Neurological complications following COVID-19 infection are not uncommon. Several putative mechanisms for CNS involvement have been suggested.
Vascular changes affecting multiple organs are among the distinctive features of COVID-19. The exact underlying pathophysiological mechanism remains mostly unknown.
In COVID-19 pneumonia, the extensive microvascular damage seems to be related to a macrophage activation syndrome (MAS)-like mechanism  which differs from disseminated intravascular coagulopathy (DIC) and induces a coagulopathic cascade with subsequent local microthrombosis and microbleeding in the small pulmonary vessels.
A similar immune-mediated microvascular damage could be responsible for CNS manifestations , but supporting data are still scarce.
In this case series we presented patients with MRI signs of brain microvascular injury, characterized by small SWI hypointensities with a peculiar distribution.
Corpus callosum is one of the more frequent location of the lesions.
Similar imaging findings are reported in severe acute respiratory distress syndromes, including high altitude cerebral edema (HACE).  Interestingly, in these published cases, microbleeds in the corpus callosum are associated with a restriction on diffusion-weighted sequences, as for cytotoxic edema. The localization of the lesions is very similar to what observed in our series; however, in none of our patient there was associated edema nor focal neither diffuse brain swelling.
Extensive and isolated WM microhemorrhages pattern is also reported in critically ill patients, resulting from long term intubation or ECMO . These findings were recently described in a small number of critically ill patients with COVID-19 . Nevertheless, only a subgroup of our patients required ICU hospitalization.
Stroke associated with a generalized thrombotic predisposition in COVID-19 is of particular interest. Four out of the eight patients had cardiovascular risk factors for stroke including atrial fibrillation. One patient had pulmonary emboli, but still the presence of microthrombi in the distal portions of the pulmonary vascular tree cannot be excluded. COVID-19 is associated with a pro- thrombotic state and highly elevated D-dimer levels, and abnormal coagulation parameters have been shown to be associated with poor outcome  I In our cohort we observed similar gross coagulation values, but an increased inflammatory response that could be linked with increased microthrombothic events.
Cerebral microbleeds are usually due to extravasation of red blood cells, and in the context of COVID-19 could be due to endothelial dysfunction related to viral binding to the ACE-2 receptors expressed on endothelial cells. Indeed, a recent report described direct viral infection of the endothelial cell and diffuse endothelial inflammation in multiple organ systems  .
Endothelial injury can occur in the smallest blood vessels and can be considered as “microangiopathy”. Furthermore, activation of the complement related to the viral infection can determine microthrombi formation. We have also to consider that the term “thrombotic” indicates the presence of blood clots. We can speculate that microthrombotic or microangiopatic lesions can occur in other organs besides the lungs, as in the kidneys, the heart, and the brain at the level of the cerebral small vessels, as previously described   .
In our series the fact that hemorrhage was not evident on gradient echo (GE) sequences (Fig 3) suggests the presence of thrombosis in the vessel walls rather than in the brain parenchyma or in the vessel lumen. SWI sequence can detect micro- and macrohemorhages and delineate cerebral microvasculature and can also reveal low-flow vascular malformations; furthermore, it provides differentiation of calcium from hemorrhage in the brain. Oxyhemoglobin is diamagnetic in nature, whereas deoxyhemoglobin is paramagnetic. The paramagnetic deoxyhemoglobin serves as an intrinsic contrast agent on SWI sequences, and is low in signal. This causes magnetic field inhomogeneity due to two effects: a reduction of T2* and a phase difference between the vessel and its surrounding tissue. This property also forms the basic principle for blood oxygen level dependent functional and venographic imaging. This physical aspect of the SWI sequence can explain why the majority of focal T2 hypointensities are not seen on GE, also supporting the presence not of a true hemorrhage but at least of microthrombosis, that can be located in the vessel wall rather than in the vessel lumen. These findings can be suspicious for endothelial microbleeds (EMBs)/microthrombi.
To support this idea more research on pathology and correlation between MRI and pathologic findings should be performed.
Limitation of this study can be the small sample size; however, to our knowledge, this is the largest series described of patients studied on 3T machine with SWI alterations
In conclusion, we hypothesize that SWI abnormalities in patients with COVID 19 disease with neurological symptoms may correspond to a microvascular endothelial damage with formation of fine thrombi that can be located everywhere in the brain, eventually associated to slow flow in vessels lodged into an area of vascular caliber reduction as in cerebral microvessels, thus configuring a thrombotic microangiopathy. A larger prospective study would be necessary to clarify if this pattern of susceptibility imaging abnormalities as observed in this subset of COVID-19 patients with neurological manifestations, may be related to a thrombotic microangiopathy. In this perspective, histopathological correlation could be enlightening.