key: cord-314822-lmoc0xwi authors: Flegel, Willy A. title: CoVID‐19 insights from transfusion medicine date: 2020-07-08 journal: Br J Haematol DOI: 10.1111/bjh.17005 sha: doc_id: 314822 cord_uid: lmoc0xwi The emergence of CoVID‐19 infection in the first months of 2020 resulted in a massive surge in admissions to hospitals and intensive care units due to the nature of the respiratory pathophysiology. In some countries, health care systems were rapidly overwhelmed, while in others their hospitals coped with the first wave and all patients received the level of care needed, depending upon both the containment measured and the level of development of the heath care systems. This article is protected by copyright. All rights reserved The emergence of CoVID-19 infection in the first months of 2020 resulted in a massive surge in admissions to hospitals and intensive care units due to the nature of the respiratory pathophysiology. In some countries, health care systems were rapidly overwhelmed, while in others their hospitals coped with the first wave and all patients received the level of care needed, depending upon both the containment measured and the level of development of the heath care systems. Transfusion medicine services have prepared for possible blood shortages caused by a drop in blood donations, if donors became reluctant to participate in blood drives at the usual rate or became symptomatic and unable to donate. 1,2 Shortages were often avoided however, when the lack of donations was more than compensated by an actual drop in blood component utilization as elective procedures with anticipated blood demand were postponed 3, 4 Planning with uncertain timelines and erring on the safe side had previously triggered surpluses with increased outdating of blood components. 5 The first analyses of patients with CoVID-19 in Wuhan, China did not report a substantial need for blood transfusion. 4 For the patients who did require transfusion, the component types and clinical indications remained to be discerned. In this issue Doyle et al 6 weeks, approximately 20% required 1 or more red cell transfusion, 3% required platelet transfusion, and 2% each required fresh frozen plasma or cryoprecipitate. More than 50% of the patients with ECMO used blood components compared to 14% without ECMO. Plasma from convalescent donors was unavailable at the centre during these first 6 weeks. The transfusion requirements were low, unless ECMO was necessary. And blood usage seemed almost restricted to red cell components. During ECMO, the red cell usage in patients with CoVID-19 6 resembled usage in patients without The indications for transfusion in patients without ECMO should be described in greater detail in future studies. One could explore the outcomes, for instance in those 15% of all red cell transfusions that were used for red cell exchanges This article is protected by copyright. All rights reserved alone. Which comorbidities are predisposing to blood transfusion and severity of viral disease? This short report from critical care at a large academic centre in London, UK 6 may not be representative of general clinical settings in primary care hospitals. Hence, more such descriptions of transfusion requirements could be informative, which will eventually allow us to compare the practice among patient cohorts in different countries. There are hardly reasons, however, to suspect blood component usage would be greater in patients with CoVID-19 outside of critical care than inside. Should there be a blood shortage, this would be induced by the supply side rather than any blood demand of this pandemic. Why then should studying transfusion requirements be worthwhile in patient with CoVID-19? To understand the pathophysiology of the CoVID-19 infection, data analysis employs stratification of patients. Transfusion indications and requirements can serve as surrogate markers for the pathophysiology, such as disease severity. For instance, blood cell counts correlated with disease onset and recovery. 8,9 Proper patient blood management should always be applied, 10 particularly to limit blood sampling for study purposes before prompting any transfusion need. In rapid reporting succession, patients with CoVID-19 infection have been documented to develop cold agglutinin disease, 11 the relatively more common autoimmune haemolytic anaemia 12, 13 or immune thrombocytopenia 14 and their combination as Evans syndrome. 15 Each of these clinical entities can progress to require transfusions of red cells or platelets. Platelet transfusions occurred in less than 3% of all patients 6 and may seem minimal, and almost not worth analyzing. However, pragmatic study designs employ such carefully conducted and documented observations. Any prospective observational study can contribute to powerful datasets of thousands of patients within a short time frame, when combined with many similar studies, no matter how small separately. 16 Many platelet components contain 100% plasma. Even when produced with platelet additive solution, such components retain more than 30% of plasma with its residual anti-A and anti-B isoagglutinin. 17 The transfusion of ABO incompatible platelet components is considered benign for known clinical entities. More attention to ABO compatibility would limit antigen-antibody This article is protected by copyright. All rights reserved interactions and complement activation, 18 being known mediators of disseminated intravascular coagulation and systemic inflammatory response syndrome. The accumulated clinical data, if accessible and suitably collated, would suffice to corroborate the safety of current transfusion practice in patients with CoVID-19. These data would also establish a baseline for other CoVID-19 therapies involving plasma. Therapeutic plasma exchange has been applied 19 to treat hyperinflammation in severe CoVID-19, with a choice among fluids, albumin, immunoglobulin, and plasma as replacement volume. The coagulopathy 20 in up to 50% of patients 21 may caution against the use of plasma from convalescent donors, despite promising reports in previous 22 and the current SARS infection. 23, 24 The safety profile has to be established, particularly for patients in early stage CoVID-19, where convalescent plasma, if safe, may be most effective. There is time for better science. 25 The ABO blood group correlates with coagulation activities, particularly von Willebrand factor. An initial report proposed an increased risk for patients with CoVID-19 and blood group A. 26 Additional data 27 and discussion indicated O individuals may be more protected than B individuals, 28, 29 both carrying anti-A albeit of different titers. If titers correlated with disease progression, plasma with high titer isoaglutinin or monoclonal antibodies could be transfused. Even 25% of blood group A patients, who express an A 2 phenotype, can receive anti-A 1. 30 A large genome-wide association study established 2 gene loci conferring susceptibility for respiratory failure. 31 The second, smaller association signal coincided with the gene of the ABO blood group system, showing a higher risk in blood group A and a protective effect in blood group O, 31 although this conclusion was critiqued on technical merits. 32 Of course, more than 10 years ago, the spike protein of SARS-CoV-1 (not today's SARS-CoV-2 of CoVID-19) was inhibited by anti-A antibodies from binding to its receptor on cell surfaces. 33 More study is needed if human red cells express angiotension-converting enzyme 2, 34 the target of the SARS-CoV-2 virus, which is currently not considered to directly bind to red cells. The anti-A effects observed in SARS-CoV-1 35 and now in SARS-CoV-2 26,27,31 deserve attention. As SARS-CoV-1 did not spread into a pandemic, the chance to resolve the mechanism or refute the association had been missed. This article is protected by copyright. All rights reserved Any viral infection has a window of viremia, which may be brief and symptomatic, when a virus is transmittable by blood transfusion. Because no signal for SARS-CoV-2 could be detected in the blood of asymptomatic patients, 36 the blood supply is considered safe without additional virus mitigation; 37,38 this situation is a fortunate coincidence. Pathogen reduction technologies could eliminate any risk posed by this novel virus and are licensed in the EU and US for platelet and plasma components. 39 The current pandemic should stimulate a wider implementation of safeguards for emerging and many unknown viruses, and eventually be applied to red cells as the most widely used blood component. Several routes of research in transfusion medicine can be pursued and contribute to better understand CoVID-19 pathophysiology. Blood supply and transfusion support in southern Italy: findings during the first four weeks of the SARS-CoV-2 pandemic Impact of COVID-19 on blood centres in Zhejiang province China The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and Transfusion Medicine: reflections from Italy Blood transfusion during the COVID-19 outbreak Blood and disaster -supply and demand Blood component use in critical care in patients with COVID-19 infection: a single centre experience Autoimmune haemolytic anaemia associated with COVID-19 infection COVID-19-associated immune thrombocytopenia Evans syndrome in a patient with COVID-19 The association between severe COVID-19 and low platelet count: evidence from 31 observational studies involving 7613 participants Quality improvement with platelet additive solution for safer out-ofgroup platelet transfusions Accepted Article This article is protected by copyright. All rights reserved 18 Pathogenesis and mechanisms of antibody-mediated hemolysis Efficacy of therapeutic plasma exchange in severe COVID-19 patients Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Coagulopathy associated with COVID-19 Convalescent Plasma Study G. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19: A randomized clinical trial Improved clinical symptoms and mortality on severe/critical COVID-19 patients utilizing convalescent plasma transfusion COVID-19 convalescent plasma: now is the time for better science Relationship between ABO blood group distribution and clinical characteristics in patients with COVID-19 Accepted Article This article is protected by copyright. All rights reserved 27 Association between ABO blood groups and risk of SARS-CoV-2 pneumonia More on 'Association between ABO blood groups and risk of SARS-CoV-2 pneumonia' COVID-19 and ABO blood group: another viewpoint Can anti-A1 cause hemolysis? COVID-19 and ABO blood groups Inhibition of the interaction between the SARS-CoV spike protein and its cellular receptor by anti-histoblood group antibodies Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme ABO blood group and susceptibility to severe acute respiratory syndrome SARS-CoV-2 asymptomatic and symptomatic patients and risk for transfusion transmission Coronavirus disease 2019: coronaviruses and blood safety Is SARS-CoV-2 transfusion transmitted? Proceedings of the Food and Drug Administration public workshop on pathogen reduction technologies for blood Accepted Article