Critically ill patients with COVID-19 are at increased risk for thrombotic complications which has led to an intense debate surrounding their anticoagulation management. In the absence of data from randomized controlled clinical trials, a number of consensus guidelines and recommendations have been published to facilitate clinical decision-making on this issue. However, substantive differences exist between these guidelines which can be difficult for clinicians. This review briefly summarizes the major societal guidelines and compares their similarities and differences. A common theme in all of the recommendations is to take an individualized approach to patient management and a call for prospective randomized clinical trials to address important anticoagulation issues in this population.

These results provide evidence that mammalian target of rapamycin is a key player involved in prevention of T2 responses by flagellin A conjugate vaccines.

Susceptibility to progressive infection with the fungus Cryptococcus neoformans is associated with an allergic pattern of lung inflammation, yet the factors that govern this host response are not clearly understood. Using a clinically relevant mouse model of inhalational infection with virulent C. neoformans H99, we demonstrate a role for IL-33–dependent signaling in host immune defense. Infection of BALB/c mice with 104 CFU of C. neoformans H99 caused a time-dependent induction of IL-33 with accumulation of type 2 pulmonary innate lymphoid cells and alternatively activated macrophages in the lungs as well as Th2-polarized CD4+ T cells in draining lymph nodes. IL-33R subunit T1/ST2-deficient (T1/ST2−/−) mice infected with C. neoformans H99 had improved survival with a decreased fungal burden in the lungs, spleen, and brain, compared with wild-type mice. Signaling through T1/ST2 was required for the accumulation and early production of IL-5 and IL-13 by lung type 2 pulmonary innate lymphoid cells. Further analysis of T1/ST2−/− mice revealed increased fungicidal exudate macrophages in the lungs and decreased C. neoformans–specific Th2 cells in the mediastinal lymph nodes. T1/ST2 deficiency also diminished goblet cell hyperplasia, mucus hypersecretion, bronchoalveolar lavage eosinophilia, alternative activation of macrophages, and serum IgE. These observations demonstrate that IL-33–dependent signaling contributes to the expansion of innate type 2 immunity and subsequent Th2-biased lung immunopathology that facilitates C. neoformans growth and dissemination.

Scavenger receptor MARCO promotes protective innate immunity against bacterial and parasitic infections; however, its role in host immunity against fungal pathogens, including the major human opportunistic fungal pathogen Cryptococcus neoformans, remains unknown. Using a mouse model of C. neoformans infection we demonstrated that MARCO deficiency leads to impaired fungal control during the afferent phase of cryptococcal infection. Diminished fungal containment in MARCO-/- mice was accompanied by impaired recruitment of Ly6Chigh monocytes and monocyte-derived dendritic cells (moDC) and lower moDC co-stimulatory maturation. The reduced recruitment and activation of mononuclear phagocytes in MARCO-/- mice was linked to diminished early expression of INF-γ along with profound suppression of CCL2 and CCL7 chemokines, providing evidence for roles of MARCO in activation of the CCR2-axis during C. neoformans infection. Lastly, we found that MARCO was involved in C. neoformans phagocytosis by resident pulmonary macrophages and DC. We conclude that MARCO facilitates early interactions between C. neoformans and lung resident cells and promotes the production of CCR2-ligands. In turn, this contributes to a more robust recruitment and activation of moDC that opposes rapid fungal expansion during the afferent phase of cryptococcal infection.