Rationale: In addition to the overwhelming lung inflammation that prevails in COVID-19, hypercoagulation and thrombosis contribute to the lethality of subjects infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Platelets are chiefly implicated in thrombosis. Moreover, they can interact with viruses and are an important source of inflammatory mediators. While a lower platelet count is associated with severity and mortality, little is known about platelet function during COVID-19. Objective: To evaluate the contribution of platelets to inflammation and thrombosis in COVID-19 patients. Methods and Results: Blood was collected from 115 consecutive COVID-19 patients presenting non-severe (n=71) and severe (n=44) respiratory symptoms. We document the presence of SARS-CoV-2 RNA associated with platelets of COVID-19 patients. Exhaustive assessment of cytokines in plasma and in platelets revealed the modulation of platelet-associated cytokine levels in both non-severe and severe COVID-19 patients, pointing to a direct contribution of platelets to the plasmatic cytokine load. Moreover, we demonstrate that platelets release their alpha- and dense-granule contents in both non-severe and severe forms of COVID-19. In comparison to concentrations measured in healthy volunteers, phosphatidylserine-exposing platelet extracellular vesicles were increased in non-severe, but not in severe cases of COVID-19. Levels of D-dimers, a marker of thrombosis, failed to correlate with any measured indicators of platelet activation. Functionally, platelets were hyperactivated in COVID-19 subjects presenting non-severe and severe symptoms, with aggregation occurring at suboptimal thrombin concentrations. Furthermore, platelets adhered more efficiently onto collagen-coated surfaces under flow conditions. Conclusions: Taken together, the data suggest that platelets are at the frontline of COVID-19 pathogenesis, as they release various sets of molecules through the different stages of the disease. Platelets may thus have the potential to contribute to the overwhelming thrombo-inflammation in COVID-19, and the inhibition of pathways related to platelet activation may improve the outcomes during COVID-19.

A popular hypothesis is that the dorsal striatum generates discrete "traffic-light" signals that initiate, maintain and terminate the execution of learned actions. Alternatively, the striatum may continuously monitor the dynamics of movements associated with action execution by processing inputs from somatosensory and motor cortices. Here we recorded the activity of striatal neurons in mice performing a run-and-stop task and characterized the diversity of firing rate modulations relative to run performance (tuning curves) across neurons. We found that the tuning curves could not be statistically clustered in discrete functional groups (start or stop neurons). Rather, their shape varied continuously according to the movement dynamics of the task. Moreover, striatal spiking activity correlated with running speed on a run-by-run basis, and was modulated by task-related non-locomotor movements such as licking. We hypothesize that such moment-to-moment movement monitoring by the dorsal striatum contributes to the learning of adaptive actions and/or updating their kinematics.