Monitoring the SARS-CoV-2 Pandemic: Prevalence of Antibodies in a Large, Repetitive Cross-Sectional Study of Blood Donors in Germany-Results from the SeBluCo Study 2020-2022.

SARS-CoV-2 serosurveillance is important to adapt infection control measures and estimate the degree of underreporting. Blood donor samples can be used as a proxy for the healthy adult population. In a repeated cross-sectional study from April 2020 to April 2021, September 2021, and April/May 2022, 13 blood establishments collected 134,510 anonymised specimens from blood donors in 28 study regions across Germany. These were tested for antibodies against the SARS-CoV-2 spike protein and nucleocapsid, including neutralising capacity. Seroprevalence was adjusted for test performance and sampling and weighted for demographic differences between the sample and the general population. Seroprevalence estimates were compared to notified COVID-19 cases. The overall adjusted SARS-CoV-2 seroprevalence remained below 2% until December 2020 and increased to 18.1% in April 2021, 89.4% in September 2021, and to 100% in April/May 2022. Neutralising capacity was found in 74% of all positive specimens until April 2021 and in 98% in April/May 2022. Our serosurveillance allowed for repeated estimations of underreporting from the early stage of the pandemic onwards. Underreporting ranged between factors 5.1 and 1.1 in the first two waves of the pandemic and remained well below 2 afterwards, indicating an adequate test strategy and notification system in Germany.

Risk Assessment of Red Cell Transfusion in Congenital Heart Disease.

BACKGROUND: The storage time of packed red blood cells (pRBC) is an indicator of change in the product's pH, potassium, and lactate levels. Blood-gas analysis is a readily available bedside tool on every intensive care ward to measure these factors prior to application, thus facilitating a calculated decision on a transfusion's quantity and duration.Our first goal is to assess the impact of storage time on pH, potassium, and lactate levels in pRBC. The influence of those parameters in the transfused children will then be evaluated. METHODS: In this retrospective study, we conducted blood-gas analyses of pRBC units before they were administered over 4 hours to neonates, infants, and children in our pediatric cardiac intensive care ward. All patients underwent regular blood-gas analyses themselves, before and after transfusion. RESULTS: We observed a highly significant correlation between the storage time of pRBC units and a drop in pH, as well as an increase in potassium and lactate of stored red cells (p< 0.0001). Median age of recipients with a complete blood-gas dataset was 0.1 (interquartile range [IQR] = 0.0-0.7) years; median pRBC storage duration was 6 (IQR = 5-8) days. Further analyses showed no statistically significant effect on children's blood gases within 4 hours after transfusion, even after stratifying for pRBC storage time ≤7 days and >7 days. CONCLUSION: Stored red blood cells show a rapid decrease in pH and increase in potassium and lactate. Slow transfusion of these units had no adverse effects on the recipients' pH, potassium, and lactate levels.

Case Series: Convalescent Plasma Therapy for Patients with COVID-19 and Primary Antibody Deficiency.

Patients with primary antibody deficiency are at risk for severe and in many cases for prolonged COVID-19. Convalescent plasma treatment of immunocompromised individuals could be an option especially in countries with limited access to monoclonal antibody therapies. While studies in immunocompetent COVID19 patients have demonstrated only a limited benefit, evidence for the safety, timing, and effectiveness of this treatment in antibody-deficient patients is lacking. Here, we describe 16 cases with primary antibody deficiency treated with convalescent plasma in four medical centers. In our cohort, treatment was associated with a reduction in viral load and improvement of clinical symptoms, even when applied over a week after onset of infection. There were no relevant side effects besides a short-term fever reaction in one patient. Longitudinal full-genome sequencing revealed the emergence of mutations in the viral genome, potentially conferring an antibody escape in one patient with persistent viral RNA shedding upon plasma treatment. However, he resolved the infection after a second course of plasma treatment. Thus, our data suggest a therapeutic benefit of convalescent plasma treatment in patients with primary antibody deficiency even months after infection. While it appears to be safe, PCR follow-up for SARS-CoV-2 is advisable and early re-treatment might be considered in patients with persistent viral shedding.

