COVID 19 and asplenia: a Janus faced issue
Venue: Internal and Emergency Medicine
Year: 2021

Over the last year, the whole scientific community has devoted most of its time to tackle the COVID 19 pandemic and the efforts put into this task have been unprecedented. Currently, one of the most pressing needs worldwide is to vaccinate against COVID 19 as many people as possible, within the shortest time lapse. This is certainly no easy matter, as important considerations and controversies are called into question. At present, vaccine prioritization is based on data regarding age related COVID 19 mortality and privileges older people and healthcare workers who have faced the pandemic in frontline. However, while the selection of these categories may be obvious and supported by either solid scientific validity or political wisdom, the prioritization of individuals categorized as "vulnerable" constitutes a gray area of uncertainty. In this regard, prioritization of patients without a spleen, either surgical or functional, represents a thought provoking example of a Janus faced issue. Indeed, asplenic patients are notoriously more exposed to severe and systemic infections, mainly because of depletion of circulating IgM memory B cells, which are generated in the marginal zone of the spleen and play a major role in mounting the immune response against infections  This should raise several concerns as to whether the lack or the defective function of the spleen could increase the risk of a more severe COVID 19 course and, possibly, could enhance the susceptibility to be infected by SARS CoV 2. In a large, registry based, cohort study assessing mortality from COVID 19, asplenia was found to have an ageand sex matched hazard ratio for mortality comparable to that of other recognized at risk categories, such as hypertension, respiratory diseases, chronic heart disease, and reduced kidney function  According to these data, splenectomised patients or patients with a defective spleen function (e.g. sickle cell disease, celiac disease) should be included in the COVID 19 vaccine prioritization programs. On the other side of the matter, the tropism of coronaviruses for the spleen had already been demonstrated, and white pulp atrophy was observed in ten out of eleven postmortem COVID 19 cases  A recent study of ours  looking at both in vivo and autoptic signs of defective spleen function, showed that IgM memory B cell depletion was very common in hospitalized COVID 19 patients (87.3% and this was associated with a higher mortality rate (28.6% Apart from three patients who had been previously splenectomized, all other patients did not have pre existing diseases that could explain such spleen defect and, furthermore, IgM memory B cell depletion occurred irrespective of older age, sex, and number of comorbidities. In the two autoptic cases, a selective SARS CoV 2 induced damage of the B cell compartment of the spleen was noticed, and this, along with the normal counts of circulating pitted red cells (i.e. erythrocytes with membrane abnormalities visible under phaseinterference microscopy and named pits, whose increase is a marker of spleen hypofunction) points to COVID 19 as a unique disease model of dissociation between the red pulp filtering function and the marginal zone immunological competence of the spleen  Notably, as this immunological defect persists beyond the resolution of SARS CoV 2 infection  this could make ineffective the prophylaxis against encapsulated bacteria through traditional polysaccharide vaccines. Antonio Di Sabatino a.disabatino@smatteo.pv.it