 1838 participants. Compliance with VTE and antibiotic guidelines was 35% and 13.2% respectively. In adjusted modelling, non-compliance with VTE guidelines was not associated with 90-day Oxford score (β = − 0.54, standard error [SE] = 0.34, p = 0.112) but was significantly associated with lower (worse) 365-day Oxford score (β = − 0.76, SE = 0.29, p = 0.009), lower EQ-5D Index scores at 90- (β = − 0.02 SE = 0.008, p = 0.011) and 365-days (β = − 0.03, SE = 0.008, p = 0.002). The changes in Oxford and EQ-5D Index scores were not clinically important. Noncompliance with antibiotic guidelines was not associated with either PROM at 90- (Oxford: β = − 0.45, standard error [SE] = 0.47, p = 0.341; EQ-5D: β = − 0.001, SE = 0.011, p = 0.891) or 365-days (Oxford score: β = − 0.06, SE = 0.41, p = 0.880 EQ-5D: β = − 0.010, SE = 0.012, p = 0.383). Results were consistent when complications were included in the model and in linear mixed-effects modelling with the insurance sector as a random effect. Conclusions: Non-compliance with VTE prophylaxis guidelines, but not antibiotic guidelines, is associated with statistically significant but not clinically meaningful differences in Oxford scores and EQ-5D Index scores at 365 days

SARS Coronavirus-2 microneutralisation and commercial serological assays correlated closely for some but not all enzyme immunoassays

Serological testing for SARS-CoV-2-specific antibodies provides important research and diagnostic information relating to COVID-19 prevalence, incidence and host immune response. A greater understanding of the relationship between functionally neutralising antibodies detected using microneutralisation assays and binding antibodies detected using scalable enzyme immunoassays (EIA) is needed in order to address protective immunity post-infection or vaccination, and assess EIA suitability as a surrogate test for screening of convalescent plasma donors. We assessed whether neutralising antibody titres correlated with signal cut-off ratios in five commercially available EIAs, and one in-house assay based on expressed spike protein targets. Sera from recovered patients or convalescent plasma donors who reported laboratory-confirmed SARS-CoV-2 infection (n = 200), and negative control sera collected prior to the COVID-19 pandemic (n = 100), were assessed in parallel. Performance was assessed by calculating EIA sensitivity and specificity with reference to microneutralisation. Neutralising antibodies were detected in 166 (83%) samples. Compared with this, the most sensitive EIAs were the Cobas Elecsys Anti-SARS-CoV-2 (98%) and Vitros Immunodiagnostic Anti-SARS-CoV-2 (100%), which detect total antibody targeting the N and S1 antigens, respectively. The assay with the best quantitative relationship with microneutralisation was the Euroimmun IgG. These results suggest the marker used (total Ab vs. IgG vs. IgA) and the target antigen are important determinants of assay performance. The strong correlation between microneutralisation and some commercially available assays demonstrates their potential for clinical and research use in assessing protection following infection or vaccination, and use as a surrogate test to assess donor suitability for convalescent plasma donation

SARS-CoV-2 neutralizing antibodies : longevity, breadth, and evasion by emerging viral variants

The Severe Acute Respiratory Syndrome Coronavirus 2 (SAU ARS-CoV-2) antibody neutralization response and its evasion by emerging viral variants and variant of concern (VOC) are unknown, but critical to understand reinfection risk and breakthrough infection following vaccination. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus–cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial samples from 233 reverse transcription polymerase chain reaction (RT-PCR)–confirmed Coronavirus Disease 2019 (COVID-19) individuals with detailed demographics and followed up to 7 months. A broad and sustained polyantigenic immunoreactivity against SARS-CoV-2 Spike, Membrane, and Nucleocapsid proteins, along with high viral neutralization, was associated with COVID-19 severity. A subgroup of “high responders” maintained high neutralizing responses over time, representing ideal convalescent plasma donors. Antibodies generated against SARS-CoV-2 during the first COVID-19 wave had reduced immunoreactivity and neutralization potency to emerging Spike variants and VOC. Accurate monitoring of SARS-CoV-2 antibody responses would be essential for selection of optimal responders and vaccine monitoring and design

Vancomycin Heteroresistance Is Associated with Reduced Mortality in ST239 Methicillin-Resistant Staphylococcus aureus Blood Stream Infections

Background: Despite hVISA infections being associated with vancomycin treatment failure, no previous study has been able to detect a mortality difference between heteroresistant vancomycin intermediate Staphylococcus aureus (hVISA) and vancomycin susceptible Staphylococcus aureus (VSSA) bloodstream infections (BSI)

Effect of Convalescent Plasma on Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial

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 Participants: The 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. Interventions: The 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 Measures: The 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 (O

Methicillin-resistant Staphylococcus aureus in veterinary practice

Staphylococcus aureus is notable for its ubiquity in human and animal hosts, mostly just colonising mammals but sometimes causing invasive disease, which ranges from common minor infections to uncommon severe, sometimes fatal infections. It is also notable for its ability to become resistant to antibiotics; in particular, multiresistant strains emerged in the late 1960s and became endemic in human hospitals almost worldwide in the 1980s. These strains were resistant to methicillin, hence the term methicillin-resistant S. aureus (MRSA), the mechanism of resistance conferring resistance to all beta-lactams (except the new anti-MRSA cephalosporins). These strains have proven challenging to control in human hospitals and multifaceted approaches involving administrative support, education, judicious use of antibiotics, MRSA surveillance, infection control precautions, environmental measures and in selected cases, decolonisation, have been recommended

VISA and hVISA in hospitals

Staphylococcus aureus is noted for its clinical spectrum of disease ranging from asymptomatic colonisation to overwhelming sepsis and death and for its ability to become resistant to antibiotics. Resistance to beta-lactams, methicillin resistance, was first described 50 years ago, becoming a clinical problem in hospitals in the 1970s and the community in the 1990s. MRSA strains that originated in hospitals are usually also resistant to most of the non-beta-lactams as well, leaving vancomycin as the main parenteral drug to treat serious MRSA infections, with the role of new drugs like daptomycin and linezolid not well defined. MRSA strains can exhibit low-level resistance to vancomycin (vancomycin-intermediate S. aureus [VISA]), probably due to a thickened cell wall, which results in the trapping of vancomycin away from the active site of the septum in dividing cells. Detecting this resistance is difficult as multiple genetic pathways lead to this resistance, obviating a molecular test, forcing reliance on phenotypic tests, all of which have issues with sensitivity, specificity and cost. Mortality of bloodstream infection correlates with vancomycin MIC so in this situation the MIC should be determined by Etest or microbroth dilution especially if endocarditis is present. Detection of resistant subpopulations (heterogeneous vancomycin-intermediate S. aureus [hVISA]) can be done with the expensive and time-consuming population analysis profile (PAP) but it is unclear if this confers additional therapeutic information