Controlled automated reperfusion of the whole body after 120 minutes of Cardiopulmonary resuscitation: first clinical report.

BACKGROUND: Cardiopulmonary resuscitation (CPR) is associated with a high mortality rate. Furthermore, the few survivors often have severe, persistent cerebral dysfunction. A potential cause for this unsatisfactory outcome after CPR is the combination of cardiac arrest (ischemia) and the inability to restore adequate hemodynamics during conventional CPR (reperfusion), resulting in ischemia/reperfusion injury of the whole body. Therefore we developed a concept counteracting this ischemia/reperfusion injury during the process of CPR. CASE PRESENTATION: We present data from a patient, in whom the concept of a novel controlled automated reperfusion of the whole body (CARL) was applied after 120 min of CPR under normothermic conditions. The patient survived without cerebral deficits and showed full recovery of all organs after prolonged cardiac arrest (CA) except for the spinal cord, where a defect at the level of the 11th thoracic vertebra caused partial loss of motoric function of the legs. CONCLUSION: This is the first reported clinical application of CARL after CA. The implementation of CARL resulted in unexpected survival and recovery after prolonged normothermic CA and CPR. In synopsis with the preclinical experience in pigs this case shows, that the new concept of CARL treating ischemia/reperfusion during the CPR may be an important element within the future treatment of CA. TRIAL REGISTRATION: Trial was retrospectively registered in the "German Clinical Trials Register" ( www.germanctr.de ) under No.: DRKS00005773 on July 28th, 2015.

Hemoglobin mass and biological passport for the detection of autologous blood doping.

PURPOSE: The most promising attempt to reveal otherwise undetectable autologous blood doping is the Athlete Biological Passport enabling a longitudinal monitoring of hematological measures. Recently, the determination of hemoglobin mass (tHb) was suggested to be incorporated in the adaptive model of the Athlete Biological Passport. The purpose therefore was to evaluate the performance of tHb as part of the adaptive model for the detection of autologous blood transfusions in a longitudinal blinded study. METHODS: Twenty-one subjects were divided into a doped group (n = 11) and a control group (n = 10). During the time course of a simulated cycling season (42 wk) including three major competitions (Classics, Grand Tour, World Championships), multiple autologous transfusions of erythrocyte concentrates were assigned in the doped group. A blinded investigator ordered up to 10 tHb measurements (carbon monoxide rebreathing) per subject, mimicking an intelligent doping testing approach in obtaining hematological data (tHb, OFFmass (novel marker including reticulocytes), and respective sequences) for the adaptive model. RESULTS: The final analysis included 199 of 206 overall tHb measurements. The use of tHb, OFFmass, and their sequences as markers of the adaptive model at the 99% specificity level allowed identification of 10 of 11 doped subjects (91% sensitivity) including one false positive in the control group. At the 99.9% specificity level, 8 of 11 subjects were identified without false positives (73% sensitivity). CONCLUSIONS: It seems that the problems of tHb determination by carbon monoxide rebreathing limit the application of this method in antidoping. Because of its potential to detect individual abnormalities associated with autologous blood transfusions shown in this study, a method for tHb determination that is compatible with today's standards of testing should be the focus of future research.

Detection of autologous blood doping with adaptively evaluated biomarkers of doping: a longitudinal blinded study.

BACKGROUND: Since no direct detection method for autologous blood transfusions exists, the most promising attempt is the Athlete Biological Passport (ABP) and its adaptive model that enables a longitudinal monitoring of hematologic measures to identify patterns of blood manipulations. The purpose therefore was to evaluate the performance of this adaptive model for the detection of autologous blood transfusions in a longitudinal blinded setting. STUDY DESIGN AND METHODS: Twenty-one subjects were divided into a doped group (multiple transfusions of 1-2 units of red blood cells, n = 11) and a control group (n = 10). The time course of a cycling season (42 weeks) was simulated including three major competitions (Classics, Grand Tour, World Championships). Up to 10 venous blood samples were ordered per subject by a blinded investigator mimicking the intelligent approach in obtaining hematologic data for the adaptive model (hemoglobin [Hb] concentration, reticulocyte percentage, OFF-score). RESULTS: Retrospective analysis allowed identification of four (probability >99%) or three (probability >99.9%) abnormal samples for Hb and eight (probability >99%) or five (probability >99.9%) abnormal samples for OFF-hr in doped subjects. Four doped subjects (36%) presented an abnormal OFF-hr sequence and three doped subjects (27%) an abnormal Hb sequence; there were no false-positive sequence results. The best possible sensitivity was 82% when a combination of all tests was used. CONCLUSIONS: This investigation provides evidence that the adaptive model allows detection of autologous blood transfusions with a good sensitivity. An intelligent testing approach and the adherence to World Anti-Doping Agency's ABP operating guidelines are nevertheless determinant in the success.

Recovery of hemoglobin mass after blood donation.

BACKGROUND: Blood donation plays an important role in every health care system. Measurement of hemoglobin (Hb) concentration or hematocrit to assess hematologic recovery after donation may not adequately reflect the true amount of blood as they are affected by plasma volume fluctuations. Instead, total Hb mass (tHb) is the variable of choice and can be determined in routine clinical practice. Therefore, the purpose was to investigate the recovery of tHb after standard blood donation. STUDY DESIGN AND METHODS: The optimized CO rebreathing method was used for evaluation of tHb before and after 1-unit (erythrocyte concentrate) standard blood donation in 29 male volunteers (30 +/- 10 years, 181 +/- 7 cm, 76.6 +/- 11.2 kg). Subsequently, tHb measurements were performed in regular intervals until one of two termination criteria was met. RESULTS: After donation of approximately 550 mL of whole blood, the lost amount of tHb of 75 +/- 15 g (8.8 +/- 1.9%) was recovered after a mean of 36 +/- 11 days (range, 20-59 days). CONCLUSIONS: The results of this study confirm the minimal, recommended donation intervals (56 days for men) as adequate when, for the first time, judged upon by tHb as a direct marker of hematologic recovery.

Hb mass measurement suitable to screen for illicit autologous blood transfusions.

PURPOSE: An increase of hemoglobin (Hb) mass is the key target of blood doping practices to enhance performance as it is a main determinant of maximal oxygen uptake. Although detection methods exist for doping with recombinant EPO and homologous blood transfusions, autologous transfusions remain virtually undetectable. In this context, the most sensitive parameter would be a determination of Hb mass itself. The purpose therefore was to establish whether Hb mass measurements by the optimized CO-rebreathing method allow screening for the withdrawal and reinfusion of autologous red blood cells. METHODS: The optimized CO-rebreathing method was used for evaluation of Hb mass in two groups at three time points (duplicate measurements: 1) baseline, 2) after donation, and 3) after reinfusion). Group I (N = 6) was to donate and receive 1 unit of packed red cells (PRC) in contrast to two PRC in group II (N = 4). The time span between withdrawal and reinfusion was 2 d. RESULTS: The mean Hb content of the blood units was 59.0 +/- 3.9 g (group I) and 108.3 +/- 1.3 g (group II). Hb mass decreased significantly after blood withdrawal (-89 +/- 16 g in group I and -120 +/- 14 g in group II) and increased significantly after reinfusion (group I: 70 +/- 16 g; group II: 90 +/- 9 g) but was lower than at baseline (group I: -19 +/- 17 g; group II: -30 +/- 14 g). The total error of measurements for the duplicate measures ranged between 0.8 and 3.1% (Hb mass: 6.4-22.1 g). CONCLUSION: Hb mass determination with the optimized CO-rebreathing method has sufficient precision to detect the absolute differences in Hb mass induced by blood withdrawal and autologous reinfusion. Thus, it may be suited to screen for artificially induced alterations in Hb mass.