key: cord-0731638-0mucve7f
authors: Sekeres, Mikkael A.
title: Under COVID of the night
date: 2020-12-17
journal: Blood
DOI: 10.1182/blood.2020009377
sha: 224f3aa7d0cb8630e91cad18c631427ac32d1fce
doc_id: 731638
cord_uid: 0mucve7f

nan

Prevalence of CMBs was also associated with lower platelet counts at the time of SWI and with higher organ bleeding scores, but not with mucosal and skin bleeding scores or with the number of previous treatments, age, and sex. In summarizing their findings, Cooper et al suggest that applying a treatment threshold based on platelet count alone could result in some patients being overtreated and others undertreated, and that SWI could provide a specific noninvasive biomarker of central nervous system hemorrhagic tendency, enabling further stratification of disease phenotypes. The inability to link the occurrence of a CMB to a specific time during the course of the disease is a major limitation of this study. Also, as suggested by the authors, longitudinal prospective studies are needed, in particular, to prove that there are increasing numbers of CMBs over time. In a similar study limited to children and adolescents, only 1 case with a single CMB was found among 27 prospectively investigated subjects, all with a platelet count #10 3 10 9 /L at diagnosis or upon symptomatic relapse. 7 Reassuringly, in patients with severe hemophilia, a much more harmful hemorrhagic disease, CMBs were only slightly increased compared with healthy controls. 8

Appropriately, Cooper et al do not recommend brain SWI outside of a research setting. Minor cognitive symptoms with memory and concentration difficulties have been reported in some patients with ITP, but they were ascribed to emotional distress and often associated with other common subjective symptoms like fatigue 9 Cautiously, the authors avoid making conjectures on the possible ominous long-term neurological consequences of CMBs in ITP.

This excellent study raises more issues than it resolves. It will encourage new areas of investigation to clarify the significance of CMBs in ITP and to better understand the mechanisms underlying different bleeding phenotypes beyond the simplistic parameter of the platelet count. 2 I came of professional age in an era when practicing evidence-based medicine was held up as the gold standard for competent and trusted physicians. When faced with a new and poorly defined contagion, with conflicting data about its etiology, transmissibility, lethality, and prevention, and few rigorous studies providing insight into this basic information, I feel unmoored.

This systematic review provides us with data we can use in the common conversations we are now holding daily with our hematologic malignancy patients: That yes, they should continue to practice social distancing, wear masks, engage in good hand hygiene, and avoid risky infectious behaviors; that if they catch the virus, their chance of landing in an intensive care unit is 1 in 5, and of requiring mechanical ventilation is 1 in 6. In fact, their chance of dying from COVID-19 is .10 times higher than the general population. However, as we weigh the relative risks and benefits of initiating treatment of their cancers, we can rest easier that chemotherapy does not appear to increase their chances of dying from the virus. We await population-based studies to answer the question of whether our patients are also at higher risk of catching COVID-19.

The song Undercover of the Night by the Rolling Stones 6 explores political corruption in Central and South America in the 1980s, an area of the world also hit hard by COVID-19. Similar to the virus' path, the sinister forces of which Mick Jagger sings take people's lives by dark of night, while the rest of us "curl up tight," hoping that we also will not get stricken. As we await widespread implementation of an effective vaccine, our best medicine against COVID-19 is to exhort our patients to engage in preventive practices to avoid a substantial risk of dying, so that we can all walk the streets safely again one day. The ultimate challenge in the field of developmental hematopoiesis is understanding the complex differentiation landscape of HSPCs in order to reproduce in vitro, and eventually in vivo, the proper environmental cues to support long-term, multilineage hematopoietic stem cells (HSCs). Blood progenitors appear in the embryo in distinct hematopoietic waves, which differ from each other by their lineage output. 2 Identification of specific cellular markers to isolate these progenitors is essential to explore the hierarchical relationships during developmental hematopoiesis. For this reason, integrative bioinformatics approaches are being used to improve our understanding of the cellular and molecular factors associated with the emergence of HSCs in vivo and in vitro. 3 Fidanza et al reported an elegant, wellconducted study in which human induced pluripotent stem cells-derived HSPCs were sequenced and compared at the single-cell level with in vivo counterparts. More than 40 000 cells were sequenced in the experiments. In the first experiment, the authors selected the CD235a 2 CD43 1 suspension cell population in order to exclude progenitors originating from the primitive wave. This heterogeneous mix of progenitors nicely clustered into clearly separable populations of uncommitted, immature progenitors and cells committed to megakaryocyte, erythroid, and granulocyte lineage, with the identity of each population marked by a unique repertoire of expressed genes. With a combination of semisolid clonogenic assays and a chimeric coculture system, the authors functionally

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