Definitive pharmacological therapies for COVID-19 have yet to be identified. Several hundred trials are ongoing globally in the hope of a solution. However, nearly all treatments rely on systemic delivery but COVID-19 damages the lungs preferentially. The use of a targeted delivery approach is reviewed where engineered products are able to reach damaged lung tissue directly, which includes catheter-based and aerosol-based approaches. In this review we have outlined various target directed approaches which include microbubbles, extracellular vesicles including exosomes, adenosine nanoparticles, novel bio-objects, direct aerosol targeted pulmonary delivery and catheter-based drug delivery with reference to their relative effectiveness for the specific lesions. Currently several trials are ongoing to determine the effectiveness of such delivery systems alone and in conjunction with systemic therapies. Such approaches may prove to be very effective in the controlled and localized COVID-19 viral lesions in the lungs and potential sites. Moreover, localized delivery offered a safer delivery mode for such drugs which may have systemic adverse effects.

The viral family Arenaviridae includes a number of viruses that can cause hemorrhagic fever. Arenavirus infection often involves multiple organs and can lead to capillary instability, impaired hemostasis, and death. There is a lack of treatment options available to those suffering from arenaviral hemorrhagic fever and a well established mouse model of arenaviral hemorrhagic fever would benefit preclinical testing for arenavirus antivirals or therapeutics. We have identified the FVB mouse strain, which succumbs to a hemorrhagic fever like illness when infected with lymphocytic choriomeningitis virus (LCMV). FVB mice infected with LCMV demonstrate high mortality associated with thrombocytopenia, hepatocellular and splenic necrosis, and cutaneous hemorrhage whereas C57BL/6 mice survive. Investigation of possible inflammatory mediators revealed increased IFN-g and IL-6, along with increased chemokine production, at early times after LCMV infection as compared to C57BL/6 mice. Removal of CD4+ or CD8+ cells from FVB mice at time of infection prevented mortality in all treated animals and treatment with FK506 early during infection delayed disease onset. This report offers a novel animal model for arenavirus research and pre-clinical therapeutic testing.

